Summary: Vascular risk factors appear to amplify the harmful effect of brain amyloid-beta, accelerating cognitive decline in older adults with early Alzheimer’s-related brain changes.
Source: Mass General.
Vascular risk factors for heart disease and stroke—such as hypertension, diabetes, smoking and elevated body mass index—may speed cognitive decline in clinically normal older adults who show early signs of Alzheimer’s disease in the brain. A team from Massachusetts General Hospital (MGH) reports in JAMA Neurology that vascular risk and brain amyloid-beta levels interact in a way that produces faster decline than would be expected from either factor alone.
“Our results indicate that common, modifiable vascular risks may accelerate cognitive decline in otherwise healthy older adults, and that this effect is greater in people who also have higher amyloid in the brain,” says Jennifer Rabin, PhD, clinical and research fellow in the MGH Department of Psychiatry and lead author of the study. “These findings support efforts to reduce vascular risk—through medical management and lifestyle change—both alone and alongside amyloid-lowering strategies, to delay cognitive deterioration. Simple vascular risk measures may also help identify individuals who are most likely to decline and who could benefit from targeted prevention trials.”
Alzheimer’s disease and cerebrovascular disease are two leading contributors to cognitive impairment in later life. Although amyloid plaques are a hallmark of Alzheimer’s disease, some people with elevated brain amyloid remain cognitively normal for years. That inconsistency has motivated the search for additional markers, beyond amyloid alone, to identify which individuals face the greatest near-term risk of decline.
The MGH team set out to determine whether vascular risk and amyloid burden act additively—each contributing independently to decline—or synergistically, where their combination produces substantially greater risk than the sum of each factor. The researchers also evaluated whether vascular risk predicts decline even after accounting for advanced imaging measures of brain health derived from PET and MRI scans.
The study used data from 223 participants in the Harvard Aging Brain Study, a longitudinal project that follows cognitively normal adults aged 50 to 90. At enrollment, participants underwent a standard panel of imaging biomarkers, including PET scans that detect brain amyloid. Vascular risk was calculated using the Framingham cardiovascular risk score, which incorporates blood pressure, body mass index, history of diabetes and smoking, and similar health factors. Participants also completed annual neuropsychological testing covering memory, attention and language.
Results showed that both higher amyloid burden and greater vascular risk measured at baseline were independently associated with faster cognitive decline during follow-up. Importantly, the most rapid decline was observed in participants who had elevations in both measures. Statistical analysis indicated that the interaction between vascular risk and amyloid burden was synergistic rather than merely additive, meaning the combined effect on cognition exceeded what would be predicted from each factor alone.
Vascular risk continued to be a robust predictor of future decline even after the researchers adjusted for other imaging biomarkers, including hippocampal volume, FDG-PET metabolic measures and white matter hyperintensities (a marker of cerebrovascular disease). Although the study did not declare one factor definitively more powerful than the other, the predictive strength of vascular risk and amyloid burden was similar in these analyses.
“Emerging evidence suggests that amyloid accumulation alone may be necessary but not always sufficient to predict imminent cognitive decline,” says Jasmeer Chhatwal, MD, PhD, senior and corresponding author and assistant professor of Neurology at Harvard Medical School. “Finding complementary measures that identify individuals at highest risk is crucial for selecting candidates for prevention trials. Remarkably, a simple vascular risk score provided additional predictive value beyond a comprehensive set of MRI and PET biomarkers. Even better, vascular risk factors are modifiable—treating high blood pressure, encouraging smoking cessation, controlling diabetes and promoting healthy weight could help slow memory loss, particularly in people with elevated brain amyloid.”
Co-author Reisa Sperling, MD, professor of Neurology at Harvard Medical School and co-principal investigator of the Harvard Aging Brain Study, notes: “The study cohort consists of relatively healthy older adults with modest vascular disease overall, yet we still observed that even modest vascular risk interacts with early Alzheimer’s pathology to accelerate decline. This underscores the importance of addressing vascular health as a strategy for preserving cognition in aging.”
Funding: The study was supported by NIH grants P01 AG036694, P50 AG005134, K24 AG035007 and K23 AG049087, and by a Canadian Institutes of Health Research Postdoctoral Fellowship.
Source: Terri Ogan – Mass General
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: “Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study” (JAMA Neurology).
DOI: 10.1001/jamaneurol.2018.1123
Mass General. “Vascular Risk Interacts with Amyloid Levels to Increase Age-Related Cognitive Decline.” NeuroscienceNews. Published May 21, 2018.
Abstract
Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study
Importance: Detecting asymptomatic individuals at high risk for imminent cognitive decline from Alzheimer’s disease is essential to prevent dementia. Vascular risk and β-amyloid (Aβ) pathology frequently coexist in older adults and both contribute to cognitive impairment.
Objective: To determine whether vascular risk and Aβ burden act additively or synergistically to drive cognitive decline in clinically normal older adults, and to assess whether vascular risk predicts decline beyond commonly used imaging biomarkers including Aβ PET, hippocampal volume, FDG-PET, and white matter hyperintensities.
Design, Setting, and Participants: Longitudinal observational analysis of clinically normal older adults enrolled in the Harvard Aging Brain Study. Inclusion required baseline imaging (FDG-PET, Aβ-PET, MRI), baseline medical data to calculate vascular risk, and at least one follow-up neuropsychological assessment. Data were collected from 2010 through 2017.
Main Outcomes and Measures: Vascular risk was quantified using the Framingham Heart Study general cardiovascular disease (FHS-CVD) risk score. Aβ burden was measured with Pittsburgh Compound-B PET. Cognition was assessed annually with the Preclinical Alzheimer Cognitive Composite. Models adjusted for baseline age, sex, education, and apolipoprotein E ε4 status.
Results: Among 223 participants (130 women; mean age 73.7 years; mean follow-up 3.7 years), faster cognitive decline correlated with a higher FHS-CVD risk score and higher Aβ burden. The interaction between vascular risk and Aβ burden over time was significant, indicating a synergistic effect. Vascular risk remained strongly associated with prospective cognitive decline even after adjustment for Aβ burden, hippocampal volume, FDG-PET uptake, and white matter hyperintensities.
Conclusions and Relevance: In clinically normal older adults, vascular risk predicts future cognitive decline both independently and synergistically with Aβ burden. Incorporating vascular risk assessment alongside imaging biomarkers may improve identification of individuals at greatest risk for preclinical Alzheimer’s disease and inform prevention strategies.