Effect Of White Matter Lesions Research Articles

Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease

Gait disturbances are common in the elderly. Cerebral small vessel disease, including white matter lesions and lacunars infarcts, is thought to disrupt white matter tracts that connect important motor regions, hence resulting in gait disturbances. Pathological studies have demonstrated abnormalities in white matter that may appear normal on brain imaging. The loss of integrity in such normal-appearing white matter may partly be due to small vessel disease and may play a role in causing gait disturbances. The white matter regions involved in these gait disturbances, both in white matter lesions and normal-appearing white matter, remain unclear. We, therefore, aimed to investigate the relation between the location of white matter lesions and gait using voxel-based morphometry analysis, as well as between white matter integrity and gait by applying tract-based spatial statistics to diffusion tensor imaging parameters. Magnetic resonance imaging was carried out on 429 individuals in the age range of 50 and 85 years, with cerebral small vessel disease without dementia or parkinsonism. Gait was assessed quantitatively. White matter lesions, especially in the centrum semiovale and periventricular frontal lobe, were related to a lower gait velocity, shorter stride length and broader stride width. Loss of white matter integrity, as indicated by a lower fractional anisotropy and higher mean diffusivity, in numerous regions was related to a lower gait performance. Most of these regions were located in the normal-appearing white matter. The strongest significant association was found in the corpus callosum, particularly the genu. Most of the associations in the normal-appearing white matter disappeared after controlling for white matter lesions and lacunar infarcts, except for some in the corpus callosum. In conclusion, our study showed that using a combination of voxel-based morphometry analysis of the white matter lesions and diffusion tensor imaging is of added value in investigating the pathophysiology of gait disturbances in subjects with small vessel disease. Our data demonstrate that, in elderly subjects with small vessel disease, widespread disruption of white matter integrity, predominantly in the normal-appearing white matter, is involved in gait disturbances. In particular, loss of fibres interconnecting bilateral cortical regions, especially the prefrontal cortex that is involved in cognitive control on motor performance, may be important. The most important mechanisms underlying affected normal-appearing white matter are probably a direct effect of small vessel disease or, indirectly, remote effects of white matter lesions and lacunar infarcts.

Vascular risk factors and the effect of white matter lesions on extrapyramidal signs in Alzheimer's disease

Extrapyramidal signs (EPSs), which are important characteristics of Parkinson's disease (PD), occur frequently in Alzheimer's disease (AD). Although AD and PD share common clinical features such as EPSs, these diseases vary with respect to vascular risk factors. The presence of vascular risk factors increases the risk of AD; however, these factors have been known to be inversely associated with PD. We aimed to assess the effect of vascular risk factors and white matter lesions (WMLs) on EPSs in AD. We recruited 1,187 AD patients and 333 controls with neither cognitive impairment nor EPSs. All participants underwent detailed clinical evaluations which included assessments of vascular risk factors, cognitive function, and EPSs, as well as WMLs on brain MRIs. EPS subtypes were classified into tremor-dominant, postural instability gait difficulty, or indeterminate; WMLs subtypes were classified into periventricular WML (pvWML) or deep WML (dWML). EPSs were present in 17.9% of subjects with AD and were significantly associated with vascular risk factors such as age, male gender, diabetes mellitus, and WMLs. Additionally, a multivariate logistic regression analysis showed that EPSs in AD were associated with pvWML (odds ratio (OR), 1.61-2.52), not with dWML. With respect to EPS subtypes, the majority (78.4%) of EPSs in AD were postural instability gait difficulty, which was also associated with WMLs (OR 1.84-2.41), pvWML (OR 2.09-3.14), and dWML (OR 1.83-3.42). EPSs in AD are associated with selected vascular risk factors as well as WMLs.

Joint Effect of White Matter Lesions and Hippocampal Volumes on Severity of Cognitive Decline: The 3C-Dijon MRI Study

