The Contribution of LATE‐NC to Neuropsychiatric Symptom Burden in Alzheimer's Disease and Lewy Body Disease: A Clinicopathological Study
Bibliographic record
Abstract
BACKGROUND: Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) frequently coexists with Alzheimer's disease (AD), Lewy body disease (LBD), and vascular pathology. While neuropsychiatric symptoms in AD/LATE-NC are beginning to be explored, the impact of LATE-NC in mixed AD/LBD and LBD is still underexamined. This study investigated neuropsychiatric symptom profiles in individuals with AD, LBD, and mixed AD/LBD with and without LATE-NC. METHOD: In this retrospective cohort study, individuals from the UBC Hospital Clinic for Alzheimer's and Related Disorders (UBCH-CARD) autopsy database with AD, LBD or both plus LATE-NC pathology (LATE+, n = 42) were matched by age and neuropathology to controls without LATE-NC (LATE-, n = 38). Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q) at initial, intermediate, and final visits before death. Outcomes included symptom severity scores at the final visit, odds ratios of symptoms at the final visit and trajectories of symptom progression. Parametric and non-parametric tests were used to compare symptom severity scores, while linear mixed-effects models analyzed longitudinal symptom data, adjusting for age, sex, education, and Clinical Dementia Rating Scale (CDR). RESULT: Mean age at death was 80.5 years (LATE+) and 77.9 years (LATE-), and participants were followed on average 5.8 years. Both groups had a high burden of moderate-to-severe AD pathology (LATE+ 97.6% vs. LATE- 94.4%) and moderate numbers had neocortical LBD (31.7% vs. 41.7%, p = 0.50). At the final visit, total NPI-Q severity scores were similar between groups (5.65 vs. 6.12, p = 0.71). Symptom severity scores for apathy (0.73 vs. 1.29, p = 0.01), hallucinations (0.24 vs. 0.82, p = 0.01), and appetite changes (0.08 vs. 0.41, p = 0.04) were lower in LATE+. Odds ratios for symptom presence at the final visit, adjusted for coexisting pathology, remained significant for hallucinations only (0.013, 95% CI 0.001-0.218, p = 0.002). Longitudinal modeling showed no significant differences in total burden of neuropsychiatric symptoms. CONCLUSION: LATE-NC did not appear to increase overall neuropsychiatric symptom burden in this autopsy cohort study of individuals with AD and/or LBD. Hallucinations were less frequent in the LATE+ group, but this may be due to incomplete adjustment for coexisting Lewy Body pathology. Further modelling of longitudinal symptom progression will be presented at the conference.
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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 | 0.001 |
| 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".