Background/Aims: We investigated the histopathological correlates of white matter hyperintensities (WMHs) in participants with Alzheimer's disease (AD) or cerebrovascular disease, and in aged controls. Methods: We reviewed 57 participants who had neuropathology and in whom neuroimaging was done. In addition to AD pathology, cortical microinfarcts, lacunes, and cerebral hemorrhages were assessed. Small-vessel disease included arteriolosclerosis and cerebral amyloid angiopathy. Postmortem brain tissue corresponding to regions of WMHs was investigated in 14 participants. The variables included: demyelination of the deep and periventricular white matter (WM), atrophy of the ventricular ependyma, and thickness of blood vessels. Partial Spearman's rank test and linear regression analysis, adjusted for age at the clinical evaluation and the duration to death, were performed. Results: The severity of arteriosclerosis was correlated with the volume of periventricular hyperintensity (PVH) estimated by magnetic resonance imaging. Deep white matter hyperintensity (DWMH) volume was correlated with the presence of cortical microinfarcts and cerebral hemorrhages. The severity of the breakdown of the ventricular lining was correlated with PVHs, and DWMHs correlated with the severity of deep WM demyelination. The diameter of small blood vessels was not associated with WMHs. Conclusion: WMHs are consistent with small-vessel disease and increase the tissue water content. We found no association between WMHs and the thickness of small blood vessels. © 2014 S. Karger AG, Basel
Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and Alzheimer disease. Diffusion tensor imaging (DTI) can estimate the microstructural integrity of white matter tracts in MCI. We evaluated the microstructural changes in the white matter of MCI patients with DTI. We recruited 11 patients with MCI who met the working criteria of MCI and 11 elderly normal controls. The mean diffusivity (MD) and fractional anisotropy (FA) were measured in 26 regions of the brain with the regions of interest (ROIs) method. In the MCI patients, FA values were significantly decreased in the hippocampus, the posterior limb of the internal capsule, the splenium of corpus callosum, and in the superior and inferior longitudinal fasciculus compared to the control group. MD values were significantly increased in the hippocampus, the anterior and posterior limbs of the internal capsules, the splenium of the corpus callosum, the right frontal lobe, and in the superior and the inferior longitudinal fasciculus. Microstructural changes of several corticocortical tracts associated with cognition were identified in patients with MCI. FA and MD values of DTI may be used as novel biomarkers for the evaluation of neurodegenerative disorders.
Typically, reversible posterior leukoencephalopathy syndrome (RPLS) involves the parieto-occipital lobes. When regions of the brain other than the parieto-occipital lobes are predominantly involved, the syndrome can be called atypical RPLS. The purpose of this study is to find radiological and pathophysiological features of atypical RPLS by using diffusion-weighted imaging (D-WI). We retrospectively reviewed seven patients (two with eclampsia, one with cyclosporine neurotoxicity, and four with hypertensive encephalopathy) with atypical MR manifestations of RPLS. Changes in signal intensity on T2-weighted imaging (T2-WI) and D-WI, and ADC ratio, were analyzed. In patients with atypical manifestation of RPLS, high signal intensities on T2-WI were noted in the frontal lobe, basal ganglia, thalamus, brainstem, and subcortical white matter in regions other than the parieto-occipital lobes. These areas of increased signal intensities on T2-WI showed increased ADC values, representing vasogenic edema in all seven patients. This result should be very useful in differentiating atypical RPLS from other metabolic brain disorders that affect the same sites with cytotoxic edema.
Multiple neurological complications have been associated with the coronavirus disease-19 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. This is a narrative review to gather information on all aspects of COVID-19 in elderly patients with cognitive impairment. First, the following three mechanisms have been proposed to underlie the neurological complications associated with COVID-19: 1) direct invasion, 2) immune and inflammatory reaction, and 3) hypoxic brain damage by COVID-19. Next, because the elderly dementia patient population is particularly vulnerable to COVID-19, we discussed risk factors and difficulties associated with cognitive disorders in this vulnerable population. We also reviewed the effects of the patient living environment in COVID-19 cases that required intensive care unit (ICU) care. Furthermore, we analyzed the impact of stringent social restrictions and COVID-19 pandemic-mediated policies on dementia patients and care providers. Finally, we provided the following strategies for working with elderly dementia patients: general preventive methods; dementia care at home and nursing facilities according to the activities of daily living and dementia characteristics; ICU care after COVID-19 infection; and public health care system and government response. We propose that longitudinal follow-up studies are needed to fully examine COVID-19 associated neurological complications, such as dementia, and the efficacy of telemedicine/telehealth care programs.
Background/Aims: The possible influence of apolipoprotein E (ApoE) genotype on the response to acetylcholinesterase inhibitor therapy in patients with Alzheimer’s disease (AD) remains a matter of controversy. In order to address this issue, we investigated the effects of ApoE genotype on the clinical response to donepezil in patients with mild to moderate AD. Methods: An open study was carried out in 51 patients with probable AD who were treated with 5–10 mg of donepezil per day for 48 weeks. Results: Eighteen (35.3%) of the 51 patients had 1 or 2 ApoE Ε4 alleles. ApoE Ε4 carriers with AD showed a mean 1.1-point increase from the baseline score of 23.9 on the 70-point Alzheimer’s Disease Assessment Scale-Cognitive Component at 48 weeks, while the ApoE Ε4 noncarrier group showed a 3.1-point increase from the baseline score of 22.5 (p = 0.03). The ApoE Ε4 carrier group exhibited a mean 0.13-point worsening from the baseline score of 0.97 on the Korean Instrumental Activities of Daily Living at 48 weeks, while the ApoE Ε4 noncarrier group exhibited a 0.17-point worsening from the baseline score of 0.64 (p = 0.05). Conclusion: AD patients who carry the ApoE Ε4 allele may respond more favorably to donepezil than Ε4 noncarriers.
These findings suggest that the entorhinal region exhibits macrostructural as well as microstructural changes in individuals with SMI, whereas the hippocampus exhibits only microstructural alterations.
Background and PurposeWhite matter hyperintensities (WMH) are frequently observed on MRI in ischemic stroke patients as well as in normal elderly individuals. Besides the progression of WMH, the regression of WMH has been rarely reported. Thus, we aimed to investigate how WMH change over time in patients with ischemic stroke, particularly focusing on regression.MethodsWe enrolled ischemic stroke patients who underwent brain MRI more than twice with at least a 6 month time-interval. Based on T2-weighted or FLAIR MRI, WMH were visually assessed, followed by semiautomatic volume measurement. Progression or regression of WMH change was defined when 0.25 cc increase or decrease was observed and it was also combined with visible change. A statistical analysis was performed on the pattern of WMH change over time and factors associated with change.ResultsA total of 100 patients were enrolled. Their age (mean±SD) was 67.5±11.8 years and 63 were male. The imaging time-interval (mean) was 28.0 months. WMH progressed in 27, regressed in 9 and progressed in distinctive regions and regressed in others in 5 patients. A multiple logistic regression model showed that age (odds ratio[OR] 2.51, 90% confidence interval[CI] 1.056-5.958), male gender (OR 2.957, 95% CI 1.051-9.037), large vessel disease (OR 1.955, 95% CI 1.171-3.366), and renal dysfunction (OR 2.900, 90% CI 1.045-8.046) were associated with progression. Regarding regression, no significant factor was found in the multivariate analysis.ConclusionsIn 21.5% of ischemic stroke patients, regression of WMH was observed. WMH progression was observed in a third of ischemic stroke patients.
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