Dedifferentiation of memory-related brain function as a potential early biomarker of Alzheimer’s disease in asymptomatic older women: Results from the PREVENT-AD Cohort
Bibliographic record
Abstract
Abstract Late-onset Alzheimer’s disease (AD) disproportionately affects women compared to men. Episodic memory decline is one of the earliest and most pronounced deficits observed in AD. However, it remains unclear whether there are sex differences in episodic memory-related brain function in cognitively intact older adults at risk of developing AD. In the current study, we used task fMRI to test for sex differences in episodic memory-related brain activity and brain activity-behavior correlations in cognitively intact older adults with a family history of AD from the PREVENT-AD cohort study in Montreal, Canada (M age =63.03±3.78; M education =15.41±3.40). Importantly, we tested women and men who were matched in age, body mass index, years of education, and proximity to the age of parental AD onset. We used data-driven task-based multivariate partial least squares (PLS) analysis to identify sex differences in brain activity during the successful encoding and retrieval of objects and their associated spatial context. We used behavior PLS to examine sex differences in the correlations between brain activity and memory performance at encoding and retrieval. Our results suggested no significant sex differences in behavioral performance on the memory task. Yet, we observed sex differences in task-related brain activity and in brain activity-behavior correlations during the encoding of object-location associative memories and object-only item memory, and the retrieval of object only item memories. Specifically, subsequent object-location associative retrieval associated with encoding related activation of caudate, cingulate, and middle occipital cortex in women and, additionally, of temporo-parietal regions in men. We also found male-specific activations in ventrolateral prefrontal cortex (PFC) and insula during associated with the encoding and retrieval of object-only information. Moreover, whereas activity in ventrolateral PFC, posterior cingulate, and inferior parietal regions during encoding supported subsequent performance in women, activity in these regions during retrieval supported object-location associative memory in men. Similarly, we found that activity in ventrolateral PFC, precuneus, parahippocampal, anterior cingulate, and occipital regions during retrieval supported general memory performance in women but object-only retrieval in men. Our findings suggest functional dedifferentiation of episodic memory-related brain activation and performance in women compared to men. Follow up analyses should test for sex differences in the relationship between brain activity patterns and performance longitudinally, in association with risk factors for AD development.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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".