Skip to main content Accessibility help
Hostname: page-component-99c86f546-t82dr Total loading time: 0.431 Render date: 2021-11-30T01:26:44.535Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true, "newUsageEvents": true }

Alzheimer’s Disease: Past, Present, and Future

Published online by Cambridge University Press:  04 December 2017

Mark W. Bondi*
Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, California Veterans Affairs San Diego Healthcare System, San Diego, California
Emily C. Edmonds
Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, California Veterans Affairs San Diego Healthcare System, San Diego, California
David P. Salmon
Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, California
Correspondence and reprint requests to: Mark W. Bondi, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603V. E-mail:


Although dementia has been described in ancient texts over many centuries (e.g., “Be kind to your father, even if his mind fail him.” – Old Testament: Sirach 3:12), our knowledge of its underlying causes is little more than a century old. Alzheimer published his now famous case study only 110 years ago, and our modern understanding of the disease that bears his name, and its neuropsychological consequences, really only began to accelerate in the 1980s. Since then we have witnessed an explosion of basic and translational research into the causes, characterizations, and possible treatments for Alzheimer’s disease (AD) and other dementias. We review this lineage of work beginning with Alzheimer’s own writings and drawings, then jump to the modern era beginning in the 1970s and early 1980s and provide a sampling of neuropsychological and other contextual work from each ensuing decade. During the 1980s our field began its foundational studies of profiling the neuropsychological deficits associated with AD and its differentiation from other dementias (e.g., cortical vs. subcortical dementias). The 1990s continued these efforts and began to identify the specific cognitive mechanisms affected by various neuropathologic substrates. The 2000s ushered in a focus on the study of prodromal stages of neurodegenerative disease before the full-blown dementia syndrome (i.e., mild cognitive impairment). The current decade has seen the rise of imaging and other biomarkers to characterize preclinical disease before the development of significant cognitive decline. Finally, we suggest future directions and predictions for dementia-related research and potential therapeutic interventions. (JINS, 2017, 23, 818–831)

Section 2 – Neurological Disorders
Copyright © The International Neuropsychological Society 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Albert, M.L., Feldman, R.G., & Willis, A.L. (1974). The ‘subcortical dementia’ of progressive supranuclear palsy. Journal of Neurology, Neurosurgery, and Psychiatry, 37, 121130.CrossRefGoogle ScholarPubMed
Albert, M.S., DeKosky, S.T., Dickson, D., Dubois, B., Feldman, H.H., Fox, N.C., & Phelps, C.H. (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7, 270279.CrossRefGoogle Scholar
Alzheimer, A. (1907). über eine eigenartige Erkankung der Hirnrinde. Allgemeine Zeitschrift fur Psychiatrie under Psychisch-Gerichtliche Medizin, 64, 146148.Google Scholar
Alzheimer, A. (1911). Über eigenartige Krankheitsfälle des späteren Alters. Zeitschrift für die Gesamte Neurologie und Psychiatrie, 4, 356385.CrossRefGoogle Scholar
American Psychiatric Association. (1968). Diagnostic and Statistical Manual of Mental Disorders (2nd Ed). Washington, DC: American Psychiatric Association.Google ScholarPubMed
