Apathy progression is associated with brain atrophy and white matter damage in Parkinson’s disease
Bibliographic record
Abstract
Abstract Apathy is a prevalent non-motor symptom that significantly impacts the quality of life in Parkinson’s disease (PD) patients. Although previous studies have investigated the neural correlates of apathy in PD, the longitudinal relationships between regional brain atrophy, white matter hyperintensities (WMHs), and apathy progression remain underexplored. Using longitudinal, multisite data of de novo PD patients from the Parkinson’s Progression Markers Initiative (PPMI), the present study aims to investigate these relationships. We used T1-weighted magnetic resonance imaging (MRI) and clinical data from 445 participants. Apathy was assessed as part of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I. We applied deformation-based morphometry (DBM) to quantify gray matter atrophy and used the Brain tISsue segmentatiON (BISON) algorithm to segment WMHs from T1-weighted images. Using linear regression models, we performed cross-sectional analyses to identify the associations between baseline brain measurements (DBM and WMH) and apathy severity. Longitudinal analyses utilized linear mixed-effects models to investigate whether baseline brain measurements were associated with future apathy progression over time, accounting for covariates such as age, sex, motion artifacts, Hoehn and Yahr stage, levodopa-equivalent daily dose (LEDD), Total Intracranial Volume (TIV), and baseline apathy. Hypothesis-based and exploratory analyses were conducted to confirm the results previously reported in the literature and explore potential new associations. No cross-sectional regional associations survived multiple comparison corrections. Longitudinal hypothesis-based models confirmed that baseline atrophy in regions such as the bilateral nucleus accumbens area, superior parietal, putamen, insula, left precuneus, right precentral, and cerebellum gray matter was significantly associated with future apathy progression. Exploratory longitudinal analyses identified additional regions, including the bilateral lingual, parahippocampal, basal forebrain, ventral diencephalon, isthmus cingulate, thalamus, hippocampus, left middle temporal, right inferior temporal, pericalcarine, medial orbitofrontal, cuneus, where baseline atrophy was correlated with progression of apathy severity. Moreover, greater WMH burden, particularly in the frontal lobe, was associated with worsening apathy. These results highlight the influence of both gray matter atrophy and WMHs on apathy progression in PD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".