Carrie D Johnston1, Eugenia L Siegler2, Michelle C Rice3, Heather M Derry-Vick2,4, Katie C Hootman5, Yuan-Shan Zhu5,6, Chelsie O Burchett2,7, Mary E Choi3, Marshall J Glesby1,5. 1. Division of Infectious Diseases, Weill Cornell Medicine, New York, NY. 2. Division of Geriatrics and Palliative Medicine, Weill Cornell Medicine, New York, NY. 3. Division of Nephrology and Hypertension, Weill Cornell Medicine, New York, NY. 4. Currently, Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ. 5. Clinical and Translational Science Center, Weill Cornell Medicine, New York, NY. 6. Division of Endocrinology, Diabetes & Metabolism, Weill Cornell Medicine, New York, NY; and. 7. Currently, Department of Psychology, Stony Brook University, Stony Brook, NY.
Abstract
BACKGROUND: Older people with HIV experience more comorbidities and geriatric syndromes than their HIV-negative peers, perhaps due to residual inflammation despite suppressive antiretroviral therapy. Cell-free mitochondrial DNA (cfmtDNA) released during necrosis-mediated cell death potentially acts as both mediator and marker of inflammatory dysregulation. Thus, we evaluated plasma cfmtDNA as a potential biomarker of geriatric syndromes. METHODS: Participants underwent the Montreal Cognitive Assessment (MoCA), frailty testing, and measurement of plasma cfmtDNA by qPCR and inflammatory markers including C-reactive protein, interleukin-6 (IL-6), interferon gamma, and tumor necrosis factor alpha in this cross-sectional study. RESULTS: Across 155 participants, the median age was 60 years (Q1, Q3: 56, 64), one-third were female, and 92% had HIV-1 viral load <200 copies/mL. The median MoCA score was 24 (21, 27). The plasma cfmtDNA level was higher in those with cognitive impairment (MoCA <23) ( P = 0.02 by the t test) and remained significantly associated with cognitive impairment in a multivariable logistic regression model controlling for age, sex, race, CD4 T-cell nadir, HIV-1 viremia, and depression. Two-thirds of participants met the criteria for a prefrail or frail state; higher plasma cfmtDNA was associated with slow walk and exhaustion but not overall frailty state. Cognitive dysfunction was not associated with C-reactive protein, IL-6, interferon gamma, or tumor necrosis factor alpha, and frailty state was only associated with IL-6. CONCLUSIONS: Plasma cfmtDNA may have a role as a novel biomarker of cognitive dysfunction and key components of frailty. Longitudinal investigation of cfmtDNA is warranted to assess its utility as a biomarker of geriatric syndromes in older people with HIV.
BACKGROUND: Older people with HIV experience more comorbidities and geriatric syndromes than their HIV-negative peers, perhaps due to residual inflammation despite suppressive antiretroviral therapy. Cell-free mitochondrial DNA (cfmtDNA) released during necrosis-mediated cell death potentially acts as both mediator and marker of inflammatory dysregulation. Thus, we evaluated plasma cfmtDNA as a potential biomarker of geriatric syndromes. METHODS: Participants underwent the Montreal Cognitive Assessment (MoCA), frailty testing, and measurement of plasma cfmtDNA by qPCR and inflammatory markers including C-reactive protein, interleukin-6 (IL-6), interferon gamma, and tumor necrosis factor alpha in this cross-sectional study. RESULTS: Across 155 participants, the median age was 60 years (Q1, Q3: 56, 64), one-third were female, and 92% had HIV-1 viral load <200 copies/mL. The median MoCA score was 24 (21, 27). The plasma cfmtDNA level was higher in those with cognitive impairment (MoCA <23) ( P = 0.02 by the t test) and remained significantly associated with cognitive impairment in a multivariable logistic regression model controlling for age, sex, race, CD4 T-cell nadir, HIV-1 viremia, and depression. Two-thirds of participants met the criteria for a prefrail or frail state; higher plasma cfmtDNA was associated with slow walk and exhaustion but not overall frailty state. Cognitive dysfunction was not associated with C-reactive protein, IL-6, interferon gamma, or tumor necrosis factor alpha, and frailty state was only associated with IL-6. CONCLUSIONS: Plasma cfmtDNA may have a role as a novel biomarker of cognitive dysfunction and key components of frailty. Longitudinal investigation of cfmtDNA is warranted to assess its utility as a biomarker of geriatric syndromes in older people with HIV.
Authors: Ziad S Nasreddine; Natalie A Phillips; Valérie Bédirian; Simon Charbonneau; Victor Whitehead; Isabelle Collin; Jeffrey L Cummings; Howard Chertkow Journal: J Am Geriatr Soc Date: 2005-04 Impact factor: 5.562
Authors: Kristine M Erlandson; Kunling Wu; Susan L Koletar; Robert C Kalayjian; Ronald J Ellis; Babafemi Taiwo; Frank J Palella; Katherine Tassiopoulos Journal: J Infect Dis Date: 2017-03-15 Impact factor: 5.226
Authors: Anna Picca; Flora Guerra; Riccardo Calvani; Cecilia Bucci; Maria Rita Lo Monaco; Anna Rita Bentivoglio; Hélio José Coelho-Júnior; Francesco Landi; Roberto Bernabei; Emanuele Marzetti Journal: Int J Mol Sci Date: 2019-02-13 Impact factor: 5.923