Late-life depression (LLD) is characterized by repeated recurrent depressive episodes even with maintenance treatment. It is unclear what clinical and cognitive phenotypic characteristics present during remission predict future recurrence.

Participants (135 with remitted LLD and 69 comparison subjects across three institutions) completed baseline phenotyping, including psychiatric, medical, and social history, psychiatric symptom and personality trait assessment, and neuropsychological testing. Participants were clinically assessed every two months for two years while receiving standard antidepressant treatment. Analyses examined group differences in phenotypic measure using general linear models. Concurrent associations between phenotypic measures and diagnostic groups were examined using LASSO logistic regression.

Sixty (44%) LLD participants experienced a relapse over the two-year period. Numerous phenotypic measures across all domains differed between remitted LLD and comparison participants. Only residual depressive symptom severity, rumination, medical comorbidity, and executive dysfunction significantly predicted LLD classification. Fewer measures differed between relapsing and sustained remission LLD subgroups, with the relapsing group exhibiting greater antidepressant treatment intensity, greater fatigue, rumination, and disability, higher systolic blood pressure, greater life stress and lower instrumental social support. Relapsing group classification was informed by antidepressant treatment intensity, lower instrumental social support, and greater life stress.

A wide range of phenotypic factors differed between remitted LLD and comparison groups. Fewer measures differed between relapsing and sustained remission LLD subgroups, with less social support and greater stress informing vulnerability to subsequent relapse. This research suggests potential targets for relapse prevention and emphasizes the need for clinically translatable relapse biomarkers to inform care.

Higher education is strongly associated with better cognitive function in older adults. Previous research has also showed that positive psychosocial factors, such as selfefficacy and emotional and instrumental support, are beneficial for late-life cognition. There is prior evidence of a buffering effect of self-efficacy on the relationship between educational disadvantage and poor cognition in older adults, however it is not known if other psychosocial factors modify the schooling-cognition relationship. We hypothesized that higher levels of emotional and instrumental support will diminish the association between lower education and lower cognitive test scores among older adults.

553 older adults without dementia (42.1% non-Latinx Black, 32.2% non-Latinx White, 25.7% Latinx; 63.2% women; average age 74.4 (SD 4.3)) from the Washington Heights-Inwood Columbia Aging Project. Neuropsychological tests assessed four cognitive domains (language, memory, psychomotor processing speed, and visuospatial function). Self-reported emotional and instrumental support were assessed with measures from NIH Toolbox. Linear regression estimated interactions between education and the two support measures on cognition in models stratified by cognitive domain and racial and ethnic group. Covariates included age, sex/gender, and chronic health conditions (e.g. heart disease, stroke, cancer, etc.).

Education was associated with cognition across racial and ethnic groups. For every one year of schooling, the processing speed z-score composite was 0.33 higher among Latinx participants, 0.10 among non-Latinx Black participants, and 0.03 higher among non-Latinx White participants. The education-cognition relationship was generally similar across cognitive domains with larger effects in non-Latinx Black and Latinx participants than in White participants. Low education was associated with slower processing speed among Black participants with low emotional support (B = 0.224, 95% CI [0.014, 0.096]), but there was no association between low education and processing speed among Black older adults with high levels of emotional support (beta for interaction = -.142, 95% CI [-0.061, -0.001]). A similar pattern of results was observed for instrumental support (beta for interaction = -.207, 95% CI [-0.064, 0.010]). There were no interactions between support and education on other cognitive domains or among Latinx and White participants.

We found that higher levels of emotional and instrumental support attenuate the detrimental effect of educational disadvantages on processing speed in older Black adults. This may occur via benefits of social capital, which provides access to health resources and knowledge, increased social interaction, an emotional outlet allowing the ability to better cope with stress. Longitudinal analyses are needed to examine temporal patterns of associations. In addition, improving equitable access to high quality schools will improve later-life cognitive outcomes for future generations of older adults. However, for the growing number of Black older adults who will not experience the benefits of structural improvements in the education system, emotional and instrumental support may represent a modifiable psychosocial factor to reduce their disproportionate burden of cognitive morbidity.