Alzheimer disease (AD) is a neurodegenerative disorder of uncertain cause and pathogenesis that primarily affects older adults . The most essential and often earliest clinical manifestation of AD is selective memory impairment. AD is the most common cause of dementia. While treatments are available that can modulate the course of the disease and/or ameliorate some symptoms, there is no cure, 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 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 — Alzheimer disease (AD) is characteristically a disease of older age . It is exceptional for AD to occur before age 60. The incidence and prevalence of AD increase exponentially with age. (See "Epidemiology of Alzheimer disease", section on 'Incidence and prevalence'.)
There are inherited forms of AD that routinely present before age 65, and frequently in the fifth decade or earlier. These account for less than one percent of all cases of AD. Early-onset AD follows 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 . Patients with PSEN1 mutations had the earliest median age of onset (43 years). The range of symptom onset across all mutation types was nonetheless fairly broad, with some presentations in the fourth decade and some mutations not manifesting symptoms until the seventh decade. (See "Genetics of Alzheimer disease", section on 'Early-onset Alzheimer Disease'.)
Individuals with Down syndrome, who have an additional gene dose of APP due to trisomy of chromosome 21, also develop AD at an earlier age, 10 to 20 years younger than the general population with AD . (See "Genetics of Alzheimer disease", section on 'Trisomy 21'.)