Brain structural correlates of trajectories to cognitive impairment in men with and without HIV disease

Popov, Mikhail; Molsberry, Samantha; Lecci, Fabrizio; Junker, Brian W.; Kingsley, Lawrence; Levine, Andrew J.; Martin, Eileen; Miller, Eric N.; Munro, Cynthia A.; Ragin, Ann B.; Sacktor, Ned; Becker, James T.

doi:10.1007/s11682-018-0026-7

Cited by 13 publications

(9 citation statements)

References 49 publications

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“…Magnetic resonance imaging (MRI) is often the initial step in the diagnostic approach for HAND, although to date, there is no unique neuroimaging technique capable of confirming a HAND diagnosis [ 15 ]. Published MRI studies of HAND patients show various alterations in brain volume and suggest that these changes may contribute to cognitive impairment [ 16 , 17 ]. A recent study used functional MRI to measure brain atrophy in aviremic ART-treated people with HIV compared to uninfected controls over a period of 2 years [ 18 ].…”

Section: Neuroimaging and Neuropathological Studies In Hand Patientsmentioning

confidence: 99%

Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders

Irollo

Luchetta

et al. 2021

Cell. Mol. Life Sci.

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HIV-associated neurocognitive disorder (HAND) is characterized by cognitive and behavioral deficits in people living with HIV. HAND is still common in patients that take antiretroviral therapies, although they tend to present with less severe symptoms. The continued prevalence of HAND in treated patients is a major therapeutic challenge, as even minor cognitive impairment decreases patient’s quality of life. Therefore, modern HAND research aims to broaden our understanding of the mechanisms that drive cognitive impairment in people with HIV and identify promising molecular pathways and targets that could be exploited therapeutically. Recent studies suggest that HAND in treated patients is at least partially induced by subtle synaptodendritic damage and disruption of neuronal networks in brain areas that mediate learning, memory, and executive functions. Although the causes of subtle neuronal dysfunction are varied, reversing synaptodendritic damage in animal models restores cognitive function and thus highlights a promising therapeutic approach. In this review, we examine evidence of synaptodendritic damage and disrupted neuronal connectivity in HAND from clinical neuroimaging and neuropathology studies and discuss studies in HAND models that define structural and functional impairment of neurotransmission. Then, we report molecular pathways, mechanisms, and comorbidities involved in this neuronal dysfunction, discuss new approaches to reverse neuronal damage, and highlight current gaps in knowledge. Continued research on the manifestation and mechanisms of synaptic injury and network dysfunction in HAND patients and experimental models will be critical if we are to develop safe and effective therapies that reverse subtle neuropathology and cognitive impairment.

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Section: Neuroimaging and Neuropathological Studies In Hand Patientsmentioning

confidence: 99%

Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders

Irollo

Luchetta

et al. 2021

Cell. Mol. Life Sci.

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“…HIV infection negatively impacts patients' brain, and the effect of HIV on brain functioning was found to be less drastic after the highly active antiretroviral therapy (HAART) became available in early 1990s. In a MACS NP substudy, participants have been repeatedly tested on a NP test battery assessing six cognitive domains which included learning, motor speed and coordination, speed of information processing, memory, working memory and attention, and executive functioning 23,24 . As of October 2017, some participants had more than 20 years of longitudinal NP data.…”

Section: Application To the Macsmentioning

confidence: 99%

Longitudinal multivariate normative comparisons

Wang

Cheng

Rubin

et al. 2020

Statistics in Medicine

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Motivated by the Multicenter AIDS Cohort Study (MACS), we develop classification procedures for cognitive impairment based on longitudinal measures. To control family‐wise error, we adapt the cross‐sectional multivariate normative comparisons (MNC) method to the longitudinal setting. The cross‐sectional MNC was proposed to control family‐wise error by measuring the distance between multiple domain scores of a participant and the norms of healthy controls and specifically accounting for intercorrelations among all domain scores. However, in a longitudinal setting where domain scores are recorded multiple times, applying the cross‐sectional MNC at each visit will still have inflated family‐wise error rate due to multiple testing over repeated visits. Thus, we propose longitudinal MNC procedures that are constructed based on multivariate mixed effects models. A χ2 test procedure is adapted from the cross‐sectional MNC to classify impairment on longitudinal multivariate normal data. Meanwhile, a permutation procedure is proposed to handle skewed data. Through simulations we show that our methods can effectively control family‐wise error at a predetermined level. A dataset from a neuropsychological substudy of the MACS is used to illustrate the applications of our proposed classification procedures.

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“…[12,13] However, insula atrophy has also been identified in AD, [14] fronto-temporal dementia, [15] and associated with cognitive impairment in HIV infected individuals. [16] Since there have been relatively few studies investigating the diagnostic utility of these two structural brain markers in mild cognitive impairment (MCI), the aim of this study was to investigate them in a cohort of probable MCI with Lewy bodies (MCI-LB) compared to MCI with no core features of Lewy body disease (MCI-AD).…”

Section: Introductionmentioning

confidence: 99%