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Alzheimer's Disease A Century Later

Richard J. Caselli, M.D.; Thomas G. Beach, M.D.; Roy Yaari, M.D., M.A.S.; and Eric M. Reiman, M.D.


Objective: To provide a current survey of the clinical and pathologic features, known genetic and suggested pathogenic contributions, diagnosis, and treatment of Alzheimer's disease (AD) and related forms of dementia.

Data Sources: PubMed was searched for specific indexing terms identified by the authors as relevant to the topic. Also included were diagnostic and consensus criteria and classic references long standing in the Alzheimer's disease literature.

Data Synthesis: AD is the most common form of disabling cognitive impairment in older persons, and its prevalence is rapidly growing as people live to older ages. Clinically, the disorder is characterized by a gradual but progressive decline in memory and other cognitive domains and the frequent occurrence of noncognitive behavioral symptoms. Neuropathologically, the cardinal features of AD include neuritic plaques, neurofibrillary tangles, and the loss of synapses and neurons. The clinical evaluation of AD includes a history and physical examination, laboratory tests, and structural brain imaging to exclude less common forms of dementia. The clinical management of AD includes medication and nonmedication strategies for addressing cognitive, behavioral, and other commonly associated symptoms of patients as well as lifestyle changes such as driving cessation and residential care. Genetic causes of familial Alzheimer's disease as well as genes that predispose to late-onset and sporadic Alzheimer's disease have led to greater understanding of the pathophysiology of the neurodegenerative process.

Conclusions: While there has been great promise in the scientific understanding, early detection, and tracking of AD and in the discovery of promising disease-slowing treatments, there remains an unmet urgent need to identify effective primary and secondary prevention therapies in order to avert a financially overwhelming public health problem.

(J Clin Psychiatry 2006;67:1784-1800)


Received Nov. 18, 2005; accepted Aug. 30, 2006. From the Department of Neurology, Mayo Clinic and Arizona Alzheimer's Disease Consortium, Scottsdale (Dr. Caselli); the W. H. Civin Laboratory for Neuropathology, Sun Health Research Institute and Arizona Alzheimer's Disease Consortium, Sun City (Dr. Beach); the Banner Alzheimer's Institute and Arizona Alzheimer's Disease Consortium, Phoenix (Dr. Yaari); and the Banner Alzheimer's Institute, Neurogenomics Division, Translational Genomics Research Institute; the Department of Psychiatry, University of Arizona; and Arizona Alzheimer's Disease Consortium, Phoenix (Dr. Reiman), Ariz.

Supported in part by grants P30 AG19610-01 from the National Institute on Aging and MH057899-06 from the National Institute of Mental Health and by the state of Arizona.

Dr. Reiman has served as a consultant to Eli Lilly, Pfizer, Forest, Intellect Neurosciences, Ceregene, and GlaxoSmithKline; has received grant/research support from National Institute of Mental Health, National Institute on Aging, GlaxoSmithKline, and the state of Arizona; and has a patent pending on the use of imaging in the evaluation of Alzheimer's disease prevention therapies. Drs. Caselli, Beach, and Yaari report no other significant commercial relationships relevant to the study.

Corresponding author and reprints: Richard J. Caselli, M.D., Department of Neurology, Mayo Clinic and Arizona Alzheimer's Disease Consortium, 13400 East Shea Blvd., Scottsdale, AZ 85259 (e-mail: Caselli.Richard@Mayo.edu).