Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

INTRODUCTION: Higher neuroticism might be associated with dementia risk. Here we investigated modification by genetic predisposition to dementia, mediation by mental health and vascular conditions, neuroimaging outcomes, and cognitive function. METHODS: Cox proportional-hazards models were used to assess the association between neuroticism score and incident dementia over up to 15 years in 1,74,164 participants. Cross-sectional analyses on dementia-related neuroimaging outcomes and cognitive function were conducted in 39,459 dementia-free participants. RESULTS: Higher neuroticism was associated with an 11% higher risk of incident dementia, especially vascular dementia (15% higher risk), regardless of genetic predisposition to dementia. Mental and vascular conditions mediated the association of neuroticism with all-cause dementia and vascular dementia. Neuroticism was associated with higher cerebrovascular pathology, lower gray matter volume, and worse function across multiple cognitive domains. DISCUSSION: Neuroticism could represent a risk factor for dementia, and vascular and mental health might drive these associations. HIGHLIGHTS: Neuroticism was associated with an increased risk of incident all-cause dementia, particularly vascular dementia. Associations were not modified by genetic predisposition to dementia. Associations were largely mediated by mental and vascular conditions. Neuroticism was associated with increased cerebrovascular pathology and lower gray matter volume. Neuroticism was associated with worse function across multiple cognitive domains.

Original publication

DOI

10.1002/alz.14071

Type

Journal article

Journal

Alzheimers Dement

Publication Date

10/07/2024

Keywords

UK Biobank, apolipoprotein E, cognitive function, dementia, genetics, longitudinal, mediation, neuroimaging, neuroticism, polygenic risk