Distinct white matter injury associated with medial temporal lobe atrophy in Alzheimer's versus semantic dementia

Abstract

This study aims at further understanding the distinct vulnerability of brain networks in Alzheimer's disease (AD) versus semantic dementia (SD) investigating the white matter injury associated with medial temporal lobe (MTL) atrophy in both conditions. Twenty-six AD patients, twenty-one SD patients, and thirty-nine controls underwent a high-resolution T1-MRI scan allowing to obtain maps of grey matter volume and white matter density. A statistical conjunction approach was used to identify MTL regions showing grey matter atrophy in both patient groups. The relationship between this common grey matter atrophy and white matter density maps was then assessed within each patient group. Patterns of grey matter atrophy were distinct in AD and SD but included a common region in the MTL, encompassing the hippocampus and amygdala. This common atrophy was associated with alterations in different white matter areas in AD versus SD, mainly including the cingulum and corpus callosum in AD, while restricted to the temporal lobe - essentially the uncinate and inferior longitudinal fasciculi - in SD. Complementary analyses revealed that these relationships remained significant when controlling for global atrophy or disease severity. Overall, this study provides the first evidence that atrophy of the same MTL region is related to damage in distinct white matter fibers in AD and SD. These different patterns emphasize the vulnerability of distinct brain networks related to the MTL in these two disorders, which might underlie the discrepancy in their symptoms. These results further suggest differences between AD and SD in the neuropathological processes occurring in the MTL. Hum Brain Mapp 38:1791-1800, 2017. © 2017 Wiley Periodicals, Inc.

Distinct Interplay Between Atrophy and Hypometabolism in Alzheimer’s Versus Semantic Dementia

“…These lesions are associated with neurodegeneration, which is at least partly reflected in gray matter atrophy and glucose hypometabolism measured with structural MRI and positron emission tomography with 18 F-fluorodeoxyglucose ( 18 FDG-PET), respectively. The overlapping alterations in Alzheimer's disease and semantic dementia have been highlighted in previous neuroimaging studies showing common gray matter atrophy to both disorders in medial temporal lobe structures (e.g., hippocampus, amygdala, entorhinal and parahippocampal cortex), lateral temporal and orbitofrontal regions (Chan et al, 2001;Galton et al, 2001;Nestor et al, 2006;Schroeter and Neumann, 2011;La Joie et al, 2013Bejanin et al, 2017). Similarly, both Alzheimer's disease and semantic dementia harbored decreased metabolism in medial and lateral temporal regions (Nestor et al, 2006;Drzezga et al, 2008).…”

“…In semantic dementia, while the hippocampus is also atrophied, the metabolism of parietal regions is relatively preserved (Nestor et al, 2006;Desgranges et al, 2007;La Joie et al, 2013). A recent study demonstrated that atrophy in the same medial temporal area was associated with distinct white matter injury in Alzheimer's versus semantic dementia, i.e., the cingulum and corpus callosum in the former versus anterior temporal white matter fibers in the latter (Bejanin et al, 2017). Hence, distinct hypometabolism profiles might reflect the involvement of distinct brain networks related to the medial temporal lobe in Alzheimer's disease versus semantic dementia (La Joie et al, 2014;Bejanin et al, 2017).…”

Distinctive functional deficiencies in axonal conduction associated with two forms of cerebral white matter injury

“…Disruption in WM maturation leads to abnormal brain function correlated with numerous neuropsychological disorders . Furthermore, WM injury occurs in various CNS conditions/diseases, such as attention deficit‐hyperactive disorder, autism, multiple sclerosis, Alzheimer's disease, TBI, and stroke . WM recovery is also related to improved neurological function .…”

“…While the majority of research on brain injury has until relatively recently focused on injury to gray matter, the importance of characterizing injury to WM is now being appreciated. Indeed, using diffusion tensor imaging, electron microscopy and/or immunohistological techniques, WM damage has been implicated in a myriad of disorders and diseases, such as traumatic brain injury, attention deficit‐hyperactive disorder, autism, Alzheimer's disease, and stroke . Although these techniques have provided important information about the microstructural changes that occur in WM after injury, less focus has been given to accompanying the functional changes that occur after WM injury.…”

Measuring tissue variations in the human brain using quantitative MRI

“…Multi-echo gradient echo sequences have been already implemented in assessing myelin, axonal and extracellular compartments in white matter architecture and the compartments have shown to be affected by orientation and tissue microstructure (70,73,181). Myelin is the main constituent of white matter and variations in myelin have been associated with neurodegenerative diseases such as Alzheimer's disease, traumatic brain injury and multiple sclerosis (182)(183)(184). Myelin sheath consists of lipids and proteins and they induce specific susceptibilities as lipids have higher magnetic susceptibility than proteins (158,185,186).…”