Comorbidity of undiagnosed mood symptoms with dementia risk in multi-regional multi-ethnic adults: evidence from epidemiological findings and plasma metabolites.

AIMS: To investigate the association of midlife and late-life undiagnosed mood symptoms, especially their comorbidity, with long-term dementia risk among multi-regional and ethnic adults.

METHODS

The prospective study used data from the UK Biobank (N = 142,670; mean follow-up 11.0 years) and three Asian studies (N = 1,610; mean follow-up 4.4 years). Undiagnosed mood symptoms (manic symptoms, depressive symptoms and comorbidity of depressive and manic symptoms) and diagnosed mood disorders (depression, mania and bipolar disorders) were classified. Plasma levels of 168 metabolites were measured. The association between undiagnosed mood symptoms and 12-year dementia (including subtypes) risk and domain-specific cognitive function was examined. The contribution of metabolites in explaining the association between symptom comorbidity and dementia risk was estimated.

RESULTS

Undiagnosed mood symptoms were prevalent (11.4% in the UK cohort and 31.2% in Asian cohorts) among 1,462 (1.0%) and 74 (19.4%) participants who developed dementia. Comorbidity of undiagnosed mood symptoms was associated with higher dementia risk (sub-distribution hazard ratios = 9.46; 95% confidence interval = 4.07-21.97), especially Alzheimer's disease, and with worse reasoning ability, poorer numeric memory and metabolic dysfunction. Glucose and total Esterified Cholesterol explained 9.1% of the association between symptom comorbidity and dementia, with most of the contribution being from glucose (6.8%).

CONCLUSIONS

Comorbidity of undiagnosed mood symptoms was associated with a higher cumulative risk of dementia in the long term. Glucose metabolism could be implicated in the development of mood disorders and dementia. The distinctive pathophysiological mechanism between psychiatric and neurodegenerative disorders warrants further exploration.