American Psychiatric Association. (1980). Task force on nomenclature and statistics. Diagnostic and statistical manual of mental disorders (DSM-III). Washington, DC: American Psychiatric Association.Google Scholar
Baddeley, A.D., Bressi, S., Della Sala, S., Logie, R., & Spinnler, H. (1991). The decline of working memory in Alzheimer’s disease: A longitudinal study. Brain, 114, 25212542.CrossRefGoogle ScholarPubMed
Bateman, R.J., Xiong, C., Benzinger, T.L., Fagan, A.M., Goate, A., Fox, N.C., & Morris, J.C.; Dominantly Inherited Alzheimer Network. (2012). Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. The New England Journal of Medicine, 367, 795804.CrossRefGoogle ScholarPubMed
Bird, T.D. (1999). Clinical genetics of familial Alzheimer’s disease. In R.D. Terry, R. Katzman, K.L. Bick & S.S. Sisodia (Eds.), Alzheimer disease (pp. 5766). Philadelphia: Lippincott Williams & Wilkens.Google ScholarPubMed
Blessed, G., Tomlinson, B., & Roth, M. (1968). The association between quantitative measures of dementia and of senile changes in the cerebral grey matter of elderly subjects. British Journal of Psychiatry, 114, 797811.CrossRefGoogle Scholar
Bondi, M.W., Edmonds, E.C., Jak, A.J., Clark, L.R., Delano-Wood, L., McDonald, C.R., & Salmon, D.P. (2014). Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and prediction of progression. Journal of Alzheimer’s Disease, 42, 275289.Google Scholar
Bondi, M.W., Monsch, A.U., Butters, N., Salmon, D.P., & Paulsen, J.S. (1993). Utility of a modified version of the Wisconsin Card Sorting Test in the detection of dementia of the Alzheimer type. Clinical Neuropsychologist, 7, 161170.CrossRefGoogle ScholarPubMed
Bondi, M.W., Monsch, A.U., Galasko, D., Butters, N., Salmon, D.P., & Delis, D.C. (1994). Preclinical cognitive markers of dementia of the Alzheimer’s type. Neuropsychology, 8, 374384.CrossRefGoogle Scholar
Bondi, M.W., Salmon, D.P., Galasko, D., Thomas, R.G., & Thal, L.J. (1999). Neuropsychological function and apolipoprotein E qgenotype in the preclinical detection of Alzheimer’s disease. Psychology and Aging, 14, 295303.CrossRefGoogle ScholarPubMed
Bondi, M.W., Salmon, D.P., Monsch, A.U., Galasko, D., Butters, N., Klauber, M.R., & Saitoh, T. (1995). Episodic memory changes are associated with the ApoE-ε4 allele in nondemented older adults. Neurology, 45, 22032206.CrossRefGoogle Scholar
Braak, H., & Braak, E. (1991). Neuropathological staging of Alzheimer-related changes. Acta Neuropathologica, 82, 239259.CrossRefGoogle Scholar
Braak, H., & Del Tredici, K. (2014). Are cases with tau pathology occurring in the absence of Aβ deposits part of the AD-related pathological process? Acta Neuropathologica, 128, 767772.CrossRefGoogle ScholarPubMed
Braak, H., & Del Tredici, K. (2015). The preclinical phase of the pathological process underlying sporadic Alzheimer’s disease. Brain, 138, 28142833.CrossRefGoogle ScholarPubMed
Braak, H., Thal, D.R., Ghebremedhin, E., & Del Tredici, K. (2011). Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. Journal of Neuropathology & Experimental Neurology, 70, 960969.CrossRefGoogle ScholarPubMed
Braak, H., Zetterberg, H., Del Tredici, K., & Blennow, K. (2013). Intraneuronal tau aggregation precedes diffuse plaque deposition, but amyloid-β changes occur before increases of tau in cerebrospinal fluid. Acta Neuropathologica, 126, 631641.CrossRefGoogle ScholarPubMed
Brosch, J.R., Farlow, M.R., Risacher, S.L., & Apostolova, L.G. (2017). Tau imaging in Alzheimer’s disease diagnosis and clinical trials. Neurotherapeutics, 14, 6268.CrossRefGoogle ScholarPubMed
Buschke, H., Sliwinski, M.J., Kuslansky, G., & Lipton, R.B. (1997). Diagnosis of early dementia by the double memory test. Neurology, 48, 989997.CrossRefGoogle ScholarPubMed
Butters, N., Granholm, E., Salmon, D.P., Grant, I., & Wolfe, J. (1987). Episodic and semantic memory: A comparison of amnesic and demented patients. Journal of Clinical and Experimental Neuropsychology, 9, 479497.CrossRefGoogle ScholarPubMed
Caine, D. (2004). Posterior cortical atrophy: a review of the literature. Neurocase, 10, 382385.CrossRefGoogle ScholarPubMed
Chertkow, H., & Bub, D. (1990). Semantic memory loss in dementia of Alzheimer’s type. Brain, 113, 397417.CrossRefGoogle ScholarPubMed
Clark, L.R., Delano-Wood, L., Libon, D.J., McDonald, C.R., Nation, D.A., Bangen, K.J., & Bondi, M.W. (2013). Are empirically derived subtypes of mild cognitive impairment consistent with conventional subtypes? Journal of the International Neuropsychological Society, 19, 635645.CrossRefGoogle ScholarPubMed
Collette, F., Van der Linden, M., Bechet, S., & Salmon, E. (1999). Phonological loop and central executive functioning in Alzheimer’s disease. Neuropsychologia, 37, 905918.CrossRefGoogle ScholarPubMed
Crary, J.F., Trojanowski, J.Q., Schneider, J.A., Abisambra, J.F., Abner, E.L., Alafuzoff, I., & Nelson, P.T. (2014). Primary age-related tauopathy (PART): A common pathology associated with human aging. Acta Neuropathologica, 128, 755766.CrossRefGoogle ScholarPubMed
Cronin-Golomb, A., & Amick, M. (2001). Spatial abilities in aging, Alzheimer’s disease, and Parkinson’s disease. In F. Boller & S.F. Cappa (Eds.), Handbook of Neuropsychology. Aging and dementia (2nd, ed.), Vol. 6., pp. 119143). Amsterdam: Elsevier.Google Scholar
Cummings, J.L. (1990). Subcortical dementia. New York: Oxford University Press.Google ScholarPubMed
Cummings, J.L., & Benson, D.F. (1992). Dementia: A clinical approach. Boston: Butterworth-Heinemann.Google Scholar
Cummings, J.L., Morstorf, T., & Zhong, K. (2014). Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimer’s Research & Therapy, 6, 37.CrossRefGoogle ScholarPubMed
Delis, D.C., Massman, P.J., Butters, N., Salmon, D.P., Cermak, L.S., & Kramer, J.H. (1991). Profiles of demented and amnesic patients on the California verbal learning test: Implications for the assessment of memory disorders. Psychological Assessment, 3, 1926.CrossRefGoogle Scholar
Drachman, D.A. (2014). The amyloid hypothesis, time to move on: Amyloid is the downstream result, not cause, of Alzheimer’s disease. Alzheimer’s & Dementia, 10, 372380.CrossRefGoogle Scholar
Edmonds, E.C., Delano-Wood, L., Clark, L.R., Jak, A.J., Nation, D.A., McDonald, C.R., & Bondi, M.W. (2015). Susceptibility of the conventional criteria for mild cognitive impairment to false-positive diagnostic errors. Alzheimer’s & Dementia, 11, 415424.CrossRefGoogle ScholarPubMed
Edmonds, E.C., Delano-Wood, L., Galasko, D.R., Salmon, D.P., & Bondi, M.W. (2015). Subtle cognitive decline and biomarker staging in preclinical Alzheimer’s disease. Journal of Alzheimer’s Disease, 47, 231242.CrossRefGoogle ScholarPubMed
Edmonds, E.C., Eppig, J., Bondi, M.W., Leyden, K.M., Goodwin, B., Delano-Wood, L., & McDonald, C.R. (2016). Heterogeneous cortical atrophy patterns not captured by conventional diagnostic criteria. Neurology, 87, 21082116.CrossRefGoogle Scholar
Folstein, M.F., Folstein, S.E., & McHugh, P.R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.CrossRefGoogle ScholarPubMed
Frisoni, G.B., Fox, N.C., Jack, C.R. Jr., Scheltens, P., & Thompson, P.M. (2010). The clinical use of structural MRI in Alzheimer’s disease. Nature Reviews Neurology, 6, 6777.CrossRefGoogle Scholar
Gomar, J.J., Conejero-Goldberg, C., Davies, P., & Goldberg, T.E., Alzheimer’s Disease Neuroimaging Initiative. (2014). Extension and refinement of the predictive value of different classes of markers in ADNI: Four-year follow-up data. Alzheimer’s & Dementia, 10, 704712.CrossRefGoogle ScholarPubMed
Gorno-Tempini, M.L., Dronkers, N.F., Rankin, K.P., Ogar, J.M., Phengrasamy, L., Rosen, H.J., & Miller, B.L. (2004). Cognition and anatomy in three variants of primary progressive aphasia. Annals of Neurology, 55, 335346.CrossRefGoogle ScholarPubMed
Gorno-Tempini, M.L., Hillis, A.E., Weintraub, S., Kertesz, A., Mendez, M., Cappa, S.F., & Grossman, M. (2011). Classification of primary progressive aphasia and its variants. Neurology, 76, 10061014.CrossRefGoogle ScholarPubMed
Gottesman, I.I. (2001). Psychopathology through a life span-genetic prism. American Psychologist, 56, 867878.CrossRefGoogle ScholarPubMed
Heister, D., Brewer, J.B., Magda, S., Blennow, K., & McEvoy, L.K., Alzheimer’s Disease Neuroimaging Initiative. (2011). Predicting MCI outcome with clinically available MRI and CSF biomarkers. Neurology, 77, 16191628.CrossRefGoogle ScholarPubMed
Hodges, J.R., & Patterson, K. (1995). Is semantic memory consistently impaired early in the course of Alzheimer’s disease? Neuroanatomical and diagnostic implications. Neuropsychologia, 33, 441459.CrossRefGoogle ScholarPubMed
Hodges, J.R., Salmon, D.P., & Butters, N. (1992). Semantic memory impairment in Alzheimer’s disease: Failure of access or degraded knowledge? Neuropsychologia, 30, 301314.CrossRefGoogle ScholarPubMed
Hof, P.R., Vogt, B.A., Bouras, C., & Morrison, J.H. (1997). Atypical form of Alzheimer’s disease with prominent posterior cortical atrophy: A review of lesion distribution and circuit disconnection in cortical visual pathways. Vision Research, 37, 36093625.CrossRefGoogle ScholarPubMed
Huber, S.J., Shuttleworth, E.C., Paulson, G.W., Bellchambers, M.J., & Clapp, L.E. (1986). Cortical vs subcortical dementia. Neuropsychological differences. Archives of Neurology, 43, 392394.CrossRefGoogle ScholarPubMed
Hyman, B.T., Damasio, A.R., Van Hoesen, G.W., & Barnes, C.L. (1984). Alzheimer’s disease: cell specific pathology isolates the hippocampal formation. Science, 225, 11681170.CrossRefGoogle ScholarPubMed
Iba, M., McBride, J.D., Guo, J.L., Zhang, B., Trojanowski, J.Q., & Lee, V.M.Y. (2015). Tau pathology spread in PS19 tau transgenic mice following locus coeruleus (LC) injections of synthetic tau fibrils is determined by the LC’s afferent and efferent connections. Acta Neuropathologica, 130, 349362.CrossRefGoogle ScholarPubMed
Jack, C.R. Jr., Bennett, D.A., Blennow, K., Carrillo, M.C., Feldman, H.H., Frisoni, G.B., & Dubois, B. (2016). A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology, 87, 539–347.CrossRefGoogle ScholarPubMed
Jack, C.R. Jr., Knopman, D.S., Chetelat, G., Dickson, D., Fagan, A.M., Frisoni, G.B., & Vos, S.J.B. (2016). Suspected non-Alzheimer disease pathophysiology – Concept and controversy. Nature Reviews Neurology, 12, 117124.CrossRefGoogle ScholarPubMed
Jack, C.R. Jr., Knopman, D.S., Jagust, W.J., Petersen, R.C., Weiner, M.W., Aisen, P.S., & Trojanowski, J.Q. (2013). Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurology, 12, 207216.CrossRefGoogle ScholarPubMed
Jack, C.R. Jr., Knopman, D.S., Jagust, W.J., Shaw, L.M., Aisen, P.S., & Weiner, M.W. (2010). Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurology, 9, 119128.CrossRefGoogle ScholarPubMed
Jacobs, D., Salmon, D.P., Tröster, A.I., & Butters, N. (1990). Intrusion errors in the figural memory of patients with Alzheimer’s and Huntington’s disease. Archives of Clinical Neuropsychology, 5, 4957.CrossRefGoogle ScholarPubMed
Jak, A.J., Bondi, M.W., Delano-Wood, L., Wierenga, C., Corey-Bloom, J., Salmon, D.P., & Delis, D.C. (2009). Quantification of five neuropsychological approaches to defining mild cognitive impairment. American Journal of Geriatric Psychiatry, 17, 368375.CrossRefGoogle ScholarPubMed
Jedynak, B.M., Lang, A., Liu, B., Katz, E., Zhang, Y., & Wyman, B.T., … Alzheimer’s Disease Neuroimaging Initiative. (2012). A computational neurodegenerative disease progression score: Method and results with the ADNI cohort. NeuroImage, 63, 14781486.CrossRefGoogle Scholar
Jessen, F., Amariglio, R.E., van Boxtel, M., Breteler, M., Ceccaldi, M., & Chételat, G., . . . Subjective Cognitive Decline Initiative (SCD-I) Working Group. (2014). A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimer’s & Dementia, 10, 844852.CrossRefGoogle ScholarPubMed
Johnson, J.K., Head, E., Kim, R., Starr, A., & Cotman, C.W. (1999). Clinical and pathological evidence for a frontal variant of Alzheimer disease. Archives of Neurology, 56, 12331239.CrossRefGoogle ScholarPubMed
Katzman, R. (1976). The prevalence and malignancy of Alzheimer disease: A major killer. Archives of Neurology, 33, 217218.CrossRefGoogle ScholarPubMed
Katzman, R., & Kawas, C. (1994). The epidemiology of dementia and Alzheimer disease. In R.D. Terry, R. Katzman & K.L. Bick (Eds.), Alzheimer disease (pp. 105122). New York: Raven Press.Google ScholarPubMed
Knopman, D.S., Jack, C.R. Jr., Wiste, H.J., Weigand, S.D., Vemuri, P., Lowe, V.J., & Petersen, R.C. (2013). Brain injury biomarkers are not dependent on β-amyloid in normal elderly. Annals of Neurology, 73, 472480.CrossRefGoogle Scholar
Kraepelin, E. (1910). Psychiatrie: Ein Lehrbuch fur studierende und artzte. In Kraepelin E. (Ed), Handbook of psychiatry (8th ed., pp. 593632). Leipzig: Barth.Google Scholar
Lefleche, G., & Albert, M.S. (1995). Executive function deficits in mild Alzheimer’s disease. Neuropsychology, 9, 313320.CrossRefGoogle Scholar
Landau, S.M., Harvey, D., Madison, C.M., Reiman, E.M., Foster, N.L., Aisen, P.S., … Alzheimer’s Disease Neuroimaging Initiative. (2010). Comparing predictors of conversion and decline in mild cognitive impairment. Neurology, 75, 230238.CrossRefGoogle ScholarPubMed
La Rue, A., Matsuyama, S.S., McPherson, S., Sherman, J., & Jarvik, L.F. (1992). Cognitive performance in relatives of patients with probable Alzheimer disease: An age at onset effect? Journal of Clinical and Experimental Neuropsychology, 14, 533538.CrossRefGoogle ScholarPubMed
Mahandra, B. (1984). Dementia: A survey of the syndrome of dementia. Lancaster, England: MTP.Google Scholar
Mathis, C.A., Wang, Y., Holt, D.P., Huang, G.-F., Debnath, M.L., & Klunk, W.E. (2003). Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. Journal of Medicinal Chemistry, 46, 27402754.CrossRefGoogle ScholarPubMed
Maurer, K., & Maurer, U. (2003). Alzheimer: The life of a physician and career of a disease. New York: Columbia University Press.Google Scholar
McHugh, P.R., & Folstein, M.F. (1975). Psychiatric symptoms of Huntington’s chorea: A clinical and phenomenologic study. In D.F. Benson & D. Blumer (Eds.), Psychiatric aspects of neurological disease (pp. 267285). New York: Raven Press.Google Scholar
McKeith, I.G., Boeve, B.F., Dickson, D.W., Halliday, G., Taylor, J.P., Weintraub, D., & Kosaka, K. (2017). Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology, 89, 88100.CrossRefGoogle ScholarPubMed
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, M. (1984). Clinical diagnosis of Alzheimer’s disease: report of the NINCD-ADRDA work group. Neurology, 34, 939944.CrossRefGoogle ScholarPubMed
McKhann, G.M., Knopman, D.S., Chertkow, H., Hyman, B.T., Jack, C.R. Jr., Kawas, C.H., & Phelps, C.H. (2011). The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging – Alzheimer’s Association workgroup. Alzheimer’s & Dementia, 7, 263269.CrossRefGoogle Scholar
Mendez, M.F., Ghajarania, M., & Perryman, K.M. (2002). Posterior cortical atrophy: Clinical characteristics and differences compared to Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders, 14, 3340.CrossRefGoogle ScholarPubMed
Mesulam, M., Wicklund, A., Johnson, N., Rogalski, E., Leger, G.C., Rademaker, A., & Bigio, E.H. (2008). Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Annals of Neurology, 63, 709719.CrossRefGoogle ScholarPubMed
Miller, E. (1971). On the nature of the memory disorder in presenile dementia. Neuropsychologia, 9, 7581.CrossRefGoogle ScholarPubMed
Miller, E. (1973). Short- and long-term memory in patients with presenile dementia (Alzheimer’s disease). Psychological Medicine, 3, 221224.CrossRefGoogle Scholar
Miller, E. (1975). Impaired recall and the memory disturbance in presenile dementia. British Journal of Social and Clinical Psychology, 14, 7379.CrossRefGoogle ScholarPubMed
Miller, E. (1978). Retrieval from long-term memory in presenile dementia: two tests of an hypothesis. British Journal of Social and Clinical Psychology, 17, 143148.CrossRefGoogle ScholarPubMed
Musiek, E.S., & Holtzman, D.M. (2015). Three dimensions of the amyloid hypothesis: Time, space and ‘wingmen’. Nature Neuroscience, 18, 800806.CrossRefGoogle Scholar
Nebes, R. (1989). Semantic memory in Alzheimer’s disease. Psychological Bulletin, 106, 377394.CrossRefGoogle ScholarPubMed
Nelson, P.T., Head, E., Schmitt, F.A., Davis, P.R., Neitner, J.H., Jicha, G.A., & Scheff, S.W. (2011). Alzheimer’s disease is not “brain aging”: Neuropathological, genetic, and epidemiological human studies. Acta Neuropathologica, 121, 571587.CrossRefGoogle Scholar
Nestor, P.J., Caine, D., Fryer, T.D., Clarke, J., & Hodges, J.R. (2003). The topography of metabolic deficits in posterior cortical atrophy (the visual variant of Alzheimer’s disease) with FDG-PET. Journal of Neurology, Neurosurgery, and Psychiatry, 74, 15211529.CrossRefGoogle ScholarPubMed
Norton, L.E., Bondi, M.W., Salmon, D.P., & Goodglass, H. (1997). Deterioration of generic knowledge in patients with Alzheimer’s disease: Evidence from the Number Information Test. Journal of Clinical and Experimental Neuropsychology, 19, 857866.CrossRefGoogle ScholarPubMed
Parasuraman, R., & Haxby, J.V. (1993). Attention and brain function in Alzheimer’s disease. Neuropsychology, 7, 242272.CrossRefGoogle Scholar
Perry, R.J., & Hodges, J.R. (1999). Attention and executive deficits in Alzheimer’s disease: A critical review. Brain, 122, 383404.CrossRefGoogle ScholarPubMed
Petersen, R.C. (2009). Early diagnosis of Alzheimer disease: Is MCI too late? Current Alzheimer Research, 6, 324330.CrossRefGoogle ScholarPubMed
Petersen, R.C. (2004). Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine, 256, 183194.CrossRefGoogle ScholarPubMed
Petersen, R.C., Knopman, D.S., Boeve, B.F., Geda, Y.E., Ivnik, R.J., Smith, G.E., & Jack, C.R. Jr. (2009). Mild cognitive impairment: Ten years later. Archives of Neurology, 66, 14471455.CrossRefGoogle ScholarPubMed
Petersen, R.C., & Morris, J.C. (2005). Mild cognitive impairment as a clinical entity and treatment target. Archives of Neurology, 62, 11601163.CrossRefGoogle ScholarPubMed
Petersen, R.C., Smith, G.E., Ivnik, R.J., Tangalos, E.G., Schaid, D.J., Thibodeau, S.N., & Kurland, L.T. (1995). Apolipoprotein E status as a predictor of the development of Alzheimer’s disease in memory-impaired individuals. Journal of the American Medical Association, 273, 12741278.CrossRefGoogle ScholarPubMed
Petersen, R.C., Smith, G.E., Waring, S.C., Ivnik, R.J., Tangalos, E.G., & Kokmen, E. (1999). Mild cognitive impairment: Clinical characterization and outcome. Archives of Neurology, 56, 303308.CrossRefGoogle ScholarPubMed
Petersen, R.C., Thomas, R.G., Grundman, M., Bennett, D., Doody, R., Ferris, S., & Thal, L.J. (2005). Vitamin E and donepezil for the treatment of mild cognitive impairment. New England Journal of Medicine, 352, 23792388.CrossRefGoogle ScholarPubMed
Rascovsky, K., Hodges, J.R., Knopman, D., Mendez, M.F., Kramer, J.H., Neuhaus, J., & Miller, B.L. (2011). Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain, 134, 24562477.CrossRefGoogle ScholarPubMed
Rascovsky, K., Salmon, D.P., Hansen, L.A., Thal, L.J., & Galasko, D. (2007). Disparate phonemic and semantic fluency deficits in autopsy-confirmed frontotemporal dementia and Alzheimer’s disease. Neuropsychology, 21, 2030.CrossRefGoogle Scholar
Rathore, S., Habes, M., Iftikhar, M.A., Shacklett, A., & Davatzikos, C. (2017). A review on neuroimaging-based classification studies and associated feature extraction methods for Alzheimer’s disease and its prodromal stages. NeuroImage, 155, 530548.CrossRefGoogle ScholarPubMed
Reed, T., Carmelli, D., Swan, G.E., Breitner, J.C.S., Welsh, K.A., Jarvik, G.P., & Auwerx, J. (1994). Lower cognitive performance in normal older adult male twins carrying the apolipoprotein E ε4 allele. Archives of Neurology, 51, 11891192.CrossRefGoogle Scholar
Renner, J.A., Burns, J.M., Hou, C.E., McKeel, D.W. Jr., Storandt, M., & Morris, J.C. (2004). Progressive posterior cortical dysfunction: a clinicopathologic series. Neurology, 63, 11751180.CrossRefGoogle ScholarPubMed
Richard, E., Schmand, B.A., Eikelenboom, P., & Van Gool, W.A., Alzheimer’s Disease Neuroimaging Initiative. (2013). MRI and cerebrospinal fluid biomarkers for predicting progression to Alzheimer’s disease in patients with mild cognitive impairment: a diagnostic accuracy study. BMJ Open, 3, e002541.CrossRefGoogle ScholarPubMed
Rosser, A., & Hodges, J.R. (1994). Initial letter and semantic category fluency in Alzheimer’s disease, Huntington’s disease, and progressive supranuclear palsy. Journal of Neurology, Neurosurgery, and Psychiatry, 57, 13891394.CrossRefGoogle ScholarPubMed
Rouleau, I., Salmon, D.P., Butters, N., Kennedy, C., & McGuire, K. (1992). Quantitative and qualitative analyses of clock drawings in Alzheimer’s and Huntington’s disease. Brain and Cognition, 18, 7087.CrossRefGoogle ScholarPubMed
Ryan, N.S., Keihaninejad, S., Shakespeare, T.J., Lehmann, M., Crutch, S.J., Malone, I.B., & Fox, N.C. (2013). Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer’s disease. Brain, 136, 13991414.CrossRefGoogle ScholarPubMed
Salmon, D.P., & Bondi, M.W. (2009). Neuropsychological assessment of dementia. Annual Review of Psychology, 60, 257282.CrossRefGoogle ScholarPubMed
Salmon, D.P., Heindel, W.C., & Lange, K.L. (1999). Differential decline in word generation from phonemic and semantic categories during the course of Alzheimer’s disease: Implications for the integrity of semantic memory. Journal of the International Neuropsychological Society, 5, 692703.CrossRefGoogle ScholarPubMed
Salmon, D.P., Kwo-on-Yuen, P.F., Heindel, W., Butters, N., & Thal, L.J. (1989). Differentiation of Alzheimer’s disease and Huntington’s disease with the Dementia Rating Scale. Archives of Neurology, 46, 12041208.CrossRefGoogle ScholarPubMed
Salmon, D.P., Thomas, R.G., Pay, M.M., Booth, A., Hofstetter, C.R., Thal, L.J., & Kaltzman, R. (2002). Alzheimer’s disease can be accurately diagnosed in very mildly impaired individuals. Neurology, 59, 10221028.CrossRefGoogle ScholarPubMed
Sheline, Y.I., Morris, J.C., Snyder, A.Z., Price, J.L., Yan, Z., D’Angelo, G., & Mintun, M.A. (2010). APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Aβ42. Journal of Neuroscience, 30, 1703517040.CrossRefGoogle ScholarPubMed
Sims, R., & Williams, J. (2016). Defining the genetic architecture of Alzheimer’s disease: Where next? Neurodegenerative Diseases, 16, 611.CrossRefGoogle ScholarPubMed
Small, B.J., Fratiglioni, L., Viitanen, M., Winblad, B., & Bäckman, L. (2000). The course of cognitive impairment in preclinical Alzheimer disease: three- and six-year follow-up of a population based sample. Archives of Neurology, 57, 839844.CrossRefGoogle Scholar
Smith, G.E., & Bondi, M.W. (2013). Mild cognitive impairment and dementia: Definitions, diagnosis, and treatment. New York: Oxford University Press.Google Scholar
Snowdon, D.A., Kemper, S.J., Mortimer, J.A., Greiner, L.H., Wekstein, D.R., & Markesbery, W.R. (1996). Linguistic ability in early life and cognitive function and Alzheimer’s disease in late life. Findings from the Nun Study. Journal of the American Medical Association, 275, 528532.CrossRefGoogle ScholarPubMed
Sperling, R.A., Aisen, P.S., Beckett, L.A., Bennett, D.A., Craft, S., Fagan, A.M., & Phelps, C.H. (2011). Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7, 280292.CrossRefGoogle ScholarPubMed
Squire, L.R. (1987). Memory and brain. New York: Oxford University Press.Google ScholarPubMed
Stelzmann, R.A., Schnitzlein, N., & Murtagh, F.R. (1995). An English translation of Alzheimer’s paper, “über eine eigenartige Erkankung der Hirnrinde.”. Clinical Anatomy, 8, 429431.CrossRefGoogle Scholar
Storandt, M., Botwinick, J., Danziger, W.L., Berg, L., & Hughes, C.P. (1984). Psychometric differentiation of mild senile dementia of the Alzheimer type. Archives of Neurology, 41, 497499.CrossRefGoogle ScholarPubMed
Strittmatter, W.J., Saunders, A.M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G.S., & Roses, A.D. (1993). Apolipoprotein-E -- High-avidity binding to B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America, 90, 96499653.Google Scholar
Tenovuo, O., Kemppainen, N., Aalto, S., Nagren, K., & Rinne, J.O. (2008). Posterior cortical atrophy: A rare form of dementia with in vivo evidence of amyloid-beta accumulation. Journal of Alzheimer’s Disease, 15, 351355.CrossRefGoogle ScholarPubMed
Weiner, M.W., Veitch, D.P., Aisen, P.S., Beckett, L.A., Cairns, N.J., Green, R.C., & Trojanowski, J.Q. (2013). The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception. Alzheimer’s & Dementia, 9, e111e194.CrossRefGoogle Scholar
Winblad, B., Palmer, K., Kivipelto, M., Jelic, V., Fratiglioni, L., Wahlund, L.O., & Petersen, R.C. (2004). Mild cognitive impairment–beyond controversies, towards a consensus: Report of the Inter-national Working Group on Mild Cognitive Impairment. Journal of Internal Medicine, 256, 240246.CrossRefGoogle Scholar
Wirth, M., Madison, C.M., Rabinovici, G.D., Oh, H., Landau, S.M., & Jagust, W.J. (2013). Alzheimer’s disease neurodegenerative biomarkers are associated with decreased cognitive function but not β-Amyloid in cognitively normal older individuals. Journal of Neuroscience, 33, 55535563.CrossRefGoogle Scholar
World Health Organization. (1992). International Classification of Diseases (10th Edition, Geneva, Switzerland: WHO.Google ScholarPubMed
Cited by

Send article to Kindle

To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Alzheimer’s Disease: Past, Present, and Future
Available formats

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Alzheimer’s Disease: Past, Present, and Future
Available formats

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Alzheimer’s Disease: Past, Present, and Future
Available formats

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *