Cortical T1w/FLAIR Ratio Associated with Cognitive Decline and Aβ Deposition in Alzheimer’s Disease
Poster No:
190
Submission Type:
Abstract Submission
Authors:
Christina Andica1,2, Koji Kamagata1, Takafumi Kitagawa1, Kaito Takabayashi1, Akifumi Hagiwara1, Rui Zou1, Rukeye Tuerxun1, Wataru Uchida2, Shigeki Aoki1,2
Institutions:
1Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan, 2Faculty of Health Data Science, Juntendo University, Chiba, Japan
First Author:
Christina Andica
Department of Radiology, Juntendo University Graduate School of Medicine|Faculty of Health Data Science, Juntendo University
Tokyo, Japan|Chiba, Japan
Department of Radiology, Juntendo University Graduate School of Medicine|Faculty of Health Data Science, Juntendo University
Tokyo, Japan|Chiba, Japan
Co-Author(s):
Takafumi Kitagawa
Department of Radiology, Juntendo University Graduate School of Medicine
Tokyo, Japan
Department of Radiology, Juntendo University Graduate School of Medicine
Tokyo, Japan
Kaito Takabayashi
Department of Radiology, Juntendo University Graduate School of Medicine
Tokyo, Japan
Department of Radiology, Juntendo University Graduate School of Medicine
Tokyo, Japan
Akifumi Hagiwara
Department of Radiology, Juntendo University Graduate School of Medicine
Tokyo, Japan
Department of Radiology, Juntendo University Graduate School of Medicine
Tokyo, Japan
Rukeye Tuerxun
Department of Radiology, Juntendo University Graduate School of Medicine
Tokyo, Japan
Department of Radiology, Juntendo University Graduate School of Medicine
Tokyo, Japan
Shigeki Aoki
Department of Radiology, Juntendo University Graduate School of Medicine|Faculty of Health Data Science, Juntendo University
Tokyo, Japan|Chiba, Japan
Department of Radiology, Juntendo University Graduate School of Medicine|Faculty of Health Data Science, Juntendo University
Tokyo, Japan|Chiba, Japan
Introduction:
Amyloid-β (Aβ) accumulation, a hallmark of Alzheimer's disease (AD), results from an imbalance between its production and clearance. In AD models, myelin dysfunction has been shown to promote Aβ production and deposition (Depp, 2023); however, myelin alterations in human AD remain unclear. While further validation is required, the T1-weighted/fluid-attenuated inversion recovery (T1w/FLAIR) ratio has emerged as a promising myelin proxy in multiple sclerosis, offering an alternative to the T1w/T2w ratio (Cappelle, 2022).
This study aimed to evaluate gray matter (GM) T1w/FLAIR ratio differences among healthy controls (HCs), individuals with subjective cognitive decline (SCD), early and late mild cognitive impairment (MCI), and AD patients using data from the Alzheimer's Disease Neuroimaging Initiative Phase 3 database (https://ida.loni.usc.edu/). Additionally, the study assessed correlations between the T1w/FLAIR ratio, cognitive scores, and Aβ deposition measured using Positron Emission Tomography (PET) scan.
This study aimed to evaluate gray matter (GM) T1w/FLAIR ratio differences among healthy controls (HCs), individuals with subjective cognitive decline (SCD), early and late mild cognitive impairment (MCI), and AD patients using data from the Alzheimer's Disease Neuroimaging Initiative Phase 3 database (https://ida.loni.usc.edu/). Additionally, the study assessed correlations between the T1w/FLAIR ratio, cognitive scores, and Aβ deposition measured using Positron Emission Tomography (PET) scan.
Methods:
This study analyzed data from 39 HCs, 39 individuals with SCD, 48 patients with early MCI, 47 with late MCI, and 39 patients AD (Table 1). Three-dimensional (3D) T1w and sagittal 3D FLAIR images were downloaded from the ADNI3 database. T1w/FLAIR ratio maps were generated using nonlinear calibration based on brain tissue, with white matter lesions excluded. (https://github.com/treanus/KUL_NIS/blob/master/docs/KUL_T1T2FLAIRMTR_ratio/KUL_T1T2FLAIRMTR_ratio.md). The GM was parcellated into 42 regions of interest (ROIs) per hemisphere using the Desikan-Killiany atlas and overlaid onto the GM-based spatial statistics skeleton (Ball, 2013).
