Hostname: page-component-848d4c4894-8kt4b Total loading time: 0 Render date: 2024-07-05T23:58:13.552Z Has data issue: false hasContentIssue false

Progress in Clinical Neurosciences: Canadian Guidelines for the Development of Antidementia Therapies: A Conceptual Summary

Published online by Cambridge University Press:  02 December 2014

Howard H. Feldman*
Affiliation:
Division of Neurology, Department of Medicine, University of British Columbia, Clinic for Alzheimer's Disease and Related Disorders, Vancouver Coastal Health, Vancouver, BC
Serge Gauthier
Affiliation:
Department of Psychiatry, Neurology & Neurosurgery, Medicine, Faculty of Medicine, McGill University, Alzheimer Disease & Related Disorders Unit, McGill Center for studies in Aging, Montreal, QC
Howard Chertkow
Affiliation:
Department of Neurology and Neurosurgery, McGill University, Memory Clinic, Department of Neurology, Sir Mortimer B. Davis, Jewish General Hospital, Montreal, QC
David K. Conn
Affiliation:
Department of Psychiatry, University of Toronto, Department of Psychiatry, Baycrest Centre for Geriatric Care, Toronto, ON
Morris Freedman
Affiliation:
Department of Medicine, Division of Neurology, Mount Sinai Hospital, University Health Network and University of Toronto and the Behavioural Neurology Program and Rotman Research Institute, Baycrest Centre For Geriatric Care, Toronto, ON
Chris MacKnight
Affiliation:
Department of Medicine, Dalhousie University, Centre for Health Care of the Elderly, Capital District Health Authority, Halifax, Nova Scotia
*
Division of Neurology, University of British Columbia, S192-2211 Wesbrook Mall, Vancouver, British Columbia, V6T 2B5, Canada.
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The magnitude of the problems faced by an aging Canadian society has been clearly identified. Perhaps the single most important problem is the increasing incidence of dementia. Alzheimer's disease (AD) accounts for 50-60% of the dementias in later life within a spectrum of other contributing dementias. Regulatory approval has been given to Acetylcholinesterase inhibitors for the symptomatic treatment of mild to moderate AD, and conditional approval to memantine for the symptoms of moderate to severe AD. There has been no regulatory approval for the treatment of the degenerative dementias beyond AD. The very rapid progress in the past decade in biotechnology and in the molecular biology of the dementias is supporting a new generation of innovative treatment strategies that will more directly target the underlying disease pathogenic mechanisms. Such treatments will foreseeably include immunotherapies, anti-aggregants that may prevent misfolding and deposition of proteins, and neuroregenerative interventions. These Guidelines follow the 2nd Canadian Conference on the Development of Antidementia Therapies, held in 2004, which covered a range of design, methodological and ethical issues facing clinical researchers and regulatory authorities. They are intended to provide a common point of reference and guidance in Canada for therapeutic development of the dementias.

Résumé

RÉSUMÉ

L'amplitude du problème auquel fait face la société canadienne vieillissante a été clairement identifiée. Le problème le plus important est l'incidence croissante de la démence. De 50 à 60% des cas de démence chez les gens âgés sont dus à la maladie d'Alzheimer (MA). Des inhibiteurs de l'acétylcholinestérase ont été approuvés pour le traitement symptomatique de la MA légère ou modérée et la mémantine a reçu une approbation conditionnelle pour le traitement des symptômes modérés ou sévères de la MA. Aucun traitement des démences dégénératives autres que la MA n'a été approuvé. Les progrès très rapides de la recherche sur les démences en biotechnologie et en biologie moléculaire pendant la dernière décennie sont à l'origine d'une nouvelle génération de stratégies novatrices de traitement qui cibleront plus directement les mécanismes pathogéniques de la maladie sous-jacente. Il est probable que différentes stratégies seront utilisées dont l'immunothérapie, les anti-agrégants qui préviennent le pliage erroné de protéines et leur dépôt et les interventions neurorégénératrices. Ces lignes directrices sont émises suite à la deuxième conférence canadienne sur le développement de traitements anti-démence en 2004. Cette conférence a examiné plusieurs questions de modèles, de méthodologies et d'éthique auxquels sont confrontés les cliniciens chercheurs et les organismes réglementaires. Elles offrent un point de référence commun et une orientation pour le développement de traitements des démences au Canada.

Type
Review Article
Copyright
Copyright © The Canadian Journal of Neurological 2006

References

1. Canadian study of health and aging working group. Canadian study ofhealth and aging: Study methods and prevalence of dementia. CMAJ. 1994; 150: 899913.Google Scholar
2. Hux, MJ, O’Brien, BJ, Iskedjian, M, et al. Relation between severity of Alzheimer’s disease and costs of caring. CMAJ. 1998; 159: 457–65.Google ScholarPubMed
3. Mohr, E, Feldman, H, Gauthier, S. Canadian guidelines for the development of antidementia therapies: a conceptual summary. Can J Neurol Sci. 1995; 22: 6271.CrossRefGoogle ScholarPubMed
4. McKhann, G, Drachman, DA, Folstein, M, et al. Clinical diagnosis of Alzheimer’s disease – report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology. 1984; 34: 939–44.CrossRefGoogle ScholarPubMed
5. American Psychiatric Association. Diagnostic and Statistical Manualof Mental Disorders. (IV-TR). Washington, D.C.: 2000.Google Scholar
6. Morris, J, McKeel, DW, Fulling, K, Torack, RM, Berg, L. Validation ofclinical diagnostic criteria for Alzheimer’s disease. Ann Neurol. 1988; 24: 1722.CrossRefGoogle Scholar
7. Lopez, OL, Swihart, AA, Becker, JT, et al. Reliability of NINCDS-ADRDA clinical criteria for the diagnosis of Alzheimer’s disease. Neurology. 1990; 40: 1517–22.CrossRefGoogle ScholarPubMed
