Vascular risk factors at midlife may help predict Alzheimer's

Adults who had two or more midlife vascular risk factors had a significantly increased risk of elevated amyloid deposition in the brain later in life compared with those with no midlife vascular risk factors, according to a prospective cohort study.

The association was not found with late-life vascular risk factors. The researchers noted that brain amyloid are protein fragments that have been linked to Alzheimer's disease.

Lead researcher Rebecca F. Gottesman, MD, PhD, of the Johns Hopkins School of Medicine in Baltimore, and colleagues published their results online in JAMA on April 11.

Previous research found that vascular risk factors such as hypertension, diabetes, smoking and hypercholesterolemia were associated with the risk of dementia and Alzheimer disease, according to the researchers.

For this analysis, they evaluated 346 adults without dementia at baseline who participated in the Atherosclerosis Risk in Communities (ARIC)–PET Amyloid Imaging Study. The participants were from Washington County, Maryland, Forsyth County, 
North Carolina and Jackson, Mississippi. They underwent a baseline visit from 1987 to 1989 and had four additional in-person visits, including one from 2011 to 2013 when they underwent florbetapir PET scans. The patients were 45 to 64 years old at their first visit and 67 to 88 years old at their final visit.

The researchers evaluated vascular risk factors at each of the in-person visits. They then tallied up the number of vascular risk factors present in midlife (the first visit) and in late life (the fifth visit. The vascular risk factors included current smoking, hypertension, diabetes, obesity (a body mass index [BMI] of 30 kg/m2 or greater) and elevated total cholesterol (200 mg/dL or greater).

The mean age was 52 years old at the time of midlife vascular risk assessment and 76 years old at the time of PET imaging. In addition, 57 percent of participants were white and 43 percent were black.

From midlife to late life, the rates of hypertension, diabetes, BMI and stroke risk score increased, while lipid levels and smoking rates decreased. At the first visit, 20 percent of participants had no risk factors, 38 percent had one risk factor and 42 percent had two or more risk factors. None of the participants had five risk factors at the first or fifth visit.

The researchers found that elevated midlife BMI was the only vascular risk factor with a statistically significant association with elevated late-life brain amyloid. In addition, a higher number of vascular risk factors in midlife was associated with elevated brain amyloid, although the association was not found for a higher number of vascular risk factors in late life.

The researchers noted that 31 percent of participants with no vascular risk factors in midlife and 61 percent of participants with two or more vascular risk factors in midlife had elevated amyloid in late life. Each additional midlife vascular risk factor was associated with a 41 percent increased odds of elevated standardized uptake value ratios (SUVR), which were calculated from PET scans. They also mentioned that the association between the number of risk factors and elevated odds of amyloid was only found in white participants, although the statistical test for interaction of race by number of risk factors was not significant.

The researchers mentioned a few limitations of the study, including a potential inadequate sample size. They also noted that the study only included a few people with very high vascular risk in midlife and had more participants who had a higher prevalence of diabetes in late life compared with earlier trials. In addition, participants did not undergo PET scans at their midlife visit.

“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,” the researchers wrote. “These findings are consistent with a role of vascular disease in the development of [Alzheimer disease].”