The T1w/FLAIR ratio in 42 GM ROIs per hemisphere were compared across five groups using a general linear model, adjusting for age, sex, education, APOE4 status, and intracranial volume. Statistical significance was set at FDR-corrected P < 0.05 (42 ROIs), with Sidak correction applied for post-hoc pairwise comparisons. Partial correlation analyses were performed between T1w/FLAIR ratios showing significant between-group differences, cognitive scores (including the Clinical Dementia Rating Scale Sum of Boxes [CDR-SB] and Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 [ADAS-Cog 13]), as well as Aβ-PET standardised uptake value ratios (SUVR) and scale. The same covariates were used, with P < 0.05 considered significant.
The T1w/FLAIR ratio in 42 GM ROIs per hemisphere were compared across five groups using a general linear model, adjusting for age, sex, education, APOE4 status, and intracranial volume. Statistical significance was set at FDR-corrected P < 0.05 (42 ROIs), with Sidak correction applied for post-hoc pairwise comparisons. Partial correlation analyses were performed between T1w/FLAIR ratios showing significant between-group differences, cognitive scores (including the Clinical Dementia Rating Scale Sum of Boxes [CDR-SB] and Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 [ADAS-Cog 13]), as well as Aβ-PET standardised uptake value ratios (SUVR) and scale. The same covariates were used, with P < 0.05 considered significant.
Results:
A significantly lower T1w/FLAIR ratio was observed in the left insula (Fig. 1-A1) in HCs compared to patients with early MCI (P = 0.032), late MCI (P = 0.003), and AD (P = 0.0004). Additionally, HCs showed a significantly lower T1w/FLAIR ratio in the left pars triangularis (Fig. 1-B1) in HCs compared to patients with late MCI (P = 0.007) and AD (P = 0.007).
The T1w/FLAIR ratio in the left insula was significantly negatively correlated with CDR-SB (Fig. 1-A2(i); r = −0.240; P = 0.0005) and ADAS-Cog 13 (Fig. 1-A2(ii); r = −0.189; P = 0.007) scores. Meanwhile, the T1w/FLAIR ratio in the left parstriangularis showed a significant negative correlation with CDR-SB score (Fig. 1-B2; r = −0.150; P = 0.032). Furthermore, lower T1w/FLAIR ratio in the left insula was significantly correlated with Aβ-PET SUVR in the left insula (Fig. 1-A2(iii); r = −0.150; P = 0.026). Although not statistically significant, there was a trend indicating that a lower T1w/FLAIR ratio in the left insula was associated with a higher centiloid Aβ-PET scale (Fig. 1-A2(iv); r = −0.125; P = 0.073).
The T1w/FLAIR ratio in the left insula was significantly negatively correlated with CDR-SB (Fig. 1-A2(i); r = −0.240; P = 0.0005) and ADAS-Cog 13 (Fig. 1-A2(ii); r = −0.189; P = 0.007) scores. Meanwhile, the T1w/FLAIR ratio in the left parstriangularis showed a significant negative correlation with CDR-SB score (Fig. 1-B2; r = −0.150; P = 0.032). Furthermore, lower T1w/FLAIR ratio in the left insula was significantly correlated with Aβ-PET SUVR in the left insula (Fig. 1-A2(iii); r = −0.150; P = 0.026). Although not statistically significant, there was a trend indicating that a lower T1w/FLAIR ratio in the left insula was associated with a higher centiloid Aβ-PET scale (Fig. 1-A2(iv); r = −0.125; P = 0.073).
Conclusions:
Although histopathological validation is required, a lower T1w/FLAIR ratio in the left insula and pars triangularis in patients with MCI and AD, compared to HCs, may reflect alterations in myelin content. These GM microstructural changes are associated with cognitive decline and disease progression in AD. Furthermore, a lower T1w/FLAIR ratio may be linked to Aβ accumulation. Further studies are needed to confirm the T1w/FLAIR ratio as a reliable biomarker for AD.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Other Methods 2
Keywords:
Cognition
Cortex
Degenerative Disease
MRI
Myelin
STRUCTURAL MRI
1|2Indicates the priority used for review
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Provide references using APA citation style.
Cappelle, S. (2022). T1w/FLAIR ratio standardization as a myelin marker in MS patients. Neuroimage Clin, 36, 103248.
Depp, C. (2023). Myelin dysfunction drives amyloid-beta deposition in models of Alzheimer's disease. Nature, 618(7964), 349-357.