Oscillatory markers of neuroHIV-related cognitive impairment and Alzheimer’s disease during attentional interference processing

Abstract

People with HIV (PWH) frequently experience mild cognitive decline, which is typically attributed to HIVassociated neurocognitive disorder (HAND). However, such declines could also be a sign of early Alzheimer's disease (AD) in older PWH. Distinguishing these two pathologies in PWH is exceedingly difficult, as there is a major knowledge gap regarding their neural and neuropsychological bases. In the current study, we begin to address this knowledge gap by recording magnetoencephalography (MEG) during a flanker interference task in 31 biomarker-confirmed patients on the AD spectrum (ADS), 25 older participants with HAND, and 31 cognitively-normal controls. MEG data was examined in the time-frequency domain using a data-driven approach. Our results indicated that the clinical groups (ADS/HAND) performed significantly worse than controls on the task and exhibited aberrations in interference-related theta and alpha oscillations, some of which were disease-specific. Specifically, patients (ADS/HAND) exhibited weaker interference activity in frontoparietal and cingulate cortices compared to controls, while the ADS group exhibited stronger theta interference than those with HAND in frontoparietal, occipital, and temporal cortices. These results reveal overlapping and distinct patterns of neurophysiological alterations among those with ADS and HAND in attentional processing centers and suggest the existence of unique oscillatory markers of each condition.

Levetiracetam Prevents Neurophysiological Changes and Preserves Cognitive Function in the Human Immunodeficiency Virus (HIV)-1 Transactivator of Transcription Transgenic Mouse Model of HIV-Associated Neurocognitive Disorder

“…However, in a clinical trial examining LEV effects on cognition in AD, only when patients were stratified by seizure status was LEV found to elicit positive effects on spatial memory and executive function (Vossel et al, 2021). Both overlapping and distinct neurophysiological aberrations were observed in AD and HAND patients using magnetoencephalography (Meehan et al, 2023). Perhaps the effects of LEV are graded with more dramatic effects observed in subjects with more enhanced network excitability, suggesting mice exposed to TAT for a prolonged period would develop overt EEG abnormalities.…”

Movement-related beta and gamma oscillations indicate parallels and disparities between Alzheimer's disease and HIV-associated neurocognitive disorder

“…The groups were matched on all key demographics except age (i.e., the HAND group was slightly younger than healthy controls and ADS patients); thus, age was included as a nuisance covariate in all statistical modeling. Note that the data reported here was included in a previous publication focused on cognitive control processing ( Meehan et al, 2023 ). However, the data were completely reanalyzed for the current investigation.…”

“…Herein, we examined the impact of cognitive interference on movement-related oscillatory activity in participants on the ADS and those with HAND using MEG. This work builds on our recent study that examined oscillatory differences in cognitive control networks in an overlapping group of participants with HAND and those on the ADS, which revealed critical differences in theta oscillations across multiple higher-level brain regions between patients and controls, as well as disease-specific findings ( Meehan et al, 2023 ). Given the limited literature on motor control, our hypotheses were broadly framed and included disparate neural dynamics in ADS versus HAND in key cognitive control and motor processing and attention areas (e.g., frontoparietal and supplementary motor cortices).…”

“…While regional hyper-activity in motor cortices is a critical feature of neuroHIV and ADS, movement-related neurological dysfunction in ADS appears to be more region dependent such that primary motor areas exhibit hyperexcitability while higher motor regions exhibit weaker activation ( Albers et al, 2015 ; Vidoni et al, 2012 ; Wilson et al, 2013 ; Zhou et al, 2017 ). Though evidence from previous work suggests potential convergences and divergences in the neural aberrations serving motor control and processing in ADS and HAND ( Casagrande et al, 2022 ; Meehan et al, 2022 , 2023 ), no neuroimaging research has directly compared the aberrant movement-related neurophysiological signatures of ADS and HAND.…”