Evidence map›Paper›PMID 38175995›Full record

ArticleNeurology2024

Neuropathologic Burden and Dementia in Nonagenarians and Centenarians: Comparison of 2 Community-Based Cohorts

Brenna Cholerton, Caitlin S Latimer, Paul K Crane, Maria M Corrada, Laura E Gibbons, Eric B Larson, Claudia H Kawas, C Dirk Keene, Thomas J Montine

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Primary age-related tauopathy.Acta neuropathologica · 2025
    Review
  3. Article
  4. Review
  5. 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

9 authors at 1 institution in 1 country.

Brenna CholertonFrom the Department of Pathology (B.C., T.J.M.), Stanford University School of Medicine, CA; Departments of Laboratory Medicine and Pathology (C.S.L., C.D.K.), Medicine (P.K.C.), and General Internal Medicine (L.E.G., E.B.L.), University of Washington, Seattle; Departments of Neurology (M.M.C., C.H.K.), Epidemiology (M.M.C.), and Neurobiology & Behavior (C.H.K.), University of California, Irvine; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle.ORCID 0000-0002-2139-987X
Caitlin S LatimerFrom the Department of Pathology (B.C., T.J.M.), Stanford University School of Medicine, CA; Departments of Laboratory Medicine and Pathology (C.S.L., C.D.K.), Medicine (P.K.C.), and General Internal Medicine (L.E.G., E.B.L.), University of Washington, Seattle; Departments of Neurology (M.M.C., C.H.K.), Epidemiology (M.M.C.), and Neurobiology & Behavior (C.H.K.), University of California, Irvine; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle.
Paul K CraneFrom the Department of Pathology (B.C., T.J.M.), Stanford University School of Medicine, CA; Departments of Laboratory Medicine and Pathology (C.S.L., C.D.K.), Medicine (P.K.C.), and General Internal Medicine (L.E.G., E.B.L.), University of Washington, Seattle; Departments of Neurology (M.M.C., C.H.K.), Epidemiology (M.M.C.), and Neurobiology & Behavior (C.H.K.), University of California, Irvine; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle.
Maria M CorradaFrom the Department of Pathology (B.C., T.J.M.), Stanford University School of Medicine, CA; Departments of Laboratory Medicine and Pathology (C.S.L., C.D.K.), Medicine (P.K.C.), and General Internal Medicine (L.E.G., E.B.L.), University of Washington, Seattle; Departments of Neurology (M.M.C., C.H.K.), Epidemiology (M.M.C.), and Neurobiology & Behavior (C.H.K.), University of California, Irvine; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle.ORCID 0000-0002-8168-8593
Laura E GibbonsFrom the Department of Pathology (B.C., T.J.M.), Stanford University School of Medicine, CA; Departments of Laboratory Medicine and Pathology (C.S.L., C.D.K.), Medicine (P.K.C.), and General Internal Medicine (L.E.G., E.B.L.), University of Washington, Seattle; Departments of Neurology (M.M.C., C.H.K.), Epidemiology (M.M.C.), and Neurobiology & Behavior (C.H.K.), University of California, Irvine; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle.
Eric B LarsonFrom the Department of Pathology (B.C., T.J.M.), Stanford University School of Medicine, CA; Departments of Laboratory Medicine and Pathology (C.S.L., C.D.K.), Medicine (P.K.C.), and General Internal Medicine (L.E.G., E.B.L.), University of Washington, Seattle; Departments of Neurology (M.M.C., C.H.K.), Epidemiology (M.M.C.), and Neurobiology & Behavior (C.H.K.), University of California, Irvine; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle.
Claudia H KawasFrom the Department of Pathology (B.C., T.J.M.), Stanford University School of Medicine, CA; Departments of Laboratory Medicine and Pathology (C.S.L., C.D.K.), Medicine (P.K.C.), and General Internal Medicine (L.E.G., E.B.L.), University of Washington, Seattle; Departments of Neurology (M.M.C., C.H.K.), Epidemiology (M.M.C.), and Neurobiology & Behavior (C.H.K.), University of California, Irvine; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle.
C Dirk KeeneFrom the Department of Pathology (B.C., T.J.M.), Stanford University School of Medicine, CA; Departments of Laboratory Medicine and Pathology (C.S.L., C.D.K.), Medicine (P.K.C.), and General Internal Medicine (L.E.G., E.B.L.), University of Washington, Seattle; Departments of Neurology (M.M.C., C.H.K.), Epidemiology (M.M.C.), and Neurobiology & Behavior (C.H.K.), University of California, Irvine; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle.
Thomas J MontineFrom the Department of Pathology (B.C., T.J.M.), Stanford University School of Medicine, CA; Departments of Laboratory Medicine and Pathology (C.S.L., C.D.K.), Medicine (P.K.C.), and General Internal Medicine (L.E.G., E.B.L.), University of Washington, Seattle; Departments of Neurology (M.M.C., C.H.K.), Epidemiology (M.M.C.), and Neurobiology & Behavior (C.H.K.), University of California, Irvine; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle.
University of California, Irvine · US

