Pathologic and cholinergic changes in the rostral prefrontal cortex of the oldest‐old
Bibliographic record
Abstract
Abstract Background The oldest‐old are a continually expanding population of people 85 years of age and older. While the majority of this population expresses some degree of cognitive impairment typically associated with the aging brain, including executive dysfunction, a subset do not present with cognitive deficits. It is hypothesized that decreased cortical cellular and synaptic density, and neurotransmitter production in the aging frontal lobe contributes to executive dysfunction. The rostral prefrontal cortex (rPFC) is a region involved in executive function in part due to high cholinergic innervation. This study aims to characterize the neuropathologic and cholinergic changes in the rPFC in the oldest‐old. Method Male and female formalin‐fixed human rPFC of cognitively intact individuals over the age of 85 will be examined compared to sex‐ and age‐matched Alzheimer’s disease rPFC. Disease‐associated neuropathological load will be examined with immunohistochemical staining using specific antibodies for β‐amyloid (Aβ) species (total Aβ, Aβ1‐40, Aβ1‐42, protofibril and fibril oligomers), tau species (total tau, 3R, and 4R), α‐synuclein, and phosphorylated‐TDP‐43. The cholinergic system will be evaluated using histochemical staining for butyrylcholinesterase and acetylcholinesterase, and immunohistochemical staining with a specific antibody for choline acetyltransferase. Result Preliminary results indicate a high prevalence of abnormal intraneuronal Aβ aggregation in a subset of neurons of the middle laminar layers of several oldest‐old brains. One of these brains has concurrent abnormal tau aggregates in the white matter. Conclusion The results of this study will further our understanding of the mechanisms that allow a subset of the oldest‐old to maintain normal cognitive function despite age related changes to neural elements and the presence of disease‐associated pathology. Abnormal sequestering of disease associated proteins may indicate neuroprotective mechanisms which prevent loss of function in the rPFC.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 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".