Evidence map›Paper›PMID 37662359›Full record

ArticlebioRxiv : the preprint server for biology2023

Disrupted excitation-inhibition balance in cognitively normal individuals at risk of Alzheimer's disease.

Igor Fortel, Liang Zhan, Olusola Ajilore, Yichao Wu, Scott Mackin, Alex Leow

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Igor FortelDepartment of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL.
Liang ZhanDepartment of Electrical and Computer Engineering, University of Pittsburgh, Pittsburgh, PA.
Olusola AjiloreDepartment of Psychiatry, University of Illinois at Chicago, Chicago, IL.
Yichao WuDepartment of Math, Statistics and Computer Science, University of Illinois at Chicago, Chicago, IL.
Scott MackinDepartment of Psychiatry, University of California - San Francisco, San Francisco, CA.
Alex LeowDepartment of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL.
University of Illinois Chicago · USUniversity of California, San Francisco · USUniversity of Pittsburgh · US

Funding

WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI Tammie Lee Smith Benzinger · 1985 to 2026
$69.5M
The natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI SCHINDLER, SUZANNE ELIZABETH · 2005 to 2025
$49.5M
Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
Research Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI DAVID M. HOLTZMAN · 2020 to 2026
$28.7M
Ultrascale Machine Learning to Empower Discovery in Alzheimers Disease BiobanksU01AG068057 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Christos Davatzikos, Heng Huang · 2020 to 2026
$20.7M
THE XNAT IMAGING INFORMATICS PLATFORMR01EB009352 · NIBIB · WASHINGTON UNIVERSITY · PI Daniel Scott Marcus · 2009 to 2026
$9.3M
DRIVING PERFORMANCE IN PRECLINICAL ALZHEIMER'S DISEASER01AG043434 · NIA · WASHINGTON UNIVERSITY · PI ROE, CATHERINE M · 2012 to 2016
$2.4M
Connecting late-life depression and cognition with statistical physics based connectomics and sparse Frechet regressionRF1MH125928 · NIMH · UNIVERSITY OF ILLINOIS AT CHICAGO · PI LEOW, ALEX, WU, YICHAO · 2021 to 2021
$1.3M
CRCNS: Investigating Brain Dynamics through the Lens of Statistical MechanicsR01AG071243 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEOW, ALEX, ZHAN, LIANG · 2020 to 2022
$882k
NCATS NIH HHS UL1 TR000448NCATS NIH HHS UL1 TR002345NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG066444NIA NIH HHS R01 AG043434NIA NIH HHS R01 AG071243NIA NIH HHS U01 AG068057NIBIB NIH HHS R01 EB009352NIMH NIH HHS RF1 MH125928
6 · The paper itself

Abstract

Background: Sex differences impact Alzheimer's disease (AD) neuropathology, but cell-to-network level dysfunctions in the prodromal phase are unclear. Alterations in hippocampal excitation-inhibition balance (EIB) have recently been linked to early AD pathology. Objective: Examine how AD risk factors (age, APOE-ɛ4, amyloid-β) relate to hippocampal EIB in cognitively normal males and females using connectome-level measures. Methods: Individuals from the OASIS-3 cohort (age 42-95) were studied (N = 437), with a subset aged 65+ undergoing neuropsychological testing (N = 231). Results: In absence of AD risk factors (APOE-ɛ4/Aβ+), whole-brain EIB decreases with age more significantly in males than females (p = 0.021, β = -0.007). Regression modeling including APOE-ɛ4 allele carriers (Aβ-) yielded a significant positive AGE-by-APOE interaction in the right hippocampus for females only (p = 0.013, β = 0.014), persisting with inclusion of Aβ+ individuals (p = 0.012, β = 0.014). Partial correlation analyses of neuropsychological testing showed significant associations with EIB in females: positive correlations between right hippocampal EIB with categorical fluency and whole-brain EIB with the trail-making test (p < 0.05). Conclusion: Sex differences in EIB emerge during normal aging and progresses differently with AD risk. Results suggest APOE-ɛ4 disrupts hippocampal balance more than amyloid in females. Increased excitation correlates positively with neuropsychological performance in the female group, suggesting a duality in terms of potential beneficial effects prior to cognitive impairment. This underscores the translational relevance of APOE-ɛ4 related hyperexcitation in females, potentially informing therapeutic targets or early interventions to mitigate AD progression in this vulnerable population.

Identifiers

PMID37662359
PMCPMC10473582
OpenAlexW4386055646

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 OpenQuestion graph.