Thalamic Fractional Anisotropy Predicts Accrual of Cerebral White Matter Damage in Older Subjects with Small-Vessel Disease

Abstract

White matter hyperintensities (WMHs) and lacunes are magnetic resonance imaging hallmarks of cerebral small-vessel disease, which increase the risk of stroke, cognitive, and mobility impairment. Although most studies of cerebral small-vessel disease have focused on white matter abnormalities, the gray matter (GM) is also affected, as evidenced by frequently observed lacunes in subcortical GM. Diffusion tensor imaging (DTI) is sensitive to subtle neurodegenerative changes in deep GM structures. We explored the relationship between baseline DTI characteristics of the thalamus, caudate, and putamen, and the volume and subsequent accrual of WMHs over a 4-year period in 56 community-dwelling older (X75 years) individuals. Baseline thalamic fractional anisotropy (FA) was an independent predictor of WMH accrual. WMH accrual also correlated with baseline lacune count and baseline WMH volume, the latter showing the strongest predictive power, explaining 27.3% of the variance. The addition of baseline thalamic FA in multivariate modeling increased this value by 70%, which explains 46.5% of the variance in WMH accrual rate. Thalamic FA might serve as a novel predictor of cerebral small-vessel disease progression in clinical settings and trials. Furthermore, our findings point to the possibility of a causal relationship between thalamic damage and the accrual of WMHs.

Thalamic involvement in paroxysmal kinesigenic dyskinesia: A combined structural and diffusion tensor MRI analysis

“…In addition, it is of interest that increased FA in the thalamus was not accompanied by a significant change in MD. One explanation for our finding is that, although reduced rather than increased FA is considered the hallmark DTI correlate of microstructural WM damage, a more restricted intracellular (intraaxonal) water compartment associated with cytotoxic edema could result in increased FA with relatively low MD or no MD change, which supports the possibility that the observed DTI changes in the thalamus might primarily reflect WM injury [Cavallari et al, 2014]. A more plausible explanation is that extraaxonal degeneration in the thalamic nuclei might lead to increased FA with little or no MD change [Hannoun et al, 2012].…”

“…A more plausible explanation is that extraaxonal degeneration in the thalamic nuclei might lead to increased FA with little or no MD change [Hannoun et al, ]. This notion suggests that increased FA in the thalamus may reflect microstructural damage within the thalamic GM nuclei rather than WM damage, as supported by our finding of thalamic GM atrophy [Cavallari et al, ]. Nevertheless, the biophysical basis of pathologically increased FA remains to be elucidated in human.…”

Review of diffusion MRI studies in chronic white matter diseases

“…Studies on LA were entirely crosssectional [47,57,62] whereas studies related to VCI were predominantly longitudinal. Longitudinal studies [63,67,70,[78][79][80][81][83][84][85][86] focused on characterizing the disease progression using DTI measures.…”

Longitudinal change of small-vessel disease-related brain abnormalities

“…Important in this context, the prognostic value of baseline local DTI parameters for WML progression within a 4-year period has been reported. 72 So far, there have been only a few studies assessing the association between microstructural tissue alterations and cerebral vascular changes. A recent longitudinal study showed an association between small asymptomatic diffusion-weighted imaging hyperintense lesions and microstructural alterations and linked these results to vascular cognitive impairment.…”