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  • Print publication year: 2014
  • Online publication date: June 2014

Section 3 - Clinical aspects of cerebral small vessel disease

References

1. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010;9:689–701.
2. Norrving B. Long-term prognosis after lacunar infarction. Lancet Neurol 2003;2:238–245.
3. Potter GM, Marlborough FJ, Wardlaw JM. Wide variation in definition, detection, and description of lacunar lesions on imaging. Stroke 2011;42:359–366.
4. Potter GM, Doubal FN, Jackson CA, et al. Counting cavitating lacunes underestimates the burden of lacunar infarction. Stroke 2010;41:267–272.
5. Moreau F, Patel S, Lauzon ML, et al. Cavitation after acute symptomatic lacunar stroke depends on time, location, and MRI sequence. Stroke 2012;43:1837–1842.
6. Kolominsky-Rabas PL, Weber M, Gefeller O, et al. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke 2001;32:2735–2740.
7. Adams HP, Jr., Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35–41.
8. Benavente OR, White CL, Pearce L, et al. The Secondary Prevention of Small Subcortical Strokes (SPS3) study. Int J Stroke 2011;6:164–175.
9. Fang XH, Wang WH, Zhang XQ, et al. Incidence and survival of symptomatic lacunar infarction in a Beijing population: a six-year prospective study. Eur J Neurol 2012;19:1114–1120.
10. White CL, Szychowski JM, Roldan A, et al. Clinical features and racial/ethnic differences among the 3020 participants in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial. J Stroke Cerebrovasc Dis 2012.
11. You R, McNeil JJ, O’Malley HM, Davis SM, Donnan GA. Risk factors for lacunar infarction syndromes. Neurology 1995;45:1483–1487.
12. Tanizaki Y, Kiyohara Y, Kato I, et al. Incidence and risk factors for subtypes of cerebral infarction in a general population: the Hisayama study. Stroke 2000;31:2616–2622.
13. Ohira T, Shahar E, Chambless LE, et al. Risk factors for ischemic stroke subtypes: the atherosclerosis risk in communities study. Stroke 2006;37:2493–2498.
14. Shah IM, Ghosh SK, Collier A. Stroke presentation in type 2 diabetes and the metabolic syndrome. Diabetes Res Clin Pract 2008;79:e1–4.
15. Sacco RL, Boden-Albala B, Abel G, et al. Race–ethnic disparities in the impact of stroke risk factors: the Northern Manhattan Stroke Study. Stroke 2001;32:1725–1731.
16. Bravata DM, Wells CK, Gulanski B, et al. Racial disparities in stroke risk factors: the impact of socioeconomic status. Stroke 2005;36:1507–1511.
17. Morgenstern LB, Smith MA, Lisabeth LD, et al. Excess stroke in Mexican Americans compared with non-Hispanic whites: the brain attack surveillance in the Corpus Christi project. Am J Epidemiol 2004;160:376–383.
18. Bailey EL, Smith C, Sudlow CL, Wardlaw JM. Pathology of lacunar ischemic stroke in humans – a systematic review. Brain Pathol 2012;22:583–591.
19. Brisset M, Boutouyrie P, Pico F, et al. Large-vessel correlates of cerebral small-vessel disease. Neurology 2013;80:662–669.
20. Cho KH, Kang DW, Kwon SU, Kim JS. Location of single subcortical infarction due to middle cerebral artery atherosclerosis: proximal versus distal arterial stenosis. J Neurol Neurosurg Psychiatry 2009;80:48–52.
21. Chan DK, Silver FL. Basilar artery stenosis mimicking the lacunar syndrome of pure motor hemiparesis. Can J Neurol Sci 2003;30:159–162.
22. Khan A, Kasner SE, Lynn MJ, Chimowitz MI, Warfarin Aspirin Symptomatic Intracranial Disease Trial I. Risk factors and outcome of patients with symptomatic intracranial stenosis presenting with lacunar stroke. Stroke 2012;43:1230–1233.
23. Arboix A, Alio J. Cardioembolic stroke: clinical features, specific cardiac disorders and prognosis. Curr Cardiol Rev 2010;6:150–161.
24. Chowdhury D, Wardlaw JM, Dennis MS. Are multiple acute small subcortical infarctions caused by embolic mechanisms? J Neurol Neurosurg Psychiatry 2004;75:1416–1420.
25. Gan R, Sacco RL, Kargman DE, et al. Testing the validity of the lacunar hypothesis: the Northern Manhattan Stroke Study experience. Neurology 1997;48:1204–1211.
26. Arboix A, Massons J, Garcia-Eroles L, et al. Clinical predictors of lacunar syndrome not due to lacunar infarction. BMC Neurol 2010;10:31.
27. Baumgartner RW, Sidler C, Mosso M, Georgiadis D. Ischemic lacunar stroke in patients with and without potential mechanism other than small-artery disease. Stroke 2003;34:653–659.
28. Mead GE, Lewis SC, Wardlaw JM, Dennis MS, Warlow CP. Severe ipsilateral carotid stenosis and middle cerebral artery disease in lacunar ischaemic stroke: innocent bystanders? J Neurol 2002;249:266–271.
29. Hougaku H, Matsumoto M, Handa N, et al. Asymptomatic carotid lesions and silent cerebral infarction. Stroke 1994;25:566–570.
30. Rajapakse A, Rajapakse S, Sharma JC. Is investigating for carotid artery disease warranted in non-cortical lacunar infarction? Stroke 2011;42:217–220.
31. Kim JS. Pure sensory stroke. Clinical–radiological correlates of 21 cases. Stroke 1992;23:983–987.
32. Tei H, Uchiyama S, Maruyama S. Capsular infarcts: location, size and etiology of pure motor hemiparesis, sensorimotor stroke and ataxic hemiparesis. Acta Neurol Scand 1993;88:264–268.
33. Schonewille WJ, Tuhrim S, Singer MB, Atlas SW. Diffusion-weighted MRI in acute lacunar syndromes. A clinical–radiological correlation study. Stroke 1999;30:2066–2069.
34. Fisher CM. Lacunes: small, deep cerebral infarcts. Neurology 1965;15:774–784.
35. Arboix A, Padilla I, Massons J, et al. Clinical study of 222 patients with pure motor stroke. J Neurol Neurosurg Psychiatry 2001;71:239–242.
36. Fisher CM, Curry HB. Pure motor hemiplegia of vascular origin. Arch Neurol 1965;13:30–44.
37. Fisher CM. Thalamic pure sensory stroke: a pathologic study. Neurology 1978;28:1141–1144.
38. Arboix A, Garcia-Plata C, Garcia-Eroles L, et al. Clinical study of 99 patients with pure sensory stroke. J Neurol 2005;252:156–162.
39. Nasreddine ZS, Saver JL. Pain after thalamic stroke: right diencephalic predominance and clinical features in 180 patients. Neurology 1997;48:1196–1199.
40. Kumar B, Kalita J, Kumar G, Misra UK. Central poststroke pain: a review of pathophysiology and treatment. Anesth Analg 2009;108:1645–1657.
41. Mohr JP, Kase CS, Meckler RJ, Fisher CM. Sensorimotor stroke due to thalamocapsular ischemia. Arch Neurol 1977;34:739–741.
42. Staaf G, Samuelsson M, Lindgren A, Norrving B. Sensorimotor stroke; clinical features, MRI findings, and cardiac and vascular concomitants in 32 patients. Acta Neurol Scand 1998;97:93–98.
43. Arboix A, Marti-Vilalta JL, Garcia JH. Clinical study of 227 patients with lacunar infarcts. Stroke 1990;21:842–847.
44. Arboix A. [Clinical study of 23 patients with ataxic hemiparesis.] Med Clin (Barc) 2004;122:342–344 [in Spanish].
45. Hiraga A, Uzawa A, Kamitsukasa I. Diffusion weighted imaging in ataxic hemiparesis. J Neurol Neurosurg Psychiatry 2007;78:1260–1262.
46. Emori T, Kuriyama Y, Imakita S, Sawada T. Ataxic hemiparesis following thalamic lacunar infarction. Intern Med 1992;31:889–892.
47. Moulin T, Bogousslavsky J, Chopard JL, et al. Vascular ataxic hemiparesis: a re-evaluation. J Neurol Neurosurg Psychiatry 1995;58:422–427.
48. Gorman MJ, Dafer R, Levine SR. Ataxic hemiparesis: critical appraisal of a lacunar syndrome. Stroke 1998;29:2549–2555.
49. Flint AC, Naley MC, Wright CB. Ataxic hemiparesis from strategic frontal white matter infarction with crossed cerebellar diaschisis. Stroke 2006;37:e1–2.
50. Arboix A, Bell Y, Garcia-Eroles L, et al. Clinical study of 35 patients with dysarthria–clumsy hand syndrome. J Neurol Neurosurg Psychiatry 2004;75:231–234.
51. Martin PJ, Chang HM, Wityk R, Caplan LR. Midbrain infarction: associations and aetiologies in the New England medical center posterior circulation registry. J Neurol Neurosurg Psychiatry 1998;64:392–395.
52. Bogousslavsky J, Maeder P, Regli F, Meuli R. Pure midbrain infarction: clinical syndromes, MRI, and etiologic patterns. Neurology 1994;44:2032–2040.
53. Umasankar U, Huwez FU. A patient with reversible pupil-sparing Weber’s syndrome. Neurol India 2003;51:388–389.
54. Silverman IE, Liu GT, Volpe NJ, Galetta SL. The crossed paralyses. The original brain-stem syndromes of Millard-Gubler, Foville, Weber, and Raymond–Cestan. Arch Neurol 1995;52:635–638.
55. Sitthinamsuwan B, Nunta-Aree S, Sitthinamsuwan P, Suwanawiboon B, Chiewvit P. Two patients with rare causes of Weber’s syndrome. J Clin Neurosci 2011;18:578–579.
56. Patel R, Jha S, Yadav RK. Pleomorphism of the clinical manifestations of neurocysticercosis. Trans R Soc Trop Med Hyg 2006;100:134–141.
57. Broadley SA, Taylor J, Waddy HM, Thompson PD. The clinical and MRI correlate of ischaemia in the ventromedial midbrain: Claude’s syndrome. J Neurol 2001;248:1087–1089.
58. Asakawa H, Yanaka K, Nose T. MRI of Claude’s syndrome. Neurology 2003;61:575.
59. Seo SW, Heo JH, Lee KY, et al. Localization of Claude’s syndrome. Neurology 2001;57:2304–2307.
60. Coppola RJ. Localization of Claude’s syndrome. Neurology 2002;58:1707; author reply 1707–1708.
61. Dhanjal T, Walters M, MacMillan N. Claude’s syndrome in association with posterior cerebral artery stenosis. Scott Med J 2003;48:91–92.
62. Serrano-Pozo A, Montes-Latorre E, Gonzalez-Marcos JR, Gil-Peralta A. Cardiac embolism in a Claude’s syndrome without involvement of the red nucleus. Eur J Neurol 2007;14:e1–2.
63. Song TJ, Suh SH, Cho H, Lee KY. Claude’s syndrome associated with neurocysticercosis. Yonsei Med J 2010;51:978–979.
64. Borras JM, Salazar FG, Grandas F. Oculomotor palsy and contralateral tremor (Benedikt’s syndrome) following a stereotactic procedure. J Neurol 1997;244:272–274.
65. Liu GT, Crenner CW, Logigian EL, Charness ME, Samuels MA. Midbrain syndromes of Benedikt, Claude, and Nothnagel: setting the record straight. Neurology 1992;42:1820–1822.
66. Paidakakos NA, Rokas E, Theodoropoulos S, Dimogerontas G, Konstantinidis E. Posttraumatic Benedikt’s syndrome: a rare entity with unclear anatomopathological correlations. World Neurosurg 2012;78:e713–715.
67. Loseke N, Retif J, Noterman J, Flament-Durand J. Inferior red nucleus syndrome (Benedikt’s syndrome) due to a single intramesencephalic metastasis from a prostatic carcinoma. Case report. Acta Neurochir (Wien) 1981;56:59–64.
68. Maduri R, Barbagallo G, Iofrida G, Signorelli M, Signorelli F. Regression of Benedikt’s syndrome after single-stage removal of mesencephalic cavernoma and temporal meningioma: a case report. Clin Neurol Neurosurg, in press.
69. Field TS, Benavente OR. Penetrating artery territory pontine infarction. Rev Neurol Dis 2011;8:30–38.
70. Kumral E, Bayulkem G, Evyapan D. Clinical spectrum of pontine infarction. Clinical–MRI correlations. J Neurol 2002;249:1659–1670.
71. Zaorsky NG, Luo JJ. A case of classic Raymond syndrome. Case Rep Neurol Med 2012;2012:583123.
72. Ogawa K, Suzuki Y, Kamei S. Two patients with abducens nerve palsy and crossed hemiplegia (Raymond syndrome). Acta Neurol Belg 2010;110:270–271.
73. Satake M, Kira J, Yamada T, Kobayashi T. Raymond syndrome (alternating abducent hemiplegia) caused by a small haematoma at the medial pontomedullary junction. J Neurol Neurosurg Psychiatry 1995;58:261.
74. Onbas O, Kantarci M, Alper F, Karaca L, Okur A. Millard–Gubler syndrome: MR findings. Neuroradiology 2005;47:35–37.
