Joint daily functional trajectory and risk of new-onset Alzheimer's disease and related dementias in older adults with normal and abnormal weight

Background: Associations between daily functional trajectories and new-onset all-cause dementia and Alzheimer's disease (AD) and the role of body weight are underexplored.

Methods: Data were from the Health and Retirement Study (HRS) 1994-2020. Daily function was assessed using (instrumental) activities of daily living ([I]ADLs). All-cause dementia and AD were defined by self- or proxy-reported physician diagnoses. Body weight was assessed using body mass index (BMI) and categorized as normal (18.5 kg/m² ≤ BMI < 30 kg/m²) and abnormal (BMI < 18.5 kg/m² or ≥30 kg/m²). The group-based trajectory modeling and Cox proportional hazards regression were utilized.

Results: Of 18,763 adults included, 1236 developed new-onset dementia during a 10-year follow-up. The associations of ADL and IADL limitations at baseline with all-cause dementia and AD were much more pronounced in those with abnormal weight (P for interaction < 0.005). Five joint trajectories of ADL and IADL limitations were identified: No (72.7 %), Recovery (4.0 %), Recent emerging (16.4 %), Early emerging (4.8 %), and Severe (2.1 %). Furthermore, the 'Severe' joint trajectory (vs. 'No') was associated with 3.57- and 3.59-times higher risks of new-onset all-cause dementia and AD in participants with abnormal weight (P for interaction = 0.002 and 0.005). Notably, the Recovery joint trajectory (vs. No) was not associated with increased risks of all-cause dementia or AD.

Limitations: Self-/proxy-reported all-cause dementia and AD may introduce misclassification bias. Lifestyle factors were not quantified. BMI at baseline, but not its trajectory, was utilized. Potential reverse causation deserved attention.

Conclusions: Body weight control can help reduce the risk of progression from functional limitations to all-cause dementia and AD.