Apathy Mediates the Association Between Diabetes Risk and Alzheimer’s Disease and Related Dementias in Older Adults: The Health and Retirement Study

Apathy is an increasingly recognized neuropsychiatric syndrome and predictor of cognitive decline, distinct from depression. Although type 2 diabetes mellitus is a well-established risk factor for cognitive impairment, longitudinal evidence examining whether apathy links diabetes risk to adverse cognitive outcomes remains limited. We used data from 4,571 U.S. adults aged ≥60 years without baseline memory problems enrolled in the U.S.Health and Retirement Study. Diabetes risk was measured using glycosylated hemoglobin (HbA1c), treated continuously. Apathy was derived from four CES-D items reflecting diminished positive affect and motivation. Outcomes included incident self-reported Alzheimer’s disease and related dementias (ADRD) and incident cognitive impairment. Accelerated time-to-failure Weibull models were used to estimate associations between HbA1c and time to each outcome. Mediation was tested using a product-of-coefficients approach incorporating survey weights. Higher HbA1c was associated with shorter time to ADRD (coefficient −0.09; 95% CI −0.16, −0.02) and cognitive impairment (−0.16; 95% CI −0.23, −0.09), as well as greater apathy (β = 0.01; 95% CI 0.007, 0.03). After including apathy in Weibull models, associations with ADRD (−0.07; 95% CI −0.14, −0.006; p = 0.032) and cognitive impairment (−0.14; 95% CI −0.21, −0.07; p < 0.001) were changed but remained significant. Indirect effects through apathy were statistically significant for both outcomes, indicating partial mediation. Overall, elevated diabetes risk was associated with accelerated onset of ADRD and cognitive impairment, with apathy partially mediating these relationships, highlighting apathy as a potential target for behavioral interventions in individuals with diabetes.