75. Matsuyama T, Masuda A. [A rare case of delayed traumatic Millard–Gubler syndrome.] No Shinkei Geka 1992;20:697–699.
76. Gardela G, Kusmiderski J, Slowik S. [Millard–Gubler syndrome in a young man after hemorrhage from arteriovenous hemangioma to the brainstem.] Neurol Neurochir Pol 1989;23:149–152 [in Polish].
77. Kesikburun S, Safaz I, Alaca R. Pontine cavernoma hemorrhage leading to Millard-Gubler syndrome. Am J Phys Med Rehabil 2011;90:263.
78. Prasad R, Kapoor K, Srivastava A, Mishra O. Neurocysticercosis presenting as Millard–Gubler syndrome. J Neurosci Rural Pract 2012;3:375–377.
79. Lee MJ, Park YG, Kim SJ, et al. Characteristics of stroke mechanisms in patients with medullary infarction. Eur J Neurol 2012;19:1433–1439.
80. Fukuoka T, Takeda H, Dembo T, et al. Clinical review of 37 patients with medullary infarction. J Stroke Cerebrovasc Dis 2012;21:594–599.
81. Kim JS. Pure lateral medullary infarction: clinical–radiological correlation of 130 acute, consecutive patients. Brain 2003;126:1864–1872.
82. Swenson AJ, Leira EC. Paroxysmal sneezing at the onset of lateral medullary syndrome: cause or consequence? Eur J Neurol 2007;14:461–463.
83. Sacco RL, Freddo L, Bello JA, et al. Wallenberg’s lateral medullary syndrome. Clinical-magnetic resonance imaging correlations. Arch Neurol 1993;50:609–614.
84. Newman-Toker DE, Kattah JC, Alvernia JE, Wang DZ. Normal head impulse test differentiates acute cerebellar strokes from vestibular neuritis. Neurology 2008;70:2378–2385.
85. Kattah JC, Talkad AV, Wang DZ, Hsieh YH, Newman-Toker DE. Hints to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke 2009;40:3504–3510.
86. Kim JS, Lee JH, Suh DC, Lee MC. Spectrum of lateral medullary syndrome. Correlation between clinical findings and magnetic resonance imaging in 33 subjects. Stroke 1994;25:1405–1410.
87. Norrving B, Cronqvist S. Lateral medullary infarction: prognosis in an unselected series. Neurology 1991;41:244–248.
88. Kim JS, Han YS. Medial medullary infarction: clinical, imaging, and outcome study in 86 consecutive patients. Stroke 2009;40:3221–3225.
89. Kameda W, Kawanami T, Kurita K, et al. Lateral and medial medullary infarction: a comparative analysis of 214 patients. Stroke 2004;35:694–699.
90. Bassetti C, Bogousslavsky J, Mattle H, Bernasconi A. Medial medullary stroke: report of seven patients and review of the literature. Neurology 1997;48:882–890.
91. Toyoda K, Imamura T, Saku Y, et al. Medial medullary infarction: analyses of 11 patients. Neurology 1996;47:1141–1147.
92. Percheron G. [Arteries of the human thalamus. II. Arteries and paramedian thalamic territory of the communicating basilar artery.] Rev Neurol (Paris) 1976;132:309–324 [in French].
93. Percheron G. [Arteries of the human thalamus. I. Artery and polar thalamic territory of the posterior communicating artery.] Rev Neurol (Paris) 1976;132:297–307 [in French].
94. Percheron G. [Arteries of the thalamus in man. Choroidal arteries. III. Absence of the constituted thalamic territory of the anterior choroidal artery. IV. Arteries and thalamic territories of the choroidal and postero-median thalamic arterial system. V. Arteries and thalamic territories of the choroidal and postero-lateral thalamic arterial system.] Rev Neurol (Paris) 1977;133:547–558 [in French].
95. Schmahmann JD. Vascular syndromes of the thalamus. Stroke 2003;34:2264–2278.
96. Carrera E, Bogousslavsky J. The thalamus and behavior: effects of anatomically distinct strokes. Neurology 2006;66:1817–1823.
97. Bogousslavsky J, Regli F, Uske A. Thalamic infarcts: clinical syndromes, etiology, and prognosis. Neurology 1988;38:837–848.
98. Swartz RH, Black SE. Anterior-medial thalamic lesions in dementia: frequent and volume-dependently associated with sudden cognitive decline. J Neurol Neurosurg Psychiatry 2006;77:1307–1312.
99. Gorelick PB, Amico LL, Ganellen R, Benevento LA. Transient global amnesia and thalamic infarction. Neurology 1988;38:496–499.
100. Melo TP, Bogousslavsky J. Hemiataxia-enhypesthesia: a thalamic stroke syndrome. J Neurol Neurosurg Psychiatry 1992;55:581–584.
101. Karnath HO, Himmelbach M, Rorden C. The subcortical anatomy of human spatial neglect: putamen, caudate nucleus and pulvinar. Brain 2002;125:350–360.
102. Neau JP, Bogousslavsky J. The syndrome of posterior choroidal artery territory infarction. Ann Neurol 1996;39:779–788.
103. Ghika J, Bogousslavsky J, Henderson J, Maeder P, Regli F. The “jerky dystonic unsteady hand”: a delayed motor syndrome in posterior thalamic infarctions. J Neurol 1994;241:537–542.
104. Donnan GA, O’Malley HM, Quang L, Hurley S, Bladin PF. The capsular warning syndrome: pathogenesis and clinical features. Neurology 1993;43:957–962.
105. Paul NL, Simoni M, Chandratheva A, Rothwell PM. Population-based study of capsular warning syndrome and prognosis after early recurrent TIA. Neurology 2012;79:1356–1362.
106. Abetz L, Allen R, Follet A, et al. Evaluating the quality of life of patients with restless legs syndrome. Clin Ther 2004;26:925–935.
107. Lee J, Albers GW, Marks MP, Lansberg MG. Capsular warning syndrome caused by middle cerebral artery stenosis. J Neurol Sci 2010;296:115–120.
108. Chen ZC, Sun JZ, Shi ZH, Lou M. Capsular warning syndrome caused by spontaneous middle cerebral artery dissection. CNS Neurosci Ther 2012;18:702–704.
109. Tang CW, Wang PN, Lin KP, et al. Microscopic polyangiitis presenting with capsular warning syndrome and subsequent stroke. J Neurol Sci 2009;277:174–175.
110. Ferro JM, Falcao F, Melo TP, Campos JG. Dural sinus thrombosis mimicking “capsular warning syndrome.” J Neurol 2000;247:802–803.
111. Farrar J, Donnan GA. Capsular warning syndrome preceding pontine infarction. Stroke 1993;24:762.
112. Saposnik G, Noel de Tilly L, Caplan LR. Pontine warning syndrome. Arch Neurol 2008;65:1375–1377.
113. Muengtaweepongsa S, Singh NN, Cruz-Flores S. Pontine warning syndrome: case series and review of literature. J Stroke Cerebrovasc Dis 2010;19:353–356.
114. Staaf G, Geijer B, Lindgren A, Norrving B. Diffusion-weighted MRI findings in patients with capsular warning syndrome. Cerebrovasc Dis 2004;17:1–8.
115. Del Bene A, Palumbo V, Lamassa M, et al. Progressive lacunar stroke: review of mechanisms, prognostic features, and putative treatments. Int J Stroke 2012;7:321–329.
116. Chalela JA, Ezzeddine M, Latour L, Warach S. Reversal of perfusion and diffusion abnormalities after intravenous thrombolysis for a lacunar infarction. J Neuroimaging 2003;13:152–154.
117. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–1587.
118. Shobha N, Fang J, Hill MD. Do lacunar strokes benefit from thrombolysis? Evidence from the Registry of the Canadian Stroke Network. Int J Stroke 2013; 8(Suppl A100):45–9.
119. Mustanoja S, Meretoja A, Putaala J, et al. Outcome by stroke etiology in patients receiving thrombolytic treatment: descriptive subtype analysis. Stroke 2011;42:102–106.
120. Lee SJ, Saver JL, Liebeskind DS, et al. Safety of intravenous fibrinolysis in imaging-confirmed single penetrator artery infarcts. Stroke 2010;41:2587–2591.
121. Vivanco-Hidalgo RM, Rodriguez-Campello A, Ois A, et al. Thrombolysis in capsular warning syndrome. Cerebrovasc Dis 2008;25:508–510.
122. Nguyen TH, Vo D, Ngo MB, et al. Thrombolysis in recurrent lacunar stroke: a case example. Eur J Neurol 2008;15:1409–1411.
123. Mistri AK, Robinson TG, Potter JF. Pressor therapy in acute ischemic stroke: systematic review. Stroke 2006;37:1565–1571.
124. Lalive PH, Mayor I, Sztajzel R. The role of blood pressure in lacunar strokes preceded by TIAs. Cerebrovasc Dis 2003;16:88–90.
125. Lim TS, Hong JM, Lee JS, et al. Induced-hypertension in progressing lacunar infarction. J Neurol Sci 2011;308:72–76.
126.Canadian Stroke Strategy. Canadian Best Practice Recommendations for Stroke Care: update 2010. http://www.strokebestpractices.ca/wp-content/uploads/2011/04/2010BPR_ENG.pdf (accessed May 5, 2013).
127. The International Stroke Trial (IST). A randomised trial of aspirin, subcutaneous heparin, both, or neither among 19 435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997;349:1569–1581.
128. Chinese Acute Stroke Trial (CAST) Collaborative Group. Randomised placebo-controlled trial of early aspirin use in 20 000 patients with acute ischaemic stroke. Lancet 1997;349:1641–1649.
129. Chen ZM, Sandercock P, Pan HC, et al. Indications for early aspirin use in acute ischemic stroke: a combined analysis of 40 000 randomized patients from the Chinese Acute Stroke Trial and the International Stroke Trial. On behalf of the CAST and IST Collaborative Groups. Stroke 2000;31:1240–1249.
130. Kennedy J, Hill MD, Ryckborst KJ, et al. Fast Assessment of Stroke and Transient Ischaemic Attack to Prevent Early Recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol 2007;6:961–969.
131. Dengler R, Diener HC, Schwartz A, et al. Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial. Lancet Neurol 2010;9:159–166.
132. Fahey CD, Alberts MJ, Bernstein RA. Oral clopidogrel load in aspirin-resistant capsular warning syndrome. Neurocrit Care 2005;2:183–184.
133. Asil T, Ir N, Karaduman F, Cagli B, Tuncel S. Combined antithrombotic treatment with aspirin and clopidogrel for patients with capsular warning syndrome: a case report. Neurologist 2012;18:68–69.
134. Philipps J, Thomalla G, Glahn J, Schwarze M, Rother J. Treatment of progressive stroke with tirofiban – experience in 35 patients. Cerebrovasc Dis 2009;28:435–438.
135. Martin-Schild S, Shaltoni H, Abraham AT, et al. Safety of eptifibatide for subcortical stroke progression. Cerebrovasc Dis 2009;28:595–600.
136. Dobkin BH. Heparin for lacunar stroke in progression. Stroke 1983;14:421–423.
137. Haley EC, Jr., Kassell NF, Torner JC. Failure of heparin to prevent progression in progressing ischemic infarction. Stroke 1988;19:10–14.
138. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011;365:993–1003.
139. Saposnik G, Hassan KA, Selchen D, et al. Stroke unit care: does ischemic stroke subtype matter? Int J Stroke 2011;6:244–250.
140. Smith EE, Hassan KA, Fang J, et al. Do all ischemic stroke subtypes benefit from organized inpatient stroke care? Neurology 2010;75:456–462.
141. Lansberg MG, Albers GW, Beaulieu C, Marks MP. Comparison of diffusion-weighted MRI and CT in acute stroke. Neurology 2000;54:1557–1561.
142. Albers GW, Lansberg MG, Norbash AM, et al. Yield of diffusion-weighted MRI for detection of potentially relevant findings in stroke patients. Neurology 2000;54:1562–1567.
143. Wessels T, Rottger C, Jauss M, et al. Identification of embolic stroke patterns by diffusion-weighted MRI in clinically defined lacunar stroke syndromes. Stroke 2005;36:757–761.
144. Kang DW, Chalela JA, Ezzeddine MA, Warach S. Association of ischemic lesion patterns on early diffusion-weighted imaging with TOAST stroke subtypes. Arch Neurol 2003;60:1730–1734.
145. Campbell BC, Weir L, Desmond PM, et al. CT perfusion improves diagnostic accuracy and confidence in acute ischaemic stroke. J Neurol Neurosurg Psychiatry 2013;84:613–618.
146. Lin K, Do KG, Ong P, et al. Perfusion CT improves diagnostic accuracy for hyperacute ischemic stroke in the three-hour window: study of 100 patients with diffusion MRI confirmation. Cerebrovasc Dis 2009;28:72–79.

