Progenitor Cells, Regenerative Capacity, and Cognition
Bibliographic record
Abstract
Abstract Background Impaired endogenous vascular regenerative capacity, reflected by reduced levels of circulating progenitor cells (CPC), has been linked to age-related diseases, especially adverse cardiovascular outcomes. We have previously reported that CPC are associated with cognitive aging, but their impact on cognitive impairment and related brain phenotypes is unclear. Here we report the impact of CPC on cognitive and neuroimaging markers of cognitive impairment. Methods We analyzed data from 283 community-dwelling participants (59% female, 39% Black) enrolled in the Brain Stress, Hemodynamics and Risk Prediction (B-SHARP) program. Participants underwent (a) cognitive assessments (including Montreal Cognitive Assessment [MoCA]); (b) brain magnetic resonance imaging (MRI) to derive white matter hyperintensity (WMH) volumes, whole-brain cortical thickness and hippocampal volumes; and (c) flow cytometry for enumerating CPCs as CD45 med mononuclear cells expressing CD34 with co-expression with either CD133, chemokine CXC motif receptor 4 (CXCR4), or vascular endothelial growth factor receptor-2 (VEGF2R). Linear regression models were adjusted for demographic and vascular risk factors. Results In fully adjusted models, lower levels of CD34⁺/CD133⁺ CPCs were associated with worse global cognition (MoCA: β = 0.59, p = 0.01), reduced cortical thickness (β = 0.01, p = 0.01), and greater WMH burden (β = -0.15, p = 0.01). Lower levels of CD34⁺ and CD34⁺/CXCR4⁺ CPCs were significantly associated with greater WMH volume burden (CD34⁺: β = -0.27, p < 0.01; CD34⁺/CXCR4⁺: β = -0.14, p = 0.03). Higher CD34⁺/VEGFR2⁺ CPCs were associated with higher MoCA scores (β = 0.37, p < 0.01) and language performance on the Boston Naming Test (β = 0.01, p = 0.03) but not with brain phenotypes. Conclusions Reduced regenerative capacity is associated with worse cognitive performance on global tests and with vascular brain injury, including WMH volume and cortical thinning. If validated in future studies, these findings may highlight regenerative capacity as a promising therapeutic target for mitigating cognitive decline.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".