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@ARTICLE{Kancheva:281113,
author = {Kancheva, Ivana Kirilova and Bouzigues, Arabella and
Russell, Lucy Louise and Foster, Phoebe H and Ferry-Bolder,
Eve and Van Swieten, John C and Jiskoot, Lize Corrine and
Seelaar, Harro and Sánchez-Valle, Raquel and Laforce,
Robert and Graff, Caroline and Galimberti, Daniela and
Vandenberghe, Rik and de Mendonça, Alexandre and
Tiraboschi, Pietro and Santana, Isabel and Gerhard,
Alexander and Levin, Johannes and Sorbi, Sandro and Otto,
Markus and Ducharme, Simon and Butler, Christopher and Le
Ber, Isabelle and Finger, Elizabeth and Tartaglia, Maria
Carmela and Masellis, Mario and Synofzik, Matthis and
Moreno, Fermin and Borroni, Barbara and Rohrer, Jonathan
Daniel and van der Weerd, Louise and Rowe, James B and
Tsvetanov, Kamen},
collaboration = {Consortium, GENFI},
title = {{C}erebrovascular {R}eactivity at {R}est and {I}ts
{A}ssociation {W}ith {C}ognitive {F}unction in {P}eople
{W}ith {G}enetic {F}rontotemporal {D}ementia.},
journal = {Neurology},
volume = {105},
number = {6},
issn = {0028-3878},
address = {Philadelphia, Pa.},
publisher = {Wolters Kluwer},
reportid = {DZNE-2025-01074},
pages = {e213677},
year = {2025},
abstract = {Cerebrovascular reactivity (CVR) is an indicator of
cerebrovascular health, and its signature in familial
frontotemporal dementia (FTD) remains unknown. The primary
aim was to investigate CVR in genetic FTD using an fMRI
index of vascular contractility termed resting-state
fluctuation amplitudes (RSFAs) and to assess whether RSFA
differences are moderated by age. A secondary aim was to
study the relationship between RSFA and
cognition.Participants included presymptomatic and
symptomatic C9orf72, GRN, and MAPT pathogenic variation
carriers, along with noncarriers, from the prospective
Genetic FTD Initiative cohort study. Cross-sectional
differences in CVR were assessed using both component-based
and voxel-level RSFA maps. To study disease
progression-related effects, the moderating effect of age on
differences between genetic status groups was analyzed using
generalized linear models. The influence of RSFA, and its
interaction with genetic status, on participants' cognitive
function was also examined. All models were adjusted for
sex, handedness, and scanning site and false discovery
rate-corrected at p < 0.05.A total of 284 presymptomatic and
124 symptomatic sequence variation carriers, and 265
noncarriers, were included in the analysis (mean age 48.17
years, $55\%$ female). Across the sample, symptomatic
carriers exhibited lower RSFA and a greater age-related RSFA
decline predominantly in the medial frontal (-0.07 standard
units, p = 0.046, $95\%$ CI -0.13 to -0.01) and posterior
parietal (-0.06 standard units, p = 0.048, $95\%$ CI -0.12
to 0.01) cortex, compared with presymptomatic carriers and
noncarriers. RSFA was inversely correlated with age (-0.43
standard units, p < 0.001, $95\%$ CI -0.48 to -0.37) and
positively associated with cognitive function (0.09 standard
units, p = 0.008, $95\%$ CI 0.04-0.15), particularly in the
prefrontal cortex, in sequence variation carriers across the
sample, independent of disease stage.CVR impairment in
genetic FTD has a predilection for the middle frontal and
posterior cortex, and its preservation may yield a cognitive
benefit for at-risk individuals. Although findings do not
provide causality and warrant replication, they support the
notion that vascular dysfunction in familial FTD may be a
target for biomarker identification and disease-modifying
efforts.},
keywords = {Humans / Male / Female / Frontotemporal Dementia: genetics
/ Frontotemporal Dementia: physiopathology / Frontotemporal
Dementia: diagnostic imaging / Frontotemporal Dementia:
psychology / Middle Aged / Magnetic Resonance Imaging /
Cognition: physiology / Aged / C9orf72 Protein: genetics /
Cross-Sectional Studies / tau Proteins: genetics /
Cerebrovascular Circulation: physiology / Progranulins:
genetics / Adult / Brain: diagnostic imaging / Brain:
physiopathology / Brain: blood supply / Rest / C9orf72
Protein (NLM Chemicals) / tau Proteins (NLM Chemicals) /
MAPT protein, human (NLM Chemicals) / C9orf72 protein, human
(NLM Chemicals) / Progranulins (NLM Chemicals) / GRN
protein, human (NLM Chemicals)},
cin = {AG Levin / Clinical Research (Munich) / AG Gasser},
ddc = {610},
cid = {I:(DE-2719)1111016 / I:(DE-2719)1111015 /
I:(DE-2719)1210000},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40906975},
doi = {10.1212/WNL.0000000000213677},
url = {https://pub.dzne.de/record/281113},
}