To determine whether non-affective psychosis or depression credibly causally influence dementia risk using a design robust to reverse causation.
Approach:
Study Design: Compared AD genetic liability among dementia cases with and without prior non-affective psychosis or depression using polygenic risk scores (PRS) in the UK Biobank.
Sample Size: Included 7936 dementia cases, with 56 having non-affective psychosis and 937 having depression.
Analysis Method: Examined correlations between schizophrenia or major depressive disorder (MDD) PRS and dementia liability.
Key Findings:
Dementia cases with prior non-affective psychosis or depression had lower AD genetic liability than those without a psychiatric history (psychosis: B=−0.29, 95% CI (−0.54 to −0.05), p=0.036; depression: B=−0.12, 95% CI (−0.18 to −0.05), p=0.0004).
Findings are inconsistent with the hypothesis that psychiatric disorders are explained by prodromal dementia effects.
Excluding individuals with psychiatric diagnoses showed no negative correlations between schizophrenia or MDD liability and AD liability.
Interpretation:
The findings suggest that exposure to non-affective psychosis and depression may be associated with dementia.
Limitations:
The study may not fully account for all potential confounding factors.
The reliance on polygenic risk scores may not capture all genetic influences on dementia.
Conclusion:
The study supports the hypothesis that psychiatric disorders are associated with increased vulnerability to dementia.
