Associations of general and specific psychopathology factors by age 35 with dementia after age 50: a Swedish population-based sibling comparison study
5 affiliations
- 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- 2Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- 3Department of Biomedicine, Aarhus University, Aarhus, Denmark
- 4Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN USA
- 5School of Medical Sciences, Örebro University, Örebro, Sweden
Abstract
Multiple psychiatric disorders are associated with later dementia, but it remains unclear whether these associations reflect a shared liability toward all psychiatric conditions (general psychopathology factor) or diagnosis-specific effects (specific psychopathology factors). In this Swedish register-based cohort study, we investigated these questions while adjusting for familial confounding shared by siblings (N = 2 543 621 individuals, 1 485 880 full-sibling pairs). Exposures were (i) six psychiatric diagnoses recorded by age 35 and (ii) a latent bifactor model fit to these diagnoses that identified one general and three specific (internalizing, externalizing, and psychotic) psychopathology factors. Outcomes were all-cause dementia and Alzheimer’s disease recorded after age 50. For observed psychiatric diagnoses, we estimated between-individual (HR) and within-sibling hazard ratios (HRwn) using Cox regression; for latent factors, we estimated between-individual (OR) and within-sibling odds ratios (ORwn) using exploratory structural equation modelling. All psychiatric diagnoses were significantly associated with increased risk of all-cause dementia (HR range 2.03–3.59; HRwn range 1.72–2.94) and Alzheimer’s disease (HR range 1.89–3.47; HRwn range 1.77–3.22). These associations were largely attributable to the general psychopathology factor, even after adjusting for familial confounding (ORwn with 95% CI: 1.25 [1.17–1.32] for dementia; 1.24 [1.16–1.32] for Alzheimer’s disease). After accounting for the general factor, only the psychotic-specific factor remained associated (ORwn with 95% CI: 1.20 [1.07–1.36] for dementia; 1.20 [1.06–1.37] for Alzheimer’s disease). These results suggest that liability toward general psychopathology and, independently, psychotic conditions, by early adulthood might be early markers of increased dementia risk and targets for timely identification and prevention.
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BibTeX
@article{liu2026associations,
title = {{Associations of general and specific psychopathology factors by age 35 with dementia after age 50: a Swedish population-based sibling comparison study}},
author = {Yangjun Liu and Sara Hägg and Isabell Brikell and Zheng Chang and Ralf Kuja-Halkola and Brian M. D’Onofrio and Henrik Larsson and Paul Lichtenstein and Erik Pettersson},
journal = {Molecular Psychiatry},
year = {2026},
month = jul,
doi = {10.1038/s41380-026-03769-z},
url = {https://doi.org/10.1038/s41380-026-03769-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Associations of general and specific psychopathology factors by age 35 with dementia after age 50: a Swedish population-based sibling comparison study
AU - Yangjun Liu
AU - Sara Hägg
AU - Isabell Brikell
AU - Zheng Chang
AU - Ralf Kuja-Halkola
AU - Brian M. D’Onofrio
AU - Henrik Larsson
AU - Paul Lichtenstein
AU - Erik Pettersson
PY - 2026
DA - 2026/07/24
JO - Molecular Psychiatry
DO - 10.1038/s41380-026-03769-z
UR - https://doi.org/10.1038/s41380-026-03769-z
AB - Multiple psychiatric disorders are associated with later dementia, but it remains unclear whether these associations reflect a shared liability toward all psychiatric conditions (general psychopathology factor) or diagnosis-specific effects (specific psychopathology factors). In this Swedish register-based cohort study, we investigated these questions while adjusting for familial confounding shared by siblings (N = 2 543 621 individuals, 1 485 880 full-sibling pairs). Exposures were (i) six psychiatric diagnoses recorded by age 35 and (ii) a latent bifactor model fit to these diagnoses that identified one general and three specific (internalizing, externalizing, and psychotic) psychopathology factors. Outcomes were all-cause dementia and Alzheimer’s disease recorded after age 50. For observed psychiatric diagnoses, we estimated between-individual (HR) and within-sibling hazard ratios (HRwn) using Cox regression; for latent factors, we estimated between-individual (OR) and within-sibling odds ratios (ORwn) using exploratory structural equation modelling. All psychiatric diagnoses were significantly associated with increased risk of all-cause dementia (HR range 2.03–3.59; HRwn range 1.72–2.94) and Alzheimer’s disease (HR range 1.89–3.47; HRwn range 1.77–3.22). These associations were largely attributable to the general psychopathology factor, even after adjusting for familial confounding (ORwn with 95% CI: 1.25 [1.17–1.32] for dementia; 1.24 [1.16–1.32] for Alzheimer’s disease). After accounting for the general factor, only the psychotic-specific factor remained associated (ORwn with 95% CI: 1.20 [1.07–1.36] for dementia; 1.20 [1.06–1.37] for Alzheimer’s disease). These results suggest that liability toward general psychopathology and, independently, psychotic conditions, by early adulthood might be early markers of increased dementia risk and targets for timely identification and prevention.
SN - 1359-4184
SN - 1476-5578
ER -