Abstract
Increased cerebral blood flow pulsatility is common in vascular dementia and is associated with macrostructural damage to cerebral white matter or leukoaraiosis (LA). In this study, we examine whether cerebral blood flow pulsatility is associated with macrostructural and microstructural changes in cerebral white matter in older adults with no or mild LA and no evidence of dementia. Diffusion Tensor Imaging was used to measure fractional anisotropy (FA), an index of the microstructural integrity of white matter, and radial diffusivity (RaD), a measure sensitive to the integrity of myelin. When controlling for age, increased arterial pulsation was associated with deterioration in both measures of white matter microstructure but not LA severity. A stepwise multiple linear regression model revealed that arterial pulsatility index was the strongest predictor of FA (R = 0.483, adjusted R2 = 0.220), followed by LA severity, but not age. These findings suggest that arterial pulsatility may provide insight into age-related reduction in white matter FA. Specifically, increased arterial pulsatility may increase perivascular shear stress and lead to accumulation of damage to perivascular oligodendrocytes, resulting in microstructural changes in white matter and contributing to proliferation of LA over time. Changes in cerebral blood flow pulsatility may therefore provide a sensitive index of white matter health that could facilitate the early detection of risk for perivascular white matter damage and the assessment of the effectiveness of preventative treatment targeted at reducing pulsatility.
Highlights
Cerebral white matter changes are prevalent in healthy ageing and are typically detected as leukoaraiosis (LA), a common radiological finding that presents as increased signal intensity on T2-weighted MR images
To determine whether increased pulsatility is related to microscopic white matter changes indicative of emerging tissue injury, we investigate the relationship between pulsation measures from cerebrospinal fluid (CSF), arterial and venous systems and measures of both macroscopic (LA severity) and microscopic (FA and radial diffusivity (RaD)) properties of the white matter in older participants with mild or no LA and no evidence of dementia
Aqueduct pulse volume was not related to LA severity (p > 0.10) but was significantly correlated with both fractional anisotropy (FA) (r = −0.404, p = 0.012 after Bonferroni correction) and RaD (r = 0.470, p = 0.001 after Bonferroni correction), and these correlations remained significant after correcting for age
Summary
Cerebral white matter changes are prevalent in healthy ageing and are typically detected as leukoaraiosis (LA), a common radiological finding that presents as increased signal intensity on T2-weighted MR images. In order to establish whether cerebral blood flow pulsatility may be a useful indicator of emerging white matter pathology in otherwise asymptomatic individuals, we examined the association between blood flow pulsatility and microstructural properties of white matter measured using Diffusion Tensor Imaging (DTI). This could, have implications for early detection of emerging white matter damage and guide interventions to stem the development of LA. The tissue damage that may result from such abnormal arterial/venous pulsatility has been termed pulse wave encephalopathy (Bateman, 2002)
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