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

这一拟议的行政补充将探讨晚年抑郁症与认知能力的关联， 衰退和认知诊断。我们建议增加广泛的临床和神经心理学措施 用于R 01 MH 121619病理生理学指标[ADRD的血浆生物标志物，包括血浆淀粉样蛋白-b 肽42/40，血浆磷酸化tau 181（p-tau 181），神经丝轻链（NFL），胶质细胞酸性蛋白 蛋白（GFAP）]、分子衰老和慢性炎症负荷[衰老相关分泌 表型蛋白质组（SASP）]，以及每个参与者的认知分类和诊断。在 结合父R 01中已收集的数据，通过本补充获得的数据将 用于未来的R 01，旨在：1）确认LLD发作对ADRD风险的累积效应， 分子衰老和慢性炎症负荷的调节作用;和2）纵向测试效果 抗抑郁治疗对ADRD生物标志物、分子衰老、炎症标志物和认知功能的影响 包括认知诊断在内的衰退（例如，MCI，痴呆）。本建议书对NOT-AG-22-025的响应如下： 1)它在已经支持的研究范围内; 2）它专注于AD和AD相关痴呆症 （ADRD）通过将AD血浆生物标志物添加到已经研究的现有病症（LLD）中; 3）它将刺激 通过引起对常见和可改变风险的关注，导致ADRD进展的额外活动 因素（LLD），并为未来探索LLD与 炎症和AD/ADRD风险。鉴于我们在母公司的成功招募，1年期设计是可行的 R 01，招募，使我们能够确定相当数量的老年参与者， LLD.此外，本补充文件中提出的措施已经制定和测试， 合作者和共同研究者（托马斯卡里卡里博士和布雷诺·迪尼兹博士）就这一提议进行了广泛的研究。 最后，合作研究者巴特斯博士有丰富的经验，领导和进行认知诊断 基于匹兹堡大学ADRC程序的裁决。 1

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