References

1. De Leeuw FE, de Groot JC, Achten E, et al. Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 2001;70:9–14.
2. Longstreth WT, Manolio TA, Arnold A. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people: the Cardiovascular Health Study. Stroke 1996;27:1274–1282.
3. Ylikoski A, Erkinjuntti T, Raininko R, et al. White matter hyperintensities on MRI in the neurologically nondiseased elderly. Analysis of cohorts of consecutive subjects aged 55 to 85 years living at home. Stroke 1995;26:1171–1177.
4. Schmidt R, Schmidt H, Haybaeck J, et al. Heterogeneity in age-related white matter changes. Acta Neuropathol 2011;122:171–185.
5. Barber R, Scheltens P, Gholkar A, et al. White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer’s disease, vascular dementia, and normal aging. J Neurol Neurosurg Psychiatry 1999;67:66–72.
6. Silbert LC, Kaye J. Neuroimaging and cognition in Parkinson’s disease dementia. Brain Pathol 2010;20:646–653.
7. Barber R, Gholkar A, Scheltens P, et al. MRI volumetric correlates of white matter lesions in dementia with Lewy bodies and Alzheimer’s disease. Int J Geriatr Psychiatry 2000;15:911–916.
8. Meyer JS, Huang J, Chowdhury MH. MRI confirms mild cognitive impairments prodromal for Alzheimer’s, vascular and Parkinson–Lewy body dementias. J Neurol Sci 2007;257:97–104.
9. Burton EJ, McKeith IG, Burn DJ, Firbank MJ, O’Brien JT. Progression of white matter hyperintensities in Alzheimer’s disease, dementia with Lewy bodies, and Parkinson disease dementia: a comparison with normal aging. Am J Geriatr Psychiatry 2006;14:842–849.
10. Skoog IBS, Johansson B, Palmertz B, Andreasson LA. The influence of white matter lesions on neuropsychological functioning in demented and non-demented 85-year-olds. Acta Neurol Scand 1996;93:142–148.
11. De Leeuw FE, de Groot JC, Oudkerk M, et al. Hypertension and cerebral white matter lesions in a prospective cohort study. Brain 2002;125:765–772.
12. Verdelho A, Madureira S, Ferro JM, et al. Differential impact of cerebral white matter changes, diabetes, hypertension and stroke on cognitive performance among non-disabled elderly. The LADIS study. J Neurol Neurosurg Psychiatry 2007;78:1325–1330.
13. Ylikoski R, Ylikoski A, Raininko R, et al. Cardiovascular diseases, health status, brain imaging findings and neuropsychological functioning in neurologically healthy elderly individuals. Arch Gerontol Geriatr 2000;30:115–130.
14. Inaba M, White L, Bell C, et al. White matter lesions on brain magnetic resonance imaging scan and five-year cognitive decline: the Honolulu–Asia Aging Study. J Am Geriatr Soc 2011;59:1484–1489.
15. Breteler MM, Swieten JCV, Bots ML. Cerebral white matter lesions, vascular risk factors and cognitive function in a population-based study: the Rotterdam Study. Neurology 1994;44:1246–1253.
16. Garde E, Mortensen EL, Krabbe K, Rostrup E, Larsson HB. Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study. Lancet 2000;356:628–634.
17. Schmidt R, Ropele S, Enzinger C, et al. White matter lesion progression, brain atrophy, and cognitive decline: the Austrian Stroke Prevention Study. Ann Neurol 2005;58:610–616.
18. Hirono N, Kitagaki H, Kazui H, Hashimoto M, Mori E. Impact of white matter changes on clinical manifestation of Alzheimer’s disease – a quantitative study Stroke 2000;31:2182–2188.
19. Mungas D, Harvey D, Reed BR, et al. Longitudinal volumetric MRI change and rate of cognitive decline. Neurology 2005;65:565–571.
20. DeCarli C, Mungas D, Harvey D, et al. Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia. Neurology 2004;63:220–227.
21. Tzourio C, Dufouil C, Ducimetiere P, Alperovitch A. Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. EVA Study Group. Epidemiology of vascular aging. Neurology 1999;53:1948–1952.
22. Prins ND, van Dijk EJ, den Heijer T, et al. Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain 2005;128:2034–2041.
23. Kramer JH, Mungas D, Reed BR, et al. Longitudinal MRI and cognitive change in healthy elderly. Neuropsychology 2007;21:412–418.
24. Tullberg M, Fletcher E, DeCarli C, et al. White matter lesions impair frontal lobe function regardless of their location. Neurology 2004;63:246–253.
25. Kuller LH, Lopez OL, Newman A, et al. Risk factors for dementia in the Cardiovascular Health Cognition Study. Neuroepidemiology 2003;22:13–22.
26. Silbert LC, Howieson DB, Dodge H, Kaye JA. Cognitive impairment risk: white matter hyperintensity progression matters. Neurology 2009;73:120–125.
27. Longstreth WT, Jr., Arnold AM, Beauchamp NJ, Jr., et al. Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke 2005;36:56–61.
28. Van Dijk EJ, Prins ND, Vrooman HA, et al. Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan Study. Stroke 2008;39:2712–2719.
29. Van den Heuvel DM, ten Dam VH, de Craen AJ, et al. Increase in periventricular white matter hyperintensities parallels decline in mental processing speed in a non-demented elderly population. J Neurol Neurosurg Psychiatry 2006;77:149–153.
30. Jokinen H, Kalska H, Ylikoski R, et al. Longitudinal cognitive decline in subcortical ischemic vascular disease – the LADIS study. Cerebrovasc Dis 2009;27:384–391.
31. Steffens DC, Potter GG, McQuoid DR, et al. Longitudinal magnetic resonance imaging vascular changes, apolipoprotein E genotype, and development of dementia in the neurocognitive outcomes of depression in the elderly study. Am J Geriatr Psychiatry 2007;15:839–849.
32. Debette S, Beiser A, DeCarli C, et al. Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study. Stroke 2010;41:600–606.
33. Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 2010;341:3666.
34. Prins ND, van Dijk EJ, den Heijer T, et al. Cerebral white matter lesions and the risk of dementia. Arch Neurol 2004;61:1531–1534.
35. Bombois S, Debette S, Bruandet A, et al. Vascular subcortical hyperintensities predict conversion to vascular and mixed dementia in mci patients. Stroke 2008;39:2046–2051.
36. Meguro K, Ishii H, Kasuya M, et al. Incidence of dementia and associated risk factors in Japan: the Osaki–Tajiri project. J Neurol Sci 2007;260:175–182.
37. Burton EJ, Kenny RA, O’Brien J, et al. White matter hyperintensities are associated with impairment of memory, attention, and global cognitive performance in older stroke patients. Stroke 2004;35:1270–1275.
38. Verdelho A, Madureira S, Moleiro C, et al. White matter changes and diabetes predict cognitive decline in the elderly: the LADIS study. Neurology 2010;75:160–167.
39. Staekenborg SS, Koedam EL, Henneman WJ, et al. Progression of mild cognitive impairment to dementia: contribution of cerebrovascular disease compared with medial temporal lobe atrophy. Stroke 2009;40:1269–1274.
40. Jagust WJ, Zheng L, Harvey DJ, et al. Neuropathological basis of magnetic resonance images in aging and dementia. Ann Neurol 2008;63:72–80.
41. Capizzano AA, Acion L, Bekinschtein T, et al. White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2004;75:822–827.
42. Acosta-Cabronero J, Williams GB, Pengas G, Nestor PJ. Absolute diffusivities define the landscape of white matter degeneration in Alzheimer’s disease. Brain 2010;133:529–539.
43. Ryberg C, Rostrup E, Paulson OB, et al. Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a three-year follow-up of the LADIS study cohort. J Neurol Sci 2011;307:100–105.
44. Jokinen H, Ryberg C, Kalska H, et al. Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS study. J Neurol Neurosurg Psychiatry 2007;78:491–496.
45. Ryberg C, Rostrup E, Stegmann MB, et al. Clinical significance of corpus callosum atrophy in a mixed elderly population. Neurobiol Aging 2007;28:955–963.
46. Di Paola M, Luders E, Di Iulio F, et al. Callosal atrophy in mild cognitive impairment and Alzheimer’s disease: different effects in different stages. Neuroimage 2010;49:141–149.
47. Teipel SJ, Bayer W, Alexander GE, et al. Progression of corpus callosum atrophy in Alzheimer disease. Arch Neurol 2002;59:243–248.
48. Frederiksen KS, Garde E, Skimminge A, et al. Corpus callosum tissue loss and development of motor and global cognitive impairment: the LADIS study. Dement Geriatr Cogn Disord 2011;32:279–286.
49. Roman GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC. Subcortical ischaemic vascular dementia. Lancet Neurol 2002;1:426–436.
50. Vermeer SE, Den Heijer T, Koudstaal PJ, et al. Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke 2003;34:392–396.
51. Carey CL, Kramer JH, Josephson SA, et al. Subcortical lacunes are associated with executive dysfunction in cognitively normal elderly. Stroke 2008;39:397–402.
52. Benisty S, Gouw AA, Porcher R, et al. Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study. J Neurol Neurosurg Psychiatry 2009;80:478–483.
53. Loeb C, Gandolfo C, Crose R, Conti M. Dementia associated with lacunar infarction. Stroke 1992;23:1225–1229.
54. Miyao S, Takano A, Teramoto J, Takahashi A. Leukoaraiosis in relation to prognosis for patients with lacunar infarction. Stroke 1992;23:1434–1438.
55. Gold G, Kovari E, Herrmann FR, et al. Cognitive consequences of thalamic, basal ganglia, and deep white matter lacunes in brain aging and dementia. Stroke 2005;36:1184–1188.
56. Jokinen H, Gouw AA, Madureira S, et al. Incident lacunes influence cognitive decline: the LADIS study. Neurology 2011;76:1872–1878.
57. Viswanathan A, Gschwendtner A, Guichard JP, et al. Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL. Neurology 2007;69:172–179.
58. Liem MK, van der Grond J, Haan J, et al. Lacunar infarcts are the main correlate with cognitive dysfunction in CADASIL. Stroke 2007;38:923–928.
59. Snowdon D, Greiner L, Mortimer J, et al. Brain infarction and the clinical expression of Alzheimer disease. JAMA 1997;277:813–817.
60. Jellinger KA, Attems J. Incidence of cerebrovascular lesions in Alzheimer’s disease: a postmortem study. Acta Neuropathol 2003;105:14–17.
61. Van de Pol LA, Korf ES, van der Flier WM, et al. Magnetic resonance imaging predictors of cognition in mild cognitive impairment. Arch Neurol 2007;64:1023–1028.
62. Hanyu H, Tanaka Y, Shimizu S, et al. Cerebral microbleeds in Binswanger’s disease: a gradient-echo T2*-weighted magnetic resonance imaging study. Neurosci Lett 2003;340:213–216.
63. Poels MM, Vernooij MW, Ikram MA, et al. Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam Scan Study. Stroke 2010;41:S103–S106.
64. Cordonnier C, van der Flier WM. Brain microbleeds and Alzheimer’s disease: innocent observation or key player? Brain 2011;134:335–344.
65. Seo SW, Hwa Lee B, Kim EJ, et al. Clinical significance of microbleeds in subcortical vascular dementia. Stroke 2007;38:1949–1951.
66. Gregoire SM, Smith K, Jager HR, et al. Cerebral microbleeds and long-term cognitive outcome: longitudinal cohort study of stroke clinic patients. Cerebrovasc Dis 2012;33:430–435.
67. Werring DJ, Frazer DW, Coward LJ, et al. Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI. Brain 2004;127:2265–2275.
68. Qiu C, Cotch MF, Sigurdsson S, et al. Cerebral microbleeds, retinopathy, and dementia: the Ages–Reykjavik study. Neurology 2010;75:2221–2228.
69. Poels MM, Ikram MA, van der Lugt A, et al. Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study. Neurology 2012;78:326–333.
70. Van Norden AG, van den Berg HA, de Laat KF, et al. Frontal and temporal microbleeds are related to cognitive function: the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study. Stroke 2011;42:3382–3386.
71. Van Es AC, van der Grond J, de Craen AJ, et al. Cerebral microbleeds and cognitive functioning in the PROSPER study. Neurology 2011;77:1446–1452.
72. Takashima Y, Mori T, Hashimoto M, et al. Clinical correlating factors and cognitive function in community-dwelling healthy subjects with cerebral microbleeds. J Stroke Cerebrovasc Dis 2011;20:105–110.
73. Yakushiji Y, Nishiyama M, Yakushiji S, et al. Brain microbleeds and global cognitive function in adults without neurological disorder. Stroke 2008;39:3323–3328.
74. Tang WK, Chen YK, Lu JY, et al. Absence of cerebral microbleeds predicts reversion of vascular “cognitive impairment no dementia” in stroke. Int J Stroke 2011;6:498–505.
75. Ayaz M, Boikov AS, Haacke EM, Kido DK, Kirsch WM. Imaging cerebral microbleeds using susceptibility weighted imaging: one step toward detecting vascular dementia. J Magn Reson Imaging 2010;31:142–148.
76. Goos JD, Kester MI, Barkhof F, et al. Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition. Stroke 2009;40:3455–3460.
77. Yakushiji Y, Noguchi T, Hara M, et al. Distributional impact of brain microbleeds on global cognitive function in adults without neurological disorder. Stroke 2012;43:1800–1805.
78. Cordonnier C, van der Flier WM, Sluimer JD, et al. Prevalence and severity of microbleeds in a memory clinic setting. Neurology 2006;66:1356–1360.
79. Nardone R, De Blasi P, Seidl M, et al. Cognitive function and cholinergic transmission in patients with subcortical vascular dementia and microbleeds: a TMS study. J Neural Transm 2011;118:1349–1358.
80. Liem MK, Lesnik Oberstein SA, Haan J, et al. MRI correlates of cognitive decline in CADASIL: a seven-year follow-up study. Neurology 2009;72:143–148.
81. Kirsch W, McAuley G, Holshouser B, et al. Serial susceptibility weighted MRI measures brain iron and microbleeds in dementia. J Alzheimers Dis 2009;17:599–609.
82. Pettersen JA, Sathiyamoorthy G, Gao FQ, et al. Microbleed topography, leukoaraiosis, and cognition in probable Alzheimer disease from the Sunnybrook Dementia Study. Arch Neurol 2008;65:790–795.
83. Tyas SL, Salazar JC, Snowdon DA, et al. Transitions to mild cognitive impairments, dementia, and death: findings from the Nun Study. Am J Epidemiol 2007;165:1231–1238.
84. Madureira S, Verdelho A, Ferro J, et al. Development of a neuropsychological battery for the Leukoaraiosis And DISability in the elderly (LADIS) study: experience and baseline data. Neuroepidemiology 2006;27:101–116.
85. Dufouil C, Alperovitch A, Tzourio C. Influence of education on the relationship between white matter lesions and cognition. Neurology 2003;60:831–836.
86. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol 2006;5:64–74.
87. Henon H, Pasquier F, Leys D. Poststroke dementia. Cerebrovasc Dis 2006;22:61–70.
88. Kivipelto M, Helkala EL, Laakso MP, et al. Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ 2001;322:1447–1451.
89. Launer LJ, Ross GW, Petrovitch H, et al. Midlife blood pressure and dementia: the Honolulu–Asia Aging Study. Neurobiol Aging 2000;21:49–55.
