(See 'Genetics of Alzheimer disease', section on 'Trisomy 21'.) Symptoms emerge at an earlier age, 10 to 20 years younger than the general population with AD. AD associated with Down syndrome – Individuals with Down syndrome have an additional gene dose of APP due to trisomy of chromosome 21 and inevitably develop AD pathology.If this is suspected, it is important to collect detailed information about family history to document a potential autosomal-dominant familial pattern. 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'). Patients wi th PSEN1 mutations had the earliest median age of onset (43 years) ( figure 1). In a meta-analysis 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. 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). These account for less than 1 percent of all cases of AD. Inherited forms of AD – These rare forms of AD routinely present before 65 years of age, and frequently in the fifth decade or earlier.People with early-onset AD often present with symptoms somewhat atypical for this disease, such as language, visual, or mood-behavioral changes rather than predominant memory loss. Some exhibit familial clustering, but usually with affected family members being older at symptom onset. Many of these patients have no clear familial pattern and thus would be considered sporadic. Such patients often present for evaluation due to concerns about job performance. Early-onset AD – Onset of symptoms before 65 years of age is uncommon, occurring in approximately five percent of patients with AD.(See 'Epidemiology, pathology, and pathogenesis of Alzheimer disease', section on 'Incidence and prevalence'.) The incidence and prevalence of AD increase exponentially with age, essentially doubling in prevalence every 5 years after the age of 65 years. It is unusual for AD to occur before age 60. Typical AD – AD is characteristically a disease of older age.(See 'Frontotemporal dementia: Clinical features and diagnosis'.).(See 'Clinical features and diagnosis of dementia with Lewy bodies'.).(See 'Etiology, clinical manifestations, and diagnosis of vascular dementia'.).(See 'Mild cognitive impairment: Epidemiology, pathology, and clinical assessment'.).(See 'Evaluation of cognitive impairment and dementia'.).Other topics review the approach to patients with cognitive impairment and dementia and the clinical features of other dementia syndromes: (See 'Epidemiology, pathology, and pathogenesis of Alzheimer disease'.).Other topics review the risk factors and treatment of AD: This topic reviews the clinical manifestations and diagnosis of AD.

The first approval by the US Food and Drug Administration (FDA) of a therapy that is potentially disease-modifying provides a mandate for a specific diagnosis of AD in patients with cognitive impairment and dementia. While treatments are available that can ameliorate some symptoms of the illness, there is no cure and the disease inevitably progresses in all patients. The most essential and often earliest clinical manifestation of AD is selective memory impairment, although there are exceptions.

INTRODUCTION - 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.

Scored 1630 on moca test