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Neurocognition & PLWH - CROI 2021
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from Jules: Neurocognition & cognitive impairment are important comorbity concerns for PLWH. Unlike the early-pre-ART days of HIV where PLWH were much more susceptible to more severe forms of brain dysfunction, now see mild cognitive impairment commonly but more often it is not perceptible & does not impair daily functioning very much for the most part. But as PLWH age the blood brain barrier can break down further & this may increase risk for neurocognitive decline for some some. Short term memory loss, fine motor skills decline as described below re reported by older PLWH that may decline for some with age; is it progressive? we do’t know but for some it might be. How can we know for whom it might be progressive, we do not know yet. Is it HIV, is it comorbidities? Likely both contribute. There is a controversy in this field with some experts saying its the comorbidities only, some say HIV is a culprit, and some say both, I say both. Take a look at the 3rd report just below on “Neuron Damage....” which discusses that prices of HIV like tat or nef contribute to the CSF reservoir & HAND. A concerning question is we are in unchartered waters & wha does the future have in store for PLW 65 years old now as they reach into their 70s, how many might experience more severe mental decline. Neurocogitive impairment may increase the risk for frailty. Frailty is a bad condition. studies show PLWH get frailty at earlier ages & in greater proportions than HIV-. US studies report 6-12% rates for older PLWH of frailty, with projections of increases intros percentages. These areas need much more attention & discussion than they get for research & more importantly for care & support services for the growing elderly HIV+ community, as its projected soon 70% in the US with HIV will be over 50 soon, already in NYC & SF 70% are >50 & 35% >60.
150+ CROI NATAP reports:
Conference on Retroviruses and Opportunistic Infections
Will be Virtual
Boston USA
March 6-10, 2021
HIV-positive participants had worse complex motor performance than HIV-negative participants - .In summary, HIV has a deleterious impact on complex motor skills, which may be partially explained by inflammatory processes. The interaction between aging and HIV disease stage suggest that complex motor skills may be particularly susceptible to aging-related progression of neurocognitive impairment among HIV-positive adults. Complex motor skills refer to a combination of cognitive and perceptual motor abilities, including perception, planning, continuous tracking, and sequential movements.6 Although the prevalence of complex motor impairment has receded in comparison with the pre-cART era, deficits in complex motor functioning are still observed in approximately 30% of those with HAND. Our sample consisted of virally suppressed, chronic HIV-positive patients; however, impairment in complex motor skills was still observed among 20% of the HIV-positive sample. This observed impairment rate is consistent with motor impairment rates (eg, 19%-25%) reported in previous literature.33 Some evidence indicates a higher impairment rate in complex motor performance among persons with chronic HIV compared to persons with acute or early HIV infection,34 which may reflect a history of immunosuppression and/or greater inflammation burden. For example, persons with AIDS performed significantly worse on a fine motor speed test than those without AIDS.35 Deficits in motor skills may indicate injury to the basal ganglia, which are part of the motor control pathways.36 The basal ganglia seem to be particularly vulnerable to alterations in blood-brain barrier permeability,37,38 immune cellular infiltration,39 and accumulation of HIV viral RNA.40 Neuropathological studies have observed higher concentrations of macrophages, microglia, and viral proteins in the basal ganglia.41
Motor function declines over time in human immunodeficiency virus and is associated with cerebrovascular disease, while HIV-associated neurocognitive disorder remains stable - We found that motor dysfunction, cognitive impairment, and cerebrovascular disease were significantly associated with each other at baseline. Cerebrovascular disease independently predicted cognitive impairment in a multivariable model. Longitudinal analysis in a subset of 78 participants with ≥4 years of follow-up showed a stable cognition but declining motor function. We conclude that the HDMS is a valid measurement of motor dysfunction in HIV-infected patients and is associated with cognitive impairment and the presence of cerebrovascular disease. Cognitive impairment is mild and stable in CART-treated HIV; however, motor function declines over time, which may be related to the accrual of comorbidities such as cerebrovascular disease. Further research should examine the mechanisms underlying motor dysfunction in HIV and its clinical impact. Our participants had a high prevalence of cardiovascular comorbidities, with around 40% having hypertension, hyperlipidemia, and being smokers. Other groups have reported similar findings. A Chicago-based cohort of 87 HIV-infected patients older than 60 years reported a prevalence of 61% for hypertension and 26% for diabetes (Adeyemi et al. 2003). A study including 13 cohorts from North America and Europe that analyzed the causes of death of HIV patients from 1996 through 2006 showed that 6.5% of the deaths were attributable to cardiovascular disease (Sackoff et al. 2006). Modeling based on data from the CHORUS cohort estimated that 41% of HIV-infected individuals will die of non-HIV-related causes, and of these 35% will be due to cardiovascular causes (Braithwaite et al. 2005).
