Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD

Abstract

Objective-To analyze the extent and spatial distribution of white matter hyperintensities (WMH) in brain regions from cognitively normal older individuals (CN) and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD).Methods-We studied 26 mild AD, 28 MCI, and 33 CN. MRI analysis included quantification of WMH volume, nonlinear mapping onto a common anatomic image, and spatial localization of each WMH voxel to create an anatomically precise frequency distribution map. Areas of greatest frequency of WMH from the WMH composite map were used to identify 10 anatomic regions involving periventricular areas and the corpus callosum (CC) for group comparisons.Results-Total WMH volumes were associated with age, extent of concurrent vascular risk factors, and diagnosis. After correcting for age, total WMH volumes remained significantly associated with diagnosis and extent of vascular risk. Regional WMH analyses revealed significant differences in WMH across regions that also differed significantly according to diagnosis. In post-hoc analyses, significant differences were seen between CN and AD in posterior periventricular regions and the splenium of the CC. MCI subjects had intermediate values at all regions. Repeated measures analysis including vascular risk factors in the model found a significant relationship between periventricular WMH and vascular risk that differed by region, but regional differences according to diagnosis remained significant and there was no interaction between diagnosis and vascular risk.Conclusions-Differences in white matter hyperintensities (WMH) associated with increasing cognitive impairment appear related to both extent and spatial location. Multiple regression analysis of regional WMH, vascular risk factors, and diagnosis suggest that these spatial differences may result from the additive effects of vascular and degenerative injury. Posterior periventricular and corpus callosum extension of WMH associated with mild cognitive impairment and Alzheimer disease indicate involvement of strategic white matter bundles that may contribute to the cognitive deficits seen with these syndromes.White matter hyperintensities (WMH) are areas of increased signal on T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI sequences of the brain. In this study, we applied image segmentation and nonlinear image mapping techniques to determine the extent and spatial location of WMH among CN, MCI, and AD. We then tested whether differences in anatomic distribution were associated with cognitive status and vascular risk. The CDR score was determined independently of neuropsychological information according to published protocol. In addition, participants received a standardized MRI scan of the brain at the baseline evaluation. Methods SubjectsThe institutional review boards at all participating institutions approved this study, and subjects or their legal representatives gave written informed consent. Vascular risk factorsThe presence or absence of six cerebrovascular risk fact...

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

“…WMH assessed in aged and early AD cases found the burden of periventricular and deep WM was similar, but there was an exacerbation of global cognitive decline with early AD (Burns et al 2005). Consistent with these earlier studies is the report of the progressive increase of hyperintensities in the posterior periventricular WM and the splenium when comparing normal, mild cognitively impaired, and AD subjects (Yoshita et al 2006).…”

Differential Impact of Acute Lesions Versus White Matter Hyperintensities on Stroke Recovery

“…WMH, viewed on fluid‐attenuated inversion recovery (FLAIR) images, can be used as a measure of chronic white matter damage, though the pathophysiology is unclear. While WMH are observed in normal aging,12 they are seen in greater amounts in individuals with cognitive impairments 13. After stroke, WMH have been linked to neglect,14 cognitive impairment,15, 16 and overall functional outcome 17, 18, 19.…”

Classification of White Matter Lesions on Magnetic Resonance Imaging in Elderly Persons

“…Furthermore, WMLs are related to various geriatric disorders: cerebrovascular diseases (11)(12)(13), cardiovascular diseases (1,9,14), dementia (15)(16)(17), psychiatric disorders such as major depressive disorder (18)(19)(20), bipolar disorder (21), and schizophrenia (22), neurologic disorders such as multiple sclerosis (23) and normal pressure hydrocephalus (24), and inflammatory diseases such as systemic lupus erythematosus (25). Therefore, the presence, form and severity of WMLs may provide additional characterization of aging, pathophysiology of geriatric disorders, and the relation between aging and geriatric disorders.…”