Differentiating apathy and depression across neurodegenerative disorders: sex‐specific associations with severity and location of white matter hyperintensities
Bibliographic record
Abstract
BACKGROUND: Apathy and depression are overlapping symptoms in neurocognitive disorders (NCDs). White matter hyperintensities (WMH), indicative of microvascular pathology, have been associated with apathy and depression individually. Less is known about these symptoms' spatial distribution and sex-specific patterns, particularly when they co-occur. It was hypothesized that individuals with comorbid apathy and depression (A+D) would exhibit higher WMH severity. METHOD: Data from the COMPASS-ND longitudinal cohort of participants with various NCDs were categorized into four groups based on the presence, absence, or comorbidity of apathy and depressive symptoms: apathy only (AO), depressive symptoms only (DO), A+D, and neither apathy nor depression (NAD). Apathy and depressive symptom presence was assessed using the Neuropsychiatric Inventory Questionnaire, while WMH severity was evaluated with the Fazekas scale (graded 0 to 3) in periventricular (PV) and subcortical (SC) regions. Ordinal regression analyses, adjusted for age, sex, and Montreal Cognitive Assessment (MoCA) scores, examined the relationships between group (AO, DO, A+D, NAD) and regional WMH severity. Separate analyses explored potential sex-specific patterns. RESULT: The 803 participants were composed of various NCDs, including mild cognitive impairment (MCI) (n = 217), vascular MCI (n = 135), Alzheimer's disease dementia (n = 72), and other diagnoses (e.g., mixed dementias, vascular dementia, Parkinson's disease, Lewy body dementia, frontotemporal dementia, etc) (n = 377). Participants had a mean (SD) MoCA score of 22.8 (4.7) (range 4-30) and a mean age of 72.1 (7.6) years, with 55.8% males. Groups included AO (n = 106, 13.2%), DO (n = 120, 15%), A+D (n = 135, 16.8%), or NAD (n = 442, 55%). Neither PVWMH nor SCWMH were associated with either AO or DO. A+D was associated with higher PVWMH severity (β=0.508, SE=0.201, p = 0.01) but not SCWMH severity. In sex-specific analyses, males with A+D exhibited higher PVWMH severity (β=0.765, SE=0.242, p = 0.002), whereas no significant associations were found between groups and WMH severity in females. CONCLUSION: This study demonstrated a positive relationship between A+D and PVWMH, particularly in males, while no associations were present in females or with separate symptoms. These findings support the need for regional and sex-specific analyses of the relationship between WMH and comorbid apathy and depression across NCDs to improve their understanding and potentially inform treatment approaches.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".