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Clinical features and diagnosis of Alzheimer disease

David A Wolk, MD
Bradford C Dickerson, MD
Section Editor
Steven T DeKosky, MD, FAAN, FACP, FANA
Deputy Editor
Janet L Wilterdink, MD


Alzheimer disease (AD) is a neurodegenerative disorder of uncertain cause and pathogenesis that primarily affects older adults and is the most common cause of dementia [1]. The most essential and often earliest clinical manifestation of AD is selective memory impairment, although there are exceptions. While treatments are available that can ameliorate some symptoms of the illness, there is no cure or disease-modifying therapy (treatment that slows the course of the illness) currently available, and the disease inevitably progresses in all patients.

This topic reviews the clinical manifestations and diagnosis of AD. Other topics review the risk factors and treatment of AD and the clinical manifestations of other causes of dementia and cognitive impairment. (See "Epidemiology, pathology, and pathogenesis of Alzheimer disease" and "Treatment of dementia" and "Cholinesterase inhibitors in the treatment of dementia" and "Mild cognitive impairment: Epidemiology, pathology, and clinical assessment" and "Clinical features and diagnosis of dementia with Lewy bodies" and "Frontotemporal dementia: Clinical features and diagnosis" and "Etiology, clinical manifestations, and diagnosis of vascular dementia".)


Age of onset — AD is characteristically a disease of older age [2]. It is exceptional for AD to occur before age 60. The incidence and prevalence of AD increase exponentially with age, essentially doubling in prevalence every 5 years after the age of 65 years. (See "Epidemiology, pathology, and pathogenesis of Alzheimer disease", section on 'Incidence and prevalence'.)

Early-onset AD (onset of symptoms before 65 years of age) is unusual, and many of these patients present for evaluation due to concerns about job performance. Many of these patients have no clear familial pattern and thus would be considered sporadic, although some exhibit familial clustering. People with early-onset AD often present with atypical symptoms, including language, visual, or mood-behavioral changes.

There are rare inherited forms of AD that routinely present before 65 years of age, and frequently in the fifth decade or earlier. These account for less than one percent of all cases of AD. They typically exhibit an autosomal dominant inheritance pattern related to mutations in genes that alter beta-amyloid (Aβ) protein production or metabolism, including amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2). In a meta-analysis with individual-level data on 1307 patients with autosomal dominant AD, the mean age of symptom onset was 46 years and was highly correlated with parental age of onset and mutation type [3]. Patients with PSEN1 mutations had the earliest median age of onset (43 years) (figure 1). The range of symptom onset across all mutation types is nonetheless fairly broad, with some presentations in the fourth decade and some mutations not manifesting symptoms until the seventh decade (see "Early-onset dementia in adults", section on 'Neurodegenerative dementias'). Individuals with Down syndrome, who have an additional gene dose of APP due to trisomy of chromosome 21, inevitably develop AD pathology, and symptoms emerge at an earlier age, 10 to 20 years younger than the general population with AD [4]. (See "Genetics of Alzheimer disease", section on 'Trisomy 21'.)

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Literature review current through: Nov 2017. | This topic last updated: Oct 04, 2017.
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