The Association of Apathy With Incident Dementia: A Multiple Mediation Analysis of Cardiovascular Risk Factors

Objectives: Despite established links between apathy, cardiovascular disease, and dementia, it remains unclear if cardiovascular risk factors (CVRF) play a mediating role in the association between apathy and dementia. If apathy increases dementia risk via lifestyle-related dementia risk factors, targeted lifestyle interventions could help high-risk individuals. Methods: We used data from the preDIVA study including 3303 individuals aged 70–78 years. Apathy was assessed using the geriatric depression scale, and CVRF (cardiovascular risk factors) (systolic blood pressure, cholesterol, diabetes, body mass index (BMI), smoking, and physical activity) were considered as potential mediators. Outcome was incident dementia during 12 years of follow-up. We assessed mediation using Multiple Mediation Analysis (MMA). Results: Of the association between apathy and dementia (HR 1.49 [95% CI 0.99–2.41]), 27% was mediated by physical inactivity, BMI and diabetes combined. Of this total, physical inactivity mediated 28% of the effect (HR 1.12, 95% CI 1.03–1.29), diabetes 9% of the effect (HR 1.04, 95% CI 1.02–1.10), and BMI counteracted these effects by −12% (HR 0.95, 95% CI 0.88–0.98). Conclusion: The relationship between apathy and dementia is partly mediated by physical inactivity, BMI and diabetes. Apathy is an important clinical marker that signals the existence of potentially modifiable pathways, providing an opportunity for lifestyle interventions. To potentially reduce dementia risk via lifestyle modification in patients with apathy, a tailored approach should be taken to overcome the characterizing symptom of diminished motivation.