90. Qiu C, Winblad B, Fratiglioni L. Low diastolic pressure and risk of dementia in very old people: a longitudinal study. Dement Geriatr Cogn Disord 2009;28:213–219.
91. Razay G, Williams J, King E, Smith AD, Wilcock G. Blood pressure, dementia and Alzheimer’s disease: the OPTIMA longitudinal study. Dement Geriatr Cogn Disord 2009;28:70–74.
92. Stewart R, Xue QL, Masaki K, et al. Change in blood pressure and incident dementia: a 32-year prospective study. Hypertension 2009;54:233–240.
93. Hebert LE, Scherr PA, Bennett DA, et al. Blood pressure and late-life cognitive function change: a biracial longitudinal population study. Neurology 2004;62:2021–2024.
94. Shah RC, Wilson RS, Bienias JL, et al. Relation of blood pressure to risk of incident Alzheimer’s disease and change in global cognitive function in older persons. Neuroepidemiology 2006;26:30–36.
95. Di Carlo A, Baldereschi M, Amaducci L, et al. Cognitive impairment without dementia in older people: prevalence, vascular risk factors, impact on disability. The Italian Longitudinal Study on Aging. J Am Geriatr Soc 2000;48:775–782.
96. Cerhan JR, Folsom AR, Mortimer JA, et al. Correlates of cognitive function in middle-aged adults. Atherosclerosis Risk in Communities (ARIC) study investigators. Gerontology 1998;44:95–105.
97. Budge MM, de Jager C, Hogervorst E, Smith AD. Total plasma homocysteine, age, systolic blood pressure, and cognitive performance in older people. J Am Geriatr Soc 2002;50:2014–2018.
98. Kilander L, Nyman H, Boberg M, Hansson L, Lithell H. Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men. Hypertension 1998;31:780–786.
99. Cacciatore F, Abete P, Ferrara N, et al. The role of blood pressure in cognitive impairment in an elderly population. Osservatorio Geriatrico Campano Group. J Hypertens 1997;15:135–142.
100. Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:2672–2713.
101. McGuinness B, Todd S, Passmore P, Bullock R. Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. Cochrane Database Syst Rev 2009;4:CD004034.
102. Guan JW, Huang CQ, Li YH, et al. No association between hypertension and risk for Alzheimer’s disease: a meta-analysis of longitudinal studies. J Alzheimers Dis 2011;27:799–807.
103. Chang-Quan H, Hui W, Chao-Min W, et al. The association of antihypertensive medication use with risk of cognitive decline and dementia: a meta-analysis of longitudinal studies. Int J Clin Pract 2011;65:1295–1305.
104. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265:3255–3264.
105. Lithell H, Hansson L, Skoog I, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003;21:875–886.
106. Peters R, Beckett N, Forette F, et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-cog): a double-blind, placebo controlled trial. Lancet Neurol 2008;7:683–689.
107. Yusuf S, Diener HC, Sacco RL, et al. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med 2008;359:1225–1237.
108. Forette F, Seux ML, Staessen JA, et al. Prevention of dementia in randomised double-blind placebo-controlled systolic hypertension in Europe (SYST-Eur) trial. Lancet 1998;352:1347–1351.
109. Tzourio C, Anderson C, Chapman N, et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med 2003;163:1069–1075.
110. Cukierman T, Gerstein HC, Williamson JD. Cognitive decline and dementia in diabetes – systematic overview of prospective observational studies. Diabetologia 2005;48:2460–2469.
111. Luchsinger JA. Adiposity, hyperinsulinemia, diabetes and Alzheimer’s disease: an epidemiological perspective. Eur J Pharmacol 2008;585:119–129.
112. Yaffe K, Falvey C, Hamilton N, et al. Diabetes, glucose control, and nine-year cognitive decline among older adults without dementia. Arch Neurol 2012;69:1170–1175.
113. Wang KC, Woung LC, Tsai MT, et al. Risk of Alzheimer’s disease in relation to diabetes: a population-based cohort study. Neuroepidemiology 2012;38:237–244.
114. Kaffashian S, Dugravot A, Brunner EJ, et al. Midlife stroke risk and cognitive decline: a 10-year follow-up of the Whitehall II Cohort Study. Alzheimers Dement 2013;9:572-579.
115. Cheng G, Huang C, Deng H, Wang H. Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies. Intern Med J 2012;42:484–491.
116. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol 2004;61:661–666.
117. Manschot SM, Brands AM, van der Grond J, et al. Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes. Diabetes 2006;55:1106–1113.
118. Liu F, Shi J, Tanimukai H, et al. Reduced O-glcNacylation links lower brain glucose metabolism and tau pathology in Alzheimer’s disease. Brain 2009;132:1820–1832.
119. De la Monte SM. Brain insulin resistance and deficiency as therapeutic targets in Alzheimer’s disease. Curr Alzheimer Res 2012;9:35–66.
120. Reitz C, Bos MJ, Hofman A, Koudstaal PJ, Breteler MM. Prestroke cognitive performance, incident stroke, and risk of dementia: the Rotterdam Study. Stroke 2008;39:36–41.
121. Douiri A, Rudd AG, Wolfe CD. Prevalence of poststroke cognitive impairment: South London Stroke Register 1995–2010. Stroke 2013;44:138–145.
122. Savva GM, Stephan BC. Epidemiological studies of the effect of stroke on incident dementia: a systematic review. Stroke 2010;41:e41–46.
123. Grau-Olivares M, Arboix A, Bartres-Faz D, Junque C. Neuropsychological abnormalities associated with lacunar infarction. J Neurol Sci 2007;257:160–165.
124. Jacova C, Pearce LA, Costello R, et al. Cognitive impairment in lacunar strokes: the SPS3 trial. Ann Neurol 2012;72:351–362.
125. Kivipelto M, Ngandu T, Fratiglioni L, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 2005;62:1556–1560.
126. Purnell C, Gao S, Callahan CM, Hendrie HC. Cardiovascular risk factors and incident Alzheimer disease: a systematic review of the literature. Alzheimer Dis Assoc Disord 2009;23:1–10.
127. Unverzagt FW, McClure LA, Wadley VG, et al. Vascular risk factors and cognitive impairment in a stroke-free cohort. Neurology 2011;77:1729–1736.
128. Li L, Wang Y, Yan J, et al. Clinical predictors of cognitive decline in patients with mild cognitive impairment: the Chongqing Aging Study. J Neurol 2012;259:1303–1311.
129. Deschaintre Y, Richard F, Leys D, Pasquier F. Treatment of vascular risk factors is associated with slower decline in Alzheimer disease. Neurology 2009;73:674–680.
130. Folstein M, Folstein S, McHugh PJ. Mini-Mental State: a practical method for grading the cognitive state of patients for clinicians. J Psychiatr Res 1975;12:189–198.
131. Smith EE, Egorova S, Blacker D, et al. Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia. Arch Neurol 2008;65:94–100.
132. Van der Flier WM, van der Vlies AE, Weverling-Rijnsburger AW, et al. MRI measures and progression of cognitive decline in nondemented elderly attending a memory clinic. Int J Geriatr Psychiatry 2005;20:1060–1066.
133. Pantoni L, Basile AM, Pracucci G, et al. Impact of age-related cerebral white matter changes on the transition to disability – the LADIS study: rationale, design and methodology. Neuroepidemiology 2005;24:51–62.
134. Fure B, Bruun Wyller T, Engedal K, Thommessen B. Cognitive impairments in acute lacunar stroke. Acta Neurol Scand 2006;114:17–22.
135. Roth M, Tym E, Mountjoy CQ, et al. CAMDEX. A standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. Br J Psychiatry 1986;149:698–709.
136. Rosen W, Mohs R, Davis K. A new rating scale for Alzheimer’s disease. Am J Psychiatry 1984;141:1356–1364.
137. Ferris S. General measures of cognition. Int Psychogeriatr 2003;15:215–217.
138. Ylikoski R, Jokinen H, Andersen P, et al. Comparison of the Alzheimer’s Disease Assessment Scale cognitive subscale and the Vascular Dementia Assessment Scale in differentiating elderly individuals with different degrees of white matter changes. The LADIS study. Dement Geriatr Cogn Disord 2007;24:73–81.
139. Madureira S, Verdelho A, Moleiro C, et al. Neuropsychological predictors of dementia in a three-year follow-up period: data from the LADIS study. Dement Geriatr Cogn Disord 2010;29:325–334.
140. Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005;53:695–699.
141. Wong A, Xiong YY, Kwan PW, et al. The validity, reliability and clinical utility of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in patients with cerebral small vessel disease. Dement Geriatr Cogn Disord 2009;28:81–87.
142. Ishikawa H, Meguro K, Ishii H, Tanaka N, Yamaguchi S. Silent infarction or white matter hyperintensity and impaired attention task scores in a nondemented population: the Osaki–Tajiri Project. J Stroke Cerebrovasc Dis 2012;21:275–282.
143. Hachinski V, Iadecola C, Petersen RC, et al. National Institute of Neurological Disorders and Stroke–Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 2006;37:2220–2241.
144. Stroop JR. Studies of interference in serial verbal reactions. J Exp Psychol 1935;18:643–662.
145. Reitan R. Validity of the Trail Making test as an indicator of organic brain damage. Percept Mot Skills 1958;8:271–276.
146. Jokinen H, Kalska H, Mantyla R, et al. White matter hyperintensities as a predictor of neuropsychological deficits post-stroke. J Neurol Neurosurg Psychiatry 2005;76:1229–1233.
147. Jokinen H, Kalska H, Mantyla R, et al. Cognitive profile of subcortical ischaemic vascular disease. J Neurol Neurosurg Psychiatry 2006;77:28–33.
148. Zhou A, Jia J. Different cognitive profiles between mild cognitive impairment due to cerebral small vessel disease and mild cognitive impairment of Alzheimer’s disease origin. J Int Neuropsychol Soc 2009;15:898–905.
149. Heaton R, Chelune G, Talley JL, Kay G, Curtiss G. Wisconsin Card Sorting Test Manual: Revised and Expanded. Odessa, FL: Psychological Assessment Resources; 1993.
150. Ylikoski R, Ylikoski A, Erkinjuntti T, et al. White matter changes in healthy elderly persons correlate with attention and speed of mental processing. Arch Neurol 1993;50:818–824.
151. Junque C, Pujol J, Vendrell P, et al. Leuko-araiosis on magnetic resonance imaging and speed of mental processing. Arch Neurol 1990;47:151–156.
152. Duering M, Zieren N, Herve D, et al. Strategic role of frontal white matter tracts in vascular cognitive impairment: a voxel-based lesion-symptom mapping study in CADASIL. Brain 2011;134:2366–2375.
153. Cummings JL. Frontal–subcortical circuits and human behavior. J Psychosom Res 1998;44:627–628.
154. Tekin S, Cummings JL. Frontal–subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res 2002;53:647–654.
155. Behrens TE, Johansen-Berg H, Woolrich MW, et al. Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nat Neurosci 2003;6:750–757.
156. Meguro K, Constans JM, Shimada M, et al. Corpus callosum atrophy, white matter lesions, and frontal executive dysfunction in normal aging and Alzheimer’s disease. A community-based study: the Tajiri Project. Int Psychogeriatr 2003;15:9–25.
157. Jokinen H, Frederiksen KS, Garde E, et al. Callosal tissue loss parallels subtle decline in psychomotor speed. A longitudinal quantitative MRI study. The LADIS study. Neuropsychologia 2012;50:1650–1655.
158. Wright CB, Festa JR, Paik MC, et al. White matter hyperintensities and subclinical infarction: associations with psychomotor speed and cognitive flexibility. Stroke 2008;39:800–805.
159. Paul R, Lane E, Jefferson A. Vascular cognitive impairment. In Ravdin LD, Katzen HL, eds. Handbook on the Neuropsychology of Aging and Dementia. New York, NY: Springer; 2012: pp. 281–294.
160. De Mendonca A, Ribeiro F, Guerreiro M, Palma T, Garcia C. Clinical significance of subcortical vascular disease in patients with mild cognitive impairment. Eur J Neurol 2005;12:125–130.
161. Loewenstein DA, Acevedo A, Agron J, et al. Cognitive profiles in Alzheimer’s disease and in mild cognitive impairment of different etiologies. Dement Geriatr Cogn Disord 2006;21:309–315.
162. Nordahl CW, Ranganath C, Yonelinas AP, et al. Different mechanisms of episodic memory failure in mild cognitive impairment. Neuropsychologia 2005;43:1688–1697.
163. Jokinen H, Lipsanen J, Schmidt R, et al. Brain atrophy accelerates cognitive decline in cerebral small vessel disease: the LADIS study. Neurology 2012;78:1785–1792.
164. Kennedy KM, Raz N. Aging white matter and cognition: differential effects of regional variations in diffusion properties on memory, executive functions, and speed. Neuropsychologia 2009;47:916–927.
165. Van der Holst HM, Tuladhar AM, van Norden AG, et al. Microstructural integrity of the cingulum is related to verbal memory performance in elderly with cerebral small vessel disease: the RUN DMC study. Neuroimage 2012;65C:416–423.
166. Van Norden AG, de Laat KF, Fick I, et al. Diffusion tensor imaging of the hippocampus and verbal memory performance: the RUN DMC study. Hum Brain Mapp 2012;33:542–551.
167. Kertesz A, Polk M, Carr T. Cognition and white matter changes on magnetic resonance imaging in dementia. Arch Neurol 1990;47:387–391.
168. Canning SJ, Leach L, Stuss D, Ngo L, Black SE. Diagnostic utility of abbreviated fluency measures in Alzheimer disease and vascular dementia. Neurology 2004;62:556–562.
169. Rao SM, Mittenberg W, Bernardin L. Neuropsychological test findings in subject with leukoaraiosis. Arch Neurol 1989;46:40–44.
170. Hunt AL, Orrison WW, Yeo RA. Clinical significance of MRI white matter lesions in the elderly. Neurology 1989;39:1470–1474.
171. Breteler M, van Amerongen N, van Swieten J, et al. Cognitive correlates of ventricular enlargement and cerebral white matter lesions on magnetic resonance imaging. The Rotterdam Study. Stroke 1994;25:1109–1115.
172. Almkvist O, Wahlund LO, Andersson-Lundman G, Basun H, Backman L. White-matter hyperintensity and neuropsychological functions in dementia and healthy aging. Arch Neurol 1992;49:626–632.
173. Kertesz A, Clydesdale S. Neuropsychological deficits in vascular dementia versus Alzheimer’s disease. Frontal lobe deficits prominent in vascular dementia. Arch Neurol 1994;51:1226–1231.
174. Tiffin J, Asher EJ. The Purdue Pegboard: norms and studies of reliability and validity. J Appl Psychol 1948;32:234.
175. Marquine MJ, Attix DK, Goldstein LB, et al. Differential patterns of cognitive decline in anterior and posterior white matter hyperintensity progression. Stroke 2010;41:1946–1950.
176. Murray ME, Senjem ML, Petersen RC, et al. Functional impact of white matter hyperintensities in cognitively normal elderly subjects. Arch Neurol 2010;67:1379–1385.

