Evidence map›Paper›PMID 41884594›Full record

ArticleBrain communications2026

Intracellular fluid accumulation underlies brain volume increases in early Alzheimer's disease.

Michalis Kassinopoulos, Paula Montesinos, Carles Falcon, Jordi Huguet, Carolina Minguillon, Karine Fauria, Gwendlyn Kollmorgen, Clara Quijano-Rubio, José Luis Molinuevo, Oriol Grau-Rivera and 6 more

Abstract read
In one paragraph

Article in Brain communications, 2026. 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.

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

16 authors.

Michalis KassinopoulosBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona 08005, Spain.ORCID https://orcid.org/0000-0003-4312-4401
Paula MontesinosPhilips Healthcare Iberia, Madrid 28050, Spain.
Carles FalconBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona 08005, Spain.
Jordi HuguetBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona 08005, Spain.
Carolina MinguillonBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona 08005, Spain.
Karine FauriaBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona 08005, Spain.
Gwendlyn KollmorgenRoche Diagnostics GmbH, Penzberg 82377, Germany.
Clara Quijano-RubioRoche Diagnostics International Ltd, Rotkreuz 6343, Switzerland.
José Luis MolinuevoBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona 08005, Spain.
Oriol Grau-RiveraBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona 08005, Spain.ORCID https://orcid.org/0000-0002-4730-5341
Henrik ZetterbergClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal 431 80, Sweden.ORCID https://orcid.org/0000-0003-3930-4354
Kaj BlennowClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal 431 80, Sweden.
Marc Suárez-CalvetBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona 08005, Spain.
Javier Sanchez-GonzalezPhilips Healthcare Iberia, Madrid 28050, Spain.
Juan Domingo GispertBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona 08005, Spain.
ALFA study

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In the preclinical stages of Alzheimer's disease, increased brain volume has been associated with amyloid-beta pathology, particularly in regions that undergo volume reductions as the disease progresses. Glial reactivity and water diffusion alterations have been linked to such macroscopic volumetric changes. Brain volume reductions have also been reported following amyloid-beta removal with anti-amyloid therapies with beneficial clinical effects, but it remains unclear whether these changes result from resolving amyloid-triggered neuroinflammation or neurodegeneration. Intravoxel incoherent motion modelling based on multi-shell diffusion-weighted imaging may provide a better understanding of the processes underlying these paradoxical changes. This study used intravoxel incoherent motion diffusion MRI to examine how alterations in cerebral water pools contribute to increased brain volume linked to amyloid-beta deposition and neuroinflammation in cognitively unimpaired individuals. We developed a three-compartment diffusion MRI model with four parameters of cerebral water diffusion: slow diffusion coefficient, fast diffusion coefficient, slow signal portion, and perfusion fraction. We computed these diffusion parameters in 297 cognitively unimpaired late middle-aged adults, 35% of whom showed evidence of amyloid deposition. We examined their correlation with demographic factors (age, sex, apolipoprotein E status), markers of Alzheimer's disease pathology, neurodegeneration, neuroinflammation, and mean diffusivity. Then, we identified regions showing grey matter volume increases related to amyloid burden and examined the association between grey matter volume and diffusion parameters within these regions. We did not find evidence of associations between diffusion parameters and amyloid-related biomarkers, whether assessed by PET or cerebrospinal fluid measures. In contrast, the four diffusion parameters showed strong and widespread associations with biomarkers of neuroinflammation and neurodegeneration, particularly in frontoparietal and cingulate regions. Additionally, in grey matter regions where volume increases were related to amyloid levels, volumes were negatively correlated with the slow diffusion coefficient (

Indexed as

amyloid PETbrain volumeearly ADmulti-shell DWIneuroinflammation

Identifiers

PMID41884594
PMCPMC13009408

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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.