Diagnostic Utility of Cerebral White Matter Integrity in Early Alzheimer's Disease

Abstract

We compared white matter integrity with brain atrophy in healthy controls and participants with very mild dementia (Clinical Dementia Rating 0 vs. 0.5) from the Brain Aging Project, a longitudinal study of aging and memory at the University of Kansas Medical Center. Structural magnetic resonance imaging and diffusion tensor imaging (DTI) including fractional anisotropy and mean diffusivity were performed on 27 patients with very mild dementia (Clinical Dementia Rating = 0.5) of the Alzheimer's type (DAT), and 32 cognitively normal subjects. Patient groups were compared across 6 volumetric measures and 14 DTI regions of interest. Very mildly demented patients showed expected disease-related patterns of brain atrophy with reductions in whole-brain and hippocampal volumes most prominent. DTI indices of white matter integrity were mixed. Right parahippocampus showed significant but small disease-related reductions in fractional anisotropy. Right parahippocampus and left internal capsule showed greater mean diffusivity in early DAT compared with controls. A series of discriminant analyses demonstrated that gray matter atrophy was a significantly better predictor of dementia status than were DTI indices. Brain atrophy was most strongly related to very mild DAT. Modest disease-related white matter anomalies were present in temporal cortex, and deep white matter had limited discriminatory diagnostic power, probably because of the very mild stage of disease in these participants.

MRI Signatures of Brain Macrostructural Atrophy and Microstructural Degradation in Frontotemporal Lobar Degeneration Subtypes

“…These microstructural alterations can be sensitively detected by using DTI. Unlike Alzheimer’s disease and mild cognitive impairment, in which white matter pathologies such as oligodendroglial apoptosis, myelin or axonal degenerations are often considered to occur secondarily to the neuron loss in cortices, and white matter alterations detected by DTI are usually to a less extent or magnitude than that detected by measuring gray matter atrophy [45, 46], white matter pathologies in FTLD may be a predominant event since the tau- or TDP- inclusions are observed directly in white matter [47, 48]. A recent pathological study further suggests that white matter pathology is a major feature of FTLD [49].…”

Promising Genetic Biomarkers of Preclinical Alzheimer's Disease: The Influence ofAPOEandTOMM40on Brain Integrity

“…Neurofibrillary tangle formation may initiate in subcortical nuclei such as the dorsal raphe and locus coeruleus, prior to spreading to transentorhinal regions [6, 7]. Findings also support that pathological changes in AD commence in the medial temporal lobe (MTL) [8–10], primarily in the entorhinal cortex (ERC) and hippocampus (HC) [11–13], which undergo initial gray matter (GM) loss. Recently, attention has also been directed towards the impact of pathological mechanisms on white matter (WM), as up to 50% of AD cases present with global WM deterioration in neuropathological examinations [14, 15].…”

White matter integrity and reaction time intraindividual variability in healthy aging and early-stage Alzheimer disease

“…Recent work suggests that examination of white matter integrity and potentially more sensitive metrics of cognitive performance beyond mean reaction time may facilitate understanding of brain-behavior associations in aging (Gunning-Dixon & Raz, 2000; Johnson et al, 2010; MacDonald, Li, & Bäckman, 2009; MacDonald, Nyberg, & Bäckman, 2006). The present paper focuses on the association between regional white matter volume and both cognitive intraindividual variability (IIV) and reaction time distribution parameters in cognitively normal and pathological aging.…”

“…White matter integrity has been shown to be compromised in both healthy aging and early-stage Alzheimer disease (AD; Gunning-Dixon et al, 2009; Johnson et al, 2010). First, consider the evidence regarding healthy aging.…”