THE SENDEP STUDY: LINKING MOLECULAR SENESCENCE CHANGES TO DEPRESSION AND COGNITIVE IMPAIRMENT IN LATE LIFE

SENDEP 研究：将分子衰老变化与晚年抑郁和认知障碍联系起来

• 批准号: 10534150
• 负责人: Breno Satler Diniz
• 金额: $ 63.18万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10534150
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Anisotropy; Atrophic; Biological; Biological Markers; Biology of Aging; Brain; Brain imaging; Cell Aging; Cell Communication; Cells; Cerebrovascular Disorders; Characteristics; Chronology; Clinical; Clinical Markers; Complex; Dementia; Depressed mood; Direct Costs; Education; Elderly; Episodic memory; Facilities and Administrative Costs; Gender; Health; High Prevalence; Hippocampus; Image; Immune; Impaired cognition; Individual; Inflammatory Response; Intervention; Length; Leukocytes; Link; MAP Kinase Gene; Measures; Mediating; Medical; Mental Depression; Mental disorders; Metabolic Control; Molecular; Molecular Profiling; Names; Neurocognitive; Outcome; Participant; Pathway interactions; Pattern; Performance; Phenotype; Positioning Attribute; Premature Mortality; Prevalence; Prevention; Process; Prognosis; Proteins; Public Health; Quality of life; Risk; Sampling; Signal Pathway; Signal Transduction; System; TP53 gene; Tissues; Vascular Dementia; age related; cingulate cortex; clinical phenotype; cognitive function; cognitive performance; comorbidity; data-driven model; dementia risk; detection of nutrient; follow-up; frailty; frontal lobe; functional disability; geriatric depression; gray matter; high risk; improved; indexing; insight; learning strategy; molecular dynamics; novel; phenotypic biomarker; public health relevance; senescence; telomere; therapy development; white matter

Project Summary Late-life depression (LLD) is a common mental disorder in the elderly, with prevalence rates ranging from 1 to 5%. Recent evidence suggests that LLD is linked to age-related negative health outcomes, such as cerebrovascular disease, increased risk of Alzheimer's disease, vascular dementia, and of premature mortality. The mechanisms of LLD are complex and involve the dysregulation of different biological pathways. Understanding the interplay between the biological changes in aging and depression can provide insight into the mechanisms by which LLD increases the risk of negative health outcomes. This study proposes to evaluate the association of Senescence-Associated Secretory Phenotype (SASP) Index with different clinical phenotypes of aging (i.e., cognitive impairment) and with cellular senescence phenotype (i.e., leukocyte telomere [LT] attrition) in LLD. Finally, we will evaluate the trajectory of changes in SASP, and its relationship with cognitive performance in these individuals. Our hypotheses are that LLD individuals will show a significantly higher SASP index compared to age- and gender-matched never-depressed control subjects. SASP index will be significantly associated with greater cognitive impairment and telomere attrition in LLD subjects. We further hypothesize that an increasing or persistently higher SASP index trajectory will lead to faster cognitive decline among study participants over two years of follow-up. To our knowledge, this will be the first study to examine the association between circulating molecular senescence markers (SASP), a cellular senescence marker (LT attrition), and neurocognitive and clinical characteristics in LLD. Based on the results of this study, we will also be able to identify novel targets for the development of interventions aiming not only the treatment of depression in the elderly but also aiming the prevention of the negative outcomes related to this condition.

项目总结

项目成果

Increased Levels of Circulating Cell-Free mtDNA in the Plasma of Subjects With Late-Life Depression and Frailty: A Preliminary Study.

在患有晚期抑郁症和脆弱的受试者血浆中无细胞的循环mtDNA水平增加：一项初步研究。

• DOI: 10.1016/j.jagp.2021.07.012
• 发表时间: 2022-03
• 期刊: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
• 作者: Ampo E;Mendes-Silva AP;Goncalves V;Bartley JM;Kuchel GA;Diniz BS
• 通讯作者: Diniz BS

Neuroimaging features of depression-frailty phenotype in older adults: a pilot study.

老年人抑郁衰弱表型的神经影像学特征：一项试点研究。

• DOI: 10.1017/s1041610223000066
• 发表时间: 2023
• 期刊: International psychogeriatrics
• 影响因子: 7
• 作者: Shuster,Ethan;Miles,AmyE;Heyland,LindsayK;Calarco,Navona;Jeyachandra,Jerrold;Mansour,Salim;Voineskos,AristotleN;Steffens,DavidC;Nikolova,YuliyaS;Diniz,BrenoS
• 通讯作者: Diniz,BrenoS

Associations between locus coeruleus integrity and diagnosis, age, and cognitive performance in older adults with and without late-life depression: An exploratory study.

• DOI: 10.1016/j.nicl.2022.103182
• 发表时间: 2022
• 期刊: NEUROIMAGE-CLINICAL
• 影响因子: 4.2
• 作者: Calarco, Navona;Cassidy, Clifford M.;Selby, Ben;Hawco, Colin;Voineskos, Aristotle N.;Diniz, Breno S.;Nikolova, Yuliya S.
• 通讯作者: Nikolova, Yuliya S.

Mild cognitive impairment and major depressive disorder are associated with molecular senescence abnormalities in older adults.

• DOI: 10.1002/trc2.12129
• 发表时间: 2021
• 期刊: Alzheimer's & dementia (New York, N. Y.)
• 作者: Diniz BS;Vieira EM;Mendes-Silva AP;Bowie CR;Butters MA;Fischer CE;Flint A;Herrmann N;Kennedy J;Lanctôt KL;Mah L;Pollock BG;Mulsant BH;Rajji TK;on behalf of the PACt‐MD Study Group
• 通讯作者: on behalf of the PACt‐MD Study Group