.....it is possible that an increasing burden of cerebrovascular disease in the aging HIV population is one explanation why motor abnormalities still accompany cognitive dysfunction, even when the most severe form (i.e., HAD) is in decline.
Neurocognition & HIV at CROI 2021
CROI: HIGHER COMORBIDITY BURDEN PREDICTS WORSENING NEUROCOGNITION IN PEOPLE WITH HIV - (03/11/21) Conclusion: The impact of comorbidities on trajectories of neurocognitive decline was greater than that of HIV disease factors. Although correlative, the temporal relationship between accumulating comorbidities and neurocognitive decline suggests that interventions to prevent or ameliorate a variety of comorbidities may improve neurocognitive prognosis for PWH.
CROI: 12-Year Cognitive Decline is Associated with Lung Disease, Diabetes, and Depression - (03/08/21) Conclusion: Nearly a quarter of treated PWH experienced cognitive decline over 12 years and worse change was associated with previously reported aging- related risk factors (e.g., diabetes) but also with other risk factors that have not been reported (chronic lung disease, MDD, cannabis use disorder). The CHARTER cohort was intended to reflect PWH who receive outpatient healthcare in the U.S. when it was first recruited but these 12-year findings may be affected by survivor bias and selection bias.
CROI: NEURON DAMAGE AND RESERVOIR ARE SECONDARY TO HIV TRANSCRIPTS DESPITE SUPPRESSIVE ART - (03/17/21) HAND persists despite suppressive cART for reasons that are unclear. We have previously shown that transcription without whole virus may explain HAND and contribute to the CSF HIV reservoir. these findings explain HAND in the context of viral suppression as current cART does not stop viral components being made. The obvious example is tat - it is not just tat but the other components that are being produced eg nef vpr and env. CSF is an HIV reservoir with high transcription activity despite ART. It is biologically significant because of compromised neuron integrity likely mediated by transcription products (tat).
CROI: DEMENTIA INCIDENCE AMONG ART-TREATED PEOPLE WITH HIV IN A PRIMARY CARE SETTING - (03/24/21) Conclusion: Despite ART use, dementia incidence is higher among PWH compared with PWoH and is diagnosed at younger ages. Further research is needed to determine factors contributing to age-specific patterns and continued elevated dementia incidence among ART-treated PWH.
CROI: STATIN USE AND COGNITIVE PERFORMANCE IN THE MULTICENTER AIDS COHORT STUDY - (03/26/21) Conclusion: After adjusting for confounders, cognitive test performance did not markedly differ between statin initiators and non-initiators at time proximal to initiation, but, longitudinally, statin initiators' test performance declined more quickly. HIV-serostatus did not modify these results.
CROI: NEUROCOGNITIVE DYSFUNCTION, INFLAMMATION, AND ADIPOSITY IN TREATED HIV PATIENTS - (03/24/21) Conclusion: For the first time in HIV, our results highlight the potential implications of inflammation, immune activation, and body fat composition measures in neurocognitive impairment among HIV-infected adults, suggesting a potential new therapeutic target for HIV-associated neurocognitive decline in this population.
CROI: PWH AND ALZHEIMER'S DISEASE RISK: CLARIFYING THE HAND PHENOTYPE OVER TIME - (03/24/21)
CROI: RANDOMIZED CONTROLLED TRIAL OF MARAVIROC FOR HIV-ASSOCIATED NEUROCOGNITIVE IMPAIRMENT - (03/22/21)
CROI: THE USE OF LESS NEUROTOXIC ANTIRETROVIRALS: SECONDARY ENDPOINTS OF THE MARAND-X STUDY - (03/22/21)
CROI: ACCELERATED CEREBRAL BLOOD-FLOW REDUCTION AND BRAIN AGING IN PEOPLE LIVING WITH HIV PLWH associated with accelerated brain age - (03/18/21) ...cerebral blood flow decline occurred with age for all - HIV- & HIV+ but those with detectable VL showed greater slope of decline than those with undetectable VL who had same decline a HIV- indicating that functional brain aging may depend on VL. "Greater brain age from structural MRI was associated with diminished psychomotor speed regardless of serostatus or viral load AND may be an important determinant of cognitive preservation"
CROI: CSF MARKERS OF AD-RELATED PATHOLOGY AND MEMORY DEFICITS IN OLDER PEOPLE WITH HIV - (03/18/21) Conclusion: The specificity of the relationship between CSF AD biomarkers and learning/memory performance suggests that these biomarkers, particularly p-Tau/Aβ42 ratio, have utility in identifying aMCI/AD-related cognitive deficits amid a background of HAND.
CROI: HIV REPLICATION IN THE CNS IS ASSOCIATED WITH NEUROCOGNITION AND DEPRESSION PRE-ART - (03/12/21)
CROI: RCT OF AN ONLINE MENTAL HEALTH INTERVENTION AMONG OLDER PLWH DURING COVID-19 PANDEMIC - Improved Depression, Anxiety & Loneliness - (03/11/21)
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