The joint effect of aging and HIV infection on microstructure of white matter bundles

Kuhn, Taylor; Jin, Yan; Huang, Chao; Kim, Yeun; Nir, Talia M.; Gullett, Joseph M.; Jones, Jacob D.; Sayegh, Phillip; Chung, Caroline; Dang, Bianca H.; Singer, Elyse J.; Shattuck, David W.; Jahanshad, Neda; Bookheimer, Susan Y.; Hinkin, Charles H.; Zhu, Hongtu; Thompson, Paul M.; Thames, April D.

doi:10.1002/hbm.24708

Cited by 26 publications

(14 citation statements)

References 61 publications

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“…Our HIV + participants had greater than normal age-dependent declines in FA in the ACR, CC and SS, regardless of MJ usage; this is consistent with findings in prior DTI studies (36,48). In addition, we observed greater than normal age-related FA decline in the EC and SLF of MJ users regardless of HIVserostatus, which is consistent with the greater than normal age-related FA decline in multiple white matter regions in MJ users (24).…”

Section: Age-related and Mj-related Changes In Dti Metrics In Hiv + Isupporting

confidence: 90%

Microstructural Brain Abnormalities in HIV+ Individuals with or without Chronic Marijuana Use

Wang

Liang

Ernst

et al. 2020

Preprint

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Objective Cognitive deficits and microstructural brain abnormalities are well documented in HIV-positive individuals (HIV+). This study evaluated whether chronic marijuana (MJ) use contributes to additional cognitive deficits or brain microstructural abnormalities that may reflect neuroinflammation or neuronal injury in HIV+. Method: Using a 2 × 2 design, 44 HIV + participants, [23 minimal/no MJ users (HIV+), 21 chronic active MJ users (HIV + MJ)], were compared to 46 seronegative participants [24 minimal/no MJ users (SN) and 22 chronic MJ users (SN + MJ)] on neuropsychological performance (7 cognitive domains) and diffusion tensor imaging metrics, using an automated atlas to assess fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities, in 18 cortical and 4 subcortical brain regions, Results Compared to SN and regardless of MJ use, the HIV + group had lower FA and higher diffusivities in multiple white matter and subcortical structures (p = 0.001–0.050), as well as poorer cognition in Fluency (p = 0.039), Attention / Working Memory (p = 0.009), Learning (p = 0.015) and Memory (p = 0.028). Regardless of HIV-serostatus, MJ users had lower AD in uncinate fasciculus (p = 0.016) but similar cognition as non-users. No additive or interactive effects were found between HIV-serostatus and MJ use on DTI metrics or cognitive function. Furthermore, higher MD in thalamus predicted poorer fluency, learning and memory in HIV + participants, while higher RD in posterior corona radiata predicted poorer learning in MJ users. Lower FA in the anterior internal capsule also predicted worse attention/working memory in all except SN subjects. Lastly, MJ users with or without HIV-infection showed greater than normal age-dependent FA declines in superior longitudinal fasciculus, external capsule and globus pallidus.

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Section: Age-related and Mj-related Changes In Dti Metrics In Hiv + Isupporting

confidence: 90%

Microstructural Brain Abnormalities in HIV+ Individuals with or without Chronic Marijuana Use

Wang

Liang

Ernst

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Our HIV+ participants had greater than normal age-dependent declines in FA, suggesting accelerated age-related loss of fiber integrity, in the corpus callosum regardless of MJ usage; this finding is consistent with those in prior DTI studies [ 40 , 69 ]. In addition, we observed greater than normal age-related FA decline in the SLF and EC of MJ users regardless of HIV serostatus, which is also consistent with the greater than normal age-related FA decline in multiple white matter regions in MJ users [ 24 ].…”

Section: Discussionsupporting

confidence: 91%

Microstructural brain abnormalities in HIV+ individuals with or without chronic marijuana use

Wang

Liang

Ernst

et al. 2020

J Neuroinflammation

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Objective: Cognitive deficits and microstructural brain abnormalities are well documented in HIV-positive individuals (HIV+). This study evaluated whether chronic marijuana (MJ) use contributes to additional cognitive deficits or brain microstructural abnormalities that may reflect neuroinflammation or neuronal injury in HIV+. Method: Using a 2 × 2 design, 44 HIV+ participants [23 minimal/no MJ users (HIV+), 21 chronic active MJ users (HIV + MJ)] were compared to 46 seronegative participants [24 minimal/no MJ users (SN) and 22 chronic MJ users (SN + MJ)] on neuropsychological performance (7 cognitive domains) and diffusion tensor imaging metrics, using an automated atlas to assess fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities, in 18 cortical and 4 subcortical brain regions. Results: Compared to SN and regardless of MJ use, the HIV+ group had lower FA and higher diffusivities in multiple white matter and subcortical structures (p < 0.001-0.050), as well as poorer cognition in Fluency (p = 0.039), Attention/ Working Memory (p = 0.009), Learning (p = 0.014), and Memory (p = 0.028). Regardless of HIV serostatus, MJ users had lower AD in uncinate fasciculus (p = 0.024) but similar cognition as nonusers. HIV serostatus and MJ use showed an interactive effect on mean diffusivity in the right globus pallidus but not on cognitive function. Furthermore, lower FA in left anterior internal capsule predicted poorer Fluency across all participants and worse Attention/Working Memory in all except SN subjects, while higher diffusivities in several white matter tracts also predicted lower cognitive domain Z-scores. Lastly, MJ users with or without HIV infection showed greater than normal age-dependent FA declines in superior longitudinal fasciculus, external capsule, and globus pallidus.

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“…Another recent study of virally suppressed patients reported that white matter alterations were present in patients with HAND, but HIV patients without cognitive impairment had similar white matter measures compared to uninfected controls [ 21 ]. Furthermore, more pronounced white matter alterations were observed in older patients with HIV [ 22 ], which may reflect accelerated brain aging. White matter alterations are also associated with impairment of several cognitive domains in patients with controlled infection and no other medical comorbidities [ 23 ].…”

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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The joint effect of aging and HIV infection on microstructure of white matter bundles

Cited by 26 publications

References 61 publications

Microstructural Brain Abnormalities in HIV+ Individuals with or without Chronic Marijuana Use

Microstructural Brain Abnormalities in HIV+ Individuals with or without Chronic Marijuana Use

Microstructural brain abnormalities in HIV+ individuals with or without chronic marijuana use

Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders

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