Current and long‐term trajectories of high BMI are associated with poorer cognitive functioning in middle‐aged adults at high Alzheimer’s risk due to a maternal family history

Abstract

The deleterious impact of adiposity on cognition in older adults is well-established. Alzheimer's disease (AD) neuropathology begins accumulating decades prior to symptoms so investigation of associations of adiposity with cognition in middle-aged adults may illuminate pathways underlying the earliest stages of cognitive decline. We examined the relationship of body mass index (BMI) with cognitive functioning in middle-aged adults at high AD risk due to a parental family history. We also investigated whether this association differs by maternal (FHm) versus paternal (FHp) family history. Participants are offspring of AD patients from the Israel Registry of Alzheimer's Prevention (IRAP Study; N=271). We examined the association of BMI at the time of cognitive assessment, and of long-term trajectories of BMI, with global cognition and specific cognitive domains. Linear regressions assessed the associations of BMI and cognition adjusting for sociodemographic and cardiovascular risk factors. An interaction term assessed whether associations of BMI with cognition differed by FHm/FHp. ANCOVAs examined the association of trajectories of BMI ("normal" BMI, N=154; "overweight/obese" N= 86), with cognition. For the whole sample, higher BMI was associated with worse language functioning (p=.045). Interactions of BMI with parental history of AD were significant for episodic memory (p=.023), language (p=.027), working memory (p=.006), and global cognition (p=.008), such that the associations of BMI with cognition were consistently stronger among FHm than for FHp. For the BMI trajectories, no significant differences in cognition were identified between normal and overweight/obese trajectories for the entire sample, but the interactions of BMI trajectories with parental history of AD were significant for episodic memory (p=.017), language (p=.013), working memory (p=.001), and global cognition (p=.005), with stronger associations for FHm than for FHp. Higher BMI and ∼20 years of trajectories of overweight/obesity were associated with poorer cognitive function in cognitively normal middle-aged adults with a maternal history of AD, but not in those with a paternal history of AD. Exposure to greater adiposity over time may have a detrimental impact on the brain already in midlife. Investigation of genetic and environmental contribution of maternal history of AD to these associations is merited.