Population-based cohort study of modifiable risk factors for dementia and Alzheimer disease mortality in Spain.

BACKGROUND: Although many modifiable factors are linked to dementia risk, their association with dementia and Alzheimer disease (AD) mortality remains unclear. We aimed to identify late-life modifiable factors associated with these outcomes and assess sex differences. METHODS: In the population-based Neurological Disorders in Central Spain (NEDICES) cohort, we followed 3085 older adults enrolled in 1994-1995 through 2017. We examined 13 modifiable factors measured at study entry. Dementia and AD deaths were defined by the underlying cause recorded on death certificates. Fine-Gray competing risk models accounted for death from other causes and generated subdistribution hazard ratio (SHR) estimates and adjusted population attributable fractions (PAFs). RESULTS: During follow-up, there were 182 dementia-coded deaths (including 105 AD-coded deaths) and 2423 deaths from other causes. Here we show that depressive symptoms are associated with higher dementia-coded mortality in women (SHR 1.52, 95% confidence interval [CI] 1.00-2.30; PAF 13.6%, 95% CI 0.0-28.4) and higher AD-coded mortality overall (SHR 1.76, 95% CI 1.11-2.79; PAF 15.4%, 95% CI 2.6-29.9), with a stronger association in women (SHR 2.23, 95% CI 1.28-3.88; PAF 27.2%, 95% CI 7.8-46.7). Several exposures show inverse associations (e.g., smoking, obesity, and arterial hypertension in men), consistent with competing mortality and late-life reverse causation. Combined positive PAFs are 10.8% for dementia-coded mortality and 18.2% for AD-coded mortality overall, reaching 41.1% in women for AD-coded mortality. CONCLUSIONS: Late-life depressive symptoms, particularly among women, emerged as the most prominent modifiable correlate of dementia- and AD-coded mortality, supporting improved recognition and management of depressive symptoms in older adults.