Tract-specific differences in white matter microstructure between young adult APOE ε4 carriers and non-carriers: A replication and extension study
Bibliographic record
Abstract
Abstract The parahippocampal cingulum bundle (PHCB) connects regions known to be vulnerable to early Alzheimer’s disease (AD) pathology, such as posteromedial cortex and medial temporal lobe. While AD-related pathology has been robustly associated with alterations in PHCB microstructure, specifically lower fractional anisotropy (FA) and higher mean diffusivity (MD), emerging evidence indicates that the reverse pattern is evident in younger adults at-risk of AD. In one such study, Hodgetts et al. (2019) reported that healthy young adult carriers of the apolipoprotein-E ( APOE ) ε4 allele – the strongest common genetic risk factor for AD – showed higher FA and lower MD in the PHCB but not the inferior longitudinal fasciculus (ILF). These results are consistent with proposals claiming that heightened neural activity and connectivity have a significant role in posteromedial cortex vulnerability to amyloid-β and tau spread beyond the medial temporal lobe. Given the implications for understanding AD risk, here we sought to replicate Hodgetts et al.’s finding in a larger sample ( N = 128; 40 APOE ε4 carriers, 88 APOE ε4 non-carriers) of young adults (age range: 19-33). Extending this work further, we also conducted exploratory analyses using a more advanced measure of microstructure: hindrance modulated orientational anisotropy (HMOA). These analyses included an investigation of hemispheric asymmetry in PHCB and ILF HMOA. Contrary to the original study, we observed no difference in PHCB microstructure between APOE ε4 carriers and non-carriers. Bayes factors (BFs) further revealed moderate-to-strong evidence in support of these null findings. APOE ε4-related differences in ILF HMOA asymmetry were evident, however, with carriers demonstrating lower leftward asymmetry. Our findings indicate that young adult APOE ε4 carriers do not show alterations in PHCB microstructure, as observed by Hodgetts et al., but may show altered asymmetry in ILF microstructure.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".