Browsing by Subject "Plasma markers"

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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 Consortium for Clarity in ADRD Research Through Imaging (CLARiTI)
    (Wiley, 2025) Mormino, Elizabeth C.; Biber, Sarah A.; Rahman-Filipiak, Annalise; Arfanakis, Konstantinos; Clark, Lindsay; Dage, Jeffrey L.; Detre, John A.; Dickerson, Bradford C.; Donohue, Michael C.; Kecskemeti, Steven; Hohman, Timothy J.; Jagust, William J.; Keene, Dirk C.; Kukull, Walter; Levendovszky, Swati R.; Rosen, Howie; Thompson, Paul M.; Villemagne, Victor L.; Wolk, David A.; Okonkwo, Ozioma C.; Rabinvovici, Gil D.; Rivera-Mindt, Monica; Foroud, Tatiana; Johnson, Sterling C.; Neurology, School of Medicine
    The presence of multiple pathologies is the largest predictor of dementia. A major gap in the field is the in vivo detection of mixed pathologies and their antecedents. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address this gap. The ADRCs longitudinally follow ≈ 17,000 participants, ranging from cognitively unimpaired to dementia, arising from Alzheimer's disease (AD) and related dementias (ADRD; e.g., AD, Lewy body disorders, vascular). Motivated by the Alzheimer's Disease Neuroimaging Initiative's (ADNI) impact, the ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) was formed. Leveraging existing ADRC infrastructure, CLARiTI will integrate standardized imaging and plasma collection to characterize mixed pathologies and use community-engaged research methods to ensure that ≥ 25% of the sample is from underrepresented populations (e.g., ethnoculturally minoritized, low education). The resulting ADRD profiles, within a more diverse sample, will provide key resources for ADRCs and an unprecedented, more generalizable publicly available imaging-plasma dataset. HIGHLIGHTS: In vivo detection of mixed pathologies is critical for Alzheimer's disease and related dementias research. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address gaps related to mixed pathologies. The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will enhance this national program by adding standardized imaging and plasma collection to existing ADRC infrastructure. This effort will provide key resources for ADRCs and an unprecedented publicly available imaging-plasma-neuropath dataset.