Variable BMI Pattern in Midlife May Serve as Indicator for Dementia in Late Life

Patterns of change in body mass index (BMI) over the life course may be useful as an indicator of an individual’s risk for dementia, according to a new longitudinal study that followed a cohort of Framingham Heart Study Offspring participants for nearly 40 years.

The study, published online in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, found that an overall trend in BMI decline was associated with a higher risk of developing dementia in late life. Among the “decliners,” the investigators identified a subgroup of individuals with a dual pattern of BMI change occurring within midlife—an initial increase followed by a decrease. This pattern they say, appeared to be central to the association between declining BMI and dementia.

Compared to “non-decliners,” those in the midlife increase/decrease BMI group were at greater increased risk for dementia (hazard ratio [HR] 3.84, 95% CI 1.39–10.60).

“These findings are important because previous studies that looked at weight trajectories didn’t consider how patterns of weight gain/stability/loss might help signal that dementia is potentially imminent,” explained corresponding author Rhoda Au, PhD, professor of anatomy and neurobiology at the Boston University Chobanian & Avedisian School of Medicine in a Boston University press statement.

The authors cite the dramatic global rise in both dementia and obesity and note that while there is some evidence of an association between the conditions, the connection remains a matter of debate. Au and colleagues describe the “BMI paradox in dementia:” being overweight (BMI ≥25 kg/m2) in mid-life has been associated with an increased risk of dementia in later life, whereas being overweight in later life has been linked to reduced dementia risk.

Given the current collection of mixed findings, Au et al chose to test a novel hypothesis: individuals whose BMI increases until late mid-life followed by BMI decline in subsequent years are more likely to develop dementia.

The investigators tapped data from the longitudinal community-based Framingham Offspring cohort and identified 2405 participants, aged 30 to 50 years without dementia. As part of Framingham protocol all participants underwent serial health examinations, an average of 4 years apart, which provided Au and colleagues with data on BMI trajectories and cognitive status over time.

FINDINGS

Mean age of the 2405-participant cohort was 40.5 years at baseline. During approximately 4 decades of follow up, dementia was identified in 76 individuals with a mean age of 72.2 years. Not surprisingly, the investigators found advancing age strongly associated with a risk for dementia (P>.001). No demographic differences were observed between those with and without dementia (P >.05)

BMI and dementia. The researchers found no association between BMI categories at baseline and future dementia. However, they observed that being overweight at midlife was associated with a risk for dementia in late life (P = .041). Average BMI increased from 25.2 (±4.4) kg/m2 at the second Framingham health exam to 28.5 (±5.2) kg/m2 at the ninth exam.

Participants who developed late-life dementia had a higher BMI at baseline (P = .026), but the researchers observed no significant difference for BMI measured at subsequent exams.

The average estimated individual slope of change in BMI was 0.13 (SD = 0.11). A BMI decline (slope <0) was recorded in 224 participants during followup. Among these “decliners,” Au and colleagues identified 3 subgroups based on BMI trajectories from mid- to late life:

• decline in BMI from early to mid-life (BMI consistently declines over 40 years of follow-up, 11.1%)
• mid-life stable BMI with a later-life BMI decline (BMI stable from 40–50 years, but decline after age 50, 76.8%)
• early mid-life BMI increase followed by BMI decline in late mid-life (BMI increased until age 50 followed by decline, 12.1%)

Among the subgroups with early decreasing and late decreasing BMI trajectories there was no significant association with risk of dementia.

Decliners with increasing BMI in early mid-life followed by declining BMI in later mid-life (age ~50 years) were at a greater increased risk of dementia compared to non-decliners. The multivariable-adjusted HR of dementia for these decliners was 3.84 (95% CI 1.39–10.60).

When investigators adjusted for being overweight/obese or not at mid-life, the HR was 3.57 (95% CI 1.28–9.95). When models were adjusted for baseline lifestyle factors the HR was 3.88 (95% CI 1.38–10.91). The multivariable-adjusted SHR of dementia was 4.34 (95% CI 1.73–10.85) after adjusting age, sex, education, and lifestyle factors at baseline.

“The current study spans nearly 40 years of longitudinal measurement of BMI and surveillance for incident dementia in a community-based cohort. It sought to provide some initial insight into how patterns of BMI from an initially middle-aged group may impact later life risk for dementia,” Au and colleagues write in their conclusion. “Future studies will be needed to determine whether these findings extend to younger adulthood…Conclusions based on current findings suggest that variable BMI patterns across the lifespan may be a prodromal marker of dementia.”

Reference: Li J, Liu C, Ang TFA, Au R. BMI decline patterns and relation to dementia risk across four decades of follow-up in the Framingham Study. Alzheimers Dement. Published online December 15, 2022. doi:10.1002/alz.12839