Several brain magnetic resonance imaging (MRI) changes are observed in older individuals including white matter lesions (WML), silent brain infarcts (SBI), and cerebral atrophy. Few studies, however, have assessed the combined association of these changes on the severity of future cognitive decline. In the prospective population-based 3C-Dijon MRI study, 1701 non-demented participants aged 65 to 80 years at entry had a brain MRI. Information on WML, hippocampal volumes, SBI presence, and brain parenchymal fraction were obtained. At 4-year follow-up, participants were screened for cognitive decline and dementia. Severity of cognitive decline was defined as none, moderate, or severe calculated from neuropsychological test performance change. The relation between brain MRI markers and longitudinal change in cognition was studied using polytomous logistic regression and multiple linear regression models controlling for potential confounders. Two-by-two interactions were tested including with the apolipoprotein E genotype. At follow-up, 46 participants showed severe cognitive deterioration and 224 participants showed moderate cognitive deterioration. In multivariable analyses, risk of severe cognitive deterioration as well as the cognitive decline rate were significantly increased in participants with higher WML volume (p< 0.01) and smaller hippocampal volume (p< 0.01). The results suggested that WML and hippocampal volumes had a cumulative effect on the future level of cognitive decline. The APOE genotype was found to be an effect modifier of this association. Vascular brain changes and degenerative processes coexist in normal older individuals. The co-occurrence of degenerative and non-degenerative pathologies could strongly affect the course of dementia expression.

White matter hyperintensities and cognitive dysfunction in Alzheimer's disease

Background: The effect of white matter lesions or vascular atherosclerosis on cognitive function is not fully understood. In this investigation the authors examined the influence of white matter lesions or cerebrovascular stenosis on cognitive decline in Alzheimer's disease. Methods: 137 patients (42 men, mean age 64.6±8.8 years; mean education period 8.0±4.9 years) were included; all were diagnosed as having Alzheimer disease at Seoul National University Hospital. Patients were divided into four groups based on the severities of white matter hyperintensities, the presence of vascular stenosis, or lacunar infarction in brain magnetic resonance (MR) images, and Mini-Mental Status Examination (MMSE) scores and Clinical Dementia Ratings (CDR) were compared.

White Matter Hyperintensities and Cognitive Dysfunction in Alzheimer Disease

The effect of white matter lesions in magnetic resonance imaging or vascular atherosclerosis on cognitive function is not fully understood in Alzheimer disease (AD). In this investigation, we examined the influence of white matter lesions on cognitive decline in AD. A total of 142 patients with AD (44 men, mean age 65.7 + 7.6 years; mean education period 7.8 + 5.0 years) were included. Patients were divided into 4 groups based on the severities of white matter hyperintensities (WMH) in brain magnetic resonance images (MRI) using Fazekas scale. Cognitive functions were determined using the Korean version of the Mini-Mental State Examination (K-MMSE) and the Clinical Dementia Rating (CDR) scale before acetylcholinesterase inhibitors were administered. Of the 142 patients, 30% (43/142) had no white matter signal abnormality (grade 0). Fourteen percentage (20/142) were grade 1, 42% (59/142) grade 2, and 14% (20/142) were grade 3. Mean K-MMSE scores declined as MRI grades increased to grade 2 and 3 compared to grade 0 (P < .01). Clinical Dementia Ratings were also aggravated by MRI grade. These results remained significant after adjusting for compounding factors affecting cognitive functions; sex, age, number of years in full-time education, hypertension, diabetes, hypercholesterolemia, smoking, and atrial fibrillation. The presence of WMHs were associated with score of MMSE and CDR impairment in patients with AD. These features could be a correctable factor hastening cognitive decline in AD.

The effect of white matter lesions on cognition in the elderly—small but detectable

The extent to which white matter changes affect brain function in elderly individuals is a matter for debate. Although there is a consensus that large confluent white matter lesions (WMLs) can be attributed to small-vessel disease and might denote anatomical damage to axons, the clinical effect of WMLs with regard to cognitive impairment is less certain. In this Review, we argue that WMLs are associated with greater detectable progressive cognitive deterioration than is normal aging, but other causes of progressive cognitive deterioration, such as Alzheimer's disease, are associated with greater cognitive decline than are WMLs. This view has important implications for the development of drugs for the treatment and prevention of cognitive impairment and dementia.

Advances in Vascular Cognitive Impairment 2006

Vascular cognitive impairment is common and represents a spectrum of cognitive dysfunction associated with stroke and cardiovascular risk factors which may be slight, moderate or severe.1 Recently and as a major advance, the National Institute of Neurological Disorders and Stroke—Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Working Group published clinical and research standards for the description and study of vascular cognitive impairment.2 In this update we report advances in vascular cognitive impairment in the following areas: clinical trials and treatment, new risk factors, white matter disease, and genetics. Cardiovascular risk factors such as blood pressure elevation and hyperglycemia are prime targets for clinical trial study because they are believed to cause negative effects on brain structure and cognitive function and may even influence risk of Alzheimer disease (AD).3 Results of recently published observational epidemiological studies have fueled controversy in relation to the role of blood pressure on cognition because some studies such as the Honolulu Asia Aging Study4 and Cache County Study5 suggest that antihypertensive therapy may reduce risk of dementia and cognitive decline or reduce incidence of AD, respectively, whereas the Religious Orders Study6 did not find an association between blood pressure and risk of AD or cognitive decline. Meta-analysis of patients with cardiovascular and/or cerebrovascular disease who received blood pressure-lowering treatment show a trend toward prevention of dementia and/or cognitive decline;7 however, a systematic analysis of 3 studies comprising 12 091 patients with hypertension who were treated with either medication or lifestyle strategies for at least 6 months show no evidence that blood pressure-lowering prevents dementia or cognitive impairment.8 Lack of definitive results in some of these trials may be explained by insufficient power to detect treatment effects, measurement error in cognitive end points, variation in treatment effects between …

