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Brain Decline in Frail PLH Not Detectable By Standard Neuropsych Tests
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We conclude that frailty in PWH can lead to structural and functional brain changes including subtle changes that are not detectable by standard neuropsychological tests. Multi-modal neuroimaging in conjunction with frailty assessment could identify pathological brain changes observed in PWH.
Frailty is categorized as a signature of a possible underlying comorbidity and is traditionally more
prevalent in PWH compared to HIV- controls. For our cohort, we observed a prevalence of 14% which is
within an expected range for PWH.39-41 We observed that PWH who were frail had worse brain integrity.
Our findings revealed that in the absence of cognitive impairment characterized by neuropsychological
assessment, imaging correlates of structural and functional integrity were reduced in frail compared to
non-frail PWH. PWH who had higher structural integrity, as assessed by FA using DTI, performed better
on tests of psychomotor speed and executive function. Therefore, incorporating multi-modal imaging
metrics with frailty assessment may identify PWH who are potentially at greater risk for future cognitive
decline.
Overall, these results implicate an underlying reduction in brain integrity imaging measures for
frail PWH compared to non-frail PWH. Frailty associated with reductions in brain structure and function
in virologically well-controlled older PWH. Lower CBF and reduced WM integrity was observed in frail
compared to non-frail PWH despite no differences in cognitive or virological measures (e.g. CD4 nadir or
current). Our data demonstrated that reductions in WM integrity due to frailty associated with worse
performance on psychomotor speed and executive function tasks. HIV associated variables did not
associate with WM integrity, suggesting that the changes are due to frailty and not severity of HIV
disease. Further longitudinal studies are needed to determine if observed changes in brain structure and
function remain stagnant or continue to progress and lead to cognitive decline in older PWH.
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April 11 2022 - Jeremy F. Strain1*, Sarah Cooley1*, Collin Kilgore1, Brittany Nelson1, John Doyle1, Regina3 Thompson1, Elizabeth Westerhaus1, Kalen J. Petersen1, Julie Wisch1, Beau M. Ances
Abstract
Background
Chronically-infected persons living with HIV (PWH) are at increased risk of frailty, a clinically recognizable state of increased vulnerability due to aging-associated decline in multiple physiologic systems. Frailty is often defined by the Fried criteria which includes subjective and objective standards concerning health resiliency. However, these frailty metrics do not incorporate cognitive performance or neuroimaging measures.
Methods
We compared structural (diffusion tensor imaging; DTI) and functional (cerebral blood flow; CBF) neuroimaging markers in PWH to frailty and cognitive performance. Virologically controlled PWH were dichotomized as either frail (≥3) or non-frail (<3) using the Fried criteria. Cognitive Z-scores, both domain (executive, psychomotor speed, language and memory) and global, were derived from a battery of tests. We identified three regions of reduced CBF, based on a voxel-wise comparison of frail PLWH compared to non-frail PWH. These clusters (bilateral frontal and posterior cingulate) were subsequently used as seed regions (ROIs) for DTI probabilistic white matter tractography.
Results
White matter integrity connecting the ROIs was significantly decreased in frail compared to non-frail PWH. No differences in cognition were observed between frail and non-frail PWH. However, reductions in WM integrity among these ROIs was significantly associated with worse psychomotor speed and executive function across the entire cohort.
Conclusions
We conclude that frailty in PWH can lead to structural and functional brain changes including subtle changes that are not detectable by standard neuropsychological tests. Multi-modal neuroimaging in conjunction with frailty assessment could identify pathological brain changes observed in PWH.
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