Research Finds Dose-Dependent Link Between Neuroticism and Dementia Risk

Higher neuroticism scores are associated with an elevated risk for dementia, according to results of a study published in Alzheimer’s & Dementia.

Although previous studies have demonstrated that neuroticism (ie, personality traits of irritability, worry, self-consciousness, vulnerability, and loneliness) is associated with adverse health outcomes, relatively little is known about the relationship between neuroticism and dementia.

To this aim, investigators from the University of Oxford conducted a study using data from the United Kingdom (UK) Biobank, a large population-based cohort study that recruited individuals between 2006 and 2010. To evaluate neuroticism as a potential risk factor for dementia, the investigators evaluated participants (N=174,164) younger than 60 years of age at baseline for incident dementia (defined as the first hospital inpatient diagnosis of dementia or dementia as an underlying or contributory cause of death) and the participants were followed for up to 15 years. Neuroticism was assessed using the Eysenck Personality Questionnaire-Revised Short Form (EPQ-RS) and a subset of participants (n=39,459) underwent neuroimaging and cognitive testing.

The study participants had a mean (SD) age of 64.36 (2.96) years, 48.1% were men, and 29.8% had a normal BMI. Individuals with higher neuroticism scores were more likely to be women, smoke, have lower socioeconomic status, and have a history of depression, anxiety, diabetes, and cardiovascular disease.

During a median follow-up of 13.5 years, incident all-cause dementia occurred among 5974 individuals. Of the individuals with incident dementia, 2741 cases were of Alzheimer disease (AD) and 1364 cases were of vascular dementia (VaD).

The investigators found a dose-dependent relationship between neuroticism scores and the risk for incident dementia, as the hazard ratio (HR) for dementia was 1.12 (95% CI, 1.01-1.24; P =.036) at an EPQ-RS score of 4 and increased to an HR of 1.72 (95% CI, 1.42-2.08; P <.001) with a neuroticism score of 12.

Every 1-point increase in neuroticism z-score increased all-cause dementia risk by 11% (HR, 1.11; 95% CI, 1.08-1.14), AD risk by 6% (HR, 1.06; 95% CI, 1.02-1.10), and VaD risk by 15% (HR, 1.15; 95% CI, 1.09-1.21).

The association between neuroticism z-score and dementia was mediated by depression (38.5%), anxiety (12.8%), ischemic heart disease (10.9%), hypertension (10.4%), and diabetes (6.0%). When stratified by dementia type, the mediating effect of depression was larger for AD (51.0%) than VaD (37.5%).

No significant interactions were observed between neuroticism scores and apolipoprotein E (APOE) genotype or non-APOE polygenic risk score.

Among the subset of individuals with neuroimaging and cognitive assessment data, neuroticism z-scores were associated with white matter hyperintensities (b, 0.02; P <.001) and total gray matter (b, -0.01; P =.038). Higher neuroticism z-scores were also associated with worse cognitive functional outcomes, specifically in complex processing speed (b, -0.05; P <.001), verbal and numerical reasoning (b, -0.03; P <.001), non-verbal reasoning (b, -0.03; P <.001), working memory (b, -0.03; P <.001), executive function in the Trail Making Test A and B (both b, -0.03; P <.001), and verbal declarative memory (b, -0.02; P <.001).

The investigators concluded, “[O]ur findings suggest that the associations between neuroticism and dementia are driven largely by mental and vascular conditions, implying that addressing the increased burden of mental and vascular health conditions in individuals with higher neuroticism could, if causal, ultimately help prevent or delay the onset of dementia.”

Study limitations include the potential underestimation of dementia prevalence, as only hospital records and death registry data were interrogated for dementia outcomes.

This article originally appeared on Psychiatry Advisor