Risk factors for β-amyloid deposition in healthy aging: vascular and genetic effects.

IMPORTANCE

Identifying risk factors for increased β-amyloid (Aβ) deposition is important for targeting individuals most at risk for developing Alzheimer disease and informing clinical practice concerning prevention and early detection.

OBJECTIVE

To investigate risk factors for Aβ deposition in cognitively healthy middle-aged and older adults. Specifically, we hypothesized that individuals with a vascular risk factor such as hypertension, in combination with a genetic risk factor for Alzheimer disease (apolipoprotein E ε4 allele), would show greater amyloid burden than those without such risk.

DESIGN

Cross-sectional study.

SETTING

General community.

PARTICIPANTS

One hundred eighteen well-screened and cognitively normal adults, aged 47 to 89 years. Participants were classified in the hypertension group if they reported a medical diagnosis of hypertension or if blood pressure exceeded 140 mm Hg systolic/90 mm Hg diastolic, as measured across 7 occasions at the time of study.

INTERVENTION

Participants underwent Aβ positron emission tomography imaging with radiotracer fluorine 18-labeled florbetapir. Participants were genotyped for apolipoprotein E and were classified as ε4(+) or ε4(-).

MAIN OUTCOME MEASURE

Amyloid burden.

RESULTS

Participants in the hypertension group with at least 1 ε4 allele showed significantly greater amyloid burden than those with only 1 risk factor or no risk factors. Furthermore, increased pulse pressure was strongly associated with increased mean cortical amyloid level for subjects with at least 1 ε4 allele.

CONCLUSIONS AND RELEVANCE

Vascular disease is a prevalent age-related condition that is highly responsive to both behavioral modification and medical treatment. Proper control and prevention of risk factors such as hypertension earlier in the life span may be one potential mechanism to ameliorate or delay neuropathological brain changes with aging.