Evidence map›Paper›PMID 41392092›Full record

ArticleMolecular psychiatry2026

In vivo-measured Lewy body pathology is associated with neuropsychiatric symptoms across the Alzheimer's disease continuum.

Douglas Teixeira Leffa, Guilherme Povala, Pamela C L Ferreira, João Pedro Ferrari-Souza, Guilherme Bauer-Negrini, Matheus Scarpatto Rodrigues, Livia Amaral, Firoza Z Lussier, Marina Scop Medeiros, Carolina Soares and 8 more

Abstract read
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In one paragraph

Article in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Douglas Teixeira LeffaDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA. teixeiraleffad@upmc.edu.ORCID 0000-0002-4890-8451
Guilherme PovalaDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Pamela C L FerreiraDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.ORCID 0000-0003-2134-9829
João Pedro Ferrari-SouzaGraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, 2600 Ramiro Barcelos, Porto Alegre, RS, 90035-003, Brazil.ORCID 0000-0003-2183-1551
Guilherme Bauer-NegriniDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Matheus Scarpatto RodriguesDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Livia AmaralDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.ORCID 0009-0005-4488-763X
Firoza Z LussierDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Marina Scop MedeirosDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.ORCID 0009-0009-4237-4565
Carolina SoaresDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.ORCID 0000-0002-2338-4495
Cristiano Schaffer AguzzoliBrain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, 6690 Avenida Ipiranga, Porto Alegre, RS, 90035-003, Brazil.ORCID 0000-0002-7378-3830
Arthur C MacedoTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, McConnell Brain Imaging Centre (BIC), Montreal Neurological Institute, Montreal Neurological Institute-Hospital, 3801 Rue University, Montréal, QC, H3A 2B4, Canada.
Joseph TherriaultTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, McConnell Brain Imaging Centre (BIC), Montreal Neurological Institute, Montreal Neurological Institute-Hospital, 3801 Rue University, Montréal, QC, H3A 2B4, Canada.
Pedro Rosa-NetoTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, McConnell Brain Imaging Centre (BIC), Montreal Neurological Institute, Montreal Neurological Institute-Hospital, 3801 Rue University, Montréal, QC, H3A 2B4, Canada.ORCID 0000-0001-9116-1376
Dana L TudorascuDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Eduardo R ZimmerGraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, 2600 Ramiro Barcelos, Porto Alegre, RS, 90035-003, Brazil.ORCID 0000-0002-5349-0053
Bruna BellaverDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.ORCID 0000-0002-2212-3373
Tharick A PascoalDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA. pascoalt@upmc.edu.

Funding

Alzheimer's Association 24AACSF-1200375Alzheimer's Association 24AARFD-1243899Alzheimer's Association AARFD-22-923814Alzheimer's Association AARFD-22-974627Alzheimer's Association AARFD-23-1150249Alzheimer's Association AARFD-24-1313939Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brazilian Federal Agency for the Support and Evaluation of Graduate Education) 88887.951210/2024-00U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) 5R01AG073267U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) 5R01AG075336
6 · The paper itself

Abstract

Intracellular alpha-synuclein aggregates, known as Lewy bodies (LB), are commonly observed in Alzheimer's disease (AD) dementia. Post-mortem studies have shown a higher frequency of neuropsychiatric symptoms among individuals with AD and LB co-pathology. However, the effects of in vivo-measured LB pathology on neuropsychiatric symptoms in AD remain underexplored. This study aimed to evaluate cross-sectional and longitudinal effects of in vivo-measured LB pathology on neuropsychiatric symptoms across the AD continuum. We analyzed data from 1169 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants had in vivo measures of LB pathology (assessed using an alpha-synuclein seed amplification assay), amyloid-beta (Aβ) and phosphorylated tau (p-tau) levels in cerebrospinal fluid, and neuropsychiatric symptoms evaluated using the Neuropsychiatric Inventory-Questionnaire (NPI-Q). Logistic and Cox proportional hazards regression models were used to assess cross-sectional and longitudinal effects, respectively, adjusting for age, sex, and cognitive status. Participants had a mean baseline age of 73.05 (SD 7.22) years, 47.13% were women, 426 (36.44%) cognitively unimpaired, and 743 (63.56%) cognitively impaired. In cross-sectional analyses, LB pathology was associated with higher rates of anxiety, apathy, motor disturbances, and appetite disturbances. In longitudinal analyses, LB pathology increased the risk of developing psychosis and anxiety. These effects were independent of Aβ and p-tau. Our results suggest that in vivo-measured LB pathology is closely associated with neuropsychiatric symptoms across the AD continuum. These findings underscore the potential of in vivo LB detection as a marker for identifying individuals at increased risk of neuropsychiatric symptoms, both in clinical trials and in clinical practice.

Indexed as

Alzheimer DiseaseLewy BodiesAgedAged, 80 and overalpha-SynucleinAmyloid beta-PeptidesCognitive DysfunctionCross-Sectional StudiesFemaleHumansLewy Body DiseaseLongitudinal StudiesMaleNeuropsychological Teststau Proteinsalpha-SynucleinAmyloid beta-Peptidestau Proteins

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.