Baseline NAWM structural integrity and CBF predict periventricular WMH expansion over time

Abstract

CBF and DTI measures independently predict WMH growth over time. DTI is a more sensitive predictor of WMH growth than CBF, with WMH progression likely due to demyelinating injury secondary to low perfusion. Findings support the use of MD as a sensitive marker of NAWM vulnerability in future trials aimed at preserving WM integrity.

White matter regions with low microstructure in young adults are associated with white matter hyperintensities in late life

“…These findings are also consistent with previous results that observed a “penumbra” in white matter areas within close proximity to WMH that was most vulnerable to later development of WMH [20–22]. Interestingly, those studies suggest that WMH represent a “tip of the iceberg” phenomenon in which white matter microstructure and cerebral blood flow abnormalities extend beyond the identified borders of WMH (2-9mm and 13-14mm, respectively)[14] and portend the later development of frank WMH. Our findings complement these observations by demonstrating that there is lower white matter microstructure potentially decades prior to the development of WMH, and suggest that regional differences in white matter maturation lead to differential susceptibility to chronic hypoperfusion and contribute to the development of WMH.…”

“…The relationship between the distribution of the underlying FA measures and the occurrence of WMH has been shown in a longitudinal study of older adults [14], but our work shows that the relationship can be observed in adults as young as 20-30 years. The normative FA template was created from representative young, healthy adults.…”

“…We further demonstrated that white matter areas with normatively lower microstructure in young, healthy adults coincide with regions that are more likely to appear as WMH in older adults. This study used stringent inclusion/exclusion criteria to recruit a normative cohort of young, healthy adults [26–28] to join previous efforts that have exploited the complementary information provided by DTI measures and WMH [13, 23] in order to understand the relationship between microstructural and macrostructural white matter abnormalities in aging [13, 14, 34].…”

“…White matter hyperintensities have been linked to suboptimal cognitive outcomes [4, 5], Alzheimer’s disease (AD) risk [6, 7], emotional and motoric dysfunction [8], and risk of later development of stroke [9, 10]. There has been recent interest in understanding the nature of the regional distribution of WMH [11, 12] and the extent to which WMH reflect restricted, discrete damage or a “tip-of-the-iceberg” phenomenon in which the abnormal signal is a harbinger of widely-distributed white matter microstructural damage [13, 14].…”

“…While clinical-pathological correlation studies show that radiologically defined WMH are strongly associated with macrostructural damage in white matter secondary to small vessel ischemic changes [15–17], they also suggest widespread diminished microvascular density among individuals with marked WMH, even in white matter that is free of frank radiological abnormalities [14, 18]. More recently, the microstructure around tissue characterized as WMH has been interrogated with diffusion tensor imaging (DTI) [19] to reveal subtle abnormalities in white matter surrounding WMH [20–22].…”