Effects of in vivo Lewy body pathology on neuropsychiatric symptoms across the Alzheimer's disease continuum
Bibliographic record
Abstract
Abstract Background In Alzheimer's disease (AD) dementia, co‐pathology is frequently observed, with Lewy body (LB) pathology among the most common findings. Post‐mortem studies support a higher frequency of neuropsychiatric symptoms in individuals with AD and LB co‐pathology. To date, however, the effects of LB pathology measured in vivo on neuropsychiatric symptoms in AD is underexplored. Here, we evaluated the cross‐sectional and longitudinal effects of in vivo measured LB pathology on neuropsychiatric symptoms across the AD continuum. Method We analyzed data from a total of 1,169 individuals from ADNI (426 cognitively unimpaired and 743 cognitively impaired; 47.13% women; mean age of 73.05 years). All participants had baseline in vivo LB pathology measured through CSF alpha‐synuclein seed amplification assays, as well as neuropsychiatric assessments using the NPI‐Q for up to 10 years. A subgroup of 977 participants had baseline CSF amyloid‐β (Aβ 1‐42 ) and p ‐tau 181 levels. We explored cross‐sectional and longitudinal effects of LB on neuropsychiatric symptoms using logistic regression and Cox proportional hazard regression models, respectively. Analyses were controlled for age, sex, and cognitive status. We further evaluated the independent effects of LB, Aβ and tau by including all three pathologies in the same model. Result In cross‐sectional analyses at baseline, the presence of LB pathology was associated with higher rates of anxiety (OR=1.61, 95% CI=1.13‐2.29, p ‐value=0.008), apathy (OR=1.66, 95% CI=1.17‐2.36, p ‐value=0.008), motor disturbances (OR=1.96, 95% CI=1.18‐3.24, p ‐value=0.008), and appetite disturbances (OR=1.63, 95% CI=1.11‐2.40, p ‐value=0.01) after correcting for multiple comparisons (Figure 1). In longitudinal analyses, the presence of LB pathology was associated with a higher risk of developing psychosis (HR=2.15, 95% CI=1.30‐3.56, p ‐value=0.003) and anxiety (HR=1.70, 95% CI=1.22‐2.36, p ‐value=0.001, Figure 2). The cross‐sectional and longitudinal effects of LB were independent of Aβ or tau. Conclusion Our results suggest that in vivo‐measured LB pathology is associated with a higher frequency of neuropsychiatric symptoms, with apathy, motor disturbances, appetite changes, anxiety, and psychosis as potential early neuropsychiatric manifestations of LB pathology in individuals across the AD continuum. These findings underscore the potential of in vivo LB detection as a marker for identifying individuals at elevated risk of neuropsychiatric symptoms, both in clinical trials and in clinical practice.
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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 | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".