Sex differences in clinical phenotypes of behavioral variant frontotemporal dementia

Xulin Liu; Sterre C.M. de Boer; Kasey Cortez; Jackie M. Poos; Ignacio Illán-Gala; Hilary Heuer; Leah K. Forsberg; Kaitlin Casaletto; Molly Memel; Brian S. Appleby; Sami Barmada; Andrea Bozoki; David Clark; Yann Cobigo; Ryan Darby; Bradford C. Dickerson; Kimiko Domoto-Reilly; Douglas R. Galasko; Daniel H. Geschwind; Nupur Ghoshal; Neill R. Graff-Radford; Ian M. Grant; Ging Yuek Robin Hsiung; Lawrence S. Honig; Edward D. Huey; David Irwin; Kejal Kantarci; Gabriel C. Léger; Irene Litvan; Ian R. Mackenzie; Joseph C. Masdeu; Mario F. Mendez; Chiadi U. Onyike; Belen Pascual; Peter Pressman; Ece Bayram; Eliana Marisa Ramos; Erik D. Roberson; Emily Rogalski; Arabella Bouzigues; Lucy L. Russell; Phoebe H. Foster; Eve Ferry-Bolder; Mario Masellis; John van Swieten; Lize Jiskoot; Harro Seelaar; Raquel Sanchez-Valle; Robert Laforce; Caroline Graff; ALLFTD Consortium and the GENFI Consortium

doi:10.1002/alz.14608

Sex differences in clinical phenotypes of behavioral variant frontotemporal dementia

Xulin Liu, Sterre C.M. de Boer, Kasey Cortez, Jackie M. Poos, Ignacio Illán-Gala, Hilary Heuer, Leah K. Forsberg, Kaitlin Casaletto, Molly Memel, Brian S. Appleby, Sami Barmada, Andrea Bozoki, David Clark, Yann Cobigo, Ryan Darby, Bradford C. Dickerson, Kimiko Domoto-Reilly, Douglas R. Galasko, Daniel H. Geschwind, Nupur GhoshalNeill R. Graff-Radford, Ian M. Grant, Ging Yuek Robin Hsiung, Lawrence S. Honig, Edward D. Huey, David Irwin, Kejal Kantarci, Gabriel C. Léger, Irene Litvan, Ian R. Mackenzie, Joseph C. Masdeu, Mario F. Mendez, Chiadi U. Onyike, Belen Pascual, Peter Pressman, Ece Bayram, Eliana Marisa Ramos, Erik D. Roberson, Emily Rogalski, Arabella Bouzigues, Lucy L. Russell, Phoebe H. Foster, Eve Ferry-Bolder, Mario Masellis, John van Swieten, Lize Jiskoot, Harro Seelaar, Raquel Sanchez-Valle, Robert Laforce, Caroline Graff, ALLFTD Consortium and the GENFI Consortium

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

INTRODUCTION: Higher male prevalence in sporadic behavioral variant frontotemporal dementia (bvFTD) has been reported. We hypothesized differences in phenotypes between genetic and sporadic bvFTD females resulting in underdiagnosis of sporadic bvFTD females. METHODS: We included genetic and sporadic bvFTD patients from two multicenter cohorts. We compared behavioral and cognitive symptoms, and gray matter volumes, between genetic and sporadic cases in each sex. RESULTS: Females with sporadic bvFTD showed worse compulsive behavior (p = 0.026) and language impairments (p = 0.024) compared to females with genetic bvFTD (n = 152). Genetic bvFTD females had smaller gray matter volumes than sporadic bvFTD females, particularly in the parietal lobe. DISCUSSION: Females with sporadic bvFTD exhibit a distinct clinical phenotype compared to females with genetic bvFTD. This difference may explain the discrepancy in prevalence between genetic and sporadic cases, as some females without genetic mutations may be misdiagnosed due to atypical bvFTD symptom presentation. HIGHLIGHTS: Sex ratio is equal in genetic behavioral variant of frontotemporal dementia (bvFTD), whereas more males are present in sporadic bvFTD. Distinct neuropsychiatric phenotypes exist between sporadic and genetic bvFTD in females. Phenotype might explain the sex ratio difference between sporadic and genetic cases.

