Association between white matter T1w/T2w ratio and cognitive function in FTD genetic mutation carriers - Poster presentation

Sep 30, 2026

Frontotemporal dementia (FTD) shows heterogeneous, progressive behavioral, language, and cognitive deficits linked to white matter (WM) abnormalities on MRI. In progranulin (GRN) mutation carriers, WM changes may relate to myelin deficits. This study tests whether GRN carriers have a reduced MRI T1w/T2w ratio relative to C9orf72 mutation carriers and noncarriers, and whether T1w/T2w associates with FTD-related cognitive functions across neuropsychological domains. GRN, C9orf72, and noncarrier controls (N=80) were assessed with z-transformed cognitive scores and WM region-of-interest T1w/T2w metrics.

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Abstract

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DOI: 10. 1002/alz70856_105626 BIOMARKERS POSTER PRESENTATION NEUROIMAGING Association between white matter T1w/T2w ratio and cognitive function in FTD genetic mutation carriers Hyunwoo Lee1 Dana Wittenberg2 Ian R MacKenzie2 Winston Huang2 Mirza Faisal Beg3 Karteek Ging-Yuek Robin Hsiung2 Popuri4 1 Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada 2 University of British Columbia, Vancouver, BC, Canada 3Simon Fraser University, Burnaby, BC, Canada 4 Memorial University Of Newfoundland, St. John’s, NF, Canada Correspondence Hyunwoo Lee, Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. Email: [hyunwoo.lee@ubc.ca](hyunwoo.lee@ubc.ca) Abstract Background: Frontotemporal dementia (FTD) presents with heterogeneous, progressive deficits in behavior, language, and cognition. These changes have been associated with white matter (WM) alterations on MRI, including white matter signal abnormalities and diffusion-based metrics. Recent pathological findings suggest that white matter changes in FTD, particularly in individuals with mutations in the progranulin gene (GRN), may be partly attributable to myelin deficits. The ratio of T1-weighed and T2-weighted images on MRI (T1w/T2w) has been demonstrated as an indicator of myelin content in the brain. We hypothesized that GRN mutation carriers would exhibit a reduced T1w/T2w ratio compared to those with mutations in the chromosome 9 open reading frame 72 (C9orf72) or noncarriers. Additionally, we hypothesized a correlation between the T1w/T2w ratio and FTD-related cognitive functions. Method: GRN, C9orf72, and noncarrier family controls(N = 80)were recruited through the University of British Columbia Familial FTD Study. Neuropsychological domains, including attention, language, visuospatial skills, working memory, verbal memory, and non-verbal memory, were examined using neuropsychological test batteries. All cognitive domain scores were transformed into z-scores. For each participant, T1wand T2w MRI were acquired using a 1.5T scanner. T1w and T2w images were spatially coregistered, followed by intensity standardization. Average T1w/T2w was calculated within the WM region-of-interest defined by the JHU WM Tractography Atlas. This was a cross-sectional analysis using baseline images. General linear models were used to:1)Conduct a group comparison between geneticvariants;and2)Find an association between T1w/T2w and the neuropsychological domains. Both models were adjusted for age, sex, white matter signal abnormalities, and symptomatic status. Result: T1w/T2w was significantly lower in GRN carriers, especially in the frontal lobar WM. There was no significant difference between C9orf72 and noncarriers. Lower This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2025;21(Suppl. 2):e105626. [https://doi.org/10.1002/alz70856_105626](https://doi.org/10.1002/alz70856_105626) wi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz) 1of2 BIOMARKERS T1w/T2w in the frontal lobe correlated with poorer working memory, language, and visuospatial scores. Conclusion: WM changes observed in GRN carriers may be associated with deficits in the maintenance of cerebral myelin. Furthermore, the association between cognitive changes and reduced T1w/T2w levels, particularly in the frontal lobar regions, suggests that further studies are warranted to understand the role of GRN in myelin health and the manifestation of FTD-related symptoms.

FAQs

What was the main hypothesis about the T1w/T2w ratio in GRN carriers?

The study hypothesized that individuals with GRN mutations would show a reduced T1w/T2w ratio compared with C9orf72 mutation carriers and noncarriers.

How were cognitive functions evaluated?

Neuropsychological domains including attention, language, visuospatial skills, working memory, verbal memory, and non-verbal memory were tested using neuropsychological test batteries, with scores transformed into z-scores.

What did the results show for differences between genetic groups?

T1w/T2w was significantly lower in GRN carriers, especially in frontal lobe WM, while there was no significant difference between C9orf72 carriers and noncarriers.

Sep 30, 2026

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