Signal Alteration of Substantia Nigra on 3.0T Susceptibility-weighted Imaging in Parkinson's Disease and Vascular Parkinsonism.

Recent researches have found that 7 Tesla SWI can detect the alteration of substantia nigra hyperintensity in Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). The aim of this study was to investigate whether 3 Tesla SWI (3T SWI) can visualize anatomical alterations occurring in a hyperintense structure of the substantia nigra in PD and vascular parkinsonism (VP), and whether the evaluation of abnormal signal can be used as a factor in the differential diagnosis of PD and VP. Using 3 Tesla MRI, we evaluated 38 healthy subjects, 33 patients with PD and 34 patients with VP. Two blinded readers independently assessed the images. We found that the dorsolateral nigral hyperintensity was absent in 31 of 33 patients with PD and 15 of 34 patients with VP. The dorsolateral nigral hyperintensity was present in 19 of 34 patients with VP and 35 of 38 healthy controls. Group comparisons of absence of dorsolateral nigral hyperintensity revealed significant differences between the patients with PD and those with VP (P<0.001). The sensitivity of SWI for PD was 93.9% and the specificity was 92.1%. Visual assessment of dorsolateral nigral hyperintensity on high-field SWI scans may serve as a new simple diagnostic imaging marker for PD. And our study results indicate that 3T SWI can be used as a tool to identify PD and VP.

[Current concepts in vascular dementia]. / Démences vasculaires : concepts actuels.

Vascular dementias, VD, are dementias due to cerebrovascular lesions. Subgroups of VD include multi-infarct dementia, single infarct (or strategic infarct) dementia, subcortical ischemic vascular dementia, hemorrhagic dementia, hypoperfusion dementia. VD are also related to post-stroke dementia, mixed Alzheimer's disease and vascular dementia and vascular cognitive impairment. These various entities allow to characterize more homogenous subgroups within the heterogeneous group of vascular dementias. However, ambiguities in their definitions, associated with frequent overlaps as well as lack of consensual definition for mixed dementia limit both their theoretical value and use in clinical practice. The diagnosis of cerebrovascular diseases should be dissociated from that of dementia, which could be associated with other pathologies.

Vascular cognitive impairment: epidemiology, subtypes, diagnosis and management.

Dementia occurs after stroke in 25% of patients but also can arise from covert cerebrovascular disease (CVD). 'Silent' lacunes occur in 25% of the elderly, often associated with focal or confluent hyperintensities on T2-weighted magnetic resonance imaging, which are detected in 95% of seniors. These covert infarcts predict future stroke and faster cognitive decline. Best practice guidelines advocate screening for cognitive impairment in all phases of overt stroke, when covert CVD is uncovered, when vascular risk factors are present and if patients present with cognitive complaints. Standardised testing is recommended, emphasising executive function and speed of processing. Cholinesterase inhibitors have cognitive enhancing effects in vascular dementia, but the major thrust is still aggressive management of vascular risk factors and healthy lifestyle choices. Given that mixed Alzheimer's dementia and CVD is likely the most common substrate for dementia and that they share common vascular risk factors, a major goal for vascular medicine is cerebrovascular protection, not just to prevent heart attack and stroke, but also to maintain brain health and delay dementia.

Increased binding to 5-HT1A and 5-HT2A receptors is associated with large vessel infarction and relative preservation of cognition.

Vascular dementia accounts for approximately 15-20% of all dementias. In addition, a significant subset of people with Alzheimer's disease have concurrent cerebrovascular disease. Vascular dementia is caused by different cerebrovascular morphological abnormalities including large artery territory infarction (multi-infarct vascular dementia) and sub-cortical ischaemic vascular dementia. Despite this distinction, there is a lack of studies examining the neurochemistry of individual vascular dementia subtypes. Serotonin is believed to play an important role in cognition, and serotonin receptors may provide a novel target for future anti-dementia therapeutics. This study aimed to determine levels of two serotonin receptors in subtypes of vascular dementia and relate any changes to cognition. We have determined, using saturation radioligand binding, the binding parameters (affinity and maximal binding) of ((3)H)-WAY 100635 binding to 5-HT(1A) receptors and ((3)H)-ketanserin binding to 5-HT(2A) receptors in post-mortem tissue from the frontal and temporal cortices of patients with either multi-infarct vascular dementia, sub-cortical ischaemic vascular dementia, mixed Alzheimer's disease/vascular dementia or stroke no dementia (SND). 5-HT(1A) and 5-HT(2A) receptor binding was significantly increased in the temporal cortex of patients with either multi-infarct vascular dementia or SND, compared to age-matched controls. 5-HT(1A) receptor maximal binding in the temporal cortex was also positively correlated with cognition as determined by Mini-Mental State Examination (MMSE) and Cambridge Assessment of Mental Health for the Elderly scores (CAMCOG). These results reveal an important distinction between the neurochemistry of multi-infarct vascular dementia/SND and sub-cortical ischaemic vascular dementia, suggesting that pharmacological manipulation of serotonin offers the possibility to develop novel therapies for stroke and multi-infarct vascular dementia patients. The results also highlight the importance of the cortical 5-HT(1A) receptor in mediating cognition.

Chronic information-processing changes in individuals with a first-ever clinical lacunar syndrome.