8. Mayeux, R, Saunders, AM, Shea, S, et al. Utility of the apolipoproteinE genotype in the diagnosis of Alzheimer’s disease. N Engl J Med. 1998; 338: 506–11.CrossRefGoogle ScholarPubMed
9. Hyman, BT, Trojanowski, JQ. Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol. 1997; 56: 1095–7.CrossRefGoogle Scholar
10. Feldman, H, Levy, AR, Hsiung, GY, et al. A Canadian cohort study of cognitive impairment and related dementias (ACCORD): Study methods and baseline results. Neuroepidemiology. 2003; 22: 265–74.CrossRefGoogle ScholarPubMed
11. Massoud, F, Devi, G, Stern, Y, et al. A clinicopathological comparisonof community-based and clinic-based cohorts of patients with dementia. Arch Neurol. 1999; 56: 1368–73.CrossRefGoogle Scholar
12. Lopez, OL, Becker, JT, Klunk, W, et al. Research evaluation anddiagnosis of possible Alzheimer’s disease over the last two decades: pt 2. Neurology. 2000; 55: 1863–9.CrossRefGoogle Scholar
13. Hachinski, VC, Lassen, NA, Marshal, J. Multi-infarct dementia: acause of mental deterioration in the elderly. Lancet. 1974; 2: 207–10.CrossRefGoogle Scholar
14. Rosen, WG, Terry, RG, Fuld, PA, Katzman, R, Peck, A. Pathological verification of ischemic score in differentiation of dementias. Ann Neurol. 1980; 7: 486–8.CrossRefGoogle ScholarPubMed
15. Roman, GC, Tatemichi, TK, Erkinjuntti, T, et al. Vascular dementia:diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 1993; 43: 250–60.CrossRefGoogle ScholarPubMed
16. Erkinjuntti, T, Kurz, A, Gauthier, S, et al. Efficacy of galantamine inprobable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomised trial. Lancet. 2002; Apr 13; 359(9314): 1283–90.CrossRefGoogle Scholar
17. Black, S, Roman, GC, Geldmacher, DS, et al. Efficacy and tolerabilityof donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlledclinical trial. Stroke. 2003 Sep 11; 34: 2323–30.CrossRefGoogle Scholar
18. Wilkinson, D, Doody, R, Helme, R, et al. Donepezil in vasculardementia: a randomized, placebo-controlled study. Neurology. 2003; 61: 479–86.CrossRefGoogle Scholar
19. Chui, HC, Mack, W, Jackson, JE, et al. Clinical criteria for the diagnosis of vascular dementia: a multicenter study of comparability and interrater reliability. Arch Neurol. 2000; 57: 191–6.CrossRefGoogle ScholarPubMed
20. Pohjasvaara, T, Mantyla, R, Ylikoski, R, Kaste, M, Erkinjuntti, T. Comparison of different clinical criteria (DSM-III, ADDTC, ICD-10, NINDS-AIREN, DSM-IV) for the diagnosis of vascular dementia. National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l’Enseignement en Neurosciences. Stroke. 2000; 31: 2952–7.CrossRefGoogle ScholarPubMed
21. Gold, G, Bouras, C, Canuto, A, et al. Clinicopathological validationstudy of four sets of clinical criteria for vascular dementia. Am J Psychiatry. 2002; 159: 82–7.CrossRefGoogle Scholar
22. McKeith, IG, Galasko, D, Kosaka, K, et al. Consensus guidelines forthe clinical and pathological diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996; 47: 1113–24.CrossRefGoogle Scholar
23. McKeith, IG, Perry, EK, Perry, RH. Report of the second dementia with Lewy body international workshop. Neurology. 1999; 53: 902–5.CrossRefGoogle ScholarPubMed
24. McKeith, I, Mintzer, J, Aarsland, D, et al. Dementia with Lewy bodies. Lancet Neurol. 2004; 3: 1928.CrossRefGoogle ScholarPubMed
25. Lopez, OL, Litvan, I, Catt, KE, et al. Accuracy of four clinical diagnostic criteria for the diagnosis of neurodegenerative dementias. Neurology. 1999; 53: 1292–9.CrossRefGoogle ScholarPubMed
26. Emre, M. Dementia associated with Parkinson’s disease. Lancet Neurol. 2003; 2: 229–37.CrossRefGoogle ScholarPubMed
27. Lund and Manchester Groups. Clinical and neuropathologicalcriteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry. 1994; 57: 416-8.Google Scholar
28. Neary, D, Snowden, JS, Gustafson, L, et al. Frontotemporal lobardegeneration: a consensus on clinical diagnostic criteria. Neurology. 1999; 51: 1546–54.CrossRefGoogle Scholar
29. McKhann, GM, Albert, MS, Grossman, M, et al. Clinical andpathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Arch Neurol. 2001; 58: 1803–9.CrossRefGoogle Scholar
30. Brun, A, Englund, B, Gustafson, L, et al. Clinical andneuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry. 1994; 57: 416–8.Google Scholar
31. Gregory, CA, Serra-Mestres, J, Hodges, JR. Early diagnosis of thefrontal variant of frontotemporal dementia: how sensitive are standard neuroimaging and neuropsychologic tests? Neuropsychiatry Neuropsychol Behav Neurol. 1999; 12: 128–35.Google ScholarPubMed
32. Hodges, JR, Miller, B. The classification, genetics andneuropathology of frontotemporal dementia. Introduction to the special topic papers: (pt 1). Neurocase. 2001; 7: 31–5.CrossRefGoogle Scholar
33. Kertesz, A, Munoz, DG. Pick’s disease and Pick complex. Toronto:Wiley-Liss, 1998.Google ScholarPubMed
34. Graham, JE, Rockwood, K, Beattie, BL, et al. Prevalence and severity of cognitive impairment with and without dementia in an elderlypopulation. Lancet. 1997; 349: 1793–6.CrossRefGoogle Scholar
35. Crook, T, Bartus, R, Ferris, SH, et al. Age-associated memoryimpairment: proposed diagnostic criteria and measures of clinical change – report of a National Institute of Mental Health Work Group. Dev Neuropsychol. 1986; 2: 261–76.CrossRefGoogle Scholar
36. Levy, R. Aging-associated cognitive decline. Int Psychogeriatr. 1994; 6: 63–8.Google ScholarPubMed
37. Ebly, EM, Hogan, DB, Parhad, IM. Cognitive impairment in the non-demented elderly: Results from the Canadian Study of Health and Aging. Arch Neurol. 1995; 52: 612–9.CrossRefGoogle Scholar
38. Petersen, RC, Smith, GE, Waring, SC, et al. Mild cognitiveimpairment: clinical characterization and outcome. Arch Neurol. 1999; 56: 303–8.CrossRefGoogle Scholar
39. Royall, DR, Chiodo, LK, Polk, MJ. Misclassification is likely in theassessment of mild cognitive impairment. Neuroepidemiology. 2004; 23: 185–91.CrossRefGoogle Scholar
40. Winblad, B, Palmer, K, Kivipelto, M, et al. Mild cognitiveimpairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004; 256: 240–6.CrossRefGoogle Scholar
