Toward Prevention of Mild Cognitive Impairment in Older Adults With Depression: An Observational Study of Potentially Modifiable Risk Factors

Objective: Late-life depression has been associated with increased risk of mild cognitive impairment (MCI) and dementia. Predictors of increased risk are incompletely understood. Identification of potentially modifiable risk factors could facilitate prevention of MCI and dementia. This study aimed to determine which clinical characteristics are associated with increased risk of MCI among older adults with depression and normal cognition at baseline. Methods: Data from the National Alzheimer's Coordinating Center dataset were used. Study participants who attended a participating Alzheimer's Disease Center from September 2005 through September 2017 with normal cognition and a history of clinically defined depression (broadly based on DSM criteria) were followed until first diagnosis of MCI (or dementia when MCI was not diagnosed). Results: A total of 2,655 study participants were followed for a median duration of 41.8 months. Of these, 586 (22.1%) developed either MCI (n = 509, 19.2%) or dementia (n = 77, 2.9%). In survival analyses, cognitive decline was associated with age, sex, education, baseline cognition, and several potentially modifiable risk factors including vascular risk factors, hearing impairment, vitamin B12 deficiency, active depression within the last 2 years, and increased severity of depression. In an adjusted survival analysis, the only variables that remained significantly associated with development of MCI or dementia were female sex (HR = 0.72; 95% CI, 0.59-0.88), higher education (HR = 0.96; 95% CI, 0.93-0.99), and higher baseline cognition (HR = 0.87; 95% CI, 0.82-0.93), which were associated with reduced risk, and older age (HR = 1.07; 95% CI, 1.05-1.08), active depression within the last 2 years (HR = 1.41; 95% CI, 1.15-1.74), and increased severity of depression (HR = 1.05; 95% CI, 1.02-1.09), which were associated with increased risk. Conclusions: Development of MCI is associated with several potentially modifiable risk factors in older adults with depression. Future studies should determine whether active management of risk factors could reduce incidence of MCI in this vulnerable population.