Heterogeneity in age-related white matter changes

Abstract

White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they provide tools for the characterization of

Risk Factors and Cognitive Relevance of Cortical Cerebral Microinfarcts in Patients With Ischemic Stroke or Transient Ischemic Attack

“…14 Because pathological studies show that early confluent to confluent lesions are likely to represent true ischemic lesions associated with cerebral small vessel disease, whereas punctate lesions are commonly nonischemic, 15 severity of WMH was dichotomized into 2 levels: nonconfluent WMH and confluent WMH, which was defined as a score of ≥2 based on the Age-Related White Matter Changes Scale in at least 1 brain region. The ventricular-brain ratio, a marker of brain atrophy, was calculated as the mean of the biventricular width at the level of the frontal and occipital horns and at the level of the body of the caudate nuclei divided by the corresponding brain width at those levels on MRI.…”

Impact of the AGTR1 A1166C polymorphism on subcortical hyperintensities and cognition in healthy older adults

“…Although subcortical hyperintensities (SH) are associated with an aged vascular system and are common in older populations (Söderlund et al 2003), the severity and cognitive impact of SH is variable among older individuals (Schmidt et al 2011). The established relationship between AngII and vascular pathology suggests that predisposing risk factors for increased AT 1 expression may influence SH severity, especially in older patients.…”

White Matter Hyperintensity Volume and Cerebral Perfusion in Older Individuals with Hypertension Using Arterial Spin-Labeling

“…WMH prevalence estimates in asymptomatic older individuals range from 45% to Ͼ90%, depending on age and severity. 1 Clinically, WMHs are associated with cognitive decline, neuropsychiatric symptoms, loss of functional independence, and increased mortality. 2,3 Advanced age and hypertension are the strongest risk factors for WMHs, especially for the confluent subtype.…”