Posttraumatic Stress Disorder, Health-Related Social Needs, and Cognitive Outcomes in US Veterans

Importance: Posttraumatic stress disorder (PTSD) and health-related social needs (HRSNs) have been associated with cognitive decline, but their joint associations with mild cognitive impairment (MCI), Alzheimer disease (AD), and AD-related dementias (ADRD) are unclear. Objective: To evaluate the independent and joint associations of PTSD and HRSNs with incident MCI, AD, and ADRD and to assess additive and multiplicative interaction. Design, Setting, and Participants: Retrospective cohort study using 2015 to 2024 National Veterans Health Administration (VHA) electronic health record data. Participants were veterans aged 55 to 100 years with a qualifying VHA encounter in 2015 and no preindex MCI, AD, or ADRD, followed up through December 31, 2024. Exposures: Time-varying PTSD, defined by at least 2 coded encounters on different dates, and time-varying HRSNs across 9 domains identified from structured data and clinical notes using natural language processing. Main Outcomes and Measures: The primary outcome was incident composite MCI, AD, or ADRD; secondary outcomes were each component separately. Time-varying Cox models estimated adjusted hazard ratios (aHRs) and 95% CIs. Multiplicative interaction was assessed using a PTSD × HRSN product term, and additive interaction using the relative excess risk due to interaction (RERI) and attributable proportion (AP). Results: The cohort included 3 817 970 veterans (mean [SD] age, 70.3 [9.1] years; 3 664 349 [96.0%] male), of whom 270 282 (7.1%) met the composite outcome with median (IQR) follow-up of 8.84 (5.02-9.03) years for the composite outcome. PTSD (aHR, 1.33; 95% CI, 1.32-1.35) and HRSNs (aHR, 2.17; 95% CI, 2.13-2.20) were independently associated with the composite outcome. Compared with neither exposure, aHRs were 2.14 (95% CI, 2.11-2.17) for HRSNs only, 1.13 (95% CI, 1.07-1.19) for PTSD only, and 2.87 (95% CI, 2.82-2.92) for both exposures. Multiplicative interaction was observed for the composite outcome (aHR, 1.19; 95% CI, 1.13-1.26), with positive additive interaction (RERI, 0.61; 95% CI, 0.54-0.67; AP, 0.21; 95% CI, 0.19-0.23). Additive interaction was observed for MCI and ADRD but not AD; multiplicative interaction was observed for ADRD but not MCI or AD. Conclusions and Relevance: In this cohort study, PTSD and HRSNs were independently associated with incident cognitive outcomes, and co-occurring PTSD and HRSNs may identify veterans with higher observed hazards of cognitive impairment and dementia.