BMI Stability Associated With Healthier Cognitive Trajectory

Michal Schnaider-Beeri, PhD

Pooled data from more than 15,000 initially nondemented elderly individuals showed that significant changes in body mass index (BMI), along with greater variability in BMI, were associated with worsened cognitive decline. Furthermore, the stability of BMI may confer protection against cognitive decline, irrespective of the initial BMI of the individual.¹

Lead author Michal Schnaider-Beeri, PhD, professor of psychiatry, Mount Sinai Icahn School of Medicine, and colleagues followed the cognitive trajectories of individuals aged at least 60 years from the Alzheimer’s Disease Centers for 5 years on average. It had been previously known that BMI plays a role in the risk of incident cognitive impairment, however, evidence on simultaneous changes in BMI were limited.

To do this, investigators defined changes in BMI as follows: the difference between BMI at last visit (∆BMI_last-bl), the mean of all follow-up BMIs minus first BMI (∆BMI_mean-bl), and the standard deviation (SD) of BMI change from baseline and all follow-up visits (∆BMI-SD) to thus represent variability. For the first and second definitions, changes in BMI were categorized as significant increases (≥5% increase), stable (<5% change), or significant decrease in BMI (≥5% decrease), as a 5% change is defined as clinically significant by the FDA.

At baseline, 36% (n = 5747) of participants had normal weight (BMI <25 kg/mg2), 39.4% (n = 6302) were overweight (BMI <30 kg/m2), and 24.6% were obese (BMI ≥30 kg/mg2). Up to the last BMI measure, 26.7% of the total sample decreased by 5% or more, 55.8% remained stable in BMI over time, and 17.5% had BMI increase more than 5%.

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After applying linear mixed models, greater changes in ∆BMI_last-bl and ∆BMI_mean-bl were associated with a faster rate of cognitive decline. Similarly, the interaction of ∆BMI-SD with time on global cognition was also significantly associated with a faster rate of global cognitive decline, with greater SDs representing greater changes in BMI over time. All groups had some degree of decline, including those with stable BMI; however, the rate of decline in the nonstable groups was more than 60% faster than the rate of decline in the stable BMI group.

"These results suggest a potential clinical value in tracking BMI in annual medical visits, which is simple, nonexpensive, noninvasive, and quick to measure, as it may point to individuals whose cognition is declining and allow for early intervention. Disentangling the biological pathways underlying different trajectories of BMI in old age, and their contribution to brain health and disease, is necessary to develop potential therapies," Schnaider-Beeri, et al wrote. The group added that as the results of this assessment showed an association between both increases and decreases in BMI and accelerated cognitive decline, irrespective of baseline BMI, plausibly, stability in BMI may be associated with reduced rates of poor cognitive outcomes.

Investigators repeated analyses to understand whether the patter of association of greater BMI over time with faster cognitive decline was specific to 1 particular baseline BMI group, mainly those who are obese. After stratifying baseline BMI groups, the results remained the same, that is, in each of the BMI groups, greater changes, whether be increases or decreases, were associated with a faster rate of cognitive decline. These results continued to remain essentially unchanged in a sensitivity analysis that used cut-off points of increases and decreases of 10% or more in BMI for ∆BMI_last-bl and ∆BMI_mean-bl. Notably, sex did not significantly change any of the interactions of the BMI measures on cognitive decline.

Ultimately, Schnaider-Beeri, et al noted that literature suggest a 1-unit annual decline in BMI in older adults was associated with an approximate 35% increase in the risk of Alzheimer disease (AD) compared with no change in BMI,² which implies that loss of BMI "may reflect pathologic processes that contribute to the subsequent development of AD." Additionally, they wrote, weight loss over 1 year is associated with a faster clinical progression of mild cognitive impairment.³ Interestingly, they noted that it is also possible that BMI represents reverse causality with AD, suggesting that brain changes related to dementia may affect BMI earlier than cognition. They added that polymorphisms in FTO, PPARG, PPARA, and APOE gene are both significant predictors of BMI variability and implicated in AD, pointing to a possible common cause.

REFERENCE
1. Schnaider-Beeri M, Tirosh A, Lin HM, et al. Stability in BMI over time is associated with a better cognitive trajectory in older adults. Alzheimer Dement. Published January 20, 2022. doi:10.1002/alz.12525
2. Buchman AS, Wilson RS, Bienias JL, Shah RC, Evans DA, Bennett DA. Change in body mass index and risk of incident Alzheimer disease. Neurology. 2005;65(6):892-897. doi:10.1212/01.wnl.0000176061.33817.90
3. Besser LM, Gill DP, Monsell SE, et al. Body mass index, weight change, and clinical progression in mild cognitive impairment and Alzheimer disease. Alzheimer Dis Assoc Disord. 2014;28(1):36-43. doi:10.1097/WAD.0000000000000005