mental health

Tips From ARIC: Midlife Vascular Risk Factors Affect Alzheimer Disease Later

Rebecca Gottesman, MD
Johns Hopkins University

Gottesman R. Tips from ARIC: midlife vascular risk factors affect Alzheimer disease later [published online February 26, 2019]. Neurology Consultant.



My colleagues and I conducted the Atherosclerosis Risk in Communities (ARIC)-PET Amyloid Imaging Study1 because we were interested in better understanding how vascular disease affects the risk for dementia, specifically Alzheimer disease. Our own studies, as well as studies done by others, have shown that vascular risk factors—particularly in middle age—are associated with a higher risk for dementia and Alzheimer disease. We were especially interested in amyloid deposition in the brain.

One of the leading hypotheses of how Alzheimer occurs is that amyloid builds up; it is not the only factor, but it is a major player in what leads to Alzheimer disease. In turn, we used a florbetapir positron emission tomography (PET) to assess amyloid deposition in the brain of a subset of participants from ARIC.

Over a span of 25 years, ARIC logged participants’ vascular risk factors as well as other exposures, serially following participants’ blood pressure, lipid status, diabetes status, smoking status, and weight. It was when the participants were aged 70 to 90 years that we performed PET scans to analyze the brains’ amyloid deposition. We only studied data on participants who did not have dementia at the time of the PET scans, so there was a combination of people with normal cognition and mild cognitive impairment.

The ARIC study subset we evaluated included 346 participants. Not only did we assess the relationship between their vascular risk factors—particularly when they were middle-aged—but we also looked at later ages and their later-life brain amyloid deposition. 

The Findings

In this study, participants who had more vascular risk factors in middle age—their first visit within this study—had a higher risk of having amyloid in the brain when they were older. This suggests that there might be a direct link between vascular risk factors and amyloid, which we think leads to Alzheimer disease. In particular, the participants who had 1 risk factor had a higher risk than people who had no risk factors, and people who had 2 or more risk factors had nearly triple the risk of people who had no risk factors. 

This relationship did not persist when factoring the number of risk factors in later life, so it really was middle age that appeared to be the most important time period. 

When we assessed individual risk factors, such as hypertension, diabetes, obesity, smoking, and hypercholesterolemia, rather than the number of risk factors, the only risk factor that independently showed an increased risk for amyloid later in life was a body mass index of more than 30 kg/m2. In fact, fitting the definition consistent with obesity in middle age puts an individual at a 2-fold increased risk for elevated amyloid later in life. 

In general, we think these findings do provide some evidence that there may be a direct increased risk associated with vascular risk factors in middle age and amyloid, which may directly link it to Alzheimer disease. While we did not look at treatments in this study, because it was not an interventional study, we do think it is important to consider that controlling and trying to reduce these modifiable risk factors is probably important in potentially reducing the risk for Alzheimer disease.


Put it into practice >>

Putting it Into Practice

The results re-emphasize the importance of tracking peoples’ risk factors, particularly when they are middle-aged or even younger. It is important that physicians who are treating people in primary prevention and treating them with their risk factor status when they are middle-aged or younger to understand that the way those risk factors are controlled might have an impact on their later-life cognitive outcomes and might directly impact Alzheimer-type changes in the brain. 

While we cannot say with any confidence that treating any of these risk factors would reduce the risk of cognitive decline or dementia, since we did not study the interventions themselves, I do think our data suggests that attention should be paid to trying to reduce these risk factors if they are present when people are younger. Will reducing obesity; telling people to quit smoking; and treating hypertension, diabetes, and high cholesterol reduce the risk for Alzheimer disease? That is uncertain, but we know those are all important factors in cardiovascular health, which would further support the importance of controlling those risk factors. 


Rebecca Gottesman, MD, PhD, is a professor of neurology and epidemiology in the Division of Cerebrovascular Neurology at Johns Hopkins University and is director of research at Johns Hopkins Bayview Neurology in Baltimore, MD.



  1. Gottesman RF, Schneider ALC, Zhou Y, et al. The ARIC-PET amyloid imaging study: brain amyloid differences by age, race, sex, and APOE. 2016;87(5).