Evidence map›Paper›PMID 36319674›Full record

Trial reportScientific reports2022

Morphometric imaging biomarker identifies Alzheimer's disease even among mixed dementia patients.

Florin V Chirila, Guang Xu, Dan Fontaine, Grant Kern, Tapan K Khan, Jason Brandt, Yoshihiro Konishi, Gerhard Nebe-von-Caron, Charles L White, Daniel L Alkon

Open access · goldAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

6 citing papers in PubMed, 5 citations in OpenAlex.

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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 at 5 institutions in 3 countries.

Florin V ChirilaSynaps Dx, 12358 Parklawn Drive, Rockville, MD, 20852, USA.
Guang XuSynaps Dx, 12358 Parklawn Drive, Rockville, MD, 20852, USA.
Dan FontaineSynaps Dx, 12358 Parklawn Drive, Rockville, MD, 20852, USA.
Grant KernSynaps Dx, 12358 Parklawn Drive, Rockville, MD, 20852, USA.
Tapan K KhanSynaps Dx, 12358 Parklawn Drive, Rockville, MD, 20852, USA.
Jason BrandtJohns Hopkins Hospital Psychiatry, 600 N Wolfe St # 384, Baltimore, MD, 21287, USA.
Yoshihiro KonishiNational Hospital Organization Tottori Medical Center Tottori, 876 Mitsu, Tottori, 689-0203, Japan.
Gerhard Nebe-von-CaronMologic, Bedford Technology Park, Thurleigh, Bedfordshire, MK44 2YA, UK.
Charles L WhiteDepartment of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9073, USA.
Daniel L AlkonSynaps Dx, 12358 Parklawn Drive, Rockville, MD, 20852, USA. dlalkon42@gmail.com.
Synaptic Research (United States) · USJohns Hopkins Hospital · USMologic (United Kingdom) · GBNational Hospital Organization · JPThe University of Texas Southwestern Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A definitive diagnosis of Alzheimer's disease (AD), even in the presence of co-morbid neuropathology (occurring in > 50% of AD cases), is a significant unmet medical need that has obstructed the discovery of effective AD therapeutics. An AD-biomarker, the Morphometric Imaging (MI) assay on cultured skin fibroblasts, was used in a double-blind, allcomers (ages 55-90) trial of 3 patient cohorts: AD dementia patients, N = 25, all autopsy confirmed, non-AD dementia patients, N = 21-all autopsy or genetically confirmed; and non-demented control (AHC) patients N = 27. Fibroblasts cells isolated from 3-mm skin punch biopsies were cultured on a 3-D Matrigel matrix with movement dynamics quantified by image analysis. From counts of all aggregates (N) in a pre-defined field image and measures of the average area (A) of aggregates per image, the number-to-area ratios in a natural logarithmic form Ln(A/N) were determined for all patient samples. AD cell lines formed fewer large aggregates (cells clustered together) than non-AD or AHC cell lines. The cut-off value of Ln(A/N) = 6.98 was determined from the biomarker values of non-demented apparently healthy control (AHC) cases. Unequivocal validation by autopsy, genetics, and/or dementia criteria was possible for all 73 patient samples. The samples were collected from multiple centers-four US centers and one center in Japan. The study found no effect of center-to-center variation in fibroblast isolation, cell growth, or cell aggregation values (Ln(A/N)). The autopsy-confirmed MI Biomarker distinguished AD from non-AD dementia (non-ADD) patients and correctly diagnosed AD even in the presence of other co-morbid pathologies at autopsy (True Positive = 25, False Negative = 0, False Positive = 0, True Negative = 21, and Accuracy = 100%. Sensitivity and specificity were calculated as 100% (95% CI = 84 to 100.00%). From these findings, the MI assay appears to detect AD with great accuracy-even with abundant co-morbidity.

Indexed as

Alzheimer DiseaseAgedAged, 80 and overAutopsyBiomarkersDouble-Blind MethodHumansMiddle AgedNeuropathologySensitivity and SpecificityBiomarkers

Identifiers

PMID36319674
PMCPMC9626495
OpenAlexW4308025759

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.