1. Association of Cognitive Outcomes and Response Status in Late Life Depression: A 12 Month Longitudinal Study David Bickford B.A., Alana Kivowitz B.A., Derek Pisner B.A., Katie Tegenkamp B.S., Ross Crothers B.A., J. Craig Nelson M.D., & R. Scott Mackin Ph.D OBJECTIVE: This study was conducted to evaluate the impact of depression outcomes on performance of specific cognitive tests after a 12 month period in participants with Late Life Major Depression (LLD). We hypothesize that LLD individuals who have reached treatment response, characterized by a 50% or greater reduction in depression severity after a 12 month period, will show improved performance on measures of information processing and show no difference in performance on cognitive measures of verbal learning and memory when compared to patients who have not reached or maintained response. BACKGROUND: Fifteen percent of adults over the age of 65 suffer from LLD. Within those individuals, up to 60% experience cognitive impairment which represents one of the most debilitating aspects of the disorder. In a previous study, our research group investigated the impact of psychotherapy on cognitive function in LLD patients 1. The results of that study showed that improvement in mood status was associated with improvement in Information Processing (IP) following 12 weeks of treatment. No improvements were observed for measures of verbal learning and memory. However, little research has looked at long-term effects of depression response over time on cognitive outcomes. The purpose of the present study is therefore to explore the effects of depression severity on cognition over a naturalistic 12 month timespan. METHODS: Assessment of Depression and Cognitive Function: Subjects: Eligibility criteria included older adults (> 65 years of age) with a diagnosis of Major Depressive Disorder (MDD) assessed with the Structured Clinical Interview for DSM-IV Disorders (SCID) diagnosis, a score of 19 or greater on the Hamilton Depression Rating Scale (HDRS), and not having dementia (Mini Mental State Exam > 24). Depression was evaluated by licensed psychologists using the SCID and criteria from the Diagnostic and Statistical Manual, 4 th edition (DSM-IV). Depression Symptom severity was evaluated using the 24-item HDRS. Depression response was coded as having a 50% or greater reduction in depression severity at 12 months relative to baseline HDRS scores. Cognitive functioning was assessed using age corrected scaled scores for the following measures at baseline assessment and a 12-month follow-up: Verbal Learning (Wechsler Memory Scale Learning Trials; WMS Learning), Memory (Wechsler Memory Scale Delayed Trial; WMS Delayed), Information Processing (Stroop Color-Word Test; Stroop-CW). DATA ANALYTIC PROCEDURE: Repeated measures mixed factorial analyses of variance (ANOVAs) were conducted between two time points– Baseline and 12-Month visits-- using IBM SPSS Statistics Pack 22.0. We also investigated any potential interactions between depression response status and the various measures of cognitive functioning assessed. Participants: Included 46 LLD individuals in an ongoing study of disability. Mean Age: 71.4 years (SD = 6.0) Mean Education: 16.1 years (SD = 2.7) Gender: 80% Female, 20% Males Mean Severity of Depressive Symptoms at baseline: 23.14 (SD = 5.5) Mean Severity of Depressive Symptoms at 12 month: 15.40 (SD = 8.0) We gratefully acknowledge grant support for this study: NIMH K08 MH081065-01, Leon Epstein Fund, the ADNI-Depression project RESULTS: At 12 months, 15 LLD participants (33%) reached 50% response status. There was no statistical difference in age, education, or gender between the response and no response groups. Individuals performed significantly better on the Stroop-CW measure at the 12 month assessment (M = 10.28, SD = 2.3) regardless of response status when compared to baseline (M = 9.24, SD = 2.8), F(1,42) = 8.84, p = 0.005) (Tables 1 & 2). Memory showed a significant interaction between time and response status, F(1,44) = 4.59, p = 0.046, while verbal learning did not achieve statistical significance, F(1,44) = 3.61, p = 0.064 (Figures 1a, 1b, & 1c). In both cases, performance by the responders increased over time. However, the “No response” group showed no significant difference between time points (Table 3). DISCUSSION: Similar to our previous findings, we found that information processing significantly increased after a 12 month naturalistic period. There was no significant interaction, however, between time and response status. Moreover, both groups’ scores increased over time, regardless of depression severity, suggesting that depression severity may not directly impact IP performance. Only the responders group improved on measures of memory, suggesting that depression may hold the potential to influence one’s performance in this domain. Additionally, cognitive outcomes may increase at a slower rate than depressive symptoms over time, and thus further research is warranted to explore the interaction between these trends. Given a longer time-span, other cognitive outcomes, along with memory, may also show improvement. CONCLUSION: Our findings suggest that memory is associated with depression severity over time. Future research should further explore the precise effects of depression severity on cognitive outcomes, while accommodating for other cognitive factors that may influence response status. Figure 1a, 1b, &1c: Cognitive Performance over a 12-month Interval SourceDFFp WMS LearningResponse Status11.300.260 Cognition over time13.070.087 Interaction13.610.064 Error44 WMS DelayedResponse Status10.520.464 Cognition over time19.000.003 Interaction14.590.046 Error44 Stroop CWResponse Status10.590.445 Cognition over time18.840.005 Interaction10.020.879 Error42 Responders/ Non-Responders Baseline12 monthMean DiffStd. err tp WMS Learning Responders12-1.600.72-2.220.031 Non-Responders120.010.500.1400.898 WMS Delayed Responders12-2.400.77-3.120.003 Non-Responders12-0.480.53-0.910.369 Table 3: Post-Hoc t-tests for Significant Interactions Poster Number: NR7-06 WMS = Wechsler Memory Scale, Stroop-CW = Stroop Color-Word Test nNo Response nResponse F p WMS Learning Baseline3111.93 (3.1)1512.00 (3.3) 0.010.949 12 Month3111.87 (2.4)1513.60 (2.6) 4.830.033 WMS Delayed Baseline3112.35 (3.0)1512.07 (4.1) 0.070.789 12 Month3112.84 (3.2)1514.47 (2.9) 2.820.100 Stroop CW Baseline299.24 (2.8)159.93 (3.4) 0.390.531 12 Month2910.28 (2.3)1510.87 (3.1) 0.260.611 References: 1. Mackin, R.S., Nelson, J.C. et al. (In Press). American Journal of Geriatric Psychiatry. Cognitive Outcomes after Psychotherapeutic Interventions for Major Depression in Older Adults with Executive Dysfunction WMS = Wechsler Memory Scale, Stroop-CW = Stroop Color-Word Test Table 1: Means of Cognitive Scores between Response Status and Time Points (N=46) Table 2: Repeated Measures, Mixed Factorial ANOVAs, and Cognition