Neuropsychiatric Symptom Clusters and their Association with Function and Brain Structure
Bibliographic record
Abstract
BACKGROUND: Neuropsychiatric symptoms (NPS) constitute a major challenge for patients with Alzheimer's disease (AD). We explored NPS clusters in AD and longitudinally evaluated their association with function and structural neuroimaging markers. METHOD: Participants with AD (N = 111) were included from the Ontario Neurodegenerative Disease Research Initiative. NPS were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). NPS clusters were identified through exploratory factor analysis at baseline. We evaluated 34 bilateral cortical regions of interest (ROIs) and 9 bilateral subcortical ROIs using volumetric information from MRI data evaluated annually over 3 years. We examined longitudinal associations between NPS clusters with basic (ADLs) and instrumental (iADLs) activities of daily living, as well as with subcortical and cortical volumes, using mixed linear regression models controlling for age, sex, MoCA, education level, and visit number. RESULT: Factor analysis identified four symptom clusters explaining 62% of the variance. These were labeled "behavioral" (disinhibition, irritability, motor disturbance, and agitation), "psychotic" (hallucinations, delusions, and euphoria), "neurovegetative" (apathy and appetite), and "affective" (depression, anxiety, nighttime behavior) clusters. The "behavior" cluster was longitudinally associated with left middle temporal (β = -382.6, p = .006), right lingual (β = -456.0, p = .01), right nucleus accumbens (β = -5656.6, p = .004), and right thalamic (β = -700.7, p = .008) volumes. The "neurovegetative" cluster was longitudinally associated with left fusiform (β = -195.4, p = .03), left middle temporal (β = -282.3, p = .001), and right nucleus accumbens (β = -3176.7, p = .01). The "affective" cluster was associated with left rostral anterior cingulate (β = -1423.4, p = .0003), right entorhinal (β = -804.3, p = .03), right medial orbitofrontal (β = -830.6, p = .001), right pars opercularis (β = -911.6, p = .001), and left putamen (β = -729.5, p = .004) volumes. Longitudinally, all clusters predicted iADL outcomes and clusters 1, 3, and 4 predicted ADL outcomes. Greater NPS burden, male sex, visit number, older age, and lower MoCA predicted worse function. CONCLUSION: NPS clusters in AD separate into behavioral, psychotic, neurovegetative, and affective dimensions. These clusters demonstrate unique associations with function and neuroimaging markers.
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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 | 0.002 |
| 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".