Original language	English (US)
Article number	e14608
Pages (from-to)	e14608
Journal	Alzheimer's & dementia : the journal of the Alzheimer's Association
Volume	21
Issue number	4
DOIs	https://doi.org/10.1002/alz.14608
State	Published - Apr 1 2025

Keywords

behavioral variant frontotemporal dementia
clinical diagnosis
diversity
sex difference
Humans
Middle Aged
Male
Sex Characteristics
Frontotemporal Dementia/genetics
Gray Matter/pathology
Neuropsychological Tests
Magnetic Resonance Imaging
Brain/pathology
Phenotype
Sex Factors
Female
Aged
Cohort Studies

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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Liu, X., de Boer, S. C. M., Cortez, K., Poos, J. M., Illán-Gala, I., Heuer, H., Forsberg, L. K., Casaletto, K., Memel, M., Appleby, B. S., Barmada, S., Bozoki, A., Clark, D., Cobigo, Y., Darby, R., Dickerson, B. C., Domoto-Reilly, K., Galasko, D. R., Geschwind, D. H., ... ALLFTD Consortium and the GENFI Consortium (2025). Sex differences in clinical phenotypes of behavioral variant frontotemporal dementia. Alzheimer's & dementia : the journal of the Alzheimer's Association, 21(4), e14608. Article e14608. https://doi.org/10.1002/alz.14608

Liu, X, de Boer, SCM, Cortez, K, Poos, JM, Illán-Gala, I, Heuer, H, Forsberg, LK, Casaletto, K, Memel, M, Appleby, BS, Barmada, S, Bozoki, A, Clark, D, Cobigo, Y, Darby, R, Dickerson, BC, Domoto-Reilly, K, Galasko, DR, Geschwind, DH, Ghoshal, N, Graff-Radford, NR, Grant, IM, Hsiung, GYR, Honig, LS, Huey, ED, Irwin, D, Kantarci, K, Léger, GC, Litvan, I, Mackenzie, IR, Masdeu, JC, Mendez, MF, Onyike, CU, Pascual, B, Pressman, P, Bayram, E, Ramos, EM, Roberson, ED, Rogalski, E, Bouzigues, A, Russell, LL, Foster, PH, Ferry-Bolder, E, Masellis, M, van Swieten, J, Jiskoot, L, Seelaar, H, Sanchez-Valle, R, Laforce, R, Graff, C & ALLFTD Consortium and the GENFI Consortium 2025, 'Sex differences in clinical phenotypes of behavioral variant frontotemporal dementia', Alzheimer's & dementia : the journal of the Alzheimer's Association, vol. 21, no. 4, e14608, pp. e14608. https://doi.org/10.1002/alz.14608

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title = "Sex differences in clinical phenotypes of behavioral variant frontotemporal dementia",

abstract = "INTRODUCTION: Higher male prevalence in sporadic behavioral variant frontotemporal dementia (bvFTD) has been reported. We hypothesized differences in phenotypes between genetic and sporadic bvFTD females resulting in underdiagnosis of sporadic bvFTD females. METHODS: We included genetic and sporadic bvFTD patients from two multicenter cohorts. We compared behavioral and cognitive symptoms, and gray matter volumes, between genetic and sporadic cases in each sex. RESULTS: Females with sporadic bvFTD showed worse compulsive behavior (p = 0.026) and language impairments (p = 0.024) compared to females with genetic bvFTD (n = 152). Genetic bvFTD females had smaller gray matter volumes than sporadic bvFTD females, particularly in the parietal lobe. DISCUSSION: Females with sporadic bvFTD exhibit a distinct clinical phenotype compared to females with genetic bvFTD. This difference may explain the discrepancy in prevalence between genetic and sporadic cases, as some females without genetic mutations may be misdiagnosed due to atypical bvFTD symptom presentation. HIGHLIGHTS: Sex ratio is equal in genetic behavioral variant of frontotemporal dementia (bvFTD), whereas more males are present in sporadic bvFTD. Distinct neuropsychiatric phenotypes exist between sporadic and genetic bvFTD in females. Phenotype might explain the sex ratio difference between sporadic and genetic cases.",