41. Jack, CRJ, Petersen, RC, Xu, YC, et al. Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology. 1999; 52: 1397–403.CrossRefGoogle ScholarPubMed
42. Ingles, JL, Fisk, JD, Merry, HR, Rockwood, K. Five-year outcomes fordementia defined solely by neuropsychological test performance. Neuroepidemiology. 2003; 22: 172–80.CrossRefGoogle ScholarPubMed
43. DeCarli, C, Mungas, D, Harvey, D, et al. Memory impairment, but not cerebrovascular disease, predicts progression of MCI todementia. Neurology. 2004; 63: 220–7.CrossRefGoogle ScholarPubMed
44. Standridge, JB. Pharmacotherapeutic approaches to the preventionof Alzheimer’s disease. Am J Geriatr Pharmacother. 2004; 2: 119–32.CrossRefGoogle Scholar
45. Forette, F, Seux, ML, Staessen, JA, et al. Prevention of dementiain randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet. 1998; 352: 1347–51.Google Scholar
46. Patterson, C, Gauthier, S, Bergman, H, et al. The recognition, assessment and management of dementing disorders: conclusions form the Canadian Consensus Conference on Dementia. Can J Neurol Sci. 2001; 28 Suppl 1: S3–16.CrossRefGoogle Scholar
47. American Psychiatric Association. Practice guidelines for treatmentof patients with Alzheimer’s disease and other dementias of late life. Am J Psychiatry. 1997; 154 Suppl 5: 139.Google Scholar
48. Fillit, H, Cummings, J. Practice guidelines for the diagnosis andtreatment of Alzheimer’s disease in a managed care setting: part II-Pharmacologic therapy. Alzheimer’s Disease (AD) Managed Care Advisory Council. Manag Care Interface. 2000; 13: 51–6.Google Scholar
49. Doody, RS, Stevens, JC, Beck, C, et al. Practice parameter:management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001; 56: 1154–66.CrossRefGoogle Scholar
50. NICE issues guidance on drugs for Alzheimer’s disease. National Institute for Clinical Excellence. Available from: http://www.nice.org.uk/article.asp?a=14406.Google Scholar
51. California Workgroup on Guidelines for Alzheimer’s Disease Management Guidelines for Alzheimer’s Disease Management Available from: http://www.alzla.org/medical/FinalReport2002.pdf Google Scholar
52. Doody, RS. Current treatments for Alzheimer’s disease:cholinesterase inhibitors. J Clin Psychiatry. 2003; 64 Suppl 9: S11–7.Google ScholarPubMed
53. Reichman, WE. Current pharmacologic options for patients with Alzheimer’s disease. Ann Gen Hosp Psychiatry. 2003; 2: 1.CrossRefGoogle ScholarPubMed
54. Orgogozo, JM, Gilman, S, Dartigues, JF, et al. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology. 2003; 61: 4654.CrossRefGoogle Scholar
55. Tri-Council Policy Statement: Ethical Conduct for ResearchInvolving Humans, Medical Research Council of Canada, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada. Public Works and Government Services Canada, June 2003.Google Scholar
56. Shapiro, E, Shapiro, A. The powerful placebo: from ancient priest tomodern physician. Baltimore: The John Hopkins University Press Ltd; 1997.Google Scholar
57. Guess, HA, Kleinman, A, Kusek, JW, Engel, LW, editors. The scienceof the placebo. London: BMJ Books; 2002.Google Scholar
58. National Placebo Working Committee, Draft Report, Health Canadaand the Canadian Institutes for Health Research, 2003. Available from: http://www.cihr-irsc.gc.ca/e/services/19301.shtml.Google Scholar
59. Gervais, F, Garceau, D, Aisen, P, Gauthier, S. Glycosaminoglycanmimetics in Alzheimer’s disease. In: Gauthier, S, Scheltens, P, Cummings, J, editors. Alzheimer Disease and related disorders annual. London: Taylor and Francis; 2005.Google Scholar
60. Davis, KL, Thal, LJ, Gamzu, ER, et al. A double-blind placebo-controlled multicenter study of tacrine for Alzheimer’s Disease. The Tacrine Collaborative Study Group. N Engl J Med. 1992; 327: 1253–9.CrossRefGoogle ScholarPubMed
61. Sano, M, Ernesto, C, Thomas, RG, et al. A controlled trial ofselegeline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. N Engl J Med. 1997; 336: 1216–22.CrossRefGoogle ScholarPubMed
62. Leber, P. Slowing the progression of Alzheimer disease:methodologic issues. Alzheimer Dis Assoc Disord. 1997; 11 Suppl 5: S10–21.Google ScholarPubMed
63. Whitehouse, PJ, Kittner, B, Roessner, M. Clinical trial designs fordemonstrating disease-course-altering effects in dementia. Alzheimer Dis Assoc Disord. 1998; 12: 281–94.CrossRefGoogle ScholarPubMed
64. Mani, RB. The evaluation of disease modifying therapies in Alzheimer’s disease: a regulatory viewpoint. Stat Med. 2004; 23: 305–14.CrossRefGoogle ScholarPubMed
65. Leber, P. Guidelines for the clinical evaluation of antidementia drugs. US FDA, Washington DC, 1990.Google Scholar
66. Fleischhacker, WW, Czobor, P, Hummer, M, et al. Placebo or activecontrol trials of antipsychotic drugs? Arch Gen Psychiatry. 2003; 60: 458–64.CrossRefGoogle ScholarPubMed
67. Streiner, DL. Unicorns do exist: a tutorial on “proving” the null hypothesis. Can J Psychiatry. 2003; 48: 756–61.CrossRefGoogle ScholarPubMed
68. Mohs, RC, Rosen, WG, Davis, KL. The Alzheimer’s diseaseassessment scale: An instrument of assessing treatment efficacy. Psychopharmacol Bull. 1983; 19: 448–50.Google Scholar
69. Rosen, WG, Mohs, RC, Davis, KL. A new rating scale for Alzheimer’sdisease. Am J Psychiatry. 1984; 141: 1356–64.Google Scholar
70. Verhey, FR, Houx, P, Van Lang, N, et al. Cross-national comparisonand validation of the Alzheimer’s disease assessment scale: results from the European Harmonization Project for Instrumentsin Dementia (EURO-HARPID). Int J Geriatr Psychiatry. 2004; 19: 4150.CrossRefGoogle Scholar
71. Zee, R, Landreth, E, Vicari, S, et al. Alzheimer’s disease assessmentscale: a subtest analysis. Alzheimer Dis Assoc Disord. 1992; 6: 164–81.Google Scholar
72. Doraiswamy, PM, Bieber, F, Kaiser, L, et al. Memory, language, andpraxis in Alzheimer’s disease: norms for outpatient clinical trial populations. Psychopharmacol Bull. 1997; 33: 123–8.Google ScholarPubMed
