Recurrence markers, cognitive burden and neurobiological homeostasis in latelife depression (REMBRANDT) - Supplement

这一建议的行政补充将探讨晚年抑郁症与认知能力的关系

This proposed administrative supplement will explore the association of late-life depression with cognitive decline and cognitive diagnoses. We propose to add to the extensive clinical and neuropsychological measures used in R01 MH121619 measures of pathophysiology [plasma biomarkers of ADRD including plasma amyloid-b peptides 42/40, plasma phosphorylated tau 181 (p-tau181), neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP)], molecular senescence and chronic inflammatory burden [senescence-associated secretory phenotype proteomic panel (SASP)], as well as cognitive classification and diagnosis of every participant. In conjunction with the data already collected in the parent R01, the data obtained through this supplement will be used for a future R01 designed: 1) to confirm the cumulative effect of LLD episodes on ADRD risk and the moderating role of molecular senescence and chronic inflammatory burden; and 2) test longitudinally the effect of antidepressant treatment on ADRD biomarkers, molecular senescence, inflammatory markers, and cognitive decline including cognitive diagnoses (e.g., MCI, dementia). This proposal is responsive to NOT-AG-22-025 as: 1) it is within the scope of the research already supported; 2) it is focused on AD and AD related dementias (ADRD) by adding AD plasma biomarkers to the existing condition already studied (LLD); 3) it will stimulate additional activity leading to progress on ADRD by drawing attention toward a common and modifiable risk factor (LLD) and by laying the groundwork for future exploration of mechanisms connecting LLD with inflammation and risk of AD/ADRD. The 1-year design is feasible given our successful recruitment in the parent R01, recruitment which allows us to identify a significant number of older participants with current and remitted LLD. Additionally, the measures proposed in this supplement have already been developed and tested extensively by collaborators and co-investigators on this proposal (Drs. Thomas Karikari and Breno Diniz). Finally, co-investigator Dr. Butters has substantial experience leading and conducting cognitive diagnostic adjudications based on the University of Pittsburgh ADRC procedures. 1