Browsing by Author "Gold, Brian T."

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    Synergistic effects of plasma S100b levels and MRI‐based water exchange rate across the blood‐brain‐barrier on memory performance among older adults
    (Wiley, 2025-01-09) Pappas, Colleen; Zachariou, Valentinos; Bauer, Christopher E.; Sudduth, Tiffany L.; Wilcock, Donna M.; Jicha, Gregory A.; Hartz, Anika M. S.; Shao, Xingfeng; Wang, Danny J. J.; Gold, Brian T.; Neurology, School of Medicine
    Background: Non‐invasive biofluid and MRI measures of blood‐brain‐barrier (BBB) dysfunction may aid early detection of cerebral small vessel disease (cSVD). Plasma markers of astrocytic function and injury, such as S100 calcium‐binding protein B (S100b), have gained increased attention in relation to BBB integrity and cognition. Here we explored the inter‐relationships between plasma S100b levels, an MRI measure of water exchange rate across the BBB (kw), and cognitive performance among older adults. Method: The participant sample consisted of 74 older adults without dementia recruited from the University of Kentucky Sanders Brown Center on Aging. Relationships between S100b and cognition (memory, executive function) and MRI‐based BBB water exchange rate were tested. Plasma S100b levels (pg/mL) were measured using Meso Scale Discovery R‐PLEX assay at the University of Kentucky’s CCTS Biomarker Analysis Lab. Composite scores were created for memory and executive function. A diffusion‐prepared arterial spin labeling (DP‐ASL) MRI sequence was used to estimate water exchange rate across the BBB (expressed as kw). All data (S100b, cognition, MRI) were collected within 1 year of each other. Multiple linear regression models examined the impact of plasma S100b on memory, executive function, and kw. Covariates included age, gender, and education (for cognition models only). Additionally, kw was tested as moderator of the S100b‐cognition relationships using the PROCESS macro. Result: A negative relationship was observed between S100b and memory, where higher S100b levels were associated with poorer memory performance. A similar relationship was not observed with executive function. S100b was also not associated with kw. However, there was an interaction between S100b levels and kw in the parietal lobe on memory performance such that participants with both lower parietal kw and higher S100b showed the poorest memory performance. Conclusion: Our results indicate that S100b levels are negatively associated with memory performance, but not MRI‐based BBB kw. However, higher S100b levels coupled with lower MRI‐based water exchange rate further contributed to the strong negative effects observed for memory performance. This suggests that plasma S100b and BBB kw may be different proxies of BBB function and may have synergistic negative effects on cognition.
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    The Effect of Sex‐Differences on the Relationship Between White Matter Hyperintensity, Cerebrovascular Reactivity, and Fluid Biomarkers
    (Wiley, 2025-01-09) Bahrani, Ahmed A.; Jiang, Yang; Powell, David K.; Katsumata, Yuriko; Nahvi, Azadeh; Lee, Tiffany; Gold, Brian T.; Goldstein, Larry B.; Wilcock, Donna M.; Jicha, Gregory A.; Nelson, Peter T.; Norris, Christopher M.; Neurology, School of Medicine
    Background: Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID) are the predominant types of dementia in older adults, associated with memory loss and cognitive deficits. White matter hyperintensities (WMH) are linked to both AD and VCID. Astrocytes play a crucial role in WM integrity, encompassing functions like neuroinflammation, oxidative stress, and Aβ clearance. Poorly reactive astrocytes could lead to implications, like WMH or vascular damage. This study aims to explore sex‐differences effect on the correlation between fluid biomarkers, WMH, and cerebrovascular reactivity (CVR). Method: Twenty‐seven participants (mean age 76.8±6.4 years, Female=15) preliminary data were collected from UK‐ADRC/MarkVCID cohorts. A correlation test was employed to examine sex‐differences based on the correlation of fluid inflammatory (GFAP, IL6, IL8, IL10), angiogenic (TDP‐43, and PlGF) biomarkers, and Aβ40 and 42, to global and regional CVR and WMH. Results: We observed several sex‐differences: the female group showed a significant correlation between WMH at occipital lobe and IL6 (P=0.031), IL10 (P=0.036), and GFAP (P=0.037), while male group only showed a significant correlation between Aβ42 and WMH at the occipital lobe (P=0.039). CVR data of the female group exhibited a correlation at the parietal lobe (right‐hemisphere) and IL8 (P=0.037) and Aβ40 (P=0.038) and between Aβ40 and CVR temporal lobe (right‐hemisphere, P=0.021). The male group showed a significant correlation between IL6 and CVR at the occipital lobe (left‐hemisphere, P=0.012. Generally, the female group showed higher mean values for all biomarkers except for IL10 and PIGF, but only significant at GFAP and TDP43. Additionally, the correlation test adjusted for age and sex showed that TDP‐43 had a significant correlation with WMH in the temporal (P=0.041), occipital (P=0.024), and parietal (P=0.024) lobes, while GFAP displayed a significant correlation only with WMH in the frontal lobe (P=0.013). Conclusions: Despite the small sample size, which warrants expansion in future studies, we observed interesting findings of sex‐differences in specific brain regions in relation to fluid biomarkers. These biomarkers may arise, in part, from reactive astrocytes, commonly found near many brain lesions, including WM pathology. Further studies are needed to gain deeper insight into astrocyte activities in diseases associated with WMH and CVR, like AD.