73. Van Belle, G, Uhlmann, R, Hughes, JP, Larson, E. Reliability of estimates of change in mental status test performance in senile dementia of the Alzheimer type. J Clin Epidemiol. 1990; 43: 389–95.CrossRefGoogle ScholarPubMed
74. Schmeidler, J, Mohs, RC, Aryan, M. Relationship of disease severityto decline on specific cognitive and functional measures in Alzheimer disease. Alzheimer Dis Assoc Disord. 1998; 12: 146–51.CrossRefGoogle ScholarPubMed
75. Mohs, RC, Knopman, D, Petersen, RC, et al. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer’s disease assessment scale that broaden its scope. The Alzheimer’s disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997; 11 Suppl 2: S13–21.CrossRefGoogle Scholar
76. Grundman, M, Petersen, RC, Ferris, SH, et al. Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. Arch Neurol. 2004; 61: 5966.CrossRefGoogle ScholarPubMed
77. Salloway, S, Ferris, S, Kluger, A, et al. Efficacy of donepezil in mildcognitive impairment: A randomized placebo-controlled trial. Neurology. 2004; 64: 651–7.CrossRefGoogle Scholar
78. Bullock, R, Erkinjuntti, T, Lilienfeld, S, et al. Management of patientswith Alzheimer’s disease plus cerebrovascular disease: 12-month treatment with galantamine. Dement Geriatr Cogn Disord. 2004; 17: 2934.CrossRefGoogle Scholar
79. Wilcock, G, Mobius, HJ, Stoffler, A, et al. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol. 2002; 17: 297305. CrossRefGoogle ScholarPubMed
80. Saxton, J, Swihart, AA. Neuropsychological assessment of the severely impaired elderly patient. Clin Geriatr Med. 1989; 5: 531–43.CrossRefGoogle ScholarPubMed
81. Schmitt, FA, Cragar, D, Ashford, JW, et al. Measuring cognition inadvanced Alzheimer’s disease for clinical trials. J Neural Transm. Suppl 2002; 62: 135–48.Google Scholar
82. Schmitt, FA, Ashford, W, Ernesto, C, et al. The severe impairmentbattery: concurrent validity and assessment of longitudinal change in Alzheimer’s disease. Alzheimer Dis Assoc Disord. 1997; 11 Suppl 2: 551–6.CrossRefGoogle ScholarPubMed
83. Panisset, M, Roudier, M, Saxton, J, Boller, F. Severe impairment battery: a neuropsychological test for severely demented patients. Arch Neurol. 1994; 51: 41–5.CrossRefGoogle ScholarPubMed
84. Tariot, PN, Farlow, MR, Grossberg, GT, et al. Memantine treatment inpatients with moderate to severe Alzheimer’s disease already receiving donepezil: a randomized controlled trial. JAMA. 2004; 291: 317–24.CrossRefGoogle Scholar
85. Gauthier, S, Feldman, H, Hecker, J, et al. Functional, cognitive, and behavioural effects of donepezil in patients with moderateAlzheimer’s disease. Curr Med Res Opin. 2002; 18: 347–54.CrossRefGoogle ScholarPubMed
86. Prasher, VP, Huxley, A, Haque, MS, et al. A 24-week, double-blind,placebo-controlled trial of donepezil in patients with Down Syndrome and Alzheimer’s disease – pilot study. Int J Geriatr Psychiatry. 2002; 17: 270–8.CrossRefGoogle ScholarPubMed
87. Folstein, MF, Folstein, SE, McHugh, PR. Mini-Mental State: apractical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12: 189–98.CrossRefGoogle Scholar
88. Ihl, R, Frolich, L, Dierks, T, Martin, EA, Maurer, K. Differential validity of psychometric tests in dementia of the Alzheimer type. Psychiatry Res. 1992; 44: 93106.CrossRefGoogle ScholarPubMed
89. Reisberg, B, Ferris, SH, Franssen, EH, et al. Mortality and temporal course of probable Alzheimer’s disease: a 5-year prospective study. Int Psychogeriatr. 1996; 8: 291311.CrossRefGoogle ScholarPubMed
90. Crum, RM, Anthony, JC, Bassett, SS, Folstein, MF. Population-basednorms for the Mini-Mental State Examination by age and educational level. JAMA. 1993; 18: 2386–91.CrossRefGoogle Scholar
91. Courtney, C, Farrell, D, Gray, R, et al. Long-term donepezil treatmentin 565 patients with Alzheimer’s disease (AD2000): randomized double-blind trial. Lancet. 2004; 363(9427): 2105–15.Google Scholar
92. Jones, RW, Soininen, H, Hager, K, et al. A multinational, randomized, 12-week study comparing the effects of donepezil and galantamine in patients with mild to moderate Alzheimer’sdisease. Int J Geriatr Psychiatry. 2004; 19: 5867.CrossRefGoogle Scholar
93. Rogers, SL, Farlow, MR, Doody, RS, Mohs, R, Friedhoff, LT. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Donepezil Study Group. Neurology. 1998; 50: 136–45.CrossRefGoogle ScholarPubMed
94. Sahakian, BJ, Owen, AM, Morant, NJ, et al. Further analysis of thecognitive effects of tetrahydroaminoacridine (THA) in Alzheimer’s disease: assessment of attentional and mnemonic function using CANTAB. Psychopharmacology (Berl). 1993; 110: 395401.CrossRefGoogle Scholar
95. Cummings, JL, Back, C. The cholinergichypothesis ofneuropsychiatric symptoms in Alzheimer’s disease. Am J Geriatr Psychiatry. 1998; 6 Suppl 1: S64–S78.CrossRefGoogle ScholarPubMed
96. Hope, T, Keene, J, Gedling, K, Fairburn, CG, Jacoby, R. Prediction of institutionalization for people with dementia living at home with a carer. Int J Geriatr Psychiatry. 1998; 13: 682–90.3.0.CO;2-Y>CrossRefGoogle ScholarPubMed
97. Winblad, B, Wimo, A, Almkvist, O. Outcome measures in Alzheimer’sdisease: do they go far enough? Dement Geriatr Cogn Disord. 2000, 11 Suppl 1: 310.CrossRefGoogle Scholar
98. Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960; 23: 5662.CrossRefGoogle ScholarPubMed
99. Montgomery, SA, Asberg, M. A new depression scale designed to besensitive to change. Br J Psychiatry. 1979; 134: 382–9.CrossRefGoogle Scholar
100. Burke, WJ, Houston, MJ, Boust, SJ, Roccaforte, WH. Use of the Geriatric Depression Scale in dementia of the Alzheimer type. J Am Geriatr Soc. 1989; 37: 856–60.CrossRefGoogle ScholarPubMed
101. Feher, EP, Larrabee, GJ, Crook, TH 3rd. Factors attenuating thevalidity of the Geriatric Depression Scale in a dementia population. J Am Geriatr Soc. 1992; 40: 906–9.CrossRefGoogle Scholar
102. Gilley, DW, Wilson, RS. Criterion-related validity of the Geriatric Depression Scale in Alzheimer’s disease. J Clin Exp Neuropsychol. 1997; 19(4): 489–99.CrossRefGoogle ScholarPubMed
