The dynamic association between body mass index and cognition from midlife through late-life, and the effect of sex and genetic influences

Abstract

Body mass index (BMI) is associated with cognitive abilities, but the nature of the relationship remains largely unexplored. We aimed to investigate the bidirectional relationship from midlife through late-life, while considering sex differences and genetic predisposition to higher BMI. We used data from 23,892 individuals of European ancestry from the Health and Retirement Study, with longitudinal data on BMI and three established cognitive indices: mental status, episodic memory, and their sum, called total cognition. To investigate the dynamic relationship between BMI and cognitive abilities, we applied dual change score models of change from age 50 through 89, with a breakpoint at age 65 or 70. Models were further stratified by sex and genetic predisposition to higher BMI using tertiles of a polygenic score for BMI (PGSBMI). We demonstrated bidirectional effects between BMI and all three cognitive indices, with higher BMI contributing to steeper decline in cognitive abilities in both midlife and late-life, and higher cognitive abilities contributing to less decline in BMI in late-life. The effects of BMI on change in cognitive abilities were more evident in men compared to women, and among those in the lowest tertile of the PGSBMI compared to those in the highest tertile, while the effects of cognition on BMI were similar across groups. In conclusion, these findings highlight a reciprocal relationship between BMI and cognitive abilities, indicating that the negative effects of a higher BMI persist from midlife through late-life, and that weight-loss in late-life may be driven by cognitive decline.

Stability in BMI over time is associated with a better cognitive trajectory in older adults

“…We and others have shown that the negative effects of a higher BMI on brain and cognition persist through late-life. 32 , 35 However, there is scarce research on changes in BMI in old age; most studies provide evidence suggesting that decreasing BMI is associated with poor health outcomes including congestive heart failure and mortality. 36 , 37 Our study showed that a decline in BMI over time was associated with accelerated cognitive decline.…”

“… 11 Although decline in BMI may represent a true risk factor for cognitive decline, it is also possible that it represents reverse causality, that is, that brain changes related to dementia affect BMI earlier than cognition. 32 Of interest, polymorphisms in FTO , PPARG , PPARA , and APOE genes, 38 implicated in AD, 39 , 40 are significant predictors of BMI variability, 41 suggesting a common cause. An alternative explanation is that both BMI variability and cognitive decline are manifestations of an underlying morbidity and are not causally related.…”

“…Changes in the cognitive domain of memory, attention/working memory, language, and executive functions were examined separately. Finally, because BMI changes in old age differ in men and women, 31 , 32 we tested the interaction of each of the BMI measures with sex on cognitive decline. All analyses were performed using Stata 13.0.…”

Sex-Specific Patterns of Body Mass Index Relationship with White Matter Connectivity

“…Despite its significant effects on both BMI [ 57 ] and cognition [ 57 ], sex as a biological modifier is relatively absent in the above literature and instead often used as a confounder in regression equations. Women are shown to be resistant to the adverse effects of BMI on cognition [ 58 ], and a recent report has shown a further risk-reducing effect for BMI on the cognitive ability in older women [ 59 ]. Differences in body composition, visceral fat distribution, glucose and lipid homeostasis, and sex steroid hormone levels in premenopausal women are all among suggested mechanisms by which sex can modify the effect of tissue adiposity on cognitive health [ 60 ].…”

Recent Updates on Associations among Various Obesity Metrics and Cognitive Impairment: from Body Mass Index to Sarcopenic Obesity

“…Nonetheless, there is some evidence that contradicts the above results. 7 , 31 - 33 In a study by Karlsson et al, 34 higher BMI contributed to a sharp decline in cognitive function in both mid-life and late-life. The study indicated that the detrimental effects of higher BMI persist from mid-life through late-life.…”