Increasing obesity trajectory in midlife tied to cognitive decline, dementia

Individuals with a persistently high or an increasing pattern of general and central obesity trajectories throughout middle and late life appear to be at greater risk of cognitive decline and developing dementia, a study has shown.

“These findings underscore the importance of longitudinally assessing obesity biomarkers beyond single anthropometric measures,” the researchers said.

In this study, a nationally representative, longitudinal, community-based cohort was used to analyse the trajectory patterns of obesity over a 14-year period beyond middle age via latent mixture modelling. Researchers examined their association with subsequent cognitive decline using linear mixed models and with the risk of developing dementia using Cox models, adjusting for confounders.

A total of 4,751 participants (mean age 58.7 years, 57 percent female) met the eligibility criteria. Five distinct BMI trajectories and four waist circumference (WC) trajectories were identified. [Obesity 2025;405-415]

Compared with individuals in the low-stable BMI group (consistent and healthy body weight; range, 22.8–22.9 kg/m²), those in the high stable BMI group (maintaining a stable obesity status; range, 34.5–35.4 kg/m²) were more likely to develop dementia (odds ratio [OR], 1.43, 95 percent confidence interval [CI], 1.02–2.00) and have a faster cognitive decline over 6 years (difference in 6-year decline, –0.11, 95 percent CI, –0.18 to –0.03).

Likewise, individuals in the high-increasing WC group (increasing trend; range, 115–122 cm) had a higher likelihood of developing dementia (OR, 1.57, 95 percent CI, 1.01–2.49) and experiencing an accelerated cognitive decline (OR, –0.18, 95 percent CI, –0.28 to –0.07) than those in the low-stable WC group (stable and healthy WC; range, 76–79).

Weight management

These findings suggest that “[s]ustaining a healthy body weight over the long term and managing weight by adhering to a healthy lifestyle may contribute to better neurocognitive health and help prevent the progression of cognitive impairment and dementia,” according to the researchers.

Other studies, however, provide evidence suggesting that being overweight in late life was associated with a lower dementia risk. Such results could be attributed to reverse causality in which weight loss occurred during the long incubation period of dementia, as noted in some case–control studies. [Lancet Diabetes Endocrinol 2015;3:431-436; Neurosci Biobehav Rev 2020;115:189-198; JAMA Psychiatry 2022;79:1180-1187; JAMA Psychiatry 2018;75:1033-1042]

“These findings suggest that the association between obesity and dementia is likely to depend on when obesity biomarkers are measured in the life course, highlighting the importance of longitudinal anthropometric assessment throughout middle to late life, beyond single measures at a fixed time point, to further clarify the association of interest,” the researchers said. [Lancet Diabetes Endocrinol 2015;3:498-499]

However, previous studies have measured BMI at just one time point, and only a few have assessed the influence of BMI change at two time points. [Alzheimers Dement 2022;18:2131-2139; Alzheimers Dement (Amst) 2021;13:e12163]

“Further research is needed to elucidate causality and validate the predictive value of specific obesity trajectories,” the researchers said. “Additionally, exploring the impact of lifestyle modifications and interventions on adverse obesity trajectories and associated cognitive outcomes is warranted.”