TY - JOUR
T1 - HIV infection across aging
T2 - Synergistic effects on intrinsic functional connectivity of the brain
AU - Egbert, Anna R.
AU - Biswal, Bharat
AU - Karunakaran, Keerthana Deepti
AU - Pluta, Agnieszka
AU - Wolak, Tomasz
AU - Rao, Stephen
AU - Bornstein, Robert
AU - Szymańska, Bogna
AU - Horban, Andrzej
AU - Firląg-Burkacka, Ewa
AU - Sobańska, Marta
AU - Gawron, Natalia
AU - Bieńkowski, Przemysław
AU - Sienkiewicz-Jarosz, Halina
AU - Ścińska-Bieńkowska, Anna
AU - Łojek, Emilia
N1 - Publisher Copyright:
© 2018
PY - 2019/1/10
Y1 - 2019/1/10
N2 - The objective of the study was to examine additive and synergistic effects of age and HIV infection on resting state (RS) intra- and inter-network functional connectivity (FC) of the brain. We also aimed to assess relationships with neurocognition and determine clinical-, treatment-, and health-related factors moderating intrinsic brain activity in aging HIV-positive (HIV+) individuals. The current report presents data on 54 HIV+ individuals (age M = 41, SD = 12 years) stabilized on cART and 54 socio-demographically matched healthy (HIV−) comparators (age M = 43, SD = 12 years), with cohort education mean of 16 years (SD = 12). Age at seroconversion ranged 20–55 years old. ANOVA assessed additive and synergistic effects of age and HIV in 133 ROIs. Bivariate statistics examined relationships of FC indices vulnerable to age-HIV interactions and neurocognitive domains T-scores (attention, executive, memory, psychomotor, semantic skills). Multivariate logistic models determined covariates of FC. This study found no statistically significant age-HIV effects on RS-FC after correcting for multiple comparisons except for synergistic effects on connectivity within cingulo-opercular network (CON) at the trending level. However, for uncorrected RS connectivity analyses, we observed HIV-related strengthening between regions of fronto-parietal network (FPN) and default mode network (DMN), and particular DMN regions and sensorimotor network (SMN). Simultaneously, FC weakening was observed within FPN and between other regions of DMN-SMN, in HIV+ vs. HIV- individuals. Ten ROI pairs revealed age-HIV interactions, with FC decreasing with age in HIV+, while increasing in controls. FC correlated with particular cognitive domains positively in HIV+ vs. negatively in HIV- group. Proportion of life prior-to-after HIV-seroconversion, post-infection years, and treatment determined within-FPN and SMN-DMN FC. In sum, highly functioning HIV+/cART+ patients do not reveal significantly altered RS-FC from healthy comparators. Nonetheless, the current findings uncorrected for multiple comparisons suggest that HIV infection may lead to simultaneous increases and decreases in FC in distinct brain regions even in patients successfully stabilized on cART. Moreover, RS-fMRI ROI-based analysis can be sensitive to age-HIV interactions, which are especially pronounced for inter-network FC in relation to neurocognition. Aging and treatment-related factors partially explain RS-FC in aging HIV+ patients.
AB - The objective of the study was to examine additive and synergistic effects of age and HIV infection on resting state (RS) intra- and inter-network functional connectivity (FC) of the brain. We also aimed to assess relationships with neurocognition and determine clinical-, treatment-, and health-related factors moderating intrinsic brain activity in aging HIV-positive (HIV+) individuals. The current report presents data on 54 HIV+ individuals (age M = 41, SD = 12 years) stabilized on cART and 54 socio-demographically matched healthy (HIV−) comparators (age M = 43, SD = 12 years), with cohort education mean of 16 years (SD = 12). Age at seroconversion ranged 20–55 years old. ANOVA assessed additive and synergistic effects of age and HIV in 133 ROIs. Bivariate statistics examined relationships of FC indices vulnerable to age-HIV interactions and neurocognitive domains T-scores (attention, executive, memory, psychomotor, semantic skills). Multivariate logistic models determined covariates of FC. This study found no statistically significant age-HIV effects on RS-FC after correcting for multiple comparisons except for synergistic effects on connectivity within cingulo-opercular network (CON) at the trending level. However, for uncorrected RS connectivity analyses, we observed HIV-related strengthening between regions of fronto-parietal network (FPN) and default mode network (DMN), and particular DMN regions and sensorimotor network (SMN). Simultaneously, FC weakening was observed within FPN and between other regions of DMN-SMN, in HIV+ vs. HIV- individuals. Ten ROI pairs revealed age-HIV interactions, with FC decreasing with age in HIV+, while increasing in controls. FC correlated with particular cognitive domains positively in HIV+ vs. negatively in HIV- group. Proportion of life prior-to-after HIV-seroconversion, post-infection years, and treatment determined within-FPN and SMN-DMN FC. In sum, highly functioning HIV+/cART+ patients do not reveal significantly altered RS-FC from healthy comparators. Nonetheless, the current findings uncorrected for multiple comparisons suggest that HIV infection may lead to simultaneous increases and decreases in FC in distinct brain regions even in patients successfully stabilized on cART. Moreover, RS-fMRI ROI-based analysis can be sensitive to age-HIV interactions, which are especially pronounced for inter-network FC in relation to neurocognition. Aging and treatment-related factors partially explain RS-FC in aging HIV+ patients.
KW - Aging
KW - Functional connectivity
KW - HIV
KW - Neurocognition
KW - ROI-based approach
KW - RS-fMRI
KW - cART
UR - http://www.scopus.com/inward/record.url?scp=85049076992&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049076992&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2018.06.006
DO - 10.1016/j.pnpbp.2018.06.006
M3 - Article
C2 - 29906495
AN - SCOPUS:85049076992
SN - 0278-5846
VL - 88
SP - 19
EP - 30
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
ER -