Severe Deep White Matter Hyperintensities Research Articles

Contribution of Cystatin C Gene Polymorphisms to Cerebral White Matter Lesions

Background: Vascular remodeling plays an important role in the development of arteriosclerosis and any of the resulting white matter lesions in the brain. An imbalance between cysteine proteases and the cysteine protease inhibitor cystatin C (CST3) may exacerbate vascular remodeling through degradation of extracellular matrix proteins. Therefore, we evaluated the association between functional polymorphisms in the CST3 gene and the development of cerebral white matter lesions. Methods: In a total of 2,676 participants, 3 CST3 genepolymorphisms were genotyped in 92 cases with severe deep white matter hyperintensity (DWMH), and 184 subjects were randomly selected age- and sex-matched controls without any signs of DWMH. The genetic effects of these polymorphisms on DWMH and plasma CST3 levels were examined. CST3 expression vectors were transfected into an astrocytoma cell line and the expression level of CST3 mRNA was analyzed by quantitative RT-PCR. Intracellular and secreted levels of CST3 in the cell culture were quantified by Western blot and ELISA, respectively. Results: A significant association was found between one CST3 gene haplotype and DWMH (p = 0.002). This haplotype was also associated with lower plasma CST3 levels (p = 0.01). An in vitro transfection study revealed that the +148A allele, which is included in the risk haplotype, significantly reduced the secretion and increased the intracellular accumulation of CST3; however, it had no effect on the mRNA expression. Conclusions: Our study shows that polymorphisms in the CST3 gene are significantly associated with the likelihood of DWMH. Substitution of A for G at +148 of the CST3 gene decreased the extracellular availability of CST3 in vitro, which might result in the activation of protease activity.

Impacts of Hyper-Homocysteinemia and White Matter Hyper-Intensity in Alzheimers Disease Patients with Normal Creatinine: An MRI-Based Study with Longitudinal Follow-up

White matter hyper-intensities (WMHs) on magnetic resonance imaging (MRI) are commonly found in Alzheimer's disease (AD). Cerebro-vascular risk factors including plasma total homocysteine (tHcy) may result in WMHs. This study examined the association between tHcy and WMHs, and their effects on cognitive functions in AD patients over a two-year follow-up period. One hundred and fifty-seven AD patients with a clinical dementia rating of 1 or 2 were enrolled and follow-up for two years. tHcy, biochemistry tests, and mini-mental state examination (MMSE) scores were collected. WMHs were visually rated on brain MRI and classified as deep white matter hyper-intensities (DWMHs) or peri-ventricular white matter hyper-intensities (PWMHs). MMSEs were performed every six months to survey cognitive decline. In the cross sectional study, tHcy was significantly associated with total WMHs especially in DWMHs even after adjusting for age and other cerebrovascular risk factors. Initial MMSE was inversely correlated with WMH severity but not with tHcy level. In the longitudinal analysis, no differences were found either in tHcy or WMHs score in the two AD groups defined by the cognitive decline rate. tHcy is an independent risk factor for developing moderate to severe DWMHs in AD but shows non-significant effect on cognitive performance. The close association between high WMH score and poor initial MMSE suggests an additive impact in AD. The long-term effect of elevated tHcy on cognitive decline was not conclusive in the two-year follow-up period.

Paradoxical embolisation and cerebral white matter lesions in dementia

The study aimed to examine the relationship between spontaneous cerebral emboli (SCE), patent foramen ovale (PFO) and white matter hyperintensities (WMH) on cerebral MRI in patients with Alzheimer's disease (AD) and vascular dementia (VaD). SCE were identified by transcranial Doppler of the middle cerebral artery for 1 h. A "significant" v-aCS (venous-to-arterial circulation shunt indicative of PFO; > or =15 embolic signals within 12 cardiac cycles) was detected by intravenous injection of "air in saline" ultrasound contrast. Deep white matter hyperintensities (DWMH) and periventricular hyperintensities (PVH) were assessed using Schelten's scale. After correction for cardiovascular risk factors, both DWMH and PVH were significantly associated with the presence of a PFO in AD (beta = 0.31, p = 0.02 for DWMH, odds ratio 8.7, p = 0.011 for PVH) but not in VaD. No consistent relationship was found between SCE and WMH in AD. In VaD, the severity of DWMH was negatively correlated with SCE (beta = -0.55; p = 0.001). In conclusion, the presence of a significant venous-to-arterial shunt is associated with more severe DWMH in AD, and may play a part in the aetiology of the disorder. In addition, there is a significant negative correlation between SCE and DWMH in VaD, which supports the hypothesis that VaD may be the result of ischaemic injury, predominantly reflecting embolic aetiology.

