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Findings Support Role of Vascular Disease in Development of Alzheimer’s

Summary: A new study reports midlife vascular risk factors are associated with elevated levels of amyloid beta in later life.

Source: JAMA Networks.

Among adults who entered a study more than 25 years ago, an increasing number of midlife vascular risk factors, such as obesity, high blood pressure, diabetes, high cholesterol and smoking, were associated with elevated levels of brain amyloid (protein fragments linked to Alzheimer disease) later in life, according to a study published by JAMA.

Midlife vascular risk factors have been associated with late-life dementia. Whether these risk factors directly contribute to brain amyloid deposition is less well understood. Rebecca F. Gottesman, M.D., Ph.D., of the Johns Hopkins University School of Medicine, Baltimore, and colleagues examined data from 346 participants without dementia at study entry who have been evaluated for vascular risk factors and markers since 1987-1989 and with PET scans in 2011-2013 as part of the Atherosclerosis Risk in Communities (ARIC)-PET Amyloid Imaging Study. Positron emission tomography image analysis was completed in 2015. Vascular risk factors at ARIC study entry (age 45-64 years; risk factors included body mass index 30 or greater, current smoking, hypertension, diabetes, and total cholesterol 200 mg/dL or greater) were evaluated in models that included age, sex, race, APOE genotype, and educational level.

The availability of imaging biomarkers for brain amyloid allows the study of individuals before the development of dementia and thereby allows consideration of the relative contributions of vascular disease and amyloid to cognition, as well as the contribution of vascular disease to amyloid deposition.

Image shows an alzheimer's brain slice.

The researchers found that a cumulative number of midlife vascular risk factors were associated with elevated brain amyloid. NeuroscienceNews.com image is for illustrative purposes only.

The researchers found that a cumulative number of midlife vascular risk factors were associated with elevated brain amyloid. Relationships between vascular risk factors and brain amyloid did not differ by race. The results were not supportive of a significant difference in association among people who were or were not carriers of an APOE ε4 allele (a variant of a gene associated with increased risk for Alzheimer disease). Late-life vascular risk factors were not associated with late-life brain amyloid deposition.

“These data support the concept that midlife, but not late-life, exposure to these vascular risk factors is important for amyloid deposition,” the authors write. “These findings are consistent with a role of vascular disease in the development of AD.”

About this Alzheimer’s disease research article

Source: Vanessa McMains – JAMA Networks
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition” by Rebecca F. Gottesman, MD, PhD; Andrea L. C. Schneider, MD, PhD; Yun Zhou, PhD; Josef Coresh, MD, PhD; Edward Green, MD; Naresh Gupta, MD; David S. Knopman, MD; Akiva Mintz, MD; Arman Rahmim, PhD; A. Richey Sharrett, MD, DrPH; Lynne E. Wagenknecht, DrPH; Dean F. Wong, MD, PhD; and Thomas H. Mosley, PhD in JAMA. Published online April 11 2017 doi:10.1001/jama.2017.3090

Cite This NeuroscienceNews.com Article
JAMA Networks “Findings Support Role of Vascular Disease in Development of Alzheimer’s.” NeuroscienceNews. NeuroscienceNews, 11 April 2017.
<http://neurosciencenews.com/alzheimers-vascular-disease-6392/>.
JAMA Networks (2017, April 11). Findings Support Role of Vascular Disease in Development of Alzheimer’s. NeuroscienceNew. Retrieved April 11, 2017 from http://neurosciencenews.com/alzheimers-vascular-disease-6392/
JAMA Networks “Findings Support Role of Vascular Disease in Development of Alzheimer’s.” http://neurosciencenews.com/alzheimers-vascular-disease-6392/ (accessed April 11, 2017).

Abstract

Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition

Importance Midlife vascular risk factors have been associated with late-life dementia. Whether these risk factors directly contribute to brain amyloid deposition is less well understood.

Objective To determine if midlife vascular risk factors are associated with late-life brain amyloid deposition, measured using florbetapir positron emission tomography (PET).

Design, Setting, and Participants The Atherosclerosis Risk in Communities (ARIC)–PET Amyloid Imaging Study, a prospective cohort study among 346 participants without dementia in 3 US communities (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi) who have been evaluated for vascular risk factors and markers since 1987-1989 with florbetapir PET scans in 2011-2013. Positron emission tomography image analysis was completed in 2015.

Exposures Vascular risk factors at ARIC baseline (age 45-64 years; risk factors included body mass index ≥30, current smoking, hypertension, diabetes, and total cholesterol ≥200 mg/dL) were evaluated in multivariable models including age, sex, race, APOE genotype, and educational level.

Main Outcomes and Measures Standardized uptake value ratios (SUVRs) were calculated from PET scans and a mean global cortical SUVR was calculated. Elevated florbetapir (defined as a SUVR >1.2) was the dependent variable.

Results Among 322 participants without dementia and with nonmissing midlife vascular risk factors at baseline (mean age, 52 years; 58% female; 43% black), the SUVR (elevated in 164 [50.9%] participants) was measured more than 20 years later (median follow-up, 23.5 years; interquartile range, 23.0-24.3 years) when participants were between 67 and 88 (mean, 76) years old. Elevated body mass index in midlife was associated with elevated SUVR (odds ratio [OR], 2.06; 95% CI, 1.16-3.65). At baseline, 65 participants had no vascular risk factors, 123 had 1, and 134 had 2 or more; a higher number of midlife risk factors was associated with elevated amyloid SUVR at follow-up (30.8% [n = 20], 50.4% [n = 62], and 61.2% [n = 82], respectively). In adjusted models, compared with 0 midlife vascular risk factors, the OR for elevated SUVR associated with 1 vascular risk factor was 1.88 (95% CI, 0.95-3.72) and for 2 or more vascular risk factors was 2.88 (95% CI, 1.46-5.69). No significant race × risk factor interactions were found. Late-life vascular risk factors were not associated with late-life brain amyloid deposition (for ≥2 late-life vascular risk factors vs 0: OR, 1.66; 95% CI, 0.75-3.69).


Conclusions and Relevance
An increasing number of midlife vascular risk factors was significantly associated with elevated amyloid SUVR; this association was not significant for late-life risk factors. These findings are consistent with a role of vascular disease in the development of Alzheimer disease.

“Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition” by Rebecca F. Gottesman, MD, PhD; Andrea L. C. Schneider, MD, PhD; Yun Zhou, PhD; Josef Coresh, MD, PhD; Edward Green, MD; Naresh Gupta, MD; David S. Knopman, MD; Akiva Mintz, MD; Arman Rahmim, PhD; A. Richey Sharrett, MD, DrPH; Lynne E. Wagenknecht, DrPH; Dean F. Wong, MD, PhD; and Thomas H. Mosley, PhD in JAMA. Published online April 11 2017 doi:10.1001/jama.2017.3090

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