Sex-specificities in anxiety and depressive symptoms across the lifespan and their links with multimodal neuroimaging

Background: Anxiety and depressive symptoms are associated with impaired well-being, higher risk of developing psychoaffective disorders and are risk factors for Alzheimer's disease (AD). To further understand their relevance and the mechanisms underlying their link with AD, our aims were to assess how anxiety and depressive symptoms changed with age and related to AD neuroimaging biomarkers across the adult lifespan, while also exploring sex specificities. Methods: 210 cognitively normal participants aged 19-86 years (101 men, 109 women) completed assessments of anxiety and depressive symptoms with the STAI-A and MADRS respectively, and neuroimaging measurements including structural MRI, FDG-PET and amyloid-PET. 167 of those were followed-up over 1.5-3 years. Multiple regressions were performed to assess the links between anxiety or depressive symptoms versus age, global cognition or each imaging modality, both cross-sectionally and longitudinally; and general linear models we used to test the interactive effect of sex on these associations. Results: Depressive symptoms decreased with age, while anxiety symptoms increased only among women. Higher anxiety symptoms were associated with lower grey matter (GM) volume and glucose metabolism, with an interaction of sex, this relationship being significant only in women. Longitudinally, only low baseline GM volume predicted an increase in anxiety symptoms with time. Limitations: Only 43% of participants reported depressive symptoms. Despite additional analyses, the low vari-ability in the measure might have prevented us from detecting subtle changes. Conclusions: This study emphasizes the need to consider anxiety symptoms in assessments for dementia risk, particularly in women.

Automated summary

The study found that depressive symptoms decrease with age, while anxiety symptoms only increase in women. Higher anxiety symptoms are associated with lower gray matter volume and glucose metabolism, with an interaction of sex in this relationship, which is significant only in women. Longitudinally, only low baseline gray matter volume predicts an increase in anxiety symptoms over time.