OBJECTIVE: The aim of this study was to examine whether chronic cognitive changes occur after a first-ever single clinical lacunar syndrome. BACKGROUND: Patients who have been diagnosed with a first-ever single clinical lacunar syndrome, on the basis of clinical rather than radiologic criteria, perform normally on general clinical neuropsychologic measures. METHOD: We examined information-processing abilities in 17 first-ever lacunar syndrome participants [lacunar anterior circulation infarct (LACI)], using 2 experimental tasks of information processing. RESULTS: At a group level, LACI participants were significantly impaired relative to stroke-free controls. Specifically, LACI participants had a reduced ability to process information under conditions of increasing attentional demand; this deficit was not caused by a fundamental impairment in speed of information processing. CONCLUSIONS: The current findings represent the first evidence of chronically impaired cognition in individuals who have suffered a single clinical lacunar syndrome event, but have no history of other clinical stroke.

Lateralization of hippocampal nitric oxide mediator system in people with Alzheimer disease, multi-infarct dementia and schizophrenia.

There is evidence that brain lateralization underlying hemispheric specialization can be observed also at biochemical level. However, hemispheric differences in nitric oxide mediator system have not yet been evaluated. The hippocampus and planum temporale are highly asymmetrical regions but the degree of their laterality is altered in demented or psychotic people. In the study, l-glutamate/l-arginine/l-citrulline concentrations, nitric oxide synthase activities/expressions and nitrites/nitrates levels were estimated in autoptic hippocampi. Right/left laterality in endothelial synthase activity and in nitrites/nitrates was observed in controls. Lateral changes were estimated in patients with Alzheimer disease (a marked increase in activities of constitutive synthases and in expression of inducible enzyme in the left side) and schizophrenia (an increase in activities of all enzymes especially in the right side). Significant shifts from positive to negative correlations were found between laterality of some components of nitric oxide pathway and of planum temporale volumetry under pathological conditions. The hippocampal nitric oxide system appears to be globally right/left lateralized, especially via actions of highly asymmetrical endothelial synthase. The results suggest a specific involvement of all synthases in the development of selected diseases and show that lateral analyses are of sufficient sensitivity to reveal subtle links. The volumetric asymmetry of the planum temporale as a marker of handedness is not probably simply linked to brain laterality at biochemical level but reflects alterations due to pathological processes.

Higher severity of frontal periventricular white matter and basal ganglia hyperintensities in first-ever lacunar stroke with multiple silent lacunes.

BACKGROUND AND PURPOSE: We investigated whether patients with a lacunar infarct (LI) syndrome exhibiting unique LI or multiple LI on magnetic resonance imaging (MRI) examinations differed in terms of topography and severity of white matter hyperintensities (WMH) ratings. METHODS: Forty consecutive patients with a first-ever acute LI, who presented a lacunar syndrome according to Miller-Fisher's classification were recruited and were classified into a group presenting isolated LI on MRI (n = 17) or multiple LI (n = 23). RESULTS: Despite equivalent demographic, clinical and cognitive characteristics, patients with multiple LI had increased ratings of WMH in frontal, occipital and subcortical regions. No significant correlations could be evidenced between the number of LI and WMH ratings. CONCLUSIONS: Present findings provide support to previous hypothesis considering single and multiple LI MRI presentations of lacunar infarct patients as distinct entities.

The pathology of "vascular dementia": a critical update.

The prevalence, morphology and pathogenesis of vascular dementia (VaD), recently termed vascular cognitive disorder (VCD), are a matter of discussion.VaD is suggested in 8-15% of cognitively impaired aged subjects. Its prevalence in autopsy series ranges from 0.03 to 58% (mean 8-15% in Western series, 22-35% in Japan). Neuropathology shows multifocal and/or diffuse lesions, ranging from lacunes and microinfarcts, often involving subcortical and strategically important brain areas (thalamus, frontobasal, limbic system), white matter lesions and hippocampal sclerosis to multi-infarct encephalopathy and diffuse post-ischemic lesions. They result from systemic, cardiac and local large and small vessel disease. Pathogenesis is multifactorial and pathophysiology affects neuronal networks involved in cognition, behavior, execution and memory. Vascular lesions often coexist with Alzheimer's disease (AD) and other pathologies. Minor vascular lesions hardly contribute to cognitive decline in full-blown AD, while both mild Alzheimer pathology and small vessel disease interact synergistically. AD pathology is less severe in the presence of vascular lesions. The lesion pattern in "pure" VaD/VCD) related to microangiopathies differs from that in "mixed dementia" (AD + vascular encephalopathy), often associated with large infarcts, suggesting different pathogenesis. Due to the heterogeneity of cerebrovascular pathology and its causative factors, no validated neuropathologic criteria for VaD are currently available, and a large variability across laboratories still exists in morphologic examination procedures and techniques. Further prospective clinico-pathologic studies are needed to validate diagnostic criteria for VaD and to clarify the impact of vascular lesions on cognitive impairment.

Autosomal dominant leukoencephalopathy with mild clinical symptoms due to cerebrovascular dysfunctions: a new disease entity?

A family with cerebrovascular dysfunctions and extensive white matter lesions was presented. The proband had suffered migraine. His brother showed syncopal episodes and migraine. His mother also suffered severe migraine with aura, and had transient hemiparesis during pregnancy. Their brain MRIs, being quite similar to each other, revealed diffuse bilateral deep white matter lesions, with no changes in serial follow-up. His grandmother showed similar white matter changes on CT, consistent with autosomal dominant inheritance. Lesions were considered to be due to chronic vasogenic edema based upon increased apparent diffusion coefficient (ADC) values on diffusion-weighted imaging, normal spectrum ratio of metabolites on (1)H MR spectroscopy, and decreased regional cerebral blood flows on single-photon emission CT (SPECT). A deficiency of genetically determined factors contributing to the autoregulation of small blood