Obesity, Poor Metabolic Health Tied to Evidence of Brain Aging

Researchers sought to evaluate the association between metabolic health and obesity and brain health measured via MRI and neurocognitive testing in community-dwelling adults.

In young to middle-aged adults without diabetes, stroke, or dementia, obesity and poor metabolic health were associated with structural and functional evidence of brain aging, as well as with poor cognitive function, according to study findings published Journal of the American Heart Association.

The relationship between subclinical cardiometabolic disease and brain health are of particular interest in adults who have not yet reached advanced age and thus in whom longer opportunities to intervene still exist. In the current study, the researchers sought to explore the association between metabolic health and obesity and brain health, measured via magnetic resonance imaging (MRI) and neurocognitive testing among community-dwelling adults.

A cross-sectional analysis—the Framingham Heart Study (FHS) Third Generation Exam 2 Cohort—was conducted to provide an opportunity to address these issues.

Participants in the FHS Third Generation were recruited beginning in 2002 and underwent examinations every 4 years. At each visit, updated medical history and cardiovascular examination–focused physical examination, blood pressure, and phlebotomy were obtained. Among the 3411 participants who attended Exam 2, a total of 3409 had data available on metabolic dysfunction. Of these individuals, 2335 received neurocognitive testing. Following exclusion of those with prior dementia, stroke, other confounding neurologic conditions, and diabetes, the resultant final sample size was 2170 participants. Of these individuals, 1977 also had undergone brain MRI scans.

The average participant age was 46±9 years; 54% of the individuals were women. The 2170 participants without prevalent diabetes, stroke, dementia, or other neurologic disorder were grouped according to metabolic unhealthiness (≥2 criteria for metabolic syndrome) and obesity (body mass index (BMI) ≥30 kg/m2): (1) metabolically healthy (MH) nonobese; (2) MH obese; (3) metabolically unhealthy (MU) nonobese; and (4) MU obese. The relationships between these groups and brain structure (per MRI) and cognitive function (per neurocognitive tests) were examined.

Per multivariable-adjusted analyses, those individuals who were considered metabolically unhealthy (ie, MU nonobese and MU obese groups) had significantly lower total cerebral brain volume compared with the MH nonobese referent group (P <.05 for both).

Further, participants placed in the MU obese cohort had significantly greater white matter hyperintensity volume (WMHV; P =.004). In contrast, no statistically significant association was observed between WMHV and either metabolic health or obesity alone.

Less favorable neurocognitive scores were reported in participants with obesity. Those placed in the MH obese group had lower scores on global cognition and Logical Memory-Delayed Recall and Similarities tests. Participants placed in the MU obese group had lower scores on Similarities and Visual Reproductions-Delayed tests (P ≤.04 for all).

Additionally, those assigned to the the obese and MU groups exhibited higher free water content and lower fractional anisotropy in several regions of the brain—which is consistent with loss of white matter integrity.

A major limitation of the current study is the relatively younger age and health of the sample population may have reduced the power to detect differences between the groups. Further, since the study cohort comprised of White participants of Western European origin, this may limit the generalizability of the findings to other racial and ethnic groups.

The investigators concluded that “Improvement in metabolic health and obesity may present opportunities to improve long-term brain health.” Additional study of preventive strategies for decreasing cardiometabolic disease burden is warranted, which may help to reduce the signs and symptoms of brain aging.

Disclosure: One of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures. 


Angoff R, Himali JJ, Maillard P, et al. Relations of metabolic health and obesity to brain aging in young to middle-aged adults. J Am Heart Assoc. Published online March 1, 2022. doi:10.1161/JAHA.121.022107