References

1. Baezner H, Hennerici M. From trepidant abasia to motor network failure – gait disorders as a consequence of subcortical vascular encephalopathy (SVE): review of historical and contemporary concepts. J Neurol Sci 2005;229:81–88.
2. Verghese J, Lipton RB, Hall CB, et al. Abnormality of gait as a predictor of non-Alzheimer’s dementia. N Engl J Med 2002;347:1761–1768.
3. Masdeu JC, Wolfson L, Lantos G, et al. Brain white-matter changes in the elderly prone to falling. Arch Neurol 1989;46:1292–1296.
4. Kerber KA, Enrietto JA, Jacobson KM, Baloh RW. Disequilibrium in older people: a prospective study. Neurology 1998;51:574–580.
5. Baezner H, Oster M, Daffertshofer M, Hennerici M. Assessment of gait in subcortical vascular encephalopathy by computerized analysis: a cross-sectional and longitudinal study. J Neurol 2000;247:841–849.
6. Baloh RW, Ying SH, Jacobson KM. A longitudinal study of gait and balance dysfunction in normal older people. Arch Neurol 2003;60:835–839.
7. Rosano C, Kuller LH, Chung H, et al. Subclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults. J Am Geriatr Soc 2005;53:649–654.
8. De Laat KF, van Norden AG, Gons RA, et al. Gait in elderly with cerebral small vessel disease. Stroke 2010;41:1652–1658.
9. Soumaré A, Elbaz A, Zhu Y, et al. White matter lesions volume and motor performances in the elderly. Ann Neurol 2009;65:706–715.
10. Baezner H, Blahak C, Poggesi A, et al. Association of gait and balance disorders with age-related white matter changes: the LADIS study. Neurology 2008;70:935–942.
11. Nutt JG, Marsden CD, Thompson PD. Human walking and higher-level gait disorders, particularly in the elderly. Neurology 1993;43:268–279.
12. Pantoni L, Basile AM, Pracucci G, et al. Impact of age-related cerebral white matter changes on the transition to disability – the LADIS study: rationale, design and methodology. Neuroepidemiology 2005;24:51–62.
13. Guralnik JM, Simonsick EM, Ferrucci L, et al. A Short Physical Performance Battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994;49:85–94.
14. Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB. Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med 1995;332:556–561.
15. Kreisel SH, Blahak C, Baezner H, et al. Deterioration of gait and balance over time: the effects of age-related white matter change. Cerebrovasc Dis 2013; 35:544–553.
16. Zheng JJ, Delbaere K, Close JC, et al. White matter hyperintensities are an independent predictor of physical decline in community-dwelling older people. Gerontology 2012;58:398–406.
17. de Laat KF, Tuladhar AM, van Norden AG, et al. Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease. Brain 2011;134:73–83.
18. de Laat KF, van Norden AG, Gons RA, et al. Diffusion tensor imaging and gait in elderly persons with cerebral small vessel disease. Stroke 2011;42:373–379.
19. de Laat KF, Reid AT, Grim DC, et al. Cortical thickness is associated with gait disturbances in cerebral small vessel disease. Neuroimage 2012;59:1478–1484.
20. Zheng JJ, Delbaere K, Close JC, Sachdev PS, Lord SR. Impact of white matter lesions on physical functioning and fall risk in older people: a systematic review. Stroke 2011;42:2086–2090.
21. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of quadas: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003;3:25.
22. Rubenstein LZ, Powers CM, MacLean CH. Quality indicators for the management and prevention of falls and mobility problems in vulnerable elders. Ann Intern Med 2001;135:686–693.
23. Murray ME, Senjem ML, Petersen RC, et al. Functional impact of white matter hyperintensities in cognitively normal elderly subjects. Arch Neurol 2010;67:1379–1385.
24. Bloem BR, Steijns JAG, Smits-Engelsman BC. An update on falls. Curr Opin Neurol 2003;16:15–26.
25. Alexander BH, Rivara FP, Wolf ME. The cost and frequency of hospitalisation for fall related injuries in older adults. Am J Public Health 1992;82:1020–1023.
26. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988;319:1701–1707.
27. Maki BE. Gait changes in older adults: predictors of falls or indicators of fear. J Am Geriatr Soc 1997;45:313–320.
28. Bloem BR, Grimbergen YAM, Cramer M, et al. Prospective assessment of falls in Parkinson’s disease. J Neurol 2001;248:950–958.
29. Ebersbach G, Sojer M, Valldeoriola F, et al. Comparative analysis of gait in Parkinson’s disease, cerebellar ataxia and subcortical arteriosclerotic encephalopathy. Brain. 1999;122:1349–1355.
30. Novak V, Haertle M, Zhao P, et al. White matter hyperintensities and dynamics of postural control. Magn Reson Imaging 2009;27:752–759.
31. Longstreth WT Jr, Manolio TA, Arnold A, et al. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. Stroke 1996;27:1274–1282.
32. Blahak C, Baezner H, Pantoni L, et al. Deep frontal and periventricular age-related white matter changes but not basal ganglia and infratentorial hyperintensities are associated with falls: cross-sectional results from the LADIS study. J Neurol Neurosurg Psychiatry 2009;80:608–613.
33. Starr JM, Leaper SA, Murray AD, et al. Brain white matter lesions detected by magnetic resonance imaging are associated with balance and gait speed. J Neurol Neurosurg Psychiatry 2003;74:94–98.
34. Camicioli R, Moore MM, Sexton G, Howieson DB, Kaye JA. Age-related brain changes associated with motor function in healthy older people. J Am Geriatr Soc 1999;47:330–334.
35. Tell GS, Lefkowitz DS, Diehr P, Elster AD. Relationship between balance and abnormalities in cerebral magnetic resonance imaging in older adults. Arch Neurol 1998;55:73–79.
36. Whitman GT, Tang T. A prospective study of cerebral white matter abnormalities in older people with gait dysfunction. Neurology 2001;57:990–994.
37. Srikanth V, Beare R, Blizzard L, et al. Cerebral white matter lesions, gait, and the risk of incident falls: a prospective population-based study. Stroke 2009;40:175–180.
38. Corti MC, Baggio G, Sartori L, et al. White matter lesions and the risk of incident hip fracture in older persons: results from the Progetto Veneto Anziani Study. Arch Intern Med 2007;167:1745–1751.
39. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 1986;9:357–381.
40. Stolze H, Kuhtz-Buschbeck JP, Drücke H, et al. Comparative analysis of the gait disorder of normal pressure hydrocephalus and Parkinson’s disease. J Neurol Neurosurg Psychiatry 2001;70:289–297.
41. Curnes JT, Burger PC, Djang WT, Boyko OB. MR imaging of compact white matter pathways. AJNR Am J Neuroradiol 1988;9:1061–1068.
42. Guttmann CR, Benson R, Warfield SK, et al. White matter abnormalities in mobility impaired older persons. Neurology 2000;54:1277–1283.
43. Kerber KA, Enrietto JA, Jacobson KM, Baloh RW. Disequilibrium in older people: a prospective study. Neurology 1998;51:574–580.
44. Sparto PJ, Aizenstein HJ, Vanswearingen JM, et al. Delays in auditory-cued step initiation are related to increased volume of white matter hyperintensities in older adults. Exp Brain Res 2008;188:633–640.
45. Liu-Ambrose T, Nagamatsu LS, Hsu CL, Bolandzadeh N. Emerging concept: “central benefit model” of exercise in falls prevention. Br J Sports Med 2013;47:115–117.
46. Tullberg M, Fletcher E, DeCarli C, et al. White matter lesions impair frontal lobe function regardless of their location. Neurology 2004;63:246–253.
47. Yakovlev PI. Paraplegias of hydrocephalics. Am J Ment Defic 1947;51:561–576.
48. Poggesi A, Gouw A, van der Flier W, et al. Cerebral white matter changes are associated with abnormalities on neurological examination in non-disabled elderly: the LADIS study. J Neurol 2013;260:1014–1021.
49. Afifi AK, Bergman RA. Functional Neuroanatomy. New York, NY: McGraw-Hill; 1998: pp. 105–179.
50. Verdelho A, Madureira S, Ferro JM, et al. Physical activity prevents progression for cognitive impairment and vascular dementia: results from the LADIS (Leukoaraiosis And DISability) study. Stroke 2012;43:3331–3335.
51. Sherrington C, Whitney JC, Lord SR, et al. Effective exercise for the prevention of falls: a systematic review and meta-analysis. J Am Geriatr Soc 2008;56:2234–2243.
52. Province MA, Hadley EC, Hornbrook MC, et al. The effects of exercise on falls in elderly patients. A preplanned meta-analysis of the FICSIT trials. Frailty and injuries: cooperative studies of intervention techniques. JAMA 1995;273:1341–1347.
53. Day L, Fildes B, Gordon I, et al. Randomised factorial trial of falls prevention among older people living in their own homes. BMJ 2002;325:128–134.
54. Lang IA, Guralnik JM, Melzer D. Physical activity in middle-aged adults reduces risks of functional impairment independent of its effect on weight. J Am Geriatr Soc 2007;55:1836–1841.

