The global prevalence of dementia is estimated to be as high as 24 million, and is predicted to double every 20 years through to 2040, leading to a costly burden of disease. Alzheimer disease (AD) is the leading cause of dementia and is characterized by a progressive decline in cognitive function, which typically begins with deterioration in memory. Before death, individuals with this disorder have usually become dependent on caregivers. The neuropathological hallmarks of the AD brain are diffuse and neuritic extracellular amyloid plaques—which are frequently surrounded by dystrophic neurites—and intracellular neurofibrillary tangles. These hallmark pathologies are often accompanied by the presence of reactive microgliosis and the loss of neurons, white matter and synapses. The etiological mechanisms underlying the neuropathological changes in AD remain unclear, but are probably affected by both environmental and genetic factors. Here, we provide an overview of the criteria used in the diagnosis of AD, highlighting how this disease is related to, but distinct from, normal aging. We also summarize current information relating to AD prevalence, incidence and risk factors, and review the biomarkers that may be used for risk assessment and in diagnosis.
The unprecedented level of aging occurring in developed nations will lead to an enormous burden of Alzheimer disease (AD)
The primary pathological hallmarks in AD brain tissue—diffuse and neuritic extracellular amyloid plaques and intracellular neurofibrillary tangles—are well known, but the underlying etiologies of these pathologies remain unclear
The diagnosis of AD in living patients is based on clinical examination—no definite diagnostic test is currently available—but may be supported by the use of clinical biomarkers
AD heritability varies from 58–79% depending on age at onset; however, only a portion of the likely substantial genetic contribution to this disease has been determined
Several nongenetic factors (including recognized vascular risk factors) have been associated with AD, but the underlying mechanisms linked to these factors are uncertain
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This work was supported by grants from the NIH and the National Institute on Aging (grants R37-AG15473 and P01-AG07232), as well as funding from The Blanchette Hooker Rockefeller Foundation and The Charles S. Robertson Gift from the Banbury Fund (R. Mayeux), and a Paul B. Beeson Career Development Award (K23AG034550) to C. Reitz.
Laurie Barclay, freelance writer and reviewer, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.
R. Mayeux has received grant support from the NIH. The other authors declare no competing interests.
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Reitz, C., Brayne, C. & Mayeux, R. Epidemiology of Alzheimer disease. Nat Rev Neurol 7, 137–152 (2011). https://doi.org/10.1038/nrneurol.2011.2
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