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

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.