Relationship Between SSRI Exposure During Later Life and Clinical and Neuropathological Correlates of Dementia

Objectives While depression is a risk factor for dementia, few studies examining the association between selective serotonin reuptake inhibitors (SSRIs) and dementia risk have controlled for confounding major depression and none to our knowledge have examined neuropathological outcomes. We examined the association between continuation of SSRIs in older adults with a lifetime history of depression and progression of cognitive and functional impairment, depression, and neuropathologic correlates of dementia. Design This retrospective cohort study analyzed data from the National Alzheimer’s Coordinating Center. Participants Participants aged 55 years or older were required to have clinician documented lifetime history of depression (n = 688). 463 (67.3%) reported continued SSRI use at every study visit prior to death. Measurements Primary clinical outcomes included the Clinical Dementia Rating-Sum of Boxes (CDR-SB), Functional Activities Questionnaire (FAQ), and the 15-item Geriatric Depression Scale (GDS-15). Neuropathological outcomes included assessments of Alzheimer’s Disease (AD) pathology and cerebrovascular changes relevant to Vascular dementia (VaD). Results Continued SSRI use during later life was associated with a significantly slower increase on the CDR-SB compared to discontinuation of SSRIs. Rates of change on the FAQ and GDS-15 did not differ significantly between groups. While rates of AD pathology did not differ significantly between groups, continued SSRI use was associated with significantly lower rates of lacunes/infarcts on autopsy after controlling for smoking years and hypertension. Conclusions Persistent use of SSRIs prior to death was associated with decreased progression of cognitive impairment and a nearly 50% reduction of lacunes/infarcts on autopsy. Our study is the first of our knowledge to identify associations between SSRI exposure in later life and neuropathological changes relevant to VaD on autopsy, which is considered the gold standard of diagnosis.