White Matter Damage Along the Uncinate Fasciculus Contributes to Cognitive Decline in AD and DLB

Abstract

This study investigates the patho-physiological implications of the uncinate fasciculus (UF) in the two most common forms of dementia, namely Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Forty-five consecutive patients diagnosed with either probable AD or DLB, and 16 individuals with amnesic mild cognitive impairment (a-MCI) were investigated using diffusion tensor MRI. Thirteen healthy subjects (HS) were also studied as controls. In each subject, the UF was bilaterally reconstructed by probabilistic tractography. From each UF, macroscopic volume and correspondent fractional anisotropy (FA) (an index of microscopic white matter integrity) were derived for the whole tract, and for the frontal and temporal portion of the UF. No significant between-group volumetric differences were found. In contrast, FA values from the UF were reduced bilaterally in patients with dementia (either AD or DLB) compared to HS. In addition, patients with AD showed reduced FA values compared to those with a-MCI. No significant FA difference was found between AD and DLB patients, nor between a-MCI and HS. Finally, in all patients, UF FA values were associated with neuropsychological scores at tests exploring memory and executive functions. This study indicates that the UF is remarkably damaged in patients at the stage of dementia, independently from the diagnostic form. Moreover, this UF damage seems to be driven by temporal involvement in AD, for which a prodromal stage (a-MCI) is defined.

Correlates of virtual navigation performance in older adults

“…Although the function of the uncinate fasciculus is not well understood, it is thought to play a role in episodic memory formation and retrieval (Diehl et al, 2008; Levine et al, 1998). Differences in microstructural integrity of the uncinate fasciculus have been observed in Alzheimer’s disease (Kiuchi et al, 2009; Yasmin et al, 2008; Larroza et al, 2014; Serra et al, 2012), with FA in the bilateral uncinate fasciculus negatively associated with severity of cognitive impairment (Morikawa et al, 2010). While the findings in the present study did not survive correction for family-wise error, they provide suggestive evidence that microstructural differences in the uncinate fasciculus may contribute to age-related spatial navigation impairment.…”

Multimodal Voxel-Based Meta-Analysis of White Matter Abnormalities in Alzheimer’s Disease

“…The bilateral inferior temporal gyrus is traversed by uncinate fasciculus and the fornix terminalis, WM tracts involved in memory formation. The uncinate fasciculus is concerned with the verbal memory and immediate recall of word pairs by connecting the frontal lobe, the insula, and the rostral part of the temporal lobe [42]. The fornix connects with other key limbic structures and projects from the hippocampus to the anterior thalamic nuclei, mammillary bodies, striatum, and frontal cortex [43].…”

Alzheimer’s Disease Pathogenesis: The Denied Access Model

“…White matter atrophy is often considered secondary to gray matter damage [111], but recent developments determined white matter damage occurs in pre-AD stages and cannot be linked to gray matter atrophy [112,113]. Furthermore, studies analyzing white matter attributed the damage to cognitive decline [114] and discovered higher levels of soluble Aβ in AD patients [115].…”