Long-term Weight Change and its Temporal Relation to Later-life Dementia in the Health and Retirement Study.

Context: Weight loss among middle-aged and older adults has been associated with a higher risk of subsequent dementia. However, most studies have limited follow-up durations or suboptimal control for the potential influence of physical frailty (PF).

Objective: Our study aimed to investigate the long-term and temporal relations of weight change to risk of dementia among middle-aged and older adults in the United States.

Methods: A total of 5985 participants aged 65 years and older were included from the Health and Retirement Study. History of long-term weight change was calculated using 9 repeated body mass index measurements during 1992-2008. We then followed participants' dementia status from 2008 to 2018. Multivariable Cox proportional hazard models were used.

Results: During the study follow-up period (mean = 7.54 years), a total of 682 (11.40%) dementia cases were documented. After adjustment for basic demographic and lifestyle factors, participants with weight loss (median: -0.23 kg/m2 per year) were at a significantly higher risk of dementia (HR = 1.60; 95% CI, 1.33, 1.92), compared with the stable weight group (median: 0.11 kg/m2 per year). This association was attenuated but remained strong and significant after further adjustment for PF (HR = 1.57; 95% CI, 1.30, 1.89). Significant association was observed for weight loss assessed approximately 14 to 18 years preceding dementia diagnosis (HR = 1.30; 95% CI, 1.07, 1.58), and was consistent closer to diagnosis.

Conclusion: Both recent and remote weight loss were associated with a higher risk of later-life dementia among middle-aged and older adults independent of PF status.