103. Sunderland, T, Minichiello, M. Dementia mood assessment scale. Int Psychogeriatr 1996; 8 Suppl 3: 329–31.CrossRefGoogle ScholarPubMed
104. Alexopoulos, GS, Abrams, RC, Young, RC, et al. Cornell scale fordepression in Dementia. Biol Psychiatry. 1988; 23: 271–84.CrossRefGoogle Scholar
105. Cummings, JL, Mega, M, Gray, K, et al: The Neuropsychiatric Inventory: comprehensive assessment of psychopathology indementia. Neurology. 1994; 44: 2308–14.CrossRefGoogle Scholar
106. Morris, JC, Cyrus, PA, Orazem, J, et al. Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer’s disease. Neurology. 1998; 50: 1222–30.CrossRefGoogle ScholarPubMed
107. Feldman, H, Gauthier, S, Hecker, J, et al. A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease. Neurology. 2001; 57: 613–20.CrossRefGoogle ScholarPubMed
108. Reisberg, B, Borenstein, J, Salob, SP, et al. Behavioral symptoms in Alzheimer’s disease: phenomenology and treatment. J Clin Psychiatry. 1987; 48 Suppl: S9–15.Google ScholarPubMed
109. Katz, IR, Jeste, DV, Mintzer, JE, et al. Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Risperidone Study Group. J Clin Psychiatry. 1999; 60: 107–15.CrossRefGoogle ScholarPubMed
110. De Deyn, PP, Rabheru, K, Rasmussen, A, et al. A randomized trial ofrisperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology. 1999; 53: 946–55.CrossRefGoogle Scholar
111. Tariot, PN, Mack, JL, Patterson, MB, et al. The behavioral ratingscale for dementia of the Consortium to Establish a Registry for Alzheimer’s Disease. Am J Psychiatry. 1995; 152: 1349–57.Google Scholar
112. Cohen-Mansfield, J. Agitated behaviors in the elderly. II. Preliminary results in the cognitively deteriorated. J Am Geriatr Soc. 1986; 34: 722–7.CrossRefGoogle ScholarPubMed
113. Reisberg, B. Functional assessment staging (FAST). Psychopharmacol Bull. 1988; 24: 653–9.Google ScholarPubMed
114. Gelinas, I, Auer, S. Functional autonomy. In: Gauthier, S, editor. Clinical diagnosis and management of Alzheimer’s disease. Second Edition Revised editor. London: Martin Dunitz; 2001: p. 213–26.Google Scholar
115. Mohs, RC, Doody, RS, Morris, JC, et al. A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology. 2001; 57: 481–8.CrossRefGoogle ScholarPubMed
116. Gelinas, I, Gauthier, L, McIntyre, M, Gauthier, S. Development of afunctional measure for persons with Alzheimer’s disease: the disability assessment for dementia. Am J Occup Ther. 1999; 53: 471–81.Google Scholar
117. Galasko, D, Bennett, D, Sano, M, et al. An inventory to assessactivities of daily living for clinical trials in Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997; 11 Suppl 2: S33–9.CrossRefGoogle ScholarPubMed
118. DeJong, R, Osterlund, OW, Roy, GW. Measurement of quality-of-lifechanges in patients with Alzheimer’s disease. Clin Ther. 1989; 11: 545–54.Google ScholarPubMed
119. Schneider, LS, Olin, JT, Doody, RS, et al. Validity and reliability of the Alzheimer’s Disease Cooperative Study-Clinical global impression of change. Alzheimer Dis Assoc Disord. 1997; 11 Suppl 2: S22–32.CrossRefGoogle ScholarPubMed
120. Hughes, CP, Berg, L, Danzinger, WL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982; 140: 566–72.CrossRefGoogle ScholarPubMed
121. Reisberg, B, Ferris, SH, de Leon, MJ, Crook, T. The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982; 139: 1136–9.Google ScholarPubMed
122. Morris, JC. The Clinical Dementia Rating (CDR): current versionand scoring rules. Neurology. 1993; 43: 2412–4.CrossRefGoogle Scholar
123. Rockwood, K. Size of the treatment effect on cognition of cholinesterase inhibition in Alzheimer’s Disease. J Neurol Neurosurg Psychiatry. 2004; 75: 677–85.CrossRefGoogle ScholarPubMed
124. Livingston, G, Katona, C. How useful are cholinesterase inhibitorsin the treatment of Alzheimer’s disease? A number needed to treat analysis. Int J Geriatr Psychiatry. 2000; 15: 203–7.3.0.CO;2-9>CrossRefGoogle Scholar
125. Whitehead, A, Perdomo, C, Pratt, RD, et al. Donepezil for the symptomatic treatment of patients with mild to moderate Alzheimer’s disease: a meta-analysis of individual patient data from randomized controlled trials. Int J Geriatr Psychiatry. 2004; 19: 624–33.CrossRefGoogle Scholar
126. Rockwood, K, Graham, J, Fay, S. Goal setting and attainment in Alzheimer’s disease patients treated with donepezil. J Neurol Neurosurg Psychiatry. 2002; 73: 500–7.CrossRefGoogle ScholarPubMed
127. Quinn, J, Moore, M, Benson, DF, et al. A videotaped CIBIC fordementia patients: validity and reliability in a simulated clinicaltrial. Neurology. 2002; 58: 433–7.CrossRefGoogle Scholar
128. Mack, JL, Whitehouse, PJ. Quality of Life in Dementia: state of theart--report of the International Working Group for Harmonization of Dementia Drug Guidelines and the Alzheimer’s Society satellite meeting. Alzheimer Dis Assoc Disord. 2001; 15: 6971.CrossRefGoogle Scholar
129. Whitehouse, PJ, Orgogozo, JM, Becker, RE, et al. Quality-of-lifeassessment in dementia drug development. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines. Alzheimer Dis Assoc Disord. 1997; 11 Suppl 3:S56–60.CrossRefGoogle Scholar
130. Maslow, K, Whitehouse, P. Defining and measuring outcomes in Alzheimer’s disease research: conference findings. Alzheimer Dis Assoc Disord. 1997; 11 Suppl 6: S186–95.Google ScholarPubMed
131. Berg, L, Montgomery, R. Metrics of effectiveness within Alzheimer’s disease research and across diseases. Alzheimer Dis Assoc Disord. 1997; 11 Suppl 6: S181–3.Google ScholarPubMed
132. Jonker, C, Gerritsen, D, Bosboom, P, et al. A model for quality of lifemeasures in patients with dementia: Lawton’s next step. Dement Geriatr Cogn Disord. 2004; 18: 159–64.CrossRefGoogle Scholar
133. Selai, C, Trimble, MR. Assessing quality of life in dementia. Aging Ment Health. 1999; 3: 101–11.CrossRefGoogle Scholar
134. Ready, RE, Ott, BR. Quality of life measures for dementia. Health Qual Life Outcomes. 2003; 1: 1119.CrossRefGoogle ScholarPubMed
135. Guyatt, GH, Feeny, DH, Patrick, DL. Measuring health-relatedquality of life. Ann Intern Med. 1993; 118: 622–9.CrossRefGoogle Scholar