P.3.a.013 Decreased bone mineral density in patients with schizophrenia treated with risperidone or olanzapine.

To elucidate the cognitive profiles of post-stroke vascular mild cognitive impairment (VaMCI) in comparison to MCI of non-vascular etiology and cognitively normal healthy controls at a tertiary-care hospital in southern India.Logistic regression analysis adjusted for age and sex comparing VaMCI [N = 50] with controls [N = 27] revealed significant impairment in visual, verbal learning-recall and executive function scores. As compared to the MCI group [N = 36], VaMCI had significantly higher scores on Weschler's Memory Scale (WMS) verbal subset delayed recall scores (p = 0.045, odds ratio [OR] = 2.62, 95% CI = 1.02–6.76) with lower scores on WMS-visual immediate learning scores (p = 0.042, OR = 0.35, 95% CI = 0.13–0.96), Rey Auditory Verbal Learning Test (RAVLT) total learning scores (p = 0.001, OR = 0.17, 95% CI = 0.06–0.48) and 20 minute recall (p = 0.026, OR = 0.33, 95% CI = 0.12–0.88), Delayed Matching to Sample test (DMS-48) abstract immediate (p = 0.002, OR = 0.20, 95% CI = 0.07–0.56), abstract delayed recognition sub-sets (p = 0.014, OR = 0.28, 95% CI = 0.10–0.78) and made more total errors on Wisconsin Card Sorting Test (WCST; p = 0.040, OR = 2.70, 95% CI = 1.05–7.14) while the MCI group significantly had more commission errors on RAVLT (p ≤ 0.001, OR = 0.13, 95% CI = 0.05–0.38) and WCST – perseverative errors (p = 0.036, OR = 0.30, 95% CI = 0.10–0.93). Significant differences were noted in word-list learning-recall (p = 0.012) and WMS verbal delayed recall (p = 0.014) between VaMCI with mild versus moderate to severe deep white matter hyperintensities on neuroimaging.Cognitive impairment following minor stroke involves episodic verbal and visual memory over and above executive function in comparison to MCI of non-vascular etiology. Close cognitive followup is warranted with adequate risk stratification and management especially in the presence of sub-cortical leukoaraiosis which is contributory to cognitive decline in this group of patients.

P.2.043 Neurocognitive function after treatment with lithium or olanzapine: a double-blind study

To elucidate the cognitive profiles of post-stroke vascular mild cognitive impairment (VaMCI) in comparison to MCI of non-vascular etiology and cognitively normal healthy controls at a tertiary-care hospital in southern India.Logistic regression analysis adjusted for age and sex comparing VaMCI [N = 50] with controls [N = 27] revealed significant impairment in visual, verbal learning-recall and executive function scores. As compared to the MCI group [N = 36], VaMCI had significantly higher scores on Weschler's Memory Scale (WMS) verbal subset delayed recall scores (p = 0.045, odds ratio [OR] = 2.62, 95% CI = 1.02–6.76) with lower scores on WMS-visual immediate learning scores (p = 0.042, OR = 0.35, 95% CI = 0.13–0.96), Rey Auditory Verbal Learning Test (RAVLT) total learning scores (p = 0.001, OR = 0.17, 95% CI = 0.06–0.48) and 20 minute recall (p = 0.026, OR = 0.33, 95% CI = 0.12–0.88), Delayed Matching to Sample test (DMS-48) abstract immediate (p = 0.002, OR = 0.20, 95% CI = 0.07–0.56), abstract delayed recognition sub-sets (p = 0.014, OR = 0.28, 95% CI = 0.10–0.78) and made more total errors on Wisconsin Card Sorting Test (WCST; p = 0.040, OR = 2.70, 95% CI = 1.05–7.14) while the MCI group significantly had more commission errors on RAVLT (p ≤ 0.001, OR = 0.13, 95% CI = 0.05–0.38) and WCST – perseverative errors (p = 0.036, OR = 0.30, 95% CI = 0.10–0.93). Significant differences were noted in word-list learning-recall (p = 0.012) and WMS verbal delayed recall (p = 0.014) between VaMCI with mild versus moderate to severe deep white matter hyperintensities on neuroimaging.Cognitive impairment following minor stroke involves episodic verbal and visual memory over and above executive function in comparison to MCI of non-vascular etiology. Close cognitive followup is warranted with adequate risk stratification and management especially in the presence of sub-cortical leukoaraiosis which is contributory to cognitive decline in this group of patients.

