Quantitative T1 mapping (qT1) is a magnetic resonance imaging (MRI) biomarker of brain microstructural changes; however, its application in Alzheimer disease (AD) remains limited. We compared cortico-limbic qT1 values between patients with AD and healthy controls (HCs) and examined their relationship with amyloid burden measured by amyloid-positron emission tomography (PET). We retrospectively identified subjects with mild cognitive impairment due to AD and HCs who underwent 3-T MRI, including a compressed-sensing MP2RAGE sequence, generating three-dimensional T1-weighted images and qT1 maps. Amyloid-PET was available for 16 patients. Hippocampal qT1 and volume were compared between groups, adjusting for age and sex; analyses were repeated after stratifying patients by Mini-Mental State Examination (MMSE). Voxel-wise group comparison was performed using SPM 12. The qT1-standardized uptake value ratio (SUVr) association was assessed with a linear mixed-effects model applied to voxel-level data, accounting for partial volume effects. Thirty-three AD subjects, aged 69.3 ± 8.2 years (mean ± standard deviation), 18 females, and 22 HCs aged 70.5 ± 13.3 years, 15 females, were evaluated. Regional hippocampal qT1 was higher in AD (1,398 ± 53.0 ms versus 1,349 ± 53.4 ms; p = 0.002), without difference across cognitive subgroups stratified by MMSE. AD subjects exhibited increased qT1 in mesial temporal gray matter and temporo-parieto-occipital cortices (1,448 ± 55.7 ms versus 1,344 ± 51.6 ms; p < 0.001). Voxel-level modelling revealed a positive association between qT1 and amyloid-PET SUVr (p < 0.001; d = 0.223). qT1 mapping can be sensitive to changes related to brain amyloidosis, supporting its role as a promising, noninvasive imaging biomarker in AD. Question Can qT1 mapping detect AD-related microstructural changes in the cortico-limbic gray matter? Findings Participants with AD showed increased cortico-limbic qT1 values. A subtle yet consistent positive association was observed between cortical qT1 values and amyloid-PET SUVr. Relevance statement qT1 mapping captures microstructural tissue alterations related to amyloid pathology in Alzheimer’s disease, supporting its role as a potential non-invasive imaging biomarker in this condition.
L. Gualco, Noemi Montobbio, M. Losa et al.· European Radiology Experimen...· 0 citations
Importance
Capturing individual multiple sclerosis (MS) progression is difficult; few studies have evaluated glial fibrillary acidic protein (GFAP) in large longitudinal cohorts with independent validation.
Objective
To investigate whether serum GFAP levels and treatment-related changes are associated with future progression independent of relapse activity (PIRA).
Design, Setting, and Participants
This was a prospective observational study using 2 large MS cohorts: the Swiss MS Cohort (SMSC; initiated in June 2012; data extraction September 22, 2025) and the Expression, Proteomics, Imaging, Clinical study (EPIC; initiated in July 2004; data extraction February 21, 2024). The study took place at tertiary MS centers (8 for SMSC and 1 for EPIC). A total of 2329 persons with MS from both cohorts with at least 1 available time point with neurofilament light chain (NfL) and GFAP measurements were included (overall 18 629 measurements).
Exposures
Clinical data and NfL and GFAP z scores, collected and calculated every 6 or 12 months.
Main Outcomes and Measures
Risk of future PIRA, defined as Expanded Disability Status Scale score worsening confirmed after 6 or more months without relapses (in SMSC), or a composite additionally including greater than 20% worsening in the 9-hole peg test or timed 25-ft walk test (in EPIC).
Results
The SMSC and EPIC cohorts consisted of 1709 (13 375 samples; median [IQR] follow-up, 6.9 [2.5-10.7] years and age, 40.6 [32.1-50.1] years; 1128 [66.0%] female) and 620 (5254 samples; median [IQR] follow-up, 13.1 [9.4-14.0] years and age, 42.0 [35.0-50.0] years; 432 [69.7%] female) persons with MS, respectively. Consistent with prior work, high NfL was associated with relapse risk within the next year, whereas high GFAP was associated with long-term PIRA risk. In addition, elevated GFAP (z score >1.0 [84th percentile]) was associated with an average 40% higher hazard of short-term PIRA in the subsequent visit interval (SMSC: median [IQR] 346 [190-375] days; hazard ratio [HR], 1.45, 95% CI, 1.21-1.75; P < .001; EPIC: 385 [355-518] days; HR, 1.36; 95% CI, 1.07-1.71; P = .01). GFAP-based cohort enrichment in clinical trials targeting PIRA as an end point could reduce sample size by approximately 20%. Further, in SMSC, every yearly GFAP z score unit reduction during the first 2 years receiving fingolimod or B-cell-depleting therapy was associated with a lower risk of subsequent PIRA (54% risk reduction; HR, 0.46; 95% CI, 0.26-0.84; P = .01 and 67% risk reduction; HR, 0.33; 95% CI, 0.18-0.61; P < .001), respectively.
Conclusions and Relevance
In this cohort study, elevated GFAP was associated with a higher risk of PIRA, while treatment-associated reductions were associated with a lower PIRA risk. Together, these results suggest that serum GFAP may serve as a biomarker for personalized risk stratification and treatment monitoring and as a screening tool to reduce cohort size in clinical trials targeting MS progression.
M. Einsiedler, S. Sandgren, S. Schaedelin et al.· JAMA Neurology· 0 citations
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