keywords = "behavioral variant frontotemporal dementia, clinical diagnosis, diversity, sex difference, Humans, Middle Aged, Male, Sex Characteristics, Frontotemporal Dementia/genetics, Gray Matter/pathology, Neuropsychological Tests, Magnetic Resonance Imaging, Brain/pathology, Phenotype, Sex Factors, Female, Aged, Cohort Studies",

author = "Xulin Liu and \{de Boer\}, \{Sterre C.M.\} and Kasey Cortez and Poos, \{Jackie M.\} and Ignacio Ill{\'a}n-Gala and Hilary Heuer and Forsberg, \{Leah K.\} and Kaitlin Casaletto and Molly Memel and Appleby, \{Brian S.\} and Sami Barmada and Andrea Bozoki and David Clark and Yann Cobigo and Ryan Darby and Dickerson, \{Bradford C.\} and Kimiko Domoto-Reilly and Galasko, \{Douglas R.\} and Geschwind, \{Daniel H.\} and Nupur Ghoshal and Graff-Radford, \{Neill R.\} and Grant, \{Ian M.\} and Hsiung, \{Ging Yuek Robin\} and Honig, \{Lawrence S.\} and Huey, \{Edward D.\} and David Irwin and Kejal Kantarci and L{\'e}ger, \{Gabriel C.\} and Irene Litvan and Mackenzie, \{Ian R.\} and Masdeu, \{Joseph C.\} and Mendez, \{Mario F.\} and Onyike, \{Chiadi U.\} and Belen Pascual and Peter Pressman and Ece Bayram and Ramos, \{Eliana Marisa\} and Roberson, \{Erik D.\} and Emily Rogalski and Arabella Bouzigues and Russell, \{Lucy L.\} and Foster, \{Phoebe H.\} and Eve Ferry-Bolder and Mario Masellis and \{van Swieten\}, John and Lize Jiskoot and Harro Seelaar and Raquel Sanchez-Valle and Robert Laforce and Caroline Graff and \{ALLFTD Consortium and the GENFI Consortium\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2025",

month = apr,

day = "1",

doi = "10.1002/alz.14608",

language = "English (US)",

volume = "21",

pages = "e14608",

journal = "Alzheimer's \& dementia : the journal of the Alzheimer's Association",

issn = "1552-5260",

publisher = "Wiley",

number = "4",

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TY - JOUR

T1 - Sex differences in clinical phenotypes of behavioral variant frontotemporal dementia

AU - Liu, Xulin

AU - de Boer, Sterre C.M.

AU - Cortez, Kasey

AU - Poos, Jackie M.

AU - Illán-Gala, Ignacio

AU - Heuer, Hilary

AU - Forsberg, Leah K.

AU - Casaletto, Kaitlin

AU - Memel, Molly

AU - Appleby, Brian S.

AU - Barmada, Sami

AU - Bozoki, Andrea

AU - Clark, David

AU - Cobigo, Yann

AU - Darby, Ryan

AU - Dickerson, Bradford C.

AU - Domoto-Reilly, Kimiko

AU - Galasko, Douglas R.

AU - Geschwind, Daniel H.

AU - Ghoshal, Nupur

AU - Graff-Radford, Neill R.

AU - Grant, Ian M.

AU - Hsiung, Ging Yuek Robin

AU - Honig, Lawrence S.

AU - Huey, Edward D.

AU - Irwin, David

AU - Kantarci, Kejal

AU - Léger, Gabriel C.

AU - Litvan, Irene

AU - Mackenzie, Ian R.

AU - Masdeu, Joseph C.

AU - Mendez, Mario F.

AU - Onyike, Chiadi U.

AU - Pascual, Belen

AU - Pressman, Peter

AU - Bayram, Ece

AU - Ramos, Eliana Marisa

AU - Roberson, Erik D.

AU - Rogalski, Emily

AU - Bouzigues, Arabella

AU - Russell, Lucy L.

AU - Foster, Phoebe H.