136. Logsdon, RG. Making the most of every day: quality of life in Alzheimer’s disease. In: Harris, PB, editor. The Person with Alzheimer’s Disease: pathways to understanding the experience. Baltimore: Johns Hopkins Press; 2002. p.7587.Google Scholar
137. Brod, M, Stewart, AL, Sands, L. Conceptualization of quality of lifein dementia. J Mental Health and Aging. 1999; 5: 719.Google Scholar
138. Kane, RA, Kling, KC, Bershadsky, B, et al. Quality of life measures for nursing home residents. J Gerontol A Biol Sci Med Sci. 2003; 58: 240–8.CrossRefGoogle ScholarPubMed
139. Selai, CE, Trimble, MR, Harvey, RJ. Assessing quality of life indementia: preliminary psychometric testing of the Quality of Life Assessment Schedule (QOLAS). Neuropsychological Rehabilitation. 2001; 11: 219–43.CrossRefGoogle Scholar
140. Mozley, CG, Huxley, P, Sutcliffe, C, et al. “Not knowing where I amdoesn’t mean I don’t know what I like”: cognitive impairment and quality of life responses in elderly people. Int J Geriatr Psychiatry. 1999; 14: 776–83.3.0.CO;2-C>CrossRefGoogle ScholarPubMed
141. Logsdon, RG, Gibbons, LE, McCurry, SM, Teri, L. Assessing quality of life in older adults with cognitive impairment. Psychosom Med. 2002; 64: 510–19.CrossRefGoogle ScholarPubMed
142. Brod, M, Stewart, AL, Sands, L, et al. Conceptualization andmeasurement of quality of life in dementia: the dementia qualityof life instrument (DQoL). Gerontologist. 1999; 39: 2535.CrossRefGoogle Scholar
143. Sprangers, MA, Aaronson, NK. The role of health care providers andsignificant others in evaluating the quality of life of patients with chronic disease: a review. J Clin Epidemiol. 1992; 45: 743–60.CrossRefGoogle Scholar
144. Ready, RE, Ott, BR, Grace, J. Patient versus informant perspectivesof quality of life in mild cognitive impairment and Alzheimer’s disease. Int J Geriatr Psychiatry. 2004; 19: 256–65.CrossRefGoogle Scholar
145. Sands, LP, Ferreira, P, Stewart, AL, et al. What explains differencesbetween dementia patients’ and their caregivers’ ratings of patients’ quality of life? Am J Geriatr Psychiatry. 2004; 12: 272–80.CrossRefGoogle Scholar
146. Edelman, P, Fulton, BR, Kuhn, D. Comparison of dementia-specificquality of life measures in adult day centres. Home Health Care Serv Q. 2004; 23: 2542.CrossRefGoogle Scholar
147. Novella, JL, Jochum, C, Jolly, D, et al. Agreement between patients’and proxies’ reports of quality of life in Alzheimer’s disease. Qual Life Res. 2001; 10: 443–52.CrossRefGoogle ScholarPubMed
148. Mador, J, Clark, M, Crotty, M, et al. Utility-weighted measures ofquality of life in Alzheimer’s disease. Alzheimer Dis Assoc Disord. 2002; 16: 202–3.CrossRefGoogle Scholar
149. Coucill, W, Bryan, S, Bentham, P, et al. EQ-5D in patients withdementia: an investigation of inter-rater agreement. Med Care. 2001; 39: 760–71.CrossRefGoogle Scholar
150. Karlawish, JH, Casarett, D, Propert, KJ, et al. Relationship between Alzheimer’s disease severity and patient participation in decisions about their medical care. J Geriatr Psychiatry Neurol. 2002; 15: 6872.CrossRefGoogle ScholarPubMed
151. Santaguida, P, Raina, P, Booker, L, et al. Pharmacological Treatmentof Dementia: Evidence Report/Technology Assessment No. 97 (Prepared by McMaster University Evidence-based Practice Center under Contract No. 290-02-0020). AHRQ Publication No. 04-E018-2. Rockville, MD: Agency for Healthcare Research and Quality; April 2004.Google Scholar
152. Rogers, SL, Doody, RS, Mohs, RC, et al. Donepezil improvescognition and global function in Alzheimer’s disease. Arch Intern Med. 1998; 158: 1021–31.CrossRefGoogle Scholar
153. Burns, A, Rossor, M, Hecker, J, et al. The effects of donepezil in Alzheimer’s disease: results from a multinational trial. DementGeriatr Cogn Dis. 1999; 10: 237–44.CrossRefGoogle ScholarPubMed
154. Rogers, SL, Friedhoff, LT. The efficacy and safety of donepezil inpatients with Alzheimer’s disease: results of a US multicentre, randomized, double-blind, placebo-controlled trial. The Donepezil Study Group. Dementia. 1996; 7: 293303.Google Scholar
155. Winblad, B, Engedal, K, Soininen, H, et al. A 1-year randomized, placebo-controlled study of donepezil in patients with mild tomoderate AD. Neurology. 2001; 57: 489–95.CrossRefGoogle Scholar
156. Rosler, M, Anand, R, Cicin-Sain, A, et al. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: international randomised controlled trial. BMJ. 1999; 318: 633–8.CrossRefGoogle ScholarPubMed
157. Knapp, MJ, Knopman, DS, Solomon, PR, et al. A 30-weekrandomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. The Tacrine Study Group. JAMA. 1994; 271: 985–91.CrossRefGoogle ScholarPubMed
158. Corey-Bloom, J, Anand, R, Veach, J. A randomized trial evaluatingthe efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer’s disease. Int J Geriatr Psychopharmacol. 1998. 1: 5565.Google Scholar
159. Wilkinson, D, Murray, J. Galantamine: a randomized, double-blind,dose comparison in patients with Alzheimer’s disease. Int J Geriatr Psychiatry. 2001; 16: 852–7.CrossRefGoogle ScholarPubMed
160. Feldman, H, Gauthier, S, Hecker, J, et al. Efficacy of donepezil onmaintenance of activities of daily living in patients with moderate-to-severe Alzheimer’s disease and the effect on care-giving burden. J Am Geriatr Soc. 2003; 51: 737–44.CrossRefGoogle Scholar
161. Bullock, R. The needs of the caregiver in the long-term treatment of Alzheimer’s disease. Alzheimer Dis Assoc Disord. 2004; 18: S17–23.CrossRefGoogle Scholar
162. Markowitz, JS, Guterman, EM, Sadik, K, et al. Health-related quality of life for caregivers of patients with Alzheimer disease. Alzheimer Dis Assoc Disord. 2003; 17: 209–14.CrossRefGoogle ScholarPubMed
163. Busschbach, JJ, Brouwer, WB, van der Donk, A, et al. An outline fora cost-effectiveness analysis of a drug for patients with Alzheimer’s disease. Pharmacoeconomic.s 1998; 13: 2134.CrossRefGoogle Scholar
