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Brain Decline & Frailty in PLWH
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PLWH aging & older are NOT receiving adequate screening & assessments. Their care is subpar. Screening & assessments for older & aging PLWH need to be addressed. Here are 2 studies reporting brain abnormalities in PLWH that may lead to frailty & that frailty and brain abnormality is associated. Elderly PLWH are uniquely susceptible to cognitive disability & frailty at once. Our HIV health care system is SO UNPREPARED to meet the care needs of this elderly & aging population , it's a disgrace. These issues have been brought to authorities - OAR, ONAP, HHS but they continue to ignore them. Jules
Brain abnormality may lead to frailty - the brain abnormality could be due to HIV, inflammation, stroke, diabetes, heart disease. Jules
The Structural and Functional Correlates of Frailty in Persons Living With HIV Clinical Infectious Diseases 11 April 2022
(average age - 56).
Across all participants regardless of frailty status, reductions in WM integrity were associated with worse performance in the psychomotor speed and executive function domains. Both cognitive domains are known to be affected by HIV [46].
Our results suggest that brain imaging measures of integrity may be more sensitive than behavioral assessments for evaluating frailty in older PWH.
Frailty is categorized as a signature of a possible underlying comorbidity and is traditionally more prevalent in PWH compared with HIV-negative 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 with nonfrail PWH [cognitive testing may NOT pick up impairment]. PWH who had higher structural integrity, as assessed by FA using DTI, performed better on tests of psychomotor speed and executive function. Therefore, incorporating multimodal imaging metrics with frailty assessment may identify PWH who are potentially at greater risk for future cognitive decline.
Persons with HIV (PWH) are at increased risk of frailty,
a clinically recognizable state of increased vulnerability resulting from 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.
We compared structural (diffusion tensor imaging [DTI]) and functional (cerebral blood flow [CBF]) neuroimaging markers in PWH with frailty and cognitive performance. Virologically controlled PWH were dichotomized as either frail (≥3) or nonfrail (<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 PWH compared with nonfrail PWH. These clusters (bilateral frontal and posterior cingulate) were subsequently used as seed regions of interest (ROIs) for DTI probabilistic white matter tractography.
White matter integrity connecting the ROIs was significantly decreased in frail compared with nonfrail PWH. No differences in cognition were observed between frail and nonfrail PWH. However, reductions in white matter integrity among these ROIs was significantly associated with worse psychomotor speed and executive function across the entire cohort.

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. Multimodal neuroimaging in conjunction with frailty assessment could identify pathological brain changes observed in PWH.
Physical Frailty and Brain White Matter Abnormalities: The Atherosclerosis Risk in Communities Study
The Journals of Gerontology 21 May 2022
Physical frailty is associated with increased risk for dementia and other neurologic sequelae. However, the neurobiological changes underlying frailty and frailty risk remain unknown. We examined the association of cerebral white matter structure with current and future frailty.
In the cross-sectional analysis (N = 1 754; mean age: 76 years), frailty was associated with greater WMH volume, lower FA, and greater MD. These associations remained consistent after excluding participants with a history of stroke or dementia. Among participants nonfrail at baseline who completed follow-up frailty assessment (N = 1 379; 6.6-year follow-up period), each standard deviation increase in WMH volume was associated with 1.46 higher odds of frailty at follow-up. Composite FA and MD measures were not associated with future frailty; however, secondary analyses found several significant white matter tract-specific associations with frailty risk.
Compared to nonfrail participants, those classified as frail were older, had less education, and demonstrated a greater prevalence of diabetes and coronary heart disease.
In a large community-based study of older adults, we found that individuals with physical frailty have greater WMH volume and white matter microstructural abnormalities than do nonfrail individuals. Importantly, this relationship was observed in participants without a history of stroke or dementia but did not persist when analyses were restricted to cognitively normal individuals. Furthermore, WMH volume was significantly associated with new-onset frailty over a 7-year follow-up period, even among cognitively normal adults. These results were consistent in Black and White participants, and in men and women. Unlike WMH volume, general measures of white matter microstructural integrity were not associated with the risk of future frailty. However, secondary analyses did find that the microstructural integrity of specific white matter tracts was associated with future frailty.
The observational nature of this study prohibits causal inferences. However, we believe it is unlikely that frailty as a syndrome causes white matter disease. One possible explanation for the robust relationship between frailty and the health of cerebral white matter is the existence of one or more shared etiologies. That is, the same systemic conditions or health factors that increase one's risk for frailty may also promote the development of cerebral white matter abnormalities. For example, there is evidence that cardiovascular disease, systemic inflammation, and impaired hemostasis are associated with frailty incidence (24-26). Each of these factors has also been consistently associated with WMH volume, white matter microstructural properties, and dementia risk (21,27-29). Thus, physical frailty may serve as an indicator of one or more of these physiological processes that also adversely affect brain health. Though frailty itself is an unlikely cause of brain changes, it is possible that structural damage to cerebral white matter promotes the development of frailty. For example, frailty features can result from damage to brain projection or commissural fibers involved in motor function, whereas white matter dysfunction in prefrontal or subcortical brain regions can result in fatigue, feelings of exhaustion, or even mood changes (23,30). The temporal ordering of our own findings also supports the mechanistic relationship between white matter disease and frailty.
Greater WMH volume at Visit 5 was associated with increased odds of frailty at a future visit in unadjusted, demographically-adjusted, and fully-adjusted models (odds ratio [OR] = 1.46 per SD increase in WMH volume; 95% CI: 1.15, 1.87; p = .002; Table 3 and Supplementary Table 4). The relationship between greater WMH volume and incident frailty was similar when participants with baseline stroke and dementia were excluded. Among cognitively normal participants, that is, excluding participants with baseline MCI and dementia, each SD higher WMH was associated with a nearly 80% higher odds of incident frailty (OR = 1.77; 95% CI: 1.24, 2.40; p = .001). After exclusion of the 858 participants who were prefrail at baseline, the relationship between WMH and frailty risk was increased further (OR = 2.00; 95% CI: 1.28, 3.11; p < .001). There was no significant association of gFA or gMD with frailty incidence.

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