AU - Ferry-Bolder, Eve

AU - Masellis, Mario

AU - van Swieten, John

AU - Jiskoot, Lize

AU - Seelaar, Harro

AU - Sanchez-Valle, Raquel

AU - Laforce, Robert

AU - Graff, Caroline

AU - ALLFTD Consortium and the GENFI Consortium

PY - 2025/4/1

Y1 - 2025/4/1

N2 - INTRODUCTION: Higher male prevalence in sporadic behavioral variant frontotemporal dementia (bvFTD) has been reported. We hypothesized differences in phenotypes between genetic and sporadic bvFTD females resulting in underdiagnosis of sporadic bvFTD females. METHODS: We included genetic and sporadic bvFTD patients from two multicenter cohorts. We compared behavioral and cognitive symptoms, and gray matter volumes, between genetic and sporadic cases in each sex. RESULTS: Females with sporadic bvFTD showed worse compulsive behavior (p = 0.026) and language impairments (p = 0.024) compared to females with genetic bvFTD (n = 152). Genetic bvFTD females had smaller gray matter volumes than sporadic bvFTD females, particularly in the parietal lobe. DISCUSSION: Females with sporadic bvFTD exhibit a distinct clinical phenotype compared to females with genetic bvFTD. This difference may explain the discrepancy in prevalence between genetic and sporadic cases, as some females without genetic mutations may be misdiagnosed due to atypical bvFTD symptom presentation. HIGHLIGHTS: Sex ratio is equal in genetic behavioral variant of frontotemporal dementia (bvFTD), whereas more males are present in sporadic bvFTD. Distinct neuropsychiatric phenotypes exist between sporadic and genetic bvFTD in females. Phenotype might explain the sex ratio difference between sporadic and genetic cases.

AB - INTRODUCTION: Higher male prevalence in sporadic behavioral variant frontotemporal dementia (bvFTD) has been reported. We hypothesized differences in phenotypes between genetic and sporadic bvFTD females resulting in underdiagnosis of sporadic bvFTD females. METHODS: We included genetic and sporadic bvFTD patients from two multicenter cohorts. We compared behavioral and cognitive symptoms, and gray matter volumes, between genetic and sporadic cases in each sex. RESULTS: Females with sporadic bvFTD showed worse compulsive behavior (p = 0.026) and language impairments (p = 0.024) compared to females with genetic bvFTD (n = 152). Genetic bvFTD females had smaller gray matter volumes than sporadic bvFTD females, particularly in the parietal lobe. DISCUSSION: Females with sporadic bvFTD exhibit a distinct clinical phenotype compared to females with genetic bvFTD. This difference may explain the discrepancy in prevalence between genetic and sporadic cases, as some females without genetic mutations may be misdiagnosed due to atypical bvFTD symptom presentation. HIGHLIGHTS: Sex ratio is equal in genetic behavioral variant of frontotemporal dementia (bvFTD), whereas more males are present in sporadic bvFTD. Distinct neuropsychiatric phenotypes exist between sporadic and genetic bvFTD in females. Phenotype might explain the sex ratio difference between sporadic and genetic cases.

KW - behavioral variant frontotemporal dementia

KW - clinical diagnosis

KW - diversity

KW - sex difference

KW - Humans

KW - Middle Aged

KW - Male

KW - Sex Characteristics

KW - Frontotemporal Dementia/genetics

KW - Gray Matter/pathology

KW - Neuropsychological Tests

KW - Magnetic Resonance Imaging

KW - Brain/pathology

KW - Phenotype

KW - Sex Factors

KW - Female

KW - Aged

KW - Cohort Studies

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UR - https://www.scopus.com/inward/citedby.url?scp=105004080507&partnerID=8YFLogxK

U2 - 10.1002/alz.14608

DO - 10.1002/alz.14608

M3 - Article

C2 - 40277074

AN - SCOPUS:105004080507

SN - 1552-5260

VL - 21

SP - e14608

JO - Alzheimer's & dementia : the journal of the Alzheimer's Association

JF - Alzheimer's & dementia : the journal of the Alzheimer's Association

IS - 4

M1 - e14608

ER -

Sex differences in clinical phenotypes of behavioral variant frontotemporal dementia

Abstract

Keywords

ASJC Scopus subject areas

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