Evidence map›Paper›PMID 42834227›Full record

ArticleJournal of neurology2026

External validation of an integrative model of functional impairment in early-stage behavioral variant frontotemporal dementia (bvFTD).

Electra Chatzidimitriou, Despina Moraitou, Panagiotis Ioannidis, Eleni Aretouli, Yu Chen, Howard J Rosen, Maria Luisa Gorno-Tempini, William W Seeley, Bruce L Miller, Katherine P Rankin

Abstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurology, 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

10 authors.

Electra ChatzidimitriouDepartment of Neurology, The Edward and Pearl Fein Memory and Aging Center, University of California, San Francisco, CA, USA. electra_hatzidimitriou@hotmail.com.ORCID http://orcid.org/0000-0003-2136-5220
Despina MoraitouDepartment of Cognition, Brain and Behavior, School of Psychology, Faculty of Philosophy, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Panagiotis Ioannidis2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Eleni AretouliDepartment of Psychology, School of Social Sciences, University of Ioannina, Ioannina, Greece.
Yu ChenDepartment of Neurology, The Edward and Pearl Fein Memory and Aging Center, University of California, San Francisco, CA, USA.
Howard J RosenDepartment of Neurology, The Edward and Pearl Fein Memory and Aging Center, University of California, San Francisco, CA, USA.
Maria Luisa Gorno-TempiniDepartment of Neurology, The Edward and Pearl Fein Memory and Aging Center, University of California, San Francisco, CA, USA.
William W SeeleyDepartment of Neurology, The Edward and Pearl Fein Memory and Aging Center, University of California, San Francisco, CA, USA.
Bruce L MillerDepartment of Neurology, The Edward and Pearl Fein Memory and Aging Center, University of California, San Francisco, CA, USA.
Katherine P RankinDepartment of Neurology, The Edward and Pearl Fein Memory and Aging Center, University of California, San Francisco, CA, USA.

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Katherine P Rankin · 2019 to 2026
$36.9M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1M
NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG062422NIA NIH HHS P50 AG023501NIH HHS P01AG019724NIH HHS P30AG062422NIH HHS P50AG023501NIH HHS R01/RFIAG029577The Fulbright Foundation in Greece and the Greek State Scholarships Foundation (IKY) "IKY-Fulbright" Scholarship Award
6 · The paper itself

Abstract

BACKGROUND/

objectivesFunctional decline in behavioral variant frontotemporal dementia (bvFTD) emerges early and significantly disrupts quality of life, yet its determinants remain incompletely understood. Integrative models capturing key disease manifestations may better explain its complexity but require validation in independent samples. This study aimed to examine whether a previously proposed model of functional impairment could be supported in a larger cohort and characterize the interrelationships among its cognitive, behavioral, personality, and neuroanatomical components.

methodsA total of 146 individuals with mild-stage bvFTD underwent structural MRI, neuropsychological assessment, and informant-based evaluation of behavioral symptoms, personality traits, and functional status. Penalized Least Absolute Shrinkage and Selection Operator (LASSO) regression identified the strongest correlates of functional impairment (Functional Activities Questionnaire/FAQ), while structural equation modeling examined their interrelationships.

resultsLASSO identified conscientiousness, apathy, global cognition, executive functioning, sarcasm perception, and semantic verbal fluency as significant correlates of functional status. The resulting path model demonstrated excellent fit and supported both neural-cognitive and behavioral-personality pathways. Reduced right superior frontal gyrus volume was associated with poorer executive and global cognitive performance, and through these variables, with greater functional impairment. In parallel, apathy demonstrated both direct and indirect associations with functional decline through conscientiousness.

conclusionsTwo partially distinct yet complementary processes appear to contribute to functional impairment in bvFTD: one reflecting the impact of frontal neurodegeneration on cognitive abilities essential for independent functioning, and another involving motivational and personality changes that directly undermine everyday engagement, thereby providing support for a multidimensional model of functional disability in bvFTD.

Indexed as

Frontotemporal DementiaPersonalityAgedFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological TestsBvFTDCognitive deficitsFunctional impairmentNeuroimagingNeuropsychiatric symptomsPath model

Identifiers

PMID42834227
PMCPMC13638733

What Socratic holds

Textmetadata
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 Socratic graph.