Dataset Information

The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus.

ABSTRACT: Background:Age-related gait speed decline is accelerated in men with human immunodeficiency virus (HIV). Mitochondrial genetic variation is associated with frailty and mortality in the general population and may provide insight into mechanisms of functional decline in people aging with HIV. Methods:Gait speed was assessed semiannually in the Multicenter AIDS Cohort Study. Mitochondrial DNA (mtDNA) haplogroups were extracted from genome-wide genotyping data, classifying men aged ≥50 years into 5 groups: mtDNA haplogroup H, J, T, Uk, and other. Differences in gait speed by haplogroups were assessed as rate of gait speed decline per year, probability of slow gait speed (<1.0 m/s), and hazard of slow gait using multivariable linear mixed-effects models, mixed-effects logistic regression models, and the Andersen-Gill model, controlling for hepatitis C virus infection, previous AIDS diagnosis, thymidine analogues exposure, education, body composition, smoking, and peripheral neuropathy. Age was further controlled for in the mixed-effects logistic regression models. Results:A total of 455 HIV-positive white men aged ≥50 years contributed 3283 person-years of follow-up. Among them, 70% had achieved HIV viral suppression. In fully adjusted models, individuals with haplogroup J had more rapid decline in gait speed (adjusted slopes, 0.018 m/s/year vs 0.011 m/s/year, pinteraction = 0.012) and increased risk of developing slow gait (adjusted odds ratio, 2.97; 95% confidence interval, 1.24-7.08) compared to those with other haplogroups. Conclusions:Among older, HIV-infected men, mtDNA haplogroup J was an independent risk factor for more rapid age-related gait speed decline.

SUBMITTER: Sun J

PROVIDER: S-EPMC6093993 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus.

Sun Jing J Brown Todd T TT Samuels David C DC Hulgan Todd T D'Souza Gypsyamber G Jamieson Beth D BD Erlandson Kristine M KM Martinson Jeremy J Palella Frank J FJ Margolick Joseph B JB Kirk Gregory D GD Schrack Jennifer A JA

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20180801 5

<h4>Background</h4>Age-related gait speed decline is accelerated in men with human immunodeficiency virus (HIV). Mitochondrial genetic variation is associated with frailty and mortality in the general population and may provide insight into mechanisms of functional decline in people aging with HIV.<h4>Methods</h4>Gait speed was assessed semiannually in the Multicenter AIDS Cohort Study. Mitochondrial DNA (mtDNA) haplogroups were extracted from genome-wide genotyping data, classifying men aged ≥5 ...[more]

PMID: 29481608

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Project description:ImportanceDual decline in gait speed and cognition has been found to be associated with increased dementia risk in previous studies. However, it is unclear if risks are conferred by a decline in domain-specific cognition and gait.ObjectiveTo examine associations between dual decline in gait speed and cognition (ie, global, memory, processing speed, and verbal fluency) with risk of dementia.Design, setting, and participantsThis cohort study used data from older adults in Australia and the US who participated in a randomized clinical trial testing low-dose aspirin between 2010 and 2017. Eligible participants in the original trial were aged 70 years or older, or 65 years or older for US participants identifying as African American or Hispanic. Data analysis was performed between October 2020 and November 2021.ExposuresGait speed, measured at 0, 2, 4, and 6 years and trial close-out in 2017. Cognitive measures included Modified Mini-Mental State examination (3MS) for global cognition, Hopkins Verbal Learning Test-Revised (HVLT-R) for memory, Symbol Digit Modalities (SDMT) for processing speed, and Controlled Oral Word Association Test (COWAT-F) for verbal fluency, assessed at years 0, 1, 3, 5, and close-out. Participants were classified into 4 groups: dual decline in gait and cognition, gait decline only, cognitive decline only, and nondecliners. Cognitive decline was defined as membership of the lowest tertile of annual change. Gait decline was defined as a decline in gait speed of 0.05 m/s or greater per year across the study.Main outcomes and measuresDementia (using Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition] criteria) was adjudicated by an expert panel using cognitive tests, functional status, and clinical records. Cox proportional hazard models were used to estimate risk of dementia adjusting for covariates, with death as competing risk.ResultsOf 19 114 randomized participants, 16 855 (88.2%) had longitudinal gait and cognitive data for inclusion in this study (mean [SD] age, 75.0 [4.4] years; 9435 women [56.0%], 7558 participants [44.8%] with 12 or more years of education). Compared with nondecliners, risk of dementia was highest in the gait plus HVLT-R decliners (hazard ratio [HR], 24.7; 95% CI, 16.3-37.3), followed by the gait plus 3MS (HR, 22.2; 95% CI, 15.0-32.9), gait plus COWAT-F (HR, 4.7; 95% CI, 3.5-6.3), and gait plus SDMT (HR, 4.3; 95% CI, 3.2-5.8) groups. Dual decliners had a higher risk of dementia than those with either gait or cognitive decline alone for 3MS and HVLT-R.Conclusions and relevanceOf domains examined, the combination of decline in gait speed with memory had the strongest association with dementia risk. These findings support the inclusion of gait speed in dementia risk screening assessments.

Dataset Information

The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus.

Publications

The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus.

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