Evidence map›Paper›PMID 35836284›Full record

ArticleActa neuropathologica communications2022

Mitochondrial genomic variation in dementia with Lewy bodies: association with disease risk and neuropathological measures.

Rebecca R Valentino, Chloe Ramnarine, Michael G Heckman, Patrick W Johnson, Alexandra I Soto-Beasley, Ronald L Walton, Shunsuke Koga, Koji Kasanuki, Melissa E Murray, Ryan J Uitti and 18 more

Open access · goldAbstract read
In one paragraph

Article in Acta neuropathologica communications, 2022. 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
0.2field-weighted citation impact, top 52% of its field
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, 3 citations in OpenAlex.

  1. Article
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

28 authors at 5 institutions in 2 countries.

Rebecca R ValentinoDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Chloe RamnarineDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Michael G HeckmanDivision of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, 32224, USA.
Patrick W JohnsonDivision of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, 32224, USA.
Alexandra I Soto-BeasleyDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Ronald L WaltonDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Shunsuke KogaDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Koji KasanukiDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Melissa E MurrayDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Ryan J UittiDepartment of Neurology, Mayo Clinic, Jacksonville, FL, 32224, USA.
Julie A FieldsDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, 55905, USA.
Hugo BothaDepartment of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
Vijay K RamananDepartment of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
Kejal KantarciDepartment of Radiology, Mayo Clinic, Rochester, MN, 55905, USA.
Val J LoweDepartment of Radiology, Mayo Clinic, Rochester, MN, 55905, USA.
Clifford R JackDepartment of Radiology, Mayo Clinic, Rochester, MN, 55905, USA.
Nilufer Ertekin-TanerDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Rodolfo SavicaDepartment of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
Jonathan Graff-RadfordDepartment of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
Joseph E ParisiLaboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
R Ross ReichardLaboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, FL, 32224, USA.
Tanis J FermanDepartment of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, 32224, USA.
Bradley F BoeveDepartment of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
Zbigniew K WszolekDepartment of Neurology, Mayo Clinic, Jacksonville, FL, 32224, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Owen A RossDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. ross.owen@mayo.edu.ORCID 0000-0003-4813-756X
Mayo Clinic · USMayo Clinic in Florida · USWinnMed · USJacksonville College · USSt. Marianna University School of Medicine · JP

Funding

Technology and Remote Assessment CoreU19AG063911 · NIA · MAYO CLINIC ROCHESTER · PI ADAM L. BOXER, Bradley F Boeve · 2019 to 2026
$120.9M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI Walter K. Kremers · 2019 to 2026
$33.5M
Integrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, PETERS, METTE · 2013 to 2022
$24.6M
Longitudinal Imaging Biomarkers of Prodromal DLBU01NS100620 · NINDS · MAYO CLINIC ROCHESTER · PI Bradley F Boeve, KEJAL KANTARCI · 2017 to 2026
$19.2M
Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS)U01AG045390 · NIA · MAYO CLINIC ROCHESTER · PI BOEVE, BRADLEY F, ROSEN, HOWARD J · 2014 to 2018
$16.9M
Prevention of Alzheimer's disease in women: risks and benefits of hormone therapyRF1AG057547 · NIA · MAYO CLINIC ROCHESTER · PI GLEASON, CAREY E, KANTARCI, KEJAL · 2017 to 2020
$11.1M
Integrative translational discovery of vascular risk factors in aging and dementiaRF1AG051504 · NIA · MAYO CLINIC JACKSONVILLE · PI BU, GUOJUN, ERTEKIN-TANER, NILUFER · 2015 to 2019
$9.8M
Sex-Specific Effects of Endocrine Disruption on Aging and Alzheimer's DiseaseU54AG044170 · NIA · MAYO CLINIC ROCHESTER · PI KAPOOR, EKTA · 2018 to 2022
$7.7M
Longitudinal multi-modality imaging in progressive apraxia of speech (Diversity Supplement)R01DC012519 · NIDCD · MAYO CLINIC ROCHESTER · PI Jennifer Louise Whitwell · 2013 to 2026
$7.2M
Project 2: Identifying genes and Pathways that impact Tau Toxicity in FTDU54NS100693 · NINDS · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 2016 to 2020
$6.2M
Identifying Factors Predicting ACcurately End-of-Life in Dementia with Lewy Bodies and Promoting Quality End-of-Life Experiences: the PACE-DLB StudyR01AG068128 · NIA · UNIVERSITY OF FLORIDA · PI ARMSTRONG, MELISSA JO · 2020 to 2024
$3.4M
NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG62677-02NIA NIH HHS R01 AG051504NIA NIH HHS R01AG 68128NIA NIH HHS R34 AG056639NIA NIH HHS R43AG 65088NIA NIH HHS RF1 AG051504NIA NIH HHS RF1 AG057547NIA NIH HHS RF1AG 57547NIA NIH HHS U01 AG046139NIA NIH HHS U01AG 45390NIA NIH HHS U19 AG063911NIA NIH HHS U19AG 63911NIA NIH HHS U19 AG63911-02NIA NIH HHS U54 AG044170NIA NIH HHS U54AG 44170NIDCD NIH HHS R01 DC12519-06NINDS NIH HHS RO3 NS114365-01NINDS NIH HHS U01 NS100620NINDS NIH HHS U01NS 100620NINDS NIH HHS U54 NS100693NINDS NIH HHS U54-NS100693NINDS NIH HHS UH3NS 95495
6 · The paper itself