References

1. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet 2001;357:169–175.
2. White L. Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu–Asia Aging Study. J Alzheimers Dis 2009;18:713–725.
3. Fisher CM. Lacunar strokes and infarcts: a review. Neurology 1982;32:871–876.
4. Black S, Gao F, Bilbao J. Understanding white matter disease: imaging–pathological correlations in vascular cognitive impairment. Stroke 2009;40:S48–S52.
5. Wen W, Sachdev PS. The topography of white matter hyperintensities on brain MRI in healthy 60- to 64-year-old individuals. Neuroimage 2004;22:144–154.
6. Wen W, Sachdev PS, Li JJ, Chen X, Anstey KJ. White matter hyperintensities in the forties: their prevalence and topography in an epidemiological sample aged 44–48. Hum Brain Mapp 2009;30:1155–1167.
7. Hachinski VC, Potter P, Merskey H. Leukoaraiosis. Arch Neurol 1987;44:21–23.
8. Ovbiagele B, Saver JL. Cerebral white matter hyperintensities on MRI: current concepts and therapeutic implications. Cerebrovasc Dis 2006;22:83–90.
9. Pantoni L, Garcia JH. Pathogenesis of leukoaraiosis: a review. Stroke 1997;28:652–659.
10. Nucifora PG, Verma R, Lee SK, Melhem ER. Diffusion-tensor MR imaging and tractography: exploring brain microstructure and connectivity. Radiology 2007;245:367–384.
11. Chavhan GB, Babyn PS, Thomas B, Shroff MM, Haacke EM. Principles, techniques, and applications of T2*-based MR imaging and its special applications. Radiographics 2009;29:1433–1449.
12. Sheline YI, Price JL, Vaishnavi SN, et al. Regional white matter hyperintensity burden in automated segmentation distinguishes late-life depressed subjects from comparison subjects matched for vascular risk factors. Am J Psychiatry 2008:524–532.
13. Sachdev P, Brodaty H, Rose N, Cathcart S. Schizophrenia with onset after age 50 years. 2: Neurological, neuropsychological and MRI investigation. Br J Psychiatry 1999;175:416–421.
14. McDonald W, Krishnan K, Doaiswamy P, Blazer D. Occurance of subcortical hyperintensities in elderly subjects with mania. Psychiatry Res 1991;40:211–220.
15. Valenti R, Poggesi A, Pescini F, Inzitari D, Pantoni L. Psychiatric disturbances in CADASIL: a brief review. Acta Neurol Scand 2008;118:291–295.
16. Jorm AF, Anstey KJ, Christensen H, et al. MRI hyperintensities and depressive symptoms in a community sample of individuals 60–64 years old. Am J Psychiatry 2005;162:699–705.
17. Khan U, Porteous L, Hassan A, Markus HS. Risk factor profile of cerebral small vessel disease and its subtypes. J Neurol Neurosurg Psychiatry 2007;78:702–706.
18. Robinson RG, Spalletta G. Poststroke depression: a review. Can J Psychiatry 2010;55:341–349.
19. Jorge RE, Starkstein SE, Raobinson RG. Apathy following stroke. Can J Psychiatry 2010;55:350–354.
20. Van Dijk EJ, Prins ND, Vrooman HA, et al. Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan Study. Stroke 2008;39:2712–2719.
21. Taylor WD, Steffens DC, MacFall JR, et al. White matter hyperintesity progression and late life depression outcomes. Arch Gen Psychiatry 2003;60:1090–1096.
22. Versluis CE, van der Mast RC, van Buchem MA, et al. Progression of cerebral white matter lesions is not associated with development of depressive symptoms in elderly subjects at risk of cardiovascular disease: the PROSPER study. Int J Geriatr Psychiatry 2006;21:375–381.
23. Hickie I, Scott E, Mitchell P, et al. Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression. Biol Psychiatry 1995;37:151–160.
24. O’Brien J, Ames D, Chiu E, et al. Severe deep white matter lesions and in elderly patients with major depressive disorder: follow up study. BMJ 1998;317:982–984.
25. Robinson RG. Poststroke depression: prevalence, diagnosis, treatment, and disease progression. Biol Psychiatry 2003;54:376–587.
26. Goodwin GM. Neuropsychological and neuroimaging evidence for the involvement of the frontal lobes in depression. J Psychopharmacol 1997;11:971–975.
27. Benisty S, Gouw AA, Porcher R, et al. Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study. J Neurol Neurosurg Psychiatry 2009;80:478–483.
28. Bunce D, Anstey KJ, Cherbuin N, et al. Cognitive deficits are associated with frontal and temporal lobe white matter lesions in middle-aged adults living in the community. PLoS One 2010;5:e13567.
29. Taylor WD, MacFall JR, Steffens DC, et al. Localization of age-associated white matter hyperintensities in late-life depression. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:539–544.
30. Steffens DC, Helms MJ, Krishnan KR, Burke GL. Cerebrovascular disease and depression symptoms in the Cardiovascular Health Study. Stroke 1999;30:2159–2166.
31. Brodaty H, Sachdev PS, Withall A, et al. Frequency and clinical, neuropsychological and neuroimaging correlates of apathy following stroke – the Sydney Stroke Study. Psychol Med 2005;35:1707–1716.
32. Djernes JK. Prevalence and predictors of depression in populations of elderly: a review. Acta Psychiatr Scand 2006;113:372–387.
33. Blazer DG. Depression in late life: review and commentary. J Gerontol Med Sci 2003;56A:249–265.
34. Bryan RN, Cai J, Burke G, et al. Prevalence and anatomic characteristics of infarct-like lesions on MR images of middle-aged adults: the Atherosclerosis Risk In Communities Study. AJNR Am J Neuroradiol 1999;20:1273–1280.
35. De Leeuw FE, de Groot JC, Achten E, et al. Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 2001;70:9–14.
36. Regier DA, Boyd JH, Burke JDJ, et al. One-month prevalence of mental disorders in the United States: based on five epidemiologic catchment area sites. Arch Gen Psychiatry 1988;45:977–986.
37. Trollor JN, Anderson TM, Sachdev PS, Brodaty H, Andrews G. Age shall not weary them: mental health in the middle-aged and the elderly. Aust N Z J Psychiatry 2007;41:581–589.
38. Taylor CB, Conrad A, Wilhelm FH, et al. Psychophysiological and cortisol responses to psychological stress in depressed and nondepressed older men and women with elevated cardiovascular disease risk. Psychosom Med 2006;68:538–546.
39. Withall A, Brodaty H, Altendorf A, Sachdev PS. A longitudinal study examining the independence of apathy and depression after stroke: the Sydney Stroke Study. Int Psychogeriatr 2011;23:264–273.
40. Robinson RG. The Clinical Neuropsychiatry of Stroke. Cambridge, MA: Cambridge University Press; 2006.
41. Sinyor D, Amato P, Kaloupek P. Post-stroke depression: relationship to functional impairment, coping strategies, and rehabilitation outcome. Stroke 1986;17:112–117.
42. Carson AJ, MacHale S, Allen K, et al. Depression after stroke and lesion location: a systematic review. Lancet 2000;356:122–126.
43. Krishnan KR, Hays JC, Blazer DG. MRI-defined vascular depression. Am J Psychiatry 1997;154:497–501.
44. Lavretsky H, Lesser IM, Wohl M, Miller BL. Relationship of age, age at onset, and sex to depression in older adults. Am J Geriatr Psychiatry 1998;6:248–256.
45. Steffens DC, Krishnan KRR, Crump C, Burke GL. Cerebrovascular disease and evolution of depressive symptoms in the Cardiovascular Health Study. Stroke 2002;33:1636–1644.
46. O’Brien J, Ames D, Chiu E, et al. Severe deep white matter lesions in elderly patients with major depressive disorder: follow up study. BMJ 1998;317.
47. Figiel GS, Krishnan KR, Doraiswamy PM. Subcortical structural changes in ECT-induced delirium. J Geriatr Psychiatry Neurol 1990;3:172–176.
48. Taragano FE, Allegri R, Vicario A, Bagnatti P, Lyketsos CG. A double blind, randomized clinical trial assessing the efficacy and safety of augmenting standard antidepressant therapy with nimodipine in the treatment of vascular depression. Int J Geriatr Psychiatry 2001;16:254–260.
49. Taragano FE, Bagnatti P, Allegri R. A double-blind, randomized clinical trial to assess the augmentation with nimodipine of antidepressant therapy in the treatment of vascular depression. Int Psychogeriatr 2005;17:487–498.
50. Godin O, Dufouil C, Maillard P, et al. White matter lesions as a predictor of depression in the elderly: the 3C-Dijon study. Biol Psychiatry 2008;63:663–669.
51. Simpson SW, Jackson A, Baldwin RC, Burns A. Subcortical hyperintensities in late-life depression: acute response to treatment and neuropsychological impairment. Int Psychogeriatr 1997;9:257–275.
52. MacFall JR, Taylor WD, Rex DE, et al. Lobar distribution of lesion volumes in late-life depression: the Biomedical Information Research Network (BIRN). Neuropsychopharmacology 2006;31:1500–1507.
53. Greenwald BS, Kramer-Ginsberg E, Krishnan KRR, et al. Neuroanatomic localization of magnetic resonance imaging signal hyperintensities in geriatric depression. Stroke 1998;29:613–617.
54. MacFall JR, Payne ME, Provenzale JM, Krishnan KRR. Medial orbital frontal lesions in late-onset depression. Biol Psychiatry 2001;49:803–806.
55. Alexopoulos GS, Kiosses DN, Choi SJ, Murphy CF, Lim KO. Frontal white matter microstructure and treatment response of late-life depression: a preliminary study. Am J Psychiatry 2002;159:1929–1923.
56. Alexopoulos GS, Meyers BS, Young RC, et al. “Vascular depression” hypothesis. Arch Gen Psychiatry 1997;54:915–922.
57. McDougall F, Brayne C. Systematic review of the depressive symptoms associated with vascular conditions. J Affect Disord 2007;104:25–35.
58. Baldwin RC. Is vascular depression a distinct sub-type of depressive disorder? A review of causal evidence. Int J Geriatr Psychiatry 2005;20:1–11.
59. Chen PS, McQuoid DR, Payne ME, Steffens DC. White matter and subcortical gray matter lesion volume changes and late-life depression outcome: a four-year magnetic resonance imaging study. Int Psychogeriatr 2006;18:445–456.
60. Sanders ML, Lyness JM, Eberly S, King DA, Caine ED. Cerebrovascular risk factors, executive dysfunction, and depression in older primary care patients. Am J Geriatr Psychiatry 2006;14:145–152.
61. Ikram MA, Luijendijk HJ, Vernooij MW, et al. Vascular brain disease and depression in the elderly. Epidemiology 2010;21:78–81.
62. Steffens DC, Conway CR, Dombeck CB, et al. Severity of subcortical gray matter hyperintensity predicts ECT response in geriatric depression. J ECT 2001;17:45–49.
63. Coffey CE, Figiel GS, Djang WT, et al. Effects of ECT on brain structure: a pilot prospective magnetic resonance imaging study. Am J Psychiatry 1988;145:701–706.
64. Krauthammer C, Klerman G. Secondary mania. Manic syndromes associated with antecedent physical illness or drugs. Arch Gen Psychiatry 1978;35:1333–1339.
65. Santos CO, Caeiro L, Ferro JM, Figueira ML. Mania and stroke: a systematic review. Cerebrovasc Dis 2011;32:11–21.
66. Robinson RG, Boston JD, Starkstein SE, Price TR. Comparison of mania and depression after brain injury: causal factors. Am J Psychiatry 1988;145:172–178.
67. Starkstein SE, Pearlson GD, Boston JD, Robinson RG. Mania after brain injury. A controlled study of causative factors. Arch Neurol 1987;44:1069–1073.
68. Lin HC, Tsai SY, Lee HC. Increased risk of developing stroke among patients with bipolar disorder after an acute mood episode: a six-year follow-up study. J Affect Disord 2007;100:49–54.
69. Newcomer JW. Medical risk in patients with bipolar disorder and schizophrenia. J Clin Psychiatry 2006;67:25–30.
70. Huang SH, Chung KH, Hsu JL, et al. The risk factors for elderly patients with bipolar disorder having cerebral infarction. J Geriatr Psychiatry Neurol 2012;25:15–19.
71. Fujikawa T, Yamawaki S, Touhouda Y. Silent cerebral infarctions in patients with late-onset mania. Stroke 1995;26:946–949.
72. Beyer JL, Young R, Kuchibhatla M, Krishnan KR. Hyperintense MRI lesions in bipolar disorder: a meta-analysis and review. Int Rev Psychiatry 2009;21:394–409.
73. Vederine FE, Wessa M, Leboyer M, Houenou J. A meta-analysis of whole-brain diffusion tensor imaging studies in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:1820–1826.
74. Bellani M, Brambilla P. Diffusion imaging studies of white matter integrity in bipolar disorder. Epidemiol Psychiatr Sci 2011;20:137–140.
75. Kennedy N, Everitt B, Boydell J, et al. Incidence and distribution of first-episode mania by age: results from a 35-year study. Psychol Med 2005;35:855–863.
76. Steffens DC, Krishnan KR. Structural neuroimaging and mood disorders: recent findings, implications for classification, and future directions. Biol Psychiatry 1998;43:705–712.
77. Howard R, Rabins PV, Seeman MV, Jeste DV. Late-onset schizophrenia and very late-onset schizophrenia-like psychosis: an international consensus. Am J Psychiatry 2000;157:172–178.
78. Östling S, Skoog I. Psychotic symptoms and paranoid ideation in a nondemented population-based sample of the very old. Arch Gen Psychiatry 2002;59:53–59.
79. Kumral E, Öztürk Ö. Delusional state following acute stroke. Neurology 2004;62:110–113.
80. Almeida OP, Xiao J. Mortality associated with incident mental health disorders after stroke. Aust N Z J Psychiatry 2007;41:274–281.
81. Ballard C, Neill D, O’Brien J, et al. Anxiety, depression and psychosis in vascular dementia: prevalence and associations. J Affective Disord 2000;59:97–106.
82. Hope T, Keene J, Gedling K, et al. Behaviour changes in dementia 1: Point of entry data of a prospective study. Int J Geriatr Psychiatry 1997;12:1062–1073.
83. Breitner JCS, Husain MM, Figiel GS, Krishnan KR, Boyko OB. Cerebral white matter disease in late-onset paranoid psychosis. Biol Psychiatry 1990;28:266–274.
84. Sachdev P, Brodaty H. Quantitative study of signal hyperintensities on T2-weighted magnetic resonance imaging in late-onset schizophrenia. Am J Psychiatry 1999;156:1958–1967.
85. Keshavan MS, Mulsant BH, Sweet RA, et al. MRI changes in schizophrenia in late life: a preliminary controlled study. Psychiatry Res 1996;60:117–123.
86. Lesser IM, Jeste DV, Boone KB, et al. Late-onset psychotic disorder, not otherwise specified: clinical and neuroimaging findings. Biol Psychiatry 1992;31:419–423.
87. Corey-Bloom J, Jernigan T, Archibald S, Harris MJ, Jeste DV. Quantitative magnetic resonance imaging of the brain in late-life schizophrenia. Am J Psychiatry 1995;152:447–449.
88. Howard R, Cox T, Almeida O, et al. White matter signal hyperintensities in the brains of patients with late paraphrenia and the normal community-living elderly. Biol Psychiatry 1995;38:86–91.
89. Rivkin P, Kraut M, Barta P, et al. White matter hyperintensity volume in late-onset and early-onset schizophrenia. Int J Geriatr Psychiatry 2000;15:1085–1089.
90. Symonds LL, Olichney JM, Jernigan TL, et al. Lack of clinically significant gross structural abnormalities in MRIs of older patients with schizophrenia and related psychoses. J Neuropsychiatry Clin Neurosci 1997;9:251–258.
91. Ogawa Y, Hashimoto M, Yatabe Y, et al. Association of cerebral small vessel disease with delusions in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 2013;28:18–25.
92. Aström M. Generalized anxiety disorder in stroke patients: a three-year longitudinal study. Stroke 1996;27:270–275.
93. Castillo CS, Schultz SK, Robinson RG. Clinical correlates of early-onset and late-onset post-stroke generalized anxiety. Am J Psychiatry 1995;152:1174–1179.
94. Sultzer DL, Mahler ME, Cummings JL, et al. Cortical abnormalities associated with subcortical lesions in vascular dementia: clinical and positron emission tomographic findings. Arch Neurol 1995;52:773–780.
95. Duggal HS. New-onset PTSD after thalamic infarct. Am J Psychiatry 2002;159:2113–2114.
96. Fan Q, Yan X, Wang J, et al. Abnormalities of white matter microstructure in unmedicated obsessive-compulsive disorder and changes after medication. PLoS One 2012;7:e35889.
97. Nestadt G, Bienvenu OJ, Cai G, Samuels J, Eaton WW. Incidence of obsessive-compulsive disorder in adults. J Nerv Ment Dis 1998:401–406.
98. Berthier ML, Kulisevsky J, Gironell A, Heras JA. Obsessive-compulsive disorder associated with brain lesions: clinical phenomenology, cognitive function, and anatomic correlates. Neurology 1996;47:353–361.
99. Weiss AP, Jenike MA. Late-onset obsessive-compulsive disorder: a case series. J Neuropsychiatry Clin Neurosci 2000;12:265–268.
100. Menzies L, Chamberlain SR, Laird AR, et al. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev 2008;32:525–549.
101. Marin RS. Apathy: a neuropsychiatric syndrome. J Neuropsychiatry Clin Neurosci 1991;3:243–254.
102. Levy R, Dubois B. Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex 2006;16:916–928.
103. Starkstein SE, Leentjens AF. The nosological position of apathy in clinical practice. J Neurol Neurosurg Psychiatry 2008;79:1088–1092.
104. Stuss DT, van Reekum R, Murphy KJ. Differentiation of states and causes of apathy. In Borod J, ed. The Neuropsychology of Emotion. New York, NY: Oxford University Press; 2000: pp. 340–363.
105. Van Reekum R, Stuss DT, Ostrander L. Apathy: why care? J Neuropsychiatry Clin Neurosci 2005;17:7–19.
106. Starkstein SE, Mizrahi R, Capizzano AA, et al. Neuroimaging correlates of apathy and depression in Alzheimer’s disease. J Neuropsychiatry Clin Neurosci 2009;21:259–265.
107. Jouvent E, Reyes S, Mangin JF, et al. Apathy is related to cortex morphology in CADASIL: a sulcal-based morphometry study. Neurology 2011;76:1472–1477.
108. Reyes S, Viswanathan A, Godin O, et al. Apathy: a major symptom in CADASIL. Neurology 2009;72:905–910.
109. Grool AM, Gerritsen L, Zuithoff NP, et al. Lacunar infarcts in deep white matter are associated with higher and more fluctuating depressive symptoms during three years follow-up. Biol Psychiatry 2013;73:169–176.
110. Grool AM, van der Graaf Y, Mali WP, et al. Location and progression of cerebral small-vessel disease and atrophy, and depressive symptom profiles: the Second Manifestations of Arterial Disease (SMART)-Medea study. Psychol Med 2011;42:359–370.
111. Jonsson M, Edman A, Lind K, et al. Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia. Int J Geriatr Psychiatry 2010;25:588–595.
112. Andersson S, Krogstad JM, Finset A. Apathy and depressed mood in acquired brain damage: relationship to lesion localization and psychophysiological reactivity. Psychol Med 1999;29:447–456.