Is apathy in late-life depressive illness related to age-at-onset, cognitive function or vascular risk?

Apathy has been shown to be an important feature of degenerative, vascular or traumatic brain disorder. Its presence is associated with high depression scores, higher age, low performance on frontal tasks, and more severe deep white matter hyperintensities. In late-life depression, lack of interest or motivation are often more prominent than depressed mood, especially in the late-onset type. It was hypothesized that in a heterogeneous sample of elderly depressed patients, apathy is associated with late-onset type of depression, cognitive dysfunction or vascular risk factors. The Apathy Evaluation Scale (AES) was administered to twenty-nine elderly (> or = 60 years) inpatients with a DSM-IV major depression or dysthymic disorder. The severity of the depression was measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and cognitive function with the Mini-mental State Examination (MMSE). The presence of vascular risk factors was traced in the patient's medical records. Apathy was found in 86% of the patients. The AES-score was correlated with the negative symptom score, but not with total MADRS or MMSE-score. No difference in AES-score between early-onset depressed (n = 16) and late-onset depressed (n = 13) patients was found, and between patients with or without vascular risk. Apathy is a main feature of moderate to severe depressive illness in elderly patients and related to the negative symptoms of the disorder. Further studies should include less severely depressed patients and investigate the relation between depression severity and apathy.

The performance of a psychomotor planning task in patients with schizophrenia

To elucidate the cognitive profiles of post-stroke vascular mild cognitive impairment (VaMCI) in comparison to MCI of non-vascular etiology and cognitively normal healthy controls at a tertiary-care hospital in southern India.Logistic regression analysis adjusted for age and sex comparing VaMCI [N = 50] with controls [N = 27] revealed significant impairment in visual, verbal learning-recall and executive function scores. As compared to the MCI group [N = 36], VaMCI had significantly higher scores on Weschler's Memory Scale (WMS) verbal subset delayed recall scores (p = 0.045, odds ratio [OR] = 2.62, 95% CI = 1.02–6.76) with lower scores on WMS-visual immediate learning scores (p = 0.042, OR = 0.35, 95% CI = 0.13–0.96), Rey Auditory Verbal Learning Test (RAVLT) total learning scores (p = 0.001, OR = 0.17, 95% CI = 0.06–0.48) and 20 minute recall (p = 0.026, OR = 0.33, 95% CI = 0.12–0.88), Delayed Matching to Sample test (DMS-48) abstract immediate (p = 0.002, OR = 0.20, 95% CI = 0.07–0.56), abstract delayed recognition sub-sets (p = 0.014, OR = 0.28, 95% CI = 0.10–0.78) and made more total errors on Wisconsin Card Sorting Test (WCST; p = 0.040, OR = 2.70, 95% CI = 1.05–7.14) while the MCI group significantly had more commission errors on RAVLT (p ≤ 0.001, OR = 0.13, 95% CI = 0.05–0.38) and WCST – perseverative errors (p = 0.036, OR = 0.30, 95% CI = 0.10–0.93). Significant differences were noted in word-list learning-recall (p = 0.012) and WMS verbal delayed recall (p = 0.014) between VaMCI with mild versus moderate to severe deep white matter hyperintensities on neuroimaging.Cognitive impairment following minor stroke involves episodic verbal and visual memory over and above executive function in comparison to MCI of non-vascular etiology. Close cognitive followup is warranted with adequate risk stratification and management especially in the presence of sub-cortical leukoaraiosis which is contributory to cognitive decline in this group of patients.

Occipital deep white matter hyperintensity as seen by MRI: 1. clinical significance

Magnetic resonance imaging was performed in 270 patients with various neurologic complaints (1-15Y) with a 0.5 tesla superconducting imaging system using a field echo T1-weighted sequence and spin echo T2-weighted and PD-weighted sequences. Twenty-seven of them had deep white matter hyperintensity (DWMH) in the occipital lobe on T2-weighted images. The frequency of mild DWMH differed in different age groups, suggesting that mild DWMH may result from delayed myelination in the central nervous system. However, the frequency of severe DWMH, which was revealed as isointense relative to cerebrospinal fluid, did not differ in different age groups and it was significantly more common in severely retarded patients. Classification of DWMH based on the signal intensity is valuable to distinguish white matter abnormalities in the occipital lobe from delayed myelination in the same site.