Abstract
IntroductionDepression, anxiety, and sleep disturbances are modifiable neuropsychiatric conditions, yet their trajectories and combined impact on dementia subtypes remain unclear.MethodsThis 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).ResultsDuring 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.ConclusionsDepression 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.</p>