Funding

National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
Translational pharmacoepidemiology: neuroprotection and neurotoxicity of antihypertensives and strong anticholinergicsU19AG066567 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI CHRISTOPHER DIRK KEENE · 2021 to 2026
$80.4M
Furthering scientific understanding of mechanisms underlying resilience to the effects of AD pathology by incorporating state of the art quantification of gliosis, inflammation, & synaptic toxicityU01AG006781 · NIA · UNIVERSITY OF WASHINGTON · PI CRANE, PAUL K, LARSON, ERIC B · 1986 to 2020
$39.3M
UC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0M
Diversity Supplement to R01AG021055; Clinical, Imaging, and Pathological Studies in the Oldest Old: The 90+ StudyR01AG021055 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI CORRADA, MARIA, KAWAS, CLAUDIA H. · 2002 to 2024
$36.9M
University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI ALI SHOJAIE · 2020 to 2026
$29.0M
The Alzheimer's Disease Research Center at the University of California, IrvineP30AG066519 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Elizabeth Head · 2020 to 2026
$27.9M
Neuropathologic substrates for motor and cognitive impairment in three existing cohort studies of Alzheimer's disease and related dementiasUF1AG057707 · NIA · STANFORD UNIVERSITY · PI MONTINE, THOMAS J, WHITE, LON RAY · 2017 to 2017
$3.9M
Cognitive resilience to Alzheimer neuropathologic changes in the Honolulu-Asia Aging Study and the Nun StudyUF1AG053983 · NIA · PACIFIC HEALTH RESEARCH/ EDUCATION INST · PI MONTINE, THOMAS J, WHITE, LON RAY · 2016 to 2016
$2.6M
Molecular Mechanisms of Synergistic TDP-43 and Tau Proteotoxicity in Alzheimer's DiseaseK08AG065426 · NIA · UNIVERSITY OF WASHINGTON · PI LATIMER, CAITLIN SHANNON · 2020 to 2024
$705k
NIA NIH HHS K08 AG065426NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066519NIA NIH HHS P50 AG016573NIA NIH HHS R01 AG021055NIA NIH HHS U01 AG006781NIA NIH HHS U19 AG066567NIA NIH HHS U24 AG021886NIA NIH HHS UF1 AG053983NIA NIH HHS UF1 AG057707
6 · The paper itself

Abstract

BACKGROUND AND

objectivesThe aim of this study was to compare 2 large clinicopathologic cohorts of participants aged 90+ and to determine whether the association between neuropathologic burden and dementia in these older groups differs substantially from those seen in younger-old adults.

methodsAutopsied participants from The 90+ Study and Adult Changes in Thought (ACT) Study community-based cohort studies were evaluated for dementia-associated neuropathologic changes. Associations between neuropathologic variables and dementia were assessed using logistic or linear regression, and the weighted population attributable fraction (PAF) per type of neuropathologic change was estimated.

resultsThe 90+ Study participants (n = 414) were older (mean age at death = 97.7 years) and had higher amyloid/tau burden than ACT <90 (n = 418) (mean age at death = 83.5 years) and ACT 90+ (n = 401) (mean age at death = 94.2 years) participants. The ACT 90+ cohort had significantly higher rates of limbic-predominant age-related TDP-43 encephalopathy (LATE-NC), microvascular brain injury (μVBI), and total neuropathologic burden. Independent associations between individual neuropathologic lesions and odds of dementia were similar between all 3 groups, with the exception of μVBI, which was associated with increased dementia risk in the ACT <90 group only (odds ratio 1.5, 95% CI 1.2-1.8, DISCUSSION: Our results suggest that specific neuropathologic features may differ in their effect on dementia among nonagenarians and centenarians from cohorts with different selection criteria and study design. Furthermore, microvascular lesions seem to have a more significant effect on dementia in younger compared with older participants. The results from this study demonstrate that different populations may require distinct dementia interventions, underscoring the need for disease-specific biomarkers.

Indexed as

Alzheimer DiseaseDementiaNervous System DiseasesAged, 80 and overBrainCentenariansHumansNonagenariansTDP-43 Proteinopathies

Identifiers

PMID38175995
PMCPMC11097771
OpenAlexW4390575643

What Socratic holds

Textmetadata
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Registered trials

None linked

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 Socratic graph.