August 05, 2020
Higher body mass index (BMI) in early adulthood is associated with an increased risk for dementia later in life, new research suggests.
The study is the first to link heightened dementia risk with higher BMI earlier in life for both women and men, investigators note.
While the study only shows association, and so cannot infer causation, "it does suggest that adult life obesity is an important risk factor for dementia risk," co-investigator Adina Zeki Al Hazzouri, PhD, assistant professor of epidemiology, Mailman School of Public Health, Columbia University, New York City, told Medscape Medical News.
The findings were presented at the Alzheimer's Association International Conference (AAIC) 2020, which was held online this year because of the COVID-19 pandemic.
It has been unclear to what extent BMI influences risk for Alzheimer's disease (AD) and other dementias. Previous studies have shown high midlife BMI increases the risk for dementia, while high late-life BMI may be protective.
However, relatively little is known about the role of earlier life BMI on risk for dementia.
"This is mostly due to lack of datasets with early life exposures and outcomes for dementia, which typically occur in late life," Zeki Al Hazzouri said.
The current study used data pooled from established US cohorts, which together spanned the adult life course.
This included 5104 older adults from two studies: 2909 from the Cardiovascular Health Study and 2195 from the Health, Aging and Body Composition study (Health ABC). At enrollment, participants were a mean age of 72.6 years. In addition, 18% were black and 56% were women.
As BMI was only collected beginning in late life in these cohorts, researchers imputed early and midlife BMI, beginning at age 18. They used linear mixed models applied to a pooled cohort that also included young and middle-aged adults from the Coronary Artery Risk Development in Young Adults (CARDI) study and the Multi-Ethnic Study of Atherosclerosis (MESA).
Researchers summarized BMI (weight divided by square of height) by time-weighted averages in early life (ages 20-49), midlife (ages 50-69), and late-life (ages 70-89). They assessed BMI using established cut-offs for overweight (BMI, 25.0 to < 30 kg/m2) and obesity (BMI ≥ 30.0 kg/m2).
They determined dementia status using well-established criteria, including a detailed neuropsychological test battery, neurological examinations, medical records, and dementia-related drug use.
Twofold Higher Risk
After adjusting for sex, race/ethnicity, education, and cohort, dementia risk increased with higher early life BMI in women. Compared with women with normal BMI in early adulthood, the dementia risk was 1.8 times higher among those who were overweight (odds ratio [OR], 1.82; 95% CI, 1.31 - 2.54; P < .001).
The risk was even higher among those who were obese in early adulthood (OR, 2.45; 95% CI, 1.47 - 4.06; P < .001).
For men, dementia risk increased with higher early life obesity (OR, 2.47; 95% CI, 1.46 - 4.19; P < .001) and with both midlife overweight (OR, 1.51; 95% CI, 1.11 - 2.05; P = .009) and midlife obesity (OR, 2.00; 95% CI, 1.16 - 3.42; P = .012), after adjusting for late-life BMI.
The relationship between late-life BMI and dementia risk was the reverse for both men and women. This suggests higher BMI at this stage may be protective, which is consistent with prior research, Zeki Al Hazzouri said.
"Reverse causation due to incipient dementia is one of the hypothesized explanations," she noted.
It is possible that higher early adult BMI could be a marker for other risk factors linked to dementia, such as diabetes, Zeki Al Hazzouri said. "However, when we further accounted for other potential cardiovascular risk factors, our findings did not change," she added.
Another Puzzle Piece
Commenting on the study for Medscape Medical News, Pierre Tariot, MD, director at Banner Alzheimer's Institute and research professor of psychiatry at the University of Arizona College of Medicine, Phoenix, said it represents "another piece of the puzzle" of what connects general health to brain health.
"There's just massive evidence that obesity is a risk factor for Alzheimer's disease and related disorders, and the mediators look to be inflammation, oxidative stress, insulin resistance, and leptin resistance," said Tariot, who was not involved with the research.
"What's new here is the fact it looks like even early age obesity can have long-term consequences," he added.
Tariot noted that the "pathological footprints" of AD can be measured 20 years before symptoms develop, "but what drove those in the first place has to be even earlier."
The notion that early oxidative stress could be a fundamental driver "makes great good sense to me," Tariot said.
He added that the finding that high late-life BMI might protect against dementia could be explained by a number of factors, including survivor bias.
"There's an interaction between obesity and APOE4 allele dose, so maybe the obese 4 folks have already died" by late life, said Tariot.
Also commenting for Medscape Medical News, Rebecca M. Edelmayer, PhD, director of scientific engagement at the Alzheimer's Association, noted that the study is part of emerging literature looking at younger-aged individuals followed all the way through adulthood.
Edelmayer acknowledged the difficulty of studying early life risk factors for dementia because cognitive decline typically doesn't manifest until much later in life. BMI is particularly complicated as it may be a risk factor early on but protective at a later stage, she added.
Although the current study included two very large cohort studies out of Columbia University, Edelmayer stressed that "this is a single study" and more research is needed.
The study was funded by the National Institutes of Health/National Institute on Aging. Al Hazzouri and Tariot have reported no relevant financial relationships.