Evidence map›Paper›PMID 41428086›Full record

ArticleActa neuropathologica2025

Associations of pathologic Parkinson's disease (PD) and co-pathologies with cognitive decline and progression of parkinsonian signs in decedents with subclinical disease.

Aron S Buchman, Lei Yu, Shahram Oveisgharan, Nili Tickotsky, Katia de Paiva Lopes, Andrea R Zammit, Veronique VanderHorst, Hans-Urich Klein, Sukriti Nag, David A Bennett

Abstract read
In one paragraph

Article in Acta neuropathologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Aron S BuchmanRush Alzheimer's Disease Center, Rush University Medical Center, 1750 W; Harrison Street, Suite 1000, Chicago, IL, 60612, USA. Aron_S_Buchman@rush.edu.
Lei YuRush Alzheimer's Disease Center, Rush University Medical Center, 1750 W; Harrison Street, Suite 1000, Chicago, IL, 60612, USA.
Shahram OveisgharanRush Alzheimer's Disease Center, Rush University Medical Center, 1750 W; Harrison Street, Suite 1000, Chicago, IL, 60612, USA.
Nili TickotskyNanoscale Science and Technology Ben Gurion University, Beer Sheva, Israel.
Katia de Paiva LopesRush Alzheimer's Disease Center, Rush University Medical Center, 1750 W; Harrison Street, Suite 1000, Chicago, IL, 60612, USA.
Andrea R ZammitRush Alzheimer's Disease Center, Rush University Medical Center, 1750 W; Harrison Street, Suite 1000, Chicago, IL, 60612, USA.
Veronique VanderHorstDepartment of Neurology, Harvard Medical School, Boston, MA, USA.
Hans-Urich KleinCenter for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
Sukriti NagRush Alzheimer's Disease Center, Rush University Medical Center, 1750 W; Harrison Street, Suite 1000, Chicago, IL, 60612, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, 1750 W; Harrison Street, Suite 1000, Chicago, IL, 60612, USA.

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Risk Factors for Cognitive Decline in African-AmericansR01AG022018 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BARNES, LISA L · 2004 to 2025
$18.2M
Identifying resilience proteins in key motor tissues that drive motor and cognitive decline and offset the negative effects of ADRD pathologies within and outside the brainR01AG075728 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI ARON S BUCHMAN · 2022 to 2026
$6.9M
Impaired Gait in Older Adults: Pathologies of Alzheimer's disease and Related DisordersR01AG056352 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BUCHMAN, ARON S · 2017 to 2021
$3.5M
Spinal cord and brainstem pathology contributions to late-life gait impairmentR01AG047976 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BUCHMAN, ARON S · 2015 to 2019
$2.6M
NIA NIH HHS P30 AG010161NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG047976NIA NIH HHS R01 AG056352NIA NIH HHS R01 AG075728
6 · The paper itself

Abstract

To advance the nosology of pathologic Parkinson's disease (PD), we examined the associations of Lewy bodies (LBs), nigral neuronal loss (NNL), and co-pathologies with cognitive decline and progression of parkinsonian signs in older decedents without clinical PD during life. Nineteen cognitive tests and 26 Unified Parkinson's Disease Rating Scale items were measured annually. We measured both elements of pathologic PD, i.e., LBs and NNL, and eight other Alzheimer's disease and related dementias (ADRD) co-pathologies in 1717 brains. A semiquantitative scale (0-3) was used to assess NNL. Pathologic PD was based on the presence of LBs plus moderate or severe NNL. Possible pathologic PD was based on LBs alone or LBs with mild NNL. A series of bivariate linear mixed effect models jointly quantified cognitive decline and progressive parkinsonian signs in each decedent. Almost 30% of decedents without a diagnosis of clinical PD showed elements of pathologic PD [pathologic PD (8%); possible pathologic PD (19%)]. On average, pathologic PD accounted for 4.9% of the variance of cognitive decline and 9.4% of the variance of progression of parkinsonian signs controlling for ADRD pathologies. Adding another term for possible pathologic PD accounted for an additional 1.8% variance of cognitive decline but did not account for additional variance of progressive parkinsonian signs. Co-pathologies accounted for an additional 19% of cognitive decline and 7% of progressive parkinsonism. Thirty-three percent of the association of LBs with cognitive decline was attributable to NNL. In contrast, more than 70% of its association with progressive parkinsonism was attributable to NNL. Subclinical pathologic PD in older adults is heterogeneous. The associations of LBs with cognition and parkinsonism may vary with the severity of NNL and together with its co-pathologies account for a minority of late-life progressive parkinsonism and cognitive decline. Synucleinopathies in older adults without clinical PD may be underestimated.

Indexed as

BrainCognitive DysfunctionParkinson DiseaseParkinsonian DisordersAgedAged, 80 and overDisease ProgressionFemaleHumansLewy BodiesMaleMiddle AgedNeuropsychological TestsSubstantia NigraCognitive declineLewy bodiesLewy body dementiaNigral neuronal lossParkinsonismParkinson’s disease

Identifiers

PMID41428086
PMCPMC13087919

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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.