Alzheimer disease-associated pseudobulbar affect conferred a higher risk of depression (68.7% vs 34.7%; HR=2.52) and anxiety (48.8% vs 24.9%; HR=1.98) than stroke-associated PBA.
Does the risk of depressive episodes and anxiety disorders differ between stroke-associated and Alzheimer disease-associated pseudobulbar affect?
Alzheimer disease-associated pseudobulbar affect confers a significantly higher and earlier risk of subsequent depression and anxiety compared to stroke-associated pseudobulbar affect.
Introduction: Pseudobulbar affect (PBA) is a disorder of emotional expression associated with neurological diseases, including stroke and Alzheimer disease. Depression and anxiety frequently co-occur, but whether psychiatric outcomes differ by neurological etiology remains unclear. Objective: To compare the risk and timing of depressive episodes and anxiety disorders in stroke-associated versus Alzheimer disease-associated PBA. Methods: We conducted a retrospective cohort study using the TriNetX Global Health Research Network (2020 to 2025). Two mutually exclusive cohorts were identified: PBA with stroke and PBA with Alzheimer disease. Outcomes were depressive episode (ICD-10-CM F32) and anxiety disorder, unspecified (ICD-10-CM F41.9), occurring after PBA diagnosis. One-to-one propensity score matching was performed for age, sex, race, and ethnicity. Kaplan-Meier analyses and Cox proportional hazards models assessed risk and timing. Results: After matching, 1074 patients per cohort were included for depression analysis. Depression occurred in 68.7% of Alzheimer disease-PBA versus 34.7% of stroke-PBA (absolute risk difference 34.0%, P <0.001; HR=2.52, 95% CI: 2.22-2.86). For anxiety (n=946 per cohort), rates were 48.8% versus 24.9% (absolute risk difference 23.9%, P <0.001; HR=1.98, 95% CI: 1.70-2.30). Conclusion: Alzheimer disease-associated PBA confers a higher and earlier risk of depression and anxiety, supporting enhanced psychiatric screening in neurodegenerative disease.
Dereschuk et al. (2026) studied this question. Alzheimer disease-associated pseudobulbar affect conferred a higher risk of depression (68.7% vs 34.7%; HR=2.52) and anxiety (48.8% vs 24.9%; HR=1.98) than stroke-associated PBA.