References

1. World Health Organization. International Classification of Impairments, Disabilities and Handicaps. Geneva: World Health Organization; 1980.
2. World Health Organization. International Classification of Functioning, Disability and Health. Geneva: World Health Organization; 2001. Available from: http://www3.who.int/icf/intros/ICF-Eng-Intro.pdf (accessed January 3, 2014).
3. Katz S. Assessing self-maintenance: Activities of Daily Living, mobility, and Instrumental Activities of Daily Living. J Am Geriatr Soc 1983;31:721–727.
4. Lawton MP, Brody EM. Assessment of older people: self-maintaining and Instrumental Activities of Daily Living. Gerontologist 1969;9:179–186.
5. Gelinàs I, Gauthier L, McIntyre M, et al. Development of a functional measure for persons with Alzheimer’s disease: the Disability Assessment for Dementia. Am J Occup Ther 1999;53:471–481.
6. Van Swieten J, Koudstaal P, Visser M, et al. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988;19:604–607.
7. Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. MD State Med J 1965;14:61–65.
8. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 1987;149:351–356.
9. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010;9:689–701.
10. Pantoni L, Garcia JH. The significance of cerebral white matter abnormalities 100 years after Binswanger’s report. A review. Stroke 1995;26:1293–1301.
11. Tarvonen-Schröder S, Kurki T, Räihä I, Sourander L. Leukoaraiosis and cause of death: a five year follow up. J Neurol Neurosurg Psychiatry 1995;58:586–589.
12. Inzitari D, Di Carlo A, Mascalchi M, Pracucci G, Amaducci L. The cardiovascular outcome of patients with motor impairment and extensive leukoaraiosis. Arch Neurol 1995;52:687–691.
13. Inzitari D, Cadelo M, Marranci ML, Pracucci G, Pantoni L. Vascular deaths in elderly neurological patients with leukoaraiosis. J Neurol Neurosurg Psychiatry 1997;62:177–181.
14. Briley DP, Haroon S, Sergent SM, Thomas S. Does leukoaraiosis predict morbidity and mortality? Neurology 2000;54:90–94.
15. Inzitari D. Leukoaraiosis: an independent risk factor for stroke? Stroke 2003;34:2067–2071.
16. Pantoni L. Leukoaraiosis: from an ancient term to an actual marker of poor prognosis. Stroke 2008;39:1401–1403.
17. Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 2010;341:3666.
18. Erkinjuntti T, Pantoni L, Scheltens P. Cooperation and networking on white matter disorders: the European Task Force on Age-Related White Matter Changes. Dement Geriatr Cogn Disord 1998;9(Suppl 1):44–45.
19. Pantoni L, Basile AM, Pracucci G, et al. Impact of age-related cerebral white matter changes on the transition to disability – the LADIS study: rationale, design and methodology. Neuroepidemiology 2005;24:51–62.
20. The LADIS Study Group. 2001–2011: a decade of the LADIS (Leukoaraiosis And DISability ) study: what have we learned about white matter changes and small-vessel disease? Cerebrovasc Dis 2011;32:577–588.
21. Pantoni L, Poggesi A, Basile AM, et al. LADIS Study Group. Leukoaraiosis predicts hidden global functioning impairment in nondisabled older people: the LADIS (Leukoaraiosis And DISability in the elderly) study. J Am Geriatr Soc 2006;54:1095–2101.
22. Inzitari D, Simoni M, Pracucci G, et al. LADIS Study Group. Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study. Arch Intern Med 2007;167:81–88.
23. Inzitari D, Pracucci G, Poggesi A, et al. LADIS Study Group. Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (Leukoaraiosis And DISability) study cohort. BMJ 2009;339:2477.
24. Norrving B. Long-term prognosis after lacunar infarction. Lancet Neurol 2003;2:238–245.
25. Fisher CM. Lacunar stroke and infarcts: a review. Neurology 1982;32:871–876.
26. Sacco S, Marini C, Totaro R, et al. A population-based study of the incidence and prognosis of lacunar stroke. Neurology 2006;66:1335–1338.
27. Bejot Y, Catteau A, Caillier M, et al. Trends in incidence, risk factors, and survival in symptomatic lacunar stroke in Dijon, France, from 1989 to 2006: a population-based study. Stroke 2008;39:1945–1951.
28. Staaf G, Lindgren A, Norrving B. Pure motor stroke from presumed lacunar infarct: long-term prognosis for survival and risk of recurrent stroke. Stroke 2001;32:2592–2596.
29. Eriksson S-E, Olsson JE. Survival and recurrent strokes in patients with different subtypes of stroke: a 14-year follow-up study. Cerebrovasc Dis 2001;12:171–180.
30. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991;337:1521–1526.
31. Samuelsson M, Söderfelt B, Olsson GB. Functional outcome in patients with lacunar infarction. Stroke 1996;27:842–846.
32. De Jong G, Kessels F, Lodder J. Two types of lacunar infarcts. Further arguments from a study on prognosis. Stroke 2002;33:2072–2076.
33. Vermeer S, Longstreth WT Jr, Koudstaal PJ. Silent brain infarcts: a systematic review. Lancet Neurology 2007;6:611–619.
34. Miyao S, Takano A, Teramoto J, Takahashi A. Leukoaraiosis in relation to prognosis for patients with lacunar infarction. Stroke 1992;23:1434–1438.
35. Yamamoto Y, Akiguchi I, Oiwa K, et al. Twenty-four-hour blood pressure and MRI as predictive factors for different outcomes in patients with lacunar infarct. Stroke 2002;33:297–305.
36. Koga H, Takashima Y, Murakawa R, et al. Cognitive consequences of multiple lacunes and leukoaraiosis as vascular cognitive impairment in community-dwelling elderly individuals. J Stroke Cerebrovasc Dis 2009;18:32–37.
37. Benisty S, Gouw AA, Porcher R, et al. Location of lacunar infarcts correlates with cognition in a sample of non disabled subjects with age-related white matter changes: the LADIS study. J Neurol Neurosurg Psychiatry 2009;80:478–483.
38. Jacova C, Pearce LA, Costello R, et al. Cognitive impairment in lacunar strokes: the SPS3 trial. Ann Neurol 2012;72:351–362.
39. Van der Flier WM, Cordonnier C. Microbleeds in vascular dementia: clinical aspects. Exp Gerontol 2012;47:853–857.
40. Cordonnier C, van der Flier WM. Brain microbleeds and Alzheimer’s disease: innocent observation or key player? Brain 2011;134:335–344.
41. Cordonnier C, Al-Shahi SR, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain 2007;130:1988–2003.
42. Biessels GJ, Zwanenburg JJ, Visser F, Frijns CJ, Luijten PR. Hypertensive cerebral hemorrhage: imaging the leak with 7-T MRI. Neurology 2010;75:572–573.
43. Theysohn JM, Kraff O, Maderwald S, et al. Seven Tesla MRI of microbleeds and white matter lesions as seen in vascular dementia. J Magn Reson Imaging 2011;33:782–791.
44. Lesnik Oberstein SA, van den Boom R, van Buchem MA, et al. Cerebral microbleeds in CADASIL. Neurology 2001;57:1066–1070.
45. Viswanathan A, Guichard JP, Gschwendtner A, et al. Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study. Brain 2006;129:2375–2383.
46. Viswanathan A, Gschwendtner A, Guichard JP, et al. Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL. Neurology 2007;69:172–179.
47. Henneman WJ, Sluimer JD, Cordonnier C, et al. MRI biomarkers of vascular damage and atrophy predicting mortality in a memory clinic population. Stroke 2009;40:492–498.
48. Altmann-Schneider I, Trompet S, de Craen AJ, et al. Cerebral microbleeds are predictive of mortality in the elderly. Stroke 2011;42:638–644.
49. Dufouil C, Chalmers J, Coskun O, et al. Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection aGainst Recurrent Stroke Study) Magnetic Resonance Imaging Substudy. Circulation 2005;112:1644–1650.
50. Mok VC, Lam WW, Fan YH, et al. Effects of statins on the progression of cerebral white matter lesion: post hoc analysis of the ROCAS (Regression of Cerebral Artery Stenosis) study. J Neurol 2009;256:750–757.
51. Ten Dam VH, van den Heuvel DM, van Buchem MA, et al. for the PROSPER Study Group. Effect of pravastatin on cerebral infarcts and white matter lesions. Neurology 2005;64:1807–1809.

References

1. Chabriat H, Vahedi K, Iba-Zizen MT, et al. Clinical spectrum of CADASIL: a study of seven families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet 1995;346:934–939.
2. Dichgans M, Mayer M, Uttner I et al. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol 1998;44:731–739.
3. Desmond DW, Moroney JT, Lynch T, et al. The natural history of CADASIL: a pooled analysis of previously published cases. Stroke 1999;30:1230–1233.
4. Adib-Samii P, Grice G, Martin RJ, Markus HS. Clinical spectrum of CADASIL and effect of cardiovascular risk factors on phenotype. Study in 200 consecutively recruited individuals. Stroke 2010;41:630–634.
5. Pescini F, Nannucci S, Bertaccini B, et al. The Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) scale: a screening tool to select patients for NOTCH3 analysis. Stroke 2012;43:2871–2876.
6. Kim Y, Choi EJ, Choi CG, et al. Characteristics of CADASIL in Korea: a novel cysteine-sparing Notch3 mutation. Neurology 2006;66:1511–1516.
7. Wang Z, Yuang Y, Zhang W, et al. NOTCH3 mutations and clinical features in 33 mainland Chinese families with CADASIL. J Neurol Neurosurg Psychiatry 2011;82:534–539.
8. Narayan SK, Gorman G, Kalaria RN, Ford GA, Chinnery PF. The minimum prevalence of CADASIL in northeast England. Neurology 2012;78:1025–1027.
9. Kalimo H, Ruchoux MM, Viitanen M, Kalaria RN. CADASIL: a common form of hereditary arteriopathy causing brain infarcts and dementia. Brain Pathol 2002;12:371–84.
10. Joutel A, Favrole P, Labauge P, et al. Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet 2001;358:2049–2051.
11. Opherk C, Peters N, Herzog J, Luedtke R, Dichgans M. Long-term prognosis and cause of death in CADASIL: a retrospective study of 411 patients. Brain 2004;127:2533–2539.
12. Viswanathan A, Gschwendtner A, Guichard JP, et al. Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL. Neurology 2007;69:172–179.
13. Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG. CADASIL. Lancet Neurol 2009;8:643–653.
14. Eikermann-Haerter K, Yuzawa I, Dilekoz E, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome mutations increase susceptibility to spreading depression. Ann Neurol 2011;69:413–418.
15. Pescini F, Cesari F, Giusti B, et al. Bone marrow-derived progenitor cells in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 2010;41:218–223.
16. Campolo J, De Maria R, Frontali M, et al. Impaired vasoreactivity in mildly disabled CADASIL patients. J Neurol Neurosurg Psychiatry 2012;83:268–274.
17. Liem MK, Lesnik Oberstein SAJ, va der Grond J, Ferrari M, Haan J. CADASIL and migraine: a narrative review. Cephalagia 2010:30:1284–1289.
18. Sacco S, Degan D, Carolei A. Diagnostic criteria for CADASIL in the International Classification of Headache Disorders (ICHD-II): are they appropriate? J Headache Pain 2010;11:181–186.
19. Charlton RA, Morris RG, Nitkunan A, Markus HS. The cognitive profile in CADASIL and sporadic small vessel disease. Neurology, 2006;66:1523–1526.
20. Epelbaum S, Benisty S, Reyes S, et al. Verbal memory impairment in subcortical ischemic vascular disease. A descriptive analysis in CADASIL. Neurobiol Aging 2011;32:2172–2182.
21. Duering M, Zieren N, Hervé D, et al. Strategic role of frontal white matter tracts in vascular cognitive impairment: a voxel-based lesion-symptom mapping study in CADASIL. Brain 2011;134:2366–2375.
22. Bianchi S, Rufa A, Ragno M, et al. High frequency of exon 10 mutations in the NOTCH3 gene in Italian CADASIL families: phenotype peculiarities. J Neurol 2010;257:1039–1042.
23. Reye S, Viswanathan A, Godin O, et al. Apathy: a major symptom in CADASIL. Neuroloy 2009;72:905–910.
24. Choi JC, Song SK, Lee JS, Kang S, Kang JH. Diversity of stroke presentation in CADASIL: study from patients harboring the predominant NOTCH3 mutation R544C. J Stroke Cerebrovasc Dis 2013;22:126–131.
25. Dotti MT, De Stefano N, Bianchi S, et al. A novel Notch3 frameshift deletion and mitochondrial abnormalities in a patient with CADASIL. Arch Neurol 2004;61:942–945.
26. Rufa A, De Stefano N, Dotti MT, et al. Acute unilateral visual loss as the first symptom of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Arch Neurol 2004;61:577–580.
27. Lesnik Oberstein SA, Jukema JW, Van Duinen SG, et al. Myocardial infarction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Medicine (Baltimore) 2003;82:251–256.
28. Zicari E, Tassi R, Stromillo ML, et al. Right-to-left shunt in CADASIL patients. Prevalence and correlation with clinical and MRI findings. Stroke 2008;39:2155–2157.
29. Rufa A, Dotti MT, Franchi M, et al. Systemic blood pressure profile in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 2005;36:2554–2558.
30. Rufa A, Guider F, Acampa M, et al. Cardiac autonomic nervous system and risk of arrhythmias in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Stroke 2007;38:276–280.
31. Singhal S, Rich P, Markus HS. The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship with age and clinical features. AJNR Am J Neuroradiol 2005;26:2481–2487.
32. Stromillo ML, Dotti MT, Battaglini M, et al. Structural and metabolic brain abnormalities in preclinical CADASIL. J Neurol Neurosurg Psychiatry 2009;80:41–47.
33. Peters N, Holtmannspotter M, Opherk C, et al. Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease. Neurology 2006;66:1517–1522.
34. Malandrini A, Gaudiano C, Gambelli S, et al. Diagnostic value of ultrastructural skin biopsy studies in CADASIL. Neurology 2007;68:1430–1432.
35. Fukutake T. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): from discovery to gene identification. J Stroke Cerebrovasc Dis 2011;20:85–93.
36. Mendioroz M, Fernández-Cadenas I, Del Río-Espinola A, et al. A missense HTRA1 mutation expands CARASIL syndrome to the Caucasian population. Neurology 2010;75:2033–2035.
37. Hara K, Shiga A, Fukutake T, et al. Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. N Engl J Med 2009;360:1729–1739.
38. Nishimoto Y, Shibata M, Nihonmatsu M, et al. A novel mutation in the HTRA1 gene causes CARASIL without alopecia. Neurology 2011;76:1353–1355.
39. Arima K, Yanagawa S, Ito N, Ikeda S. Cerebral arterial pathology of CADASIL and CARASIL (Maeda syndrome). Neuropathology 2003;23:327–334.
40. Shiga A, Nozaki H, Yokoseki A, et al. Cerebral small-vessel disease protein HTRA1 controls the amount of TGF-β1 via cleavage of proTGF-β1. Hum Mol Genet 2011;20:1800–1810.
41. Gould DB, Phalan FC, Breedveld GJ. Mutations in COL4A1 cause perinatal cerebral hemorrhage and porencephaly. Science 2005;308:1167–1171.
42. De Vries LS, Koopman C, Groenendaal F, et al. COL4A1 mutation in two preterm siblings with antenatal onset of parenchymal hemorrhage. Ann Neurol 2009;65:12–18.
43. Plaisier E, Gribouval O, Alamowitch S, et al. Role of COL4A1 mutations in the hereditary angiopathy with nephropathy, aneurysm and cramps (HANAC) syndrome. New Engl J Med 2007;357:2687–2695.
44. Van der Knaap MS, Smit LM, Barkhof F, et al. Neonatal porencephaly and adult stroke related to mutations in collagen IV A1. Ann Neurol 2006;59:504–511.
45. Vahedi K, Boukobza M, Massin P, et al. Clinical and brain MRI follow up study of a family with COL4A1 mutation. Neurology 2007;69:1564–1568.
46. Lemmens R, Maugeri A, Niessen HWM, et al. Novel COL4A1 cause cerebral small vessel disease by haploinsufficiency. Hum Mol Genet 2013;22:391–397.
47. Weng YC, Sonni A, Labelle-Dumais C, et al. COL4A1 mutations in patients with sporadic late-onset intracerebral hemorrhage. Ann Neurol 2012;71:470–477.
48. Jeanne M, Labelle-Dumais C, Jorgensen J, et al. COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke. Am J Hum Genet 2012;90:91–101.
49. Grand MG, Kaine J, Fulling K, et al. Cerebroretinal vasculopathy. Ophthalmology 1988;95:649–659.
50. Gutmann DH, Fischbeck KH, Sergott RC. Hereditary retinal vasculopathy with cerebral white matter lesions. Am J Med Genet 1989;34:217–220.
51. Mateen FJ, Krecke K, Younge BR, et al. Evolution of a tumor-like lesion in cerebroretinal vasculopathy and TREX1 mutation. Neurology 2010;75:1211–1213.
52. Ophoff RA, DeYoung J, Service S, et al. Hereditary vascular retinopathy, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke map to a single locus on chromosome 3p21.1–p21.3. Am J Hum Genet 2001;69:447–453.
53. Richards A, van den Maagdenberg AM, Jen JC, et al. C-terminal truncations in human 3′-5′ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nature Genet 2007;39:1068–1070.
54. Tagliavini F, Pietrini V, Gemignani F, et al. Anderson–Fabry’s disease: neuropathological and neurochemical investigations. Acta Neuropathol 1982;56:93–98.
55. Sims K, Politei J, Banikazemi M, Lee P. Stroke in Fabry disease frequently occurs before diagnosis and in absence of other clinical events: natural history data from the Fabry Registry. Stroke 2009;40:788–794.
56. Takanashi J, Barkovich AJ, Dillon WP, et al. T1 hyperintensity in the pulvina: key imaging feature for diagnosis of Fabry disease. AJNR Am J Neuroradiol 2003;24:916–921.
57. Federico A. Fabry’s disease and cerebrovascular disorders. Neurol Sci 2002;23:47–48.
58. Bersano A, Lanfranconi S, Valcarenghi C, et al. Neurological features of Fabry disease: clinical, pathophysiological aspects and therapy. Acta Neurol Scand 2012;126:77–97.

