Psychiatric symptoms and alzheimer's disease: Depression-anxiety comorbidity effects and their neurobiological mediating mechanisms.

Journal of affective disorders 2026

Yang J, Xue W, Zheng W, Zhang H, Tang C

Abstract

BACKGROUND: Depression and anxiety are common in Alzheimer’s disease (AD), but their mechanisms of impact on disease progression remain unclear. This study investigates the relationships between psychiatric symptoms and AD, exploring potential neurobiological mediating mechanisms. METHODS: The study analyzed 6209 participants divided into four groups: AD control, AD with depression, AD with anxiety, and AD with comorbid depression and anxiety. Multivariate regression and structural equation modeling assessed the impact of psychiatric symptoms on AD onset, examining 8 potential mediating variables: tau pathology, amyloid pathology (CERAD score, Thal score), brain weight, cortical atrophy, hippocampal atrophy, Lobar score and APOE genotype, while controlling for age, gender, and education. RESULTS: Both depressive (β = -1.8 years) and anxiety symptoms (β = -1.5 years) were associated with earlier AD onset, with a more significant effect when coexisting (β = -2.3 years). Depressive symptoms primarily affected executive function through cortical atrophy (32 %) and tau pathology (24 %), while anxiety symptoms mainly influenced memory function through hippocampal atrophy (61 %). The APOE ε4 allele significantly moderated these relationships, with more pronounced effects in ε4 carriers. Subgroup analyses showed more evident impacts in females and late-onset AD. CONCLUSION: The study provides evidence that depressive and anxiety symptoms are associated with earlier AD onset and affect cognitive function through specific neuropathological pathways. These findings highlight the importance of screening and treating psychiatric symptoms in AD patients and suggest potential intervention strategies.

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