White matter integrity and key structures affected in Alzheimer's disease characterized by diffusion tensor imaging

Abstract

White matter (WM) degeneration is suggested to predict the early signs of Alzheimer's disease (AD). The exact structural regions of brain circuitry involved are not known. This study aims to examine the associations between WM tract integrity, represented by the diffusion tensor imaging (DTI) measures, and AD diagnosis and to denote the key substrates in predicting AD. It included DTI measures of mean diffusivity (MD), fractional anisotropy, radial diffusivity and axial diffusivity of 18 main WM tracts in 84 non‐Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative dataset. The multivariable general linear model was used to examine the association of AD diagnosis with each DTI measure adjusting for age, gender and education. The corpus callosum, fornix, cingulum hippocampus, uncinate fasciculus, sagittal striatum, left posterior thalamic radiation and fornix‐stria terminalis showed significant increases in MD, radial and axial diffusivity, whereas the splenium of corpus callosum and the fornix showed significant decreases in fractional anisotropy among AD patients. Variable cluster analysis identified that hippocampus volume, mini‐mental state examination (MMSE), cingulate gyrus/hippocampus, inferior fronto‐occipital fasciculus and uncinate fasciculus are highly correlated in one cluster with MD measures. In conclusion, there were significant differences in DTI measures between the brain WM of AD patients and controls. Age is the risk factor associated with AD, not gender or education. Right cingulum gyrus and right uncinate fasciculus are particularly affected, correlating well with a cognitive test MMSE and MD measures for dementia in AD patients and could be a region of focus for AD staging.

White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer’s disease (AD) neuropathology: A hypothesis and review

“…Interest in white matter (WM) injury was stirred by the development of brain MRI techniques (Diffusion Tensor Imaging-DTI, and Diffusion Imaging) that made it possible to detect early injury to WM (Gold et al, 2012;Radanovic et al, 2013;Nasrabady et al, 2018;Xiao et al, 2022). Bartzokis et al (2004) examined human brains from normal aging and AD brains during life.…”

Aberrant microstructural integrity of white matter in mild and severe orthostatic hypotension: A NODDI study

“…A host of studies have documented the association of ATR, IFOF, ILF, and SLF with memory, 38 that of FM and ATR with executive function, 39 the role of ILF in visual processing and language understanding, 40,41 the putative role of UF in episodic memory, language and social emotional processing, 34 and that of CgC in episodic memory and executive function 29 . In a similar line, the damaged WM area is also associated with OH‐induced neurological diseases 29,42–44 and with cognition‐related plasma biomarkers, 45–47 which also supports that OH contributes to the occurrence of cognitive diseases 48–50 …”

Brain asymmetries from mid- to late life and hemispheric brain age

“…The strongest age-associations of asymmetries were observed for subcortical, ventricle-near structures. The general age-sensitivity of such structures 21,58,59 might be a reason for the observed age-associations in asymmetries, and hence pointing towards one hemisphere being stronger affected by degradation effects, or even the involvement of such regions in psychiatric and neurodegenerative disorders 40,55,58,[60][61][62][63][64][65] . For example, the hippocampus, a prominent limbic structure, presents relatively high levels of adult neurogenesis, which might potentially explain repeated findings of the region's associations with psychiatric disorders and disorder states such as depression, anxiety, schizophrenia, addiction, and psychosis 66,67 , and neurdegenerative disorders, especially Alzheimer's Disease 68 , but also ageing in general 69 .…”

“…The strongest positive age-relationships for T 1 -weighted features' asymmetry were observed for accumbens and WM surface area, as well as limbic structures such as amygdala, hippocampus, and cingulate. Limbic structures have previously been outlined as highly age-sensitive 21,58,59,69 . Higher asymmetrylevels might speak to asymmetric atrophy in these limbic regions, potentially explaining several ageing-related effects 9 .…”