164. Fillit, HM, Gutterman, EM, Brooks, RL. Impact of donepezil on care-giving burden for patients with Alzheimer’s disease. Int Psychogeriatr. 2000; 12: 389401.CrossRefGoogle ScholarPubMed
165. Consensus recommendations for the postmortem diagnosis of Alzheimer’s disease. The National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease. Neurobiol Aging. 1997; 18: S1–2.Google Scholar
166. Burger, K, Zinkowski, R, Teipel, SJ, et al. Differential diagnosis of Alzheimer’s disease with CSF tau protein phosphorylated atthreonine 231. Arch Neurol. 2002; 59(8): 1267–72.CrossRefGoogle Scholar
167. de Leon, MJ, Segal, CY, Tarshish, CY, et al. Longitudinal CSF tauload increases in mild cognitive impairment. Neurosci Lett. 2002; 333: 183–6.CrossRefGoogle ScholarPubMed
168. Grundman, M, Sencakova, D, Jack, CRJ, et al. Brain MR Ihippocampal volume and prediction of clinical status in a mild cognitive impairment trial. J Mol Neurosci. 2002; 19: 23–7.CrossRefGoogle Scholar
169. Shoghi-Jadid, K, Small, GW, Agdeppa, ED, et al. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002; 10: 2435.CrossRefGoogle ScholarPubMed
170. Klunk, WE, Engler, H, Nordberg, A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004; 55: 306–19.CrossRefGoogle ScholarPubMed
171. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH). Guidance for Industry: Pharmacogenomic Data Submission. Available from: http://www.fda.gov/cder/guidance/6400fnl.pdf Google Scholar
172. Feldman, H, Scheltens, P, Scarpini, E, et al. Behavioral symptoms inmild cognitive impairment. Neurology. 2004; 62: 1199–201.CrossRefGoogle Scholar
173. Thal, LJ, Ferris, SH, Kirby, L, et al. A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology. 2005; [Epub ahead of print].CrossRefGoogle ScholarPubMed
174. Ritchie, K, Artero, S, Touchon, J. Classification criteria for mildcognitive impairment: a population-based validation study. Neurology. 2001; 56: 3742.CrossRefGoogle Scholar
175. Erkinjuntti, T, Roman, G, Gauthier, S, Feldman, H, Rockwood, K. Emerging therapies for vascular dementia and vascular cognitive impairment. Stroke. 2004; 35: 1010–7.CrossRefGoogle ScholarPubMed
176. Rockwood, K, Howard, K, MacKnight, C, Darvesh, S. Spectrum of disease in vascular cognitive impairment. Neuroepidemiology. 1999; 18: 248–54.CrossRefGoogle ScholarPubMed
177. Erkinjuntti, T, Inzitari, D, Pantoni, L, et al. Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm. Suppl 2000; 59: 2330.Google ScholarPubMed
178. Roman, GC, Erkinjuntti, T, Wallin, A, Pantoni, L, Chui, HC. Subcortical ischaemic vascular dementia. Lancet Neurol. 2002; 1: 426–36.CrossRefGoogle ScholarPubMed
179. Erkinjuntti, T, Kurz, A, Gauthier, SG, Bullock, R, Lilienfeld, S, Damaraju, CV. Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomised trial. Lancet. 2002; 359: 1283–90.CrossRefGoogle ScholarPubMed
180. Orgogozo, JM, Rigaud, AS, Stoffler, A, Mobius, HJ, Forette, F. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlledtrial (MMM 300). Stroke. 2002; 33: 1834–9.CrossRefGoogle ScholarPubMed
181. McKeith, I, del Ser, T, Spano, P, et al. Efficacy of rivastigmine indementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet. 2000; 356: 2031–6.CrossRefGoogle Scholar
182. Emre, M, Aarsland, D, Albanese, A, et al. Rivastigmine for dementiaassociated with Parkinson’s disease. N Engl J Med. 2004; 351: 2509–18.Google Scholar
183. The French Clozapine Parkinson Study Group. Clozapine in Drug-Induced Psychosis in Parkinson’s disease. Lancet. 1999; 353: 2041–2.CrossRefGoogle Scholar
184. The Parkinson Study Group. Low-dose clozapine for the treatmentof drug-induced psychosis in Parkinson’s disease. N Engl J Med. 1999; 340: 757–63.CrossRefGoogle Scholar
185. Fernandez, HH, Trieschmann, ME, Burke, MA, Friedman, JH. Quetiapine for psychosis in Parkinson’s disease versus dementia with Lewy bodies. J Clin Psychiatry. 2002; 63: 513–5.CrossRefGoogle ScholarPubMed
186. Fernandez, HH, Trieschmann, ME, Burke, MA, Jacques, C, Friedman, JH. Long-term outcome of quetiapine use for psychosis among Parkinsonian patients. Mov Disord. 2003; 18: 510–4.CrossRefGoogle ScholarPubMed
187. Kertesz, A, Munoz, DG, Hillis, A. Preferred terminology. Ann Neurol. 2003; 54 Suppl. 5: S3–6.CrossRefGoogle ScholarPubMed
188. Ratnavelli, E, Brayne, C, Dawson, RGN, Hodges, JR. The prevalence of frontotemporal dementia. Neurology. 2002; 58: 1615–21.CrossRefGoogle Scholar
189. Ikeda, M, Ishikawa, T, Tanabe, H. Epidemiology of frontotemporal lobar degeneration. Dement Geriatr Cogn Disord. 2004; 17: 265–8.CrossRefGoogle ScholarPubMed
190. Gustafson, L, Brun, A. Frontal lobe degeneration of non-Alzheimertype and its relation to other frontotemporal dementias and Alzheimer’s disease. In: Kertesz, A, Munoz, DG, editors. Pick’s Disease and Pick Complex. Toronto: Wiley-Liss, 1998. p.3346.Google Scholar
191. Sparks, D L, Markesbery, W R. Altered serotonergic and cholinergicsynaptic markers in Pick’s disease. Arch Neurol. 1991; 48: 796–9.CrossRefGoogle ScholarPubMed
192. Sjögren, M, Minthon, L, Passant, U, Blennow, K, Wallin, A. Decreased monoamine metabolites in frontotemporal dementia and Alzheimer’s disease. Neurobiol Aging. 1998; 19(379): 384.CrossRefGoogle ScholarPubMed
193. Proctor, AW, Qurne, M, Francis, PT. Neurochemical features of Frontotemporal dementia. Dement Geriatr Cogn Disord. 1999; 10 Suppl 1: S80–4.Google Scholar
194. Lebert, F, Pasquier, F. Trazodone in the treatment of behavior in frontotemporal dementia. Hum Psychopharmacol Clin Exp. 1999; 14: 279–81.3.0.CO;2-1>CrossRefGoogle Scholar
195. Lebert, F, Stekke, W, Hasenbroekx, C, Pasquier, F. Frontotemporaldementia: a randomized, controlled trial with Trazodone. Dement Geriatr Cogn Disord. 2004; 17: 355–9.CrossRefGoogle Scholar
196. Sahakian, BJ, Coull, BL, Hodges, JR. Selective enhancement of executive function by idazoxan in a patient with dementia of the frontal lobe type. J Neurol Neurosurg Psychiatry. 1994; 57: 120–1.CrossRefGoogle Scholar
197. Anderson, IM, Scott, K, Harborne, G. Serotonin and depression infrontal lobe dementia. Am J Psychiatry. 1995; 152: 645.Google Scholar
