Body Mass Index Trajectories Preceding Incident Mild Cognitive Impairment and Dementia

Importance Body mass index (BMI) trajectories before the onset of mild cognitive impairment (MCI) and during the progression from MCI to dementia remain unclear. Objective To assess the long-term BMI trajectories preceding incident MCI and dementia and explore whether they are associated with brain pathologies. Design, Setting, and Participants The Rush Memory and Aging Project (MAP) was an ongoing community-based cohort study. This study included cognitively intact participants aged 60 to 90 years at baseline with annual follow-up from October 1997 to December 2020 (maximum follow-up of 22 years). During the follow-up, participants underwent brain autopsies. Data were analyzed from August 2021 to February 2022 using mixed-effect models. Exposures BMI was calculated using height and weight measured at baseline and follow-ups. Main Outcomes and Measures Incident MCI and dementia were diagnosed following standard criteria. Neuropathological assessments (including global Alzheimer disease and vascular pathology) were performed for autopsies. Results A total of 1390 participants (mean [SD] age, 78.4 [6.5] years; 1063 female [76.5%]) were included in the study. In the analysis of BMI trajectories before MCI (n = 939), during the follow-up (median [IQR] duration, 6 [3-9] years), 371 participants (39.5%) developed MCI, of whom 88 (23.7%) progressed to dementia. Those who developed MCI were older (mean [SD] age, 79.6 [5.9] years vs 76.9 [6.6] years), consumed less alcohol (median [IQR] consumption, 0 [0-5.8] g/day vs 1.1 [0-6.9] g/day), had a lower BMI (mean [SD], 27.2 [4.9] vs 28.2 [5.9]), and were more likely to be apolipoprotein E ( APOE ) ε4 carriers (89 of 371 [24.0%] vs 98 of 568 [17.3%]) compared with those who remained cognitively intact over follow-up. Those who developed dementia were older (mean [SD] age, 81.0 [5.2] years vs 79.1 [6.0] years), had a lower level of physical activity (median [IQR] activity, 1.0 [0-2.5] h/week vs 1.8 [0.2-3.8] h/week), and were more likely to be APOE ε4 carriers than those who were dementia-free (33 of 88 [37.5%] vs 56 of 283 [19.8%]). Compared with participants who remained cognitively intact, in those with incident MCI, BMI tended to decline earlier and faster. From 7 years before diagnosis, people with incident MCI had an associated significantly lower BMI (mean difference, −0.96; 95% CI, −1.85 to −0.07) than those who were cognitively intact. Among people with incident MCI, the slopes of BMI decline did not differ significantly between those who did and did not develop dementia (β, −0.03; 95% CI, −0.21 to 0.15). In the analysis of BMI trajectories before autopsy (n = 358), BMI was associated with a faster declination among participants with a high burden of global Alzheimer disease pathology (β for pathology × time highest vs lowest tertile, −0.14; 95% CI, −0.26 to −0.02) or vascular pathology (β for pathology × time 2 highest vs lowest tertile, 0.02; 95% CI, 0-0.05). Conclusions and Relevance Results of this cohort study suggest that among cognitively intact people, significantly lower BMI occurs beginning approximately 7 years before MCI diagnosis. After MCI diagnosis, BMI declines at the same pace in people who develop dementia and those who do not. High brain pathologies may underly the BMI decline preceding dementing disorders.