Download PDF
Semin Neurol 2007; 27(1): 032-041
DOI: 10.1055/s-2006-956753
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Alzheimer's Disease

Roy Yaari1 , Jody Corey-Bloom1
  • 1Department of Neurosciences and the Alzheimer's Disease Research Center, University of California, San Diego, La Jolla, California
Further Information

Publication History

Publication Date:
17 January 2007 (online)

    Permissions and Reprints

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.

KEYWORDS

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)
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 6 Carter J, Lippa C F. Beta-amyloid, neuronal death and Alzheimer's disease.  Curr Mol Med. 2001;  1 733-737
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 23 DeCarli C. The role of neuroimaging in dementia.  Clin Geriatr Med. 2001;  17 255-279
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 31 Areosa S A, Sherriff F, McShane R. Memantine for dementia.  Cochrane Database Syst Rev. 2005;  (3) CD003154
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 34 Tabet N, Birks J, Grimley Evans J. Vitamin E for Alzheimer's disease.  Cochrane Database Syst Rev. 2000;  (4) CD002854
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 36 Birks J, Grimley E V, Van Dongen M. Ginkgo biloba for cognitive impairment and dementia.  Cochrane Database Syst Rev. 2002;  (4) CD003120
    PubMedGoogle Scholar

Jody Corey-BloomM.D. Ph.D. 

UCSD Department of Neurosciences

3350 La Jolla Village Drive, San Diego, CA 92161

      >