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Original Contribution |

Risk Factors for β-Amyloid Deposition in Healthy Aging:  Vascular and Genetic Effects

Karen M. Rodrigue, PhD; Jennifer R. Rieck, MS; Kristen M. Kennedy, PhD; Michael D. Devous, PhD; Ramon Diaz-Arrastia, MD, PhD; Denise C. Park, PhD
JAMA Neurol. 2013;70(5):600-606. doi:10.1001/jamaneurol.2013.1342.
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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.

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Figures

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Grahic Jump Location

Figure 1. β-Amyloid deposition by vascular and genetic risk groups. Individuals with hypertension and at least 1 apolipoprotein E (APOE) ϵ4 allele have greater β-amyloid deposition than all other groups. SUVR indicates standardized uptake value ratio. *Significant interaction (P = .05) between vascular risk and genetic status, with ϵ4+ participants with hypertension showing the greatest amounts of β-amyloid deposition.

Place holder to copy figure label and caption
Grahic Jump Location

Figure 2. Mean β-amyloid deposition by genetic risk and hypertensive subgroup. Individuals with uncontrolled hypertension and at least 1 apolipoprotein E (APOE) ϵ4 allele show greater β-amyloid deposition. SUVR indicates standardized uptake value ratio. *Significant interaction (P = .02) between vascular risk group and genetic status, with unmedicated ϵ4+ participants with hypertension showing the greatest amounts of β-amyloid deposition.

Place holder to copy figure label and caption
Grahic Jump Location

Figure 3. Association of pulse pressure and β-amyloid deposition. Increased pulse pressure is associated with increased β-amyloid deposition in individuals with genetic risk for Alzheimer disease (ie, apolipoprotein E (APOE) ϵ4+).

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