References

1. Jellinger KA, Attems J. Neuropathology and general autopsy findings in nondemented aged subjects. Clin Neuropathol 2012;31:87–98.
2. Polvikoski TM, Van Straaten EC, Barkhof F, et al. Frontal lobe white matter hyperintensities and neurofibrillary pathology in the oldest old. Neurology 2010;75:2071–2078.
3. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association Work Groups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7:263–269.
4. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association Work Groups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7:270–279.
5. Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS–ADRDA criteria. Lancet Neurol 2007;6:734–746.
6. Dubois B, Feldman HH, Jacova C, et al. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 2010;9:1118–11127.
7. Román GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS–AIREN international workshop. Neurology 1993;43:250–260.
8. Hejl A, Hogh P, Waldemar G. Potentially reversible conditions in 1000 consecutive memory clinic patients. J Neurol Neurosurg Psychiatry 2002;73:390–394.
9. Lobo A, Launer LJ, Fratiglioni L, et al. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000;54:S4–S9.
10. Barker WW, Luis CA, Kashuba A, et al. Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank. Alzheimer Dis Assoc Disord 2002;16:203–212.
11. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet 2001;357:169–175.
12. O’Brien JT, Erkinjuntti T, Reisberg B, et al. Vascular cognitive impairment. Lancet Neurol 2003;2:89–98.
13. Hachinski V, Iadecola C, Petersen RC, et al. National Institute of Neurological Disorders and Stroke–Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 2006;37:2220–2241.
14. Gorelick PB, Scuteri A, Black SE, et al. Vascular Contributions to Cognitive Impairment and Dementia: a Statement for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:2672–2713.
15. Erkinjuntti T, Inzitari D, Pantoni L, et al. Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm Suppl 2000;59:23–30.
16. Staekenborg SS, Van Straaten EC, van der Flier WM, et al. Small vessel versus large vessel vascular dementia: risk factors and MRI findings. J Neurol 2008;255:1644–1651.
17. Gold G, Giannakopoulos P, Herrmann FR, Bouras C, Kovari E. Identification of Alzheimer and vascular lesion thresholds for mixed dementia. Brain 2007;130:2830–2836.
18. Schneider JA, Wilson RS, Bienias JL, Evans DA, Bennett DA. Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology. Neurology 2004;62:1148–1155.
19. Esiri MM, Nagy Z, Smith MZ, Barnetson L, Smith AD. Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer’s disease. Lancet 1999;354:919–920.
20. Snowdon DA, Greiner LH, Mortimer JA, et al. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA 1997;277:813–817.
21. Scheltens P, Fox N, Barkhof F, De Carli C. Structural magnetic resonance imaging in the practical assessment of dementia: beyond exclusion. Lancet Neurol 2002;1:13–21.
22. Sluimer JD, van der Flier WM, Karas GB, et al. Accelerating regional atrophy rates in the progression from normal aging to Alzheimer’s disease. Eur Radiol 2009;19:2826–2833.
23. Lehmann M, Koedam EL, Barnes J, et al. Posterior cerebral atrophy in the absence of medial temporal lobe atrophy in pathologically-confirmed Alzheimer’s disease. Neurobiol Aging 2012;33:672.
24. Frisoni GB, Pievani M, Testa C, et al. The topography of grey matter involvement in early and late onset Alzheimer’s disease. Brain 2007;130:720–730.
25. Koedam EL, Lehmann M, van der Flier WM, et al. Visual assessment of posterior atrophy development of a MRI rating scale. Eur Radiol 2011;21:2618–2625.
26. Fernando MS, Ince PG. Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 2004;226:13–17.
27. Gouw AA, Seewann A, Vrenken H, et al. Heterogeneity of white matter hyperintensities in Alzheimer’s disease: postmortem quantitative MRI and neuropathology. Brain 2008;131:3286–3298.
28. Gouw AA, Seewann A, van der Flier WM, et al. Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry 2011;82:126–135.
29. Barkhof F, Scheltens P. Is the whole brain periventricular? J Neurol Neurosurg Psychiatry 2006;77:143–144.
30. Fazekas F, Kleinert R, Roob G, et al. Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. AJNR Am J Neuroradiol 1999;20:637–642.
31. Goos JD, Kester MI, Barkhof F, et al. Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition. Stroke 2009;40:3455–3460.
32. Vernooij MW, van der Lugt A, Ikram MA, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology 2008;70:1208–1214.
33. Vernooij MW, Haag MD, van der Lugt A, et al. Use of antithrombotic drugs and the presence of cerebral microbleeds: the Rotterdam Scan Study. Arch Neurol 2009;66:714–720.
34. Goos JD, van der Flier WM, Knol DL, et al. Clinical relevance of improved microbleed detection by susceptibility-weighted magnetic resonance imaging. Stroke 2011;42:1894–1900.
35. Ihara M, Polvikoski TM, Hall R, et al. Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer’s disease, and dementia with Lewy bodies. Acta Neuropathol 2010;119:579–589.
36. Okamoto Y, Yamamoto T, Kalaria RN, et al. Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts. Acta Neuropathol 2012;123:381–394.
37. Kalaria RN, Erkinjuntti T. Small vessel disease and subcortical vascular dementia. J Clin Neurol 2006;2:1–11.
38. DeCarli CS. When two are worse than one: stroke and Alzheimer disease. Neurology 2006;67:1326–1327.
39. Staekenborg SS, Koedam EL, Henneman WJ, et al. Progression of mild cognitive impairment to dementia: contribution of cerebrovascular disease compared with medial temporal lobe atrophy. Stroke 2009;40:1269–1274.
40. Verdelho A, Madureira S, Moleiro C, et al. White matter changes and diabetes predict cognitive decline in the elderly: the LADIS study. Neurology 2010;75:160–167.
41. Smith EE, Egorova S, Blacker D, et al. Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia. Arch Neurol 2008;65:94–100.
42. Prins ND, van Dijk EJ, den Heijer T, et al. Cerebral white matter lesions and the risk of dementia. Arch Neurol 2004;61:1531–1534.
43. Debette S, Beiser A, DeCarli C, et al. Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study. Stroke 2010;41:600–606.
44. Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215–1222.
45. Prins ND, van Dijk EJ, den Heijer T, et al. Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain 2005;128:2034–2041.
46. Van der Flier WM, Van Straaten EC, Barkhof F, et al. Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study. Stroke 2005;36:2116–2120.
47. Schmidt R, Ropele S, Enzinger C, et al. White matter lesion progression, brain atrophy, and cognitive decline: the Austrian Stroke Prevention Study. Ann Neurol 2005;58:610–616.
48. Schmidt R, Ropele S, Ferro J, et al. Diffusion-weighted imaging and cognition in the Leukoariosis And DISability in the elderly study. Stroke 2010;41:e402–e408.
49. Van Norden AG, van Uden IW, de Laat KF, van Dijk EJ, de Leeuw FE. Cognitive function in small vessel disease: the additional value of diffusion tensor imaging to conventional magnetic resonance imaging: the RUN DMC study. J Alzheimers Dis 2012;32:667–676.
50. Kalaria RN. Cerebrovascular disease and mechanisms of cognitive impairment: evidence from clinicopathological studies in humans. Stroke 2012;43:2526–2534.
51. Brundel M, de Bresser J, van Dillen JJ, Kappelle LJ, Biessels GJ. Cerebral microinfarcts: a systematic review of neuropathological studies. J Cereb Blood Flow Metab 2012;32:425–436.
52. Cordonnier C, van der Flier WM. Brain microbleeds and Alzheimer’s disease: innocent observation or key player? Brain 2011;134:335–344.
53. Cordonnier C, van der Flier WM, Sluimer JD, et al. Prevalence and severity of microbleeds in a memory clinic setting. Neurology 2006;66:1356–1360.
54. Pettersen JA, Sathiyamoorthy G, Gao FQ, et al. Microbleed topography, leukoaraiosis, and cognition in probable Alzheimer disease from the Sunnybrook Dementia Study. Arch Neurol 2008;65:790–795.
55. Goos JD, Teunissen CE, Veerhuis R, et al. Microbleeds relate to altered amyloid-β metabolism in Alzheimer’s disease. Neurobiol Aging 2012;33:1011–1019.
56. Van der Vlies AE, Goos JD, Barkhof F, Scheltens P, van der Flier WM. Microbleeds do not affect rate of cognitive decline in Alzheimer disease. Neurology 2012;79:763–769.
57. Van der Flier WM. Clinical aspects of microbleeds in Alzheimer’s disease. J Neurol Sci 2012;322:56–58.
58. Henneman WJ, Sluimer JD, Cordonnier C, et al. MRI biomarkers of vascular damage and atrophy predicting mortality in a memory clinic population. Stroke 2009;40:492–498.
59. Altmann-Schneider I, Trompet S, de Craen AJ, et al. Cerebral microbleeds are predictive of mortality in the elderly. Stroke 2011;42:638–644.
60. Sperling RA, Jack CR, Jr., Black SE, et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Work Group. Alzheimers Dement 2011;7:367–385.
61. Boche D, Zotova E, Weller RO, et al. Consequence of Aβ immunization on the vasculature of human Alzheimer’s disease brain. Brain 2008;131:3299–3310.
62. Damoiseaux JS, Smith SM, Witter MP, et al. White matter tract integrity in aging and Alzheimer’s disease. Hum Brain Mapp 2009;30:1051–1059.
63. Clerx L, Visser PJ, Verhey F, Aalten P. New MRI markers for Alzheimer’s disease: a meta-analysis of diffusion tensor imaging and a comparison with medial temporal lobe measurements. J Alzheimers Dis 2012;29:405–429.
64. Spilt A, Weverling-Rijnsburger AW, Middelkoop HA, et al. Late-onset dementia: structural brain damage and total cerebral blood flow. Radiology 2005;236:990–995.
65. Binnewijzend MA, Kuijer JP, Benedictus MR, et al. Cerebral blood flow measured with 3D pseudocontinuous arterial spin-labeling MR imaging in Alzheimer disease and mild cognitive impairment: a marker for disease severity. Radiology 2013;267:221–230.
66. Allan LM, Rowan EN, Firbank MJ, et al. Long term incidence of dementia, predictors of mortality and pathological diagnosis in older stroke survivors. Brain 2011;134:3716–3727.
67. Lewis H, Beher D, Cookson N, et al. Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-β42 peptide in vascular dementia. Neuropathol Appl Neurobiol 2006;32:103–118.
68. Bastos-Leite AJ, van der Flier WM, Van Straaten EC, et al. The contribution of medial temporal lobe atrophy and vascular pathology to cognitive impairment in vascular dementia. Stroke 2007;38:3182–3185.
69. Firbank MJ, Burton EJ, Barber R, et al. Medial temporal atrophy rather than white matter hyperintensities predict cognitive decline in stroke survivors. Neurobiol Aging 2007;28:1664–1669.
70. Vogels RL, Oosterman JM, van Harten B, et al. Neuroimaging and correlates of cognitive function among patients with heart failure. Dement Geriatr Cogn Disord 2007;24:418–423.
71. Gemmell E, Bosomworth H, Allan L, et al. Hippocampal neuronal atrophy and cognitive function in delayed poststroke and aging-related dementias. Stroke 2012;43:808–814.
72. Firbank MJ, He J, Blamire AM, et al. Cerebral blood flow by arterial spin labeling in poststroke dementia. Neurology 2011;76:1478–1484.
73. Huang KL, Lin KJ, Ho MY, et al. Amyloid deposition after cerebral hypoperfusion: evidenced on [(18)F]AV-45 positron emission tomography. J Neurol Sci 2012;319:124–129.
74. Grimmer T, Faust M, Auer F, et al. White matter hyperintensities predict amyloid increase in Alzheimer’s disease. Neurobiol Aging 2012;33:2766–2773.
75. Deramecourt V, Slade JY, Oakley AE, et al. Staging and natural history of cerebrovascular pathology in dementia. Neurology 2012;78:1043–1050.
76. Van Veluw SJ, Zwanenburg JJ, Engelen-Lee J, et al. In vivo detection of cerebral cortical microinfarcts with high-resolution 7T MRI. J Cereb Blood Flow Metab 2013;33:322–329.
77. Pantoni L, Basile AM, Pracucci G, et al. Impact of age-related cerebral white matter changes on the transition to disability – the LADIS study: rationale, design and methodology. Neuroepidemiology 2005;24:51–62.
78. Inzitari D, Simoni M, Pracucci G, et al. Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study. Arch Intern Med 2007;167:81–88.
79. Inzitari D, Pracucci G, Poggesi A, et al. Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (Leukoaraiosis And DISability) study cohort. BMJ 2009;339:2477.
80. Van der Flier WM, Van Straaten EC, Barkhof F, et al. Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study. J Neurol Neurosurg Psychiatry 2005;76:1497–1500.
81. Jokinen H, Lipsanen J, Schmidt R, et al. Brain atrophy accelerates cognitive decline in cerebral small vessel disease: the LADIS study. Neurology 2012;78:1785–1792.
82. De Leeuw FE, Korf E, Barkhof F, Scheltens P. White matter lesions are associated with progression of medial temporal lobe atrophy in Alzheimer disease. Stroke 2006;37:2248–2252.
83. Murray ME, Graff-Radford NR, Ross OA, et al. Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: a retrospective study. Lancet Neurol 2011;10:785–796.
84. Van de Pol LA, Hensel A, van der Flier WM, et al. Hippocampal atrophy on MRI in frontotemporal lobar degeneration and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2006;77:439–442.
85. De Bresser J, Brundel M, Conijn MM, et al. Visual cerebral microbleed detection on 7T MR imaging: reliability and effects of image processing. AJNR Am J Neuroradiol 2013;34:E61–E64.