198. Swartz, JR, Miller, BL, Lesser, IM, Darby, AL. Frontotemporaldementia: treatment response to serotonin selective reuptake inhibitors. J Clin Psychiatry. 1997; 58: 212–6.CrossRefGoogle Scholar
199. Chow, TW. Goals in symptomatic pharmacologic management of frontotemporal lobar degeneration. Am J Alzheimers Dis Other Demen. 2002; 17: 267–72.CrossRefGoogle ScholarPubMed
200. Ikeda, M, Shigenobu, K, Fukuhara, R, et al. Efficacy of fluvoxamineas a treatment for behavioral symptoms in frontotemporal lobar degeneration patients. Dement Geriatr Cogn Disord. 2004; 17: 117–21.CrossRefGoogle ScholarPubMed
201. Moretti, R, Torre, P, Antonello, RM, Cazzato, G, Bava, A. Frontotemporal dementia: paroxetine as a possible treatment of behavior symptoms. A randomized, controlled, open 14-monthstudy. Eur Neurol. 2003; 49: 13–9.CrossRefGoogle Scholar
202. Moretti, R, Torre, P, Antonello, RM, Cazzato, G, Bava, A. Effects of selegiline on fronto-temporal dementia: a neuropsychological evaluation. Int J Geriatr Psychiatry. 2002; 17: 391–2.CrossRefGoogle ScholarPubMed
203. Adler, G, Teufel, M, Drach, LM. Pharmacological treatment of frontotemporal dementia: treatment response to the MAO-A inhibitor moclobemide. Int J Geriatr Psychiatry. 2003; 18: 653–5.CrossRefGoogle Scholar
204. Goforth, HW, Konopka, L, Primeau, M, et al. Quantitative electroencephalography in frontotemporal dementia with methylphenidate response: a case study. Clin EEG Neurosci. 2004; 35: 108–11.CrossRefGoogle ScholarPubMed
205. Gregory, C, Lough, S, Stone, V, et al. Theory of mind in patients withfrontal variant frontotemporal dementia and Alzheimer’s disease: theoretical and practical implications. Brain. 2002; 125 pt. 4: 752–64.CrossRefGoogle ScholarPubMed
206. Freedman, M, Black, S, Ebert, P, Binns, M. Orbitofrontal function, object alternation, and perseveration. Cereb Cortex. 1998; 8: 1827.CrossRefGoogle ScholarPubMed
207. Freedman, M, Binns, MA, Black, SE, et al. Object Alternation: acognitive and diagnostic measure of orbitofrontal function in frontotemporal dementia. Neurology. 2003; Suppl 1: A264.Google Scholar
208. Royall, D, Mahurin, RK, Gray, KF. Bedside assessment of executivecognitive impairment: the executive interview. J Am Geriatr Soc. 1992; 40: 1221–6.CrossRefGoogle Scholar
209. Dubois, B, Slachevsky, A, Litvan, I, Pillon, B. The FAB: a frontal assessment battery at bedside. Neurology. 2000; 55: 1621–6.CrossRefGoogle ScholarPubMed
210. Mathuranath, PS, Nestor, PJ, Berrios, GE, Rakowicz, W, Hodges, JR. A brief cognitive test battery to differentiate Alzheimer’s disease and frontotemporal dementia. Neurology. 2000; 55: 1613–20.CrossRefGoogle ScholarPubMed
211. Heaton, RK. Wisconsin Card Sorting Test Manual. Florida: Psychological Assessment Resources Inc., 1981.Google Scholar
212. Freedman, M, Leach, L, Kaplan, E, et al. Clock drawing: aneuropsychological analysis. New York: Oxford University Press.Google Scholar
213. Kertesz, A, Davidson, W, Fox, H. Frontal behavioral inventory:diagnostic criteria for frontal lobe dementia. Can J Neurol Sci. 1997; 24: 2936.CrossRefGoogle ScholarPubMed
214. Kertesz, A, Nadkarni, N, Davidson, W, Thomas, AW. The frontal behavioral inventory in the differential diagnosis of frontotemporal dementia. J Int Neuropsychol Soc. 2004; 61(460):468.Google Scholar
215. Kertesz, A, Davidson, W, McCabe, P, Munoz, D. Behavioral quantitation is more sensitive than cognitive testing in frontotemporal dementia. Alzheimer Dis Assoc Disord. 2003; 17: 223–9. CrossRefGoogle ScholarPubMed
216. Grace, J, Stout, JC, Malloy, PF. Assessing frontal lobe behavioral syndromes with The Frontal Lobe Personality Scale. Assessment. 1999; 6: 269–84.CrossRefGoogle ScholarPubMed
217. Stout, JC, Ready, RE, Grace, J, Malloy, PF, Paulsen, JS. Factoranalysis of the frontal systems behavior scale (FrSBe). Assessment. 2003; 10: 7985.CrossRefGoogle Scholar
218. Hodes, RJ, Testimony, United States Department of Health and Human Services. Available from: http://www.hhs.gov/asl/testify/t040511c.html Google Scholar
219. Christen, Y. Ginkgo biloba and neurodegenerative disorders. Front Biosci. 2004; 9: 3091–104.CrossRefGoogle ScholarPubMed
220. Le Bars, PL, Katz, MM, Berman, N, et al. A placebo-controlled,double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA. 1997; 278: 1327–32.Google ScholarPubMed
221. Blesch, A, Tuszynski, MH. Gene therapy and cell transplantation for Alzheimer’s disease and spinal cord injury. Yonsei Med J. 2004; 45 Suppl: S28–31.CrossRefGoogle ScholarPubMed
222. May, PC. Current progress on new therapies for Alzheimer’sdisease. Drug Discov Today. 2001; 6: 459–62.CrossRefGoogle Scholar
223. Schenk, D, Hagen, M, Seubert, P. Current progress in beta-amyloidimmunotherapy. Curr Opin Immunol. 2004; 16(5): 599606.CrossRefGoogle Scholar
224. Chou, KC. Insights from modeling the tertiary structure of humanBACE2. J Proteome Res. 2004; 3: 1069–72.CrossRefGoogle Scholar
225. Ritchie, CW, Bush, AI, Mackinnon, A, et al. Metal-proteinattenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch Neurol. 2003; 60: 1685–91.CrossRefGoogle ScholarPubMed
226. Di Vaira, M, Bazzicalupi, C, Orioli, P, et al. Clioquinol, a drug for Alzheimer’s disease specifically interfering with brain metal metabolism: structural characterization of its zinc (II) and copper(II) complexes. Inorg Chem. 2004; 43: 3795–7.CrossRefGoogle ScholarPubMed
227. Gervais, F, Chalifour, R, Garceau, D, et al. Glycosaminoglycan mimetics: a therapeutic approach to cerebral amyloid angiopathy. Amyloid. 2001; 8 Suppl 1: S28–35.Google ScholarPubMed
228. Ritchie, CW, Bush, AI, Masters, CL. Metal-protein attenuating compounds and Alzheimer’s disease. Expert Opin Investig Drugs. 2004; 13: 1585–92.CrossRefGoogle ScholarPubMed
229. Watson, GS, Craft, S. The role of insulin resistance in the pathogenesis of Alzheimer’s disease: implications for treatment. CNS Drugs. 2003; 17: 2745.CrossRefGoogle ScholarPubMed