IC‐P‐187: CORTICAL T1‐W/T2‐W RATIO VALUES ARE HIGHER IN ALZHEIMER'S DISEASE COMPARED TO CONTROLS

Field: Neuroscience (Life Sciences)

The structural integrity of myelin decreases during normal ageing and neurological diseases. It is conceivable that alterations of myelin integrity in the brain contribute to cognitive decline in Alzheimer's disease (AD). Recently, Glasser & Van Essen (2011) have proposed that the ratio of T1-weighted by T2-weighted MRI reflects myelin content in grey matter of the cortex. Here, we used this technique to test the hypothesis that myelin is reduced in AD by comparing T1-w/T2-w ratios between subjects with AD-type dementia and cognitively intact controls (CN). High-resolution 3T structural T1-w and T2-w MRI scans of 260 CN (60±8years, 41%female, MMSE 28±2) and 378 AD (66±8years, 53%female, MMSE 21±5) patients were collected from the Amsterdam Dementia Cohort. First, T2-weighted images were registered to the T1-weighted images using SPM12. After segmentation and bias correction, the AAL atlas was warped from standard to subject space using inverse normalization parameters. Next, the T1-w images were divided by the T2-w images. T1/T2 ratios were computed across the whole cortex and within 78 cortical AAL atlas regions. T1/T2 ratios were compared between groups using general linear models with Bonferroni correction. We further explored whether T1/T2 ratios were related to AD pathological hallmarks by comparing T1/T2 ratios of patients with abnormal/normal levels of cerebrospinal fluid (CSF) amyloid-ß 1-42 (Aß42<680 pg/ml) and tau (>375 pg/ml). AD subjects showed a slight increased T1/T2 ratio across the whole cortex (p=.05; Fig.1a). At the regional level 9 anatomical areas showed higher T1/T2 ratios in AD-related brain regions in AD subjects, including the inferior parietal lobule, angular gyrus, anterior cingulate gyrus, and precuneus (Fig.2, all p<.0006(=Bonferroni)). Analysis of CSF Aβ42 showed higher global T1/T2 ratio values with abnormal Aβ42 (p=.03) and abnormal total tau concentrations (p=.05) (Fig.1b&c). Violin plot representation of mean T1/T2 ratios values of the whole cortex for (A.) AD and control subjects (F(1)=3.852.p= 050), (B.) subjects with normal and abnormal CSF Aβ42 values, (F(1)=4.922,p=.027), (C.) subjects with normal and abnormal CSF total tauvalues, (F(l)=3.867, p=.050). Sex, age, MRI scanner type, and total intracranial volume were taken as covariates. Statistical map of the difference in cortical T1/T2-weighted ratio values between AD and CN groups using a p value of < .0006. Images are scaled from moderate (yellow) to highly (red) significant. Brain regions: Anterior Cingulate Gyrus, Inferior Parietal Lobule, right Supramarginal Gyrus, Angular Gyrus, Precuneus. Contrary to our hypothesis, AD patients showed higher T1-w/T2-w ratios than controls. These increases tended to be most pronounced in anatomical areas known to be affected in AD, including the precuneus and parietal cortex. Increases in T1/T2 ratios were associated with amyloid and tau pathology. In future research we will further study which precise biological processes are associated with T1-w/T2-w ratios in AD. References: Glasser, M. F.,& Van Essen, D. C. (2011). Mapping Human Cortical Areas In Vivo Based on Myelin Content as Revealed by T1- and T2-Weighted MRI. Journal of Neuroscience, 31 (32), 11597–11616.