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Cognitive Impairment among HIV-Infected
Men with Longitudinal Follow-ups
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There are several studies in this report on the issue of does cognitive impairment (CI) occur for HIV+ more than for HIV-, is HIV responsible for this, does it contribute, does HIV accelerate CI in older HIV over 55. These questions were addressed in numerous studies over the years and at CROI several years ago there were a bunch of studies on this question with conflicting out comes but generally that HIV does cause CI but whether its accelerated or not was a difference of between studies, I think this remains a question where opinions differ. There has been a controversy over what methods are used to collect CI data and as you can see below in Table 2 where 3 different methods were used, there was no difference in CI by serostatus & a big difference in CI between Frascati & Gissen compared to MNC. This MACS study immediatelty below found HIV+ did not have greater CI. At CROI there was a poster (in this report below) from the same MACS published study reporting: "The rates of impairment and mean T-scores across visits did not differ between the HIV- and HIV+ men.
This newly developed LMNC successfully controlled the FDR at the pre-specified level across study visits. This means that the estimates of impairment over repeated testing is more accurate than simply applying cross-sectional criteria multiple times".
Below prior to the CROI poster report I included numerous studies but not all finding HIV is associated & a cause for CI at greater rates than HIV- - you will remember CHARTER study found nadir CD4 associated with worse CI in HIV+. The Goodkin MACS study linked to below found accelerated CI in older HIV+ in MACS.
COBRA - Increased brain-predicted aging in treated HIV disease: controls (n = 105) were recruited from 2 sites, London and Amsterdam as part of the Comorbidity in Relation to AIDS (COBRA) collaboration.....average age was 56 (50-62)....We observed lower brain volumes in HIV-positive individuals, presumably due to atrophy" http://www.natap.org/2017/HIV/092217_02.htm
CROI 2020
Zheng Wang1, Yu Cheng1, Eric C. Seaberg2and James T. Becker1,for the Neuropsychology Working Group of the Multicenter AIDS Cohort Study
serostatus was not associated with cognitive impairment.
Download the PDF here
HIV-associated neurocognitive disorder 2013 Lant Inf Disease (David Clifford, Beau Ances)....Comorbid disorders contribute to neurocognitive impairment but do not fully explain......Cardiovascular disease and infl ammatory markers are associated with impairment.....http://www.natap.org/2013/HIV/PIIS147330991370269X.pdf
Goodkin is his study published in 2017 controlled for comorbidities and diabetes: Goodkin MACS Study - HIV prematurely ages the brain - new study & Commentary - (07/19/17).....
"In an Article in The Lancet HIV,1 Karl Goodkin and colleagues answer the controversial question of whether chronic HIV infection leads to premature ageing in the combination antiretroviral therapy (ART) era: it does." Commentary by Bruce Brew & Lucette Cysique
HIV Infection and Aging Independently Affect Brain Function as Measured by Functional Magnetic Resonance Imaging - BRIEF REPORT - (01/25/09)
Functional brain demands in HIV-positive subjects were equivalent to those of HIV-negative subjects who were 15-20 years older.....HIV infection was equivalent to a 21-year increase in brain age, compared with HIV-negative control subjects. This same group 8 years later from Wash U Ances et all reported this just below declaring HIV brain damage aging was not accelerated.
CHARTER:
Increased Rate of HIV Neurocognitive Impairment (NCI) among non-AIDS Cases in the Post-CART versus Pre-CART era
CROI: Cognitive Trajectories in Suppressed HIV Infection Indicate Evolving Disease Activity - (02/24/17).
MIDLIFE ADIPOSITY PREDICTS COGNITIVE DECLINE IN
THE MULTICENTER AIDS COHORT STUDY (MACS)......http://www.natap.org/2019/CROI/croi_61.htm
Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Over Age 60 - (07/19/17)
MACS: HIV Accelerates Brain Damage ;
"Neurological Complications of HIV Infection" Review
http://www.natap.org/2018/HIV/020618_01.htm
Increased Prevalence of Neurocognitive Impairment in Aging People Living With Human Immunodeficiency Virus: The ANRS EP58 HAND 55-70 Study - (02/27/20)
Accelerated Cognitive Decline Women with HIV
• CROI: Longitudinal Phenotyping of Declarative Memory Among Women Living with HIV - (01/24/20)
In the HIV+ AA's, we identified four distinct subgroups with differential patterns of change in memory: a subgroup with minimal decline, two with accelerated decline, and a subgroup with stable impairment in learning and memory (Fig 1A). In the HIV- AA's, we identified three subgroups: one with lesser decline and two with accelerated decline (Fig 1B). In multivariable adjusted models, individuals with accelerated decline were more likely to be less educated (P<0.001) and have a history of depression (P<0.001) versus those in the minimal decline subgroups (Fig 1C). Similarly classified subgroups were identified in W/O HIV+ and W/O HIV- participants.
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Cognitive Impairment among HIV-Infected Men with Longitudinal Follow-ups
CROI 2020
Zheng Wang1, Yu Cheng1, Eric C. Seaberg2and James T. Becker1,
for the Neuropsychology Working Group of the Multicenter AIDS Cohort Study1University of Pittsburgh, Pittsburgh, PA, USA, 2The Johns Hopkins University, Baltimore, MD, USA
Abstract
To control false discovery rate (FDR) in identifying cognitive impairment among individuals infected with HIV, the multivariate normative comparisons (MNC) method has been used to account for intercorrelations among cognitive domains. However, the existing MNC is for cross-sectional data and does not account for the intercorrelations among repeated visits. That is, the best predictor of future test performance is current test performance. This work developed a novel longitudinal MNC (LMNC) to classify cognitive status for individuals with multiple visits, yielding more accurate results than naïvely applying the cross-sectional MNC to each visit.
Data used in this work were collected before April 2017 among MSM from the Neuropsychological (NP) Substudy of the Multicenter AIDS Cohort Study. Six cognitive domains were evaluated bi-/semi-annually among these men: learning, memory, executive functioning, working memory & attention, motor speed & coordination, and speed of information processing. The final analysis included data from 22,900 visits by 3,701 men (mean age 34.9, 55.0% HIV+, mean 6.2 visits, mean follow-up 8.3 yrs) with complete data from all 6 domains. T-scores, at every domain, were adjusted for race, age, education and number of tests. HIV- men without comorbidities (n=922) were treated as healthy controls, and the LMNC was used to classify cognitive impairment among HIV- and HIV+ men. Also, the cross-sectional MNC was applied to each visit with and without Benjamini-Hochberg (BH) corrections.
Among healthy controls the LMNC identified 5.5% with cognitive impairment. This suggests that the LMNC guarded FDR at the pre-determined 5% level. With the cross-sectional MNC applied with and without the BH correction, impairment rates were 19.8% and 9.5% in the healthy controls, respectively. In the HIV+ group, 7.3% men were identified as impaired with the LMNC, compared with 16.4% and 29.5% using the MNC method (with and without the BH correction). In the HIV- group, the rates are 9.3%, 11.7% and 24.1%, respectively. The rates of impairment and mean T-scores across visits did not differ between the HIV- and HIV+ men.
This newly developed LMNC successfully controlled the FDR at the pre-specified level across study visits. This means that the estimates of impairment over repeated testing is more accurate than simply applying cross-sectional criteria multiple times.
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