The association between depression, anxiety, sleep disturbances and dementia: a prospective cohort study of 350,186 adults

INTRODUCTION: Depression, anxiety, and sleep disturbances are modifiable neuropsychiatric conditions, yet their trajectories and combined impact on dementia subtypes remain unclear. METHODS: This prospective cohort study included 350 ,186 dementia-free UK Biobank participants (mean age 56.5 ± 8.1 years). Depression and anxiety were classified as new onset, remitted, or persistent, and sleep quality was rated on a five-point scale and categorized as good, intermediate, or poor. Cox models estimated dementia hazard ratios (HRs). RESULTS: During a median follow-up of 8.9 years, 4 227 participants developed dementia. Both new onset and remitted depression increased the risk of ACD (HR 1.38 and 1.32, p < 0.05) and OD (HR 1.37 and 1.85, p < 0.05). Anxiety remission raised the risk of ACD (HR 1.17, p < 0.05) and AD (HR 1.29, p < 0.05), whereas new onset anxiety mainly increased ACD and OD risk (HR 1.32 and 1.36, p < 0.05). Higher mood-sleep scores of 2 or 3 were associated with markedly higher dementia risk across all subtypes. CONCLUSIONS: Depression trajectories, specifically new onset and remitted were most consistently associated with increased dementia risk, and sleep disturbances amplifies dementia risk when co-existing with mood disorders. Integrated screening and management of these neuropsychiatric factors may offer a multidimensional approach to dementia prevention.