Association of neuroticism with incident dementia and cognitive function: 26-year follow-up of EPIC-Norfolk study.

BACKGROUND: Neuroticism is a stable personality trait associated with increased vulnerability to mental and physical disorders. This study examined whether neuroticism is associated with the risk of dementia, particularly across the adult life course and over long-term follow-up. METHODS: We analysed data from 19,678 dementia-free participants (mean [standard deviation, SD] age, 60.8 [9.3] years) who had neuroticism assessed between 1996 and 2000. Incident dementia was identified via linked hospital inpatient, mental health and mortality records through 2022. Cox proportional hazards models estimated hazard ratios (HRs) per 1-SD increase in neuroticism. Secondary analyses examined interactions, mediation and associations with cognitive performance on eight tests. RESULTS: Over a median follow-up of 22.7 years, 2488 participants developed dementia. Neuroticism was associated with increased dementia risk in a dose-response manner (HR per 1-SD: 1.14; 95% CI: 1.10-1.19). The association persisted even after ≥20 years of follow-up (1.09 [1.01-1.17]) and across baseline ages 41-60 (1.16 [1.04-1.30]), 60-70 (1.11 [1.04-1.18]) and 70-81 years (1.14 [1.07-1.22]). Associations were stronger among APOE ε4 carriers and heavy drinkers, and may be partly explained by depression, hypertension and ischaemic heart disease. Higher neuroticism was linked to poorer cognitive function, particularly episodic memory and to impairment across more cognitive domains. DISCUSSION: Neuroticism was associated with increased long-term dementia risk and poorer cognitive performance across mid- and later life, supporting its role in disease development rather than merely reflecting prodromal symptoms. Addressing vascular and mental health in high-neuroticism individuals may offer opportunities for dementia risk reduction.