The apolipoprotein E genotype predicts longitudinal transitions to mild cognitive impairment but not to Alzheimer's dementia: findings from a nationally representative study.

OBJECTIVE: The ε4 allele of the apolipoprotein E (APOE) genotype is the most widely accepted genetic risk factor for Alzheimer's dementia (AD), but findings on whether it is a risk factor for the AD prodrome, mild cognitive impairment (MCI), have been inconsistent. In a prospective longitudinal design, we investigated (a) whether transitions to MCI and other forms of neurocognitive impairment without dementia (CIND) are more frequent among normal ε4 carriers than among noncarriers and (b) whether subsequent transitions to AD from MCI and from other forms of CIND are more frequent among ε4 carriers than among noncarriers. METHOD: The frequency of the ε4 allele was studied in older adults (mean age > 70), who had participated in two or more waves of neuropsychological testing and diagnosis in the Aging, Demographics, and Memory Study (ADAMS) of the United States Department of Health and Human Services, National Institutes of Health, National Institute on Aging's Health and Retirement Study, conducted by the University of Michigan. The association between ε4 and longitudinal transitions to specific types of CIND and dementia can be determined with this data set. RESULTS: Epsilon 4 increased the rate of progression from normal functioning to MCI (58% of new diagnoses were carriers) but not to other forms of CIND. The rate of progression to AD from MCI or from other forms of CIND was not increased by ε4. CONCLUSIONS: The results support the hypothesis that ε4 is a risk factor for transitions from normal functioning to MCI but not for subsequent transitions to AD. In the ADAMS sample, the reason ε4 is elevated in AD individuals is because it is already elevated in MCI individuals, who are the primary source of new AD diagnoses.

Prevalence of dementia in the United States: the aging, demographics, and memory study.

AIM: To estimate the prevalence of Alzheimer's disease (AD) and other dementias in the USA using a nationally representative sample. METHODS: The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the nationally representative Health and Retirement Study (HRS) who were evaluated for dementia using a comprehensive in-home assessment. An expert consensus panel used this information to assign a diagnosis of normal cognition, cognitive impairment but not demented, or dementia (and dementia subtype). Using sampling weights derived from the HRS, we estimated the national prevalence of dementia, AD and vascular dementia by age and gender. RESULTS: The prevalence of dementia among individuals aged 71 and older was 13.9%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0% of those aged 71-79 years to 37.4% of those aged 90 and older. CONCLUSIONS: Dementia prevalence estimates from this first nationally representative population-based study of dementia in the USA to include subjects from all regions of the country can provide essential information for effective planning for the impending healthcare needs of the large and increasing number of individuals at risk for dementia as our population ages.