Abstract
Myelin determines the conduction of neuronal signals along axonal connections in networks of the brain. Loss of myelin integrity in neuronal circuits might result in cognitive decline in Alzheimer's disease (AD). Recently, the ratio of T1‐weighted by T2‐weighted MRI has been used as a proxy for myelin content in gray matter of the cortex. With this approach, we investigated whether AD dementia patients show lower cortical myelin content (i.e., a lower T1‐w/T2‐w ratio value). We selected structural T1‐w and T2‐w MR images of 293 AD patients and 172 participants with normal cognition (NC). T1‐w/T2‐w ratios were computed for the whole brain and within 90 automated anatomical labeling atlas regions using SPM12, compared between groups and correlated with the neuronal injury marker tau in cerebrospinal fluid (CSF) and Mini Mental State Examination (MMSE). In contrast to our hypothesis, AD patients showed higher whole brain T1‐w/T2‐w ratios than NC, and regionally in 31 anatomical areas (p < .0005; d = 0.21 to 0.48), predominantly in the inferior parietal lobule, angular gyrus, anterior cingulate, and precuneus. Regional higher T1‐w/T2‐w values were associated with higher CSF tau concentrations (p < .0005; r = .16 to .22) and worse MMSE scores (p < .0005; r = −.16 to −.21). These higher T1‐w/T2‐w values in AD seem to contradict previous pathological findings of demyelination and disconnectivity in AD. Future research should further investigate the biological processes reflected by increases in T1‐w/T2‐w values.
Highlights
Alzheimer's disease (AD), the most common cause of dementia, is characterized by a progressive decline in cognition and is one of the major public health challenges of the 21st century (Scheltens et al, 2016)
We further investigated the influence of factors that are associated with AD, including cerebrospinal fluid (CSF) total-tau protein concentration, white matter hyperintensities (WMH), and global cognitive functioning that may contribute to alterations in T1-w/T2-w values
The main finding of our study was that T1-w/T2-w ratio values were higher in AD compared to controls, which was contrary to our expectation
Summary
Alzheimer's disease (AD), the most common cause of dementia, is characterized by a progressive decline in cognition and is one of the major public health challenges of the 21st century (Scheltens et al, 2016). An alternative approach of determining regional variation in cortical myelin content, the ratio of the signal intensity of the T1-weighted (T1-w) and T2-weighted (T2-w) image, has been proposed (Glasser & Van Essen, 2011). Recent studies have raised controversy on the interpretation of the T1-w/T2-w ratio, showing that this measure may reflect tissue microstructure other than myelin, such as axon and dendrite density or iron content (Arshad, Stanley, & Raz, 2017; Righart et al, 2017; Uddin, Figley, Marrie, & Figley, 2018; van Rooden et al, 2014). To better understand what this myelin proxy in AD reflects, we compared T1-w/T2-w ratio values between older adults with normal cognition and patients with AD-type dementia for the whole brain and on a regional level. We further investigated the influence of factors that are associated with AD, including cerebrospinal fluid (CSF) total-tau protein concentration, white matter hyperintensities (WMH), and global cognitive functioning that may contribute to alterations in T1-w/T2-w values
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