Abstract

Dementia with Lewy bodies (DLB) is clinically diagnosed when patients develop dementia less than a year after parkinsonism onset. Age is the primary risk factor for DLB and mitochondrial health influences ageing through effective oxidative phosphorylation (OXPHOS). Patterns of stable polymorphisms in the mitochondrial genome (mtDNA) alter OXPHOS efficiency and define individuals to specific mtDNA haplogroups. This study investigates if mtDNA haplogroup background affects clinical DLB risk and neuropathological disease severity. 360 clinical DLB cases, 446 neuropathologically confirmed Lewy body disease (LBD) cases with a high likelihood of having DLB (LBD-hDLB), and 910 neurologically normal controls had European mtDNA haplogroups defined using Agena Biosciences MassARRAY iPlex technology. 39 unique mtDNA variants were genotyped and mtDNA haplogroups were assigned to mitochondrial phylogeny. Striatal dopaminergic degeneration, neuronal loss, and Lewy body counts were also assessed in different brain regions in LBD-hDLB cases. Logistic regression models adjusted for age and sex were used to assess associations between mtDNA haplogroups and risk of DLB or LBD-hDLB versus controls in a case-control analysis. Additional appropriate regression models, adjusted for age at death and sex, assessed associations of haplogroups with each different neuropathological outcome measure. No mtDNA haplogroups were significantly associated with DLB or LBD-hDLB risk after Bonferroni correction.Haplogroup H suggests a nominally significant reduced risk of DLB (OR=0.61, P=0.006) but no association of LBD-hDLB (OR=0.87, P=0.34). The haplogroup H observation in DLB was consistent after additionally adjusting for the number of APOE ε4 alleles (OR=0.59, P=0.004). Haplogroup H also showed a suggestive association with reduced ventrolateral substantia nigra neuronal loss (OR=0.44, P=0.033). Mitochondrial haplogroup H may be protective against DLB risk and neuronal loss in substantia nigra regions in LBD-hDLB cases but further validation is warranted.

Indexed as

Genome, MitochondrialLewy Body DiseaseGenomicsHumansLewy BodiesSubstantia NigraDementia with Lewy-bodiesLewy body diseaseMitochondrial DNAMitochondrial haplogroupsNeuropathology

Identifiers

PMID35836284
PMCPMC9281088
OpenAlexW4285391231

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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.