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Alzheimer's Disease Research and Treatments / Dementia and Cognitive Impairment Research · Journal article
Communications Health · September 2, 2026
Encouraging direction, but not yet definitive.
In a 23-year Spanish cohort of 3,085 older adults, depressive symptoms at baseline were associated with increased dementia and Alzheimer disease mortality, particularly in women, using competing risk methods to account for other causes of death. The outcome was defined by death certificate coding rather than clinical diagnosis, and reverse causation (depression secondary to early cognitive decline) cannot be excluded.
Population-based prospective cohort study with competing risk analysis. Older adults from the Neurological Disorders in Central Spain (NEDICES) cohort, population-based sample enrolled 1994–1995.. Intervention: No intervention; observational measurement of 13 modifiable factors at baseline. Compared with: Stratified by presence or absence of each modifiable factor, including depressive symptoms, with competing risk accounting for other causes of death. n = 3,085. Spain (Central Spain).
Depressive symptoms associated with AD-coded mortality overall: SHR 1.76 (95% CI 1.11–2.79; PAF 15.4%, 95% CI 2.6–29.9) In women, depressive symptoms showed stronger association with AD-coded mortality: SHR 2.23 (95% CI 1.28–3.88; PAF 27.2%, 95% CI 7.8–46.7) Depressive symptoms associated with dementia-coded mortality in women: SHR 1.52 (95% CI 1.00–2.30; PAF 13.6%, 95% CI 0.0–28.4)
Outcome defined by death certificate coding, not clinical diagnosis or neuropathology; dementia-coded mortality may misclassify underlying cause Inverse associations for smoking, obesity, and hypertension in men suggest late-life competing mortality and survivor bias; interpretation of sex differences unclear
Clinicians should prioritize recognition and management of depressive symptoms in older adults as a potentially modifiable correlate of dementia mortality, with heightened attention to older women. However, the use of death certificate coding and the acknowledged risk of reverse causation mean this should inform clinical vigilance rather than causal inference about depression's role in dementia pathogenesis.
Population-based cohort with 23-year follow-up and competing risk methodology identifies depressive symptoms as associated with dementia mortality, but uses death-certificate-coded outcomes rather than clinically confirmed dementia diagnoses, limiting causal inference.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians should prioritize recognition and management of depressive symptoms in older adults as a potentially modifiable correlate of dementia mortality, with heightened attention to older women. However, the use of death certificate coding and the acknowledged risk of reverse causation mean this should inform clinical vigilance rather than causal inference about depression's role in dementia pathogenesis.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Abstract 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.
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