JHU Study Offers Additional Evidence that Cardiovascular Risk Factors Drive Alzheimer’s Development

Cardiovascular risk factors in middle age contribute later in life to amyloid-beta plaque in the brain, according to a comprehensive study that followed adults for more than 20 years. The findings underscore the idea that lifestyle factors are crucial drivers of Alzheimer’s disease.

Importantly, this signals that Alzheimer’s is not inevitable, since these risk factors are potentially preventable.

Numerous studies have proven the links between the so-called metabolic syndrome — including obesity, diabetes, high cholesterol and high blood pressure, as well as smoking — and Alzheimer’s. But whether these factors increase the risk of the disease through actions on amyloid-beta was previously unknown.

The study, “Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition,” appeared in the journal JAMA.

In 1987-89, researchers at Baltimore’s Johns Hopkins University School of Medicine recruited 346 adults without dementia to the study. Participants were then 45 to 64 years old and lived in three communities: Washington County, Md.; Forsyth County, N.C., and Jackson, Miss. At study entry, they were screened for cardiovascular risk factors and markers.

Between 2011 and 2013, JHU researchers again examined participants with a brain imaging method, capable of measuring how much amyloid-beta has accumulated in the brain. Researchers then analyzed the associations, taking into account factors such as age, sex, ethnicity, presence of the APOE risk gene and educational level.

The final analysis included 322 participants, 58 percent of whom were women, and 43 percent of whom were black. Researchers linked a body mass index (BMI) of 30 or more — indicating obesity at study start — to a higher risk of having amyloid plaques. But the analysis showed that the more cardiovascular risk factors a person had, the larger was the likelihood of developing plaque.

One risk factor increased the risk by 1.88, and two or more factors by 2.88, relative those with no risk factors. Yet having an APOE4 e4 gene variant, which is thought to increase the risk of Alzheimer’s, did not affect the link between lifestyle factors and amyloid aggregates.

This finding differed from earlier studies, in which the link between certain risk factors, such as diabetes, and amyloid deposits was only seen in people with the APOE e4 gene variant or was stronger in those groups.

Only midlife vascular risk factors were linked to amyloid brain deposits. The same risk factors, when appearing later in life, were not linked to aggregates of the Alzheimer’s-linked protein.

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