Sex Differences in the Relationship between Depressive Symptoms and Risk of Amnestic Mild Cognitive Impairment

Objective: The relationship between depressive symptoms and subsequent cognitive impairment in older adults is controversial. Sex differences and the differences in the method of categorizing depressive symptoms may contribute to the inconsistencies. The authors examined the effect of severity of baseline depressive symptoms on risk of incident amnestic mild cognitive impairment (aMCI) separately in men and women. Methods: Community-dwelling and cognitively healthy older adults (aged >= 70 years) from the Einstein Aging Study completed the 15-item Geriatric Depression Scale (GDS-15) at their baseline visit. Participants were categorized into no/low symptoms(GDS-15 score = 0-2),mild symptoms(GDS-15 score = 3-5), and moderate/severe symptoms (GDS-15 score > 6) groups. Sex-stratified Cox proportional hazards models, adjusted for age, education, and antidepressant medication, estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident aMCI as a function of depressive symptoms group. Results: We followed 572 women (mean age: 78) and 345 men (mean age: 77) for 4.2 years on average (range: 1.0-14.6 years). Ninety women and 64 men developed aMCI during follow-up. Cox models revealed that compared with no/low depressive symptoms, mild symptoms were associated with a two times greater risk of developing aMCI in men (HR: 2.22; 95% CI: 1.26-3.89) but not in women (HR: 1.26; 95% CI: 0.77-2.06). Conversely, moderate/severe depressive symptoms were associated with a two times greater risk of developing aMCI in women (HR: 1.99; 95% CI: 1.05-3.77) but not in men (HR: 0.28; 95% CI: 0.04-2.11), possibly because of low statistical power in this subgroup. Conclusion: Results indicate that mild depressive symptoms in men and moderate/severe symptoms in women may represent a marker for future cognitive impairment.