P2-331: Differential effects of white matter lesions on medial temporal lobe atrophy in early versus late onset Alzheimer’s disease

P2-331: Differential effects of white matter lesions on medial temporal lobe atrophy in early versus late onset Alzheimer’s disease

O3-04-08: Effect of white matter lesions on incidence of dementia in patients with stroke

O3-04-08: Effect of white matter lesions on incidence of dementia in patients with stroke

IC-102-05: Differential effects of white matter lesions on medial temporal lobe atrophy in early versus late onset Alzheimer’s disease

IC-102-05: Differential effects of white matter lesions on medial temporal lobe atrophy in early versus late onset Alzheimer’s disease

246 Novel ATP-competitive Akt inhibitors slow the progression of tumors in vivo

Interstitial concentration of amyloid beta (Aß) is positively related to synaptic activity in animal experiments. In humans, Aß deposition in Alzheimer's disease overlaps with cortical regions highly active earlier in life. White matter lesions (WML) disrupt connections between gray matter (GM) regions which in turn changes their activation patterns. Here, we tested if WML are related to Aß accumulation (measured with PiB-PET) and glucose uptake (measured with FDG-PET) in connected GM. WML masks from 72 cognitively normal (age 61.7 ± 9.6 years, 71% women) individuals were obtained from T2-FLAIR. MRI and PET images were normalized into common space, segmented and parcellated into gray matter (GM) regions. The effects of WML on connected GM regions were assessed using the Change in Connectivity (ChaCo) score. Defined for each GM region, ChaCo is the percentage of WM tracts connecting to that region that pass through the WML mask. The regional relationship between ChaCo, glucose uptake and Aß was explored via linear regression. Subcortical regions of the bilateral caudate, putamen, calcarine, insula, thalamus and anterior cingulum had WM connections with the most lesions, followed by frontal, occipital, temporal, parietal and cerebellar regions. Regional analysis revealed that GM with more lesions in connecting WM and thus impaired connectivity had lower FDG-PET (r = 0.20, p < 0.05 corrected) and lower PiB uptake (r = 0.28, p < 0.05 corrected). Regional regression also revealed that both ChaCo (β = 0.045) and FDG-PET (β = 0.089) were significant predictors of PiB. In conclusion, brain regions with more lesions in connecting WM had lower glucose metabolism and lower Aß deposition.

White matter lesions and dementia: MRI-pathological correlation.

An MRI-pathological correlation study was performed to determine the pathological background of white matter lesions depicted on MR images. The pathological findings were various combinations of myelin loss, axonal loss, scattered microinfarcts, astrogliosis, dilatation of perivascular space, and relative preservation of subcortical U-fibers. Concerning the dilated perivascular space, we proposed a new classification according to the present study: (1) état criblé in the basal ganglia and the thalamus, (2) état criblé in the cerebral white matter, (3) enlarged perivascular space of the lenticulostriate arteries, and (4) état criblé in other sites. In conclusion, when effects of white matter lesions on cognitive function are to be evaluated, it is necessary to clarify tissues in at least three sequences: T2-weighted, T1-weighted, and FLAIR method.

Cortical effects of white matter lesions identified by Tc-99m HMPAO spect: James M. Mountz, M.D., Ph.D., G. Deutsch, Ph.D., E. San Pedro, M.D., H.G. Lin, M.S., L.E. Harrell, M.D., Ph.D. University of Alabama at Birmingham Medical Center, Birmingham, AL

Cortical effects of white matter lesions identified by Tc-99m HMPAO spect: James M. Mountz, M.D., Ph.D., G. Deutsch, Ph.D., E. San Pedro, M.D., H.G. Lin, M.S., L.E. Harrell, M.D., Ph.D. University of Alabama at Birmingham Medical Center, Birmingham, AL