Cognitive reserve for memory performance is mediated by preclinical frontotemporal and limbic amyloid deposition in subjects with normal cognition in early MCI
Bibliographic record
Abstract
Abstract Background The neuroanatomic substrate for cognitive reserve has been poorly elucidated. The development of antemortem biomarkers such as amyloid‐PET afford the potential to begin to explore regional pathologic burden with overt cognitive performance as well as cognitive resilience in relation to neuroanatomic distributions of pathology. The present study sought to identify the relationship between regional amyloid burden and objective measures of cognitive reserve for memory function. Method Sixty‐two subjects with normal cognition or mild cognitive impairment from the INCREASE randomized controlled trial (R01AG054130) underwent amyloid‐PET imaging with Amyvid® tracer, and regional SUVr was determined using the Siemens Syngo.via® Neurology software package. Participants underwent cognitive testing with the Montréal Cognitive Assessment (MOCA) and California Verbal Learning Test (CVLT) while challenged with 1.5mg transdermal scopolamine and four weeks later in an unchallenged state. Cognitive reserve (CR) was operationalized by subtracting the scopolamine‐challenged score from unchallenged test performance for CVLT trials 1‐5 total learning. The relationship between regional SUVr and unchallenged as well as CR cognitive test performance was analyzed using adjusted linear regression models. Result Subjects included 39 women (63%) and 23 men (37%) with a mean age of 73.1±6.2 years, education 16.5±2.7 years, MOCA 25.8± 2.5, and CVLT 45.2± 11.6. Global amyloid‐PET SUVr ranged from 0.9‐2.0 and CVLT CR scores ranged from ‐12 to 34. While, age and education adjusted linear regression analysis demonstrated that unchallenged MOCA and CVLT scores were not significantly related to global SUVr in this sample, reduced CVLT CR was associated with increased global SUVr (p<0.05). Regional analysis demonstrated that this effect was mediated by amyloid deposition in the frontal ((p=0.009), medial temporal (p=0.019), and limbic (p=0.030) regions. Conclusion These data demonstrate that cognitive reserve for memory functions is particularly sensitive to amyloid deposition in frontotemporal regions intrinsic or connected to the Papez circuit. While this finding is not surprising, it does provide convincing evidence that even preclinical amyloid deposition can have significant clinical consequences when neuroanatomic circuits are stressed. Further work investigating whether transient decline in memory performance at times of medical, emotional, or physical stress might be indicative of preclinical amyloid deposition is warranted.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".