Alzheimer's Disease

ABSTRACT

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Currently, 4.5 million individuals in the United States are estimated to have AD, and that number is projected to increase to at least 14 million by the year 2050. AD is a major cause of disability and mortality, and its impact on health care costs, including direct and indirect medical and social service costs, is estimated to be greater than $100 billion per year. AD typically presents with an insidious decline in memory that progresses to affect language, visuospatial perception, calculations, and executive functioning. Behavioral and psychiatric symptoms are also frequent in AD. Diagnosis is determined clinically, as there is currently no laboratory test to confirm AD in life. The neuropathologic hallmarks of AD are neuritic plaques and neurofibrillary tangles. Currently available medical therapies have demonstrated modest benefits but likely do not alter disease progression. Caregivers play a large role in managing the patient and should be encouraged to seek out adult day care centers, home health services, respite care, and additional social support.

Alzheimer's disease - dementia - pathophysiology - clinical presentation - diagnosis - treatment

REFERENCES

• 1 Alzheimer A. Uber eine eigenartige Erkangkung der Hirnrinde.  Allgemaine Zeitschrift fur Psychiatrie und Psychisch-Gerichtliche Medizin. 1907;  64 146-148 , (English translation in: Arch Neurol 1967;21:109-110)
• 2 Hebert L E, Scherr P A, Bienias J L, Bennett D A, Evans D A. Alzheimer disease in the US population: prevalence estimates using the 2000 census.  Arch Neurol. 2003;  60 1119-1122
• 3 Ernst R L, Hay J W. Economic research on Alzheimer disease: a review of the literature.  Alzheimer Dis Assoc Disord. 1997;  11(suppl 6) 135-145
• 4 Bayer T A, Wirths O, Majtenyi K et al.. Key factors in Alzheimer's disease: beta-amyloid precursor protein processing, metabolism and intraneuronal transport.  Brain Pathol. 2001;  11 1-11
• 5 Hardy J, Selkoe D J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics.  Science. 2002;  297 353-356
• 6 Carter J, Lippa C F. Beta-amyloid, neuronal death and Alzheimer's disease.  Curr Mol Med. 2001;  1 733-737
• 7 Cummings J L, Vinters H V, Cole G M, Khachaturian Z S. Alzheimer's disease: etiologies, pathophysiology, cognitive reserve, and treatment opportunities.  Neurology. 1998;  51(suppl 1) S2-S17
• 8 Mirra S S, Hart M N, Terry R D. Making the diagnosis of Alzheimer's disease: a primer for practicing pathologists.  Arch Pathol Lab Med. 1993;  117 132-144
• 9 Mirra S S, Heyman A, McKeel D et al.. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II: standardization of the neuropathologic assessment of Alzheimer's disease.  Neurology. 1991;  41 479-486
• 10 Hyman B T, Trojanowski J Q. 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 1095-1097
• 11 Kawas C, Gray S, Brookmeyer R, Fozard J, Zonderman A. Age-specific incidence rates of Alzheimer's disease: the Baltimore Longitudinal Study of Aging.  Neurology. 2000;  54 2072-2077
• 12 Gao S, Hendrie H C, Hall K S, Hui S. The relationships between age, sex, and the incidence of dementia and Alzheimer disease: a meta-analysis.  Arch Gen Psychiatry. 1998;  55 809-815
• 13 van Duijn C M, Clayton D, Chandra V et al.. Familial aggregation of Alzheimer's disease and related disorders: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group.  Int J Epidemiol. 1991;  20(suppl 2) S13-S20
• 14 Farrer L A, Cupples L A, Haines J L et al.. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis.  JAMA. 1997;  278 1349-1356
• 15 Stern Y, Gurland B, Tatemichi T K, Tang M X, Wilder D, Mayeux R. Influence of education and occupation on the incidence of Alzheimer's disease.  JAMA. 1994;  271 1004-1010
• 16 Schmand B, Smit J H, Geerlings M I, Lindeboom J. The effects of intelligence and education on the development of dementia: a test of the brain reserve hypothesis.  Psychol Med. 1997;  27 1337-1344
• 17 Snowdon D A, Kemper S J, Mortimer J A, Greiner L H, Wekstein D R, Markesbery W R. Linguistic ability in early life and cognitive function and Alzheimer's disease in late life: findings from the Nun Study.  JAMA. 1996;  275 528-532
• 18 McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan E M. 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;  34 939-944
• 19 Galasko D, Hansen L A, Katzman R et al.. Clinical-neuropathological correlations in Alzheimer's disease and related dementias.  Arch Neurol. 1994;  51 888-895
• 20 Salmon D P, Thomas R G, Pay M M et al.. Alzheimer's disease can be accurately diagnosed in very mildly impaired individuals.  Neurology. 2002;  59 1022-1028
• 21 Knopman D S, DeKosky S T, Cummings J L 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 1143-1153
• 22 Andreasen N, Minthon L, Davidsson P et al.. Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice.  Arch Neurol. 2001;  58 373-379
• 23 DeCarli C. The role of neuroimaging in dementia.  Clin Geriatr Med. 2001;  17 255-279
• 24 Hoffman J M, Welsh-Bohmer K A, Hanson M et al.. FDG PET imaging in patients with pathologically verified dementia.  J Nucl Med. 2000;  41 1920-1928
• 25 Bergman H, Chertkow H, Wolfson C et al.. HM-PAO (CERETEC) SPECT brain scanning in the diagnosis of Alzheimer's disease.  J Am Geriatr Soc. 1997;  45 15-20
• 26 Mathis C A, Wang Y, Holt D P, Huang G F, Debnath M L, Klunk W E. Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents.  J Med Chem. 2003;  46 2740-2754
• 27 Thal L J, Kantarci K, Reiman E M et al.. The role of biomarkers in clinical trials for Alzheimer disease.  Alzheimer Dis Assoc Disord. 2006;  20 6-15
• 28 Francis P T, Palmer A M, Snape M, Wilcock G K. The cholinergic hypothesis of Alzheimer's disease: a review of progress.  J Neurol Neurosurg Psychiatry. 1999;  66 137-147
• 29 Doody R S, Stevens J C, 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 1154-1166
• 30 Rogawski M A, Wenk G L. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease.  CNS Drug Rev. 2003;  9 275-308
• 31 Areosa S A, Sherriff F, McShane R. Memantine for dementia.  Cochrane Database Syst Rev. 2005;  (3) CD003154
• 32 Tariot P N, Farlow M R, Grossberg G T, Graham S M, McDonald S, Gergel I. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial.  JAMA. 2004;  291 317-324
• 33 Sano M, Ernesto C, Thomas R G et al.. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study.  N Engl J Med. 1997;  336 1216-1222
• 34 Tabet N, Birks J, Grimley Evans J. Vitamin E for Alzheimer's disease.  Cochrane Database Syst Rev. 2000;  (4) CD002854
• 35 Miller III E R, Pastor-Barriuso R, Dalal D, Riemersma R A, Appel L J, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality.  Ann Intern Med. 2005;  142 37-46
• 36 Birks J, Grimley E V, Van Dongen M. Ginkgo biloba for cognitive impairment and dementia.  Cochrane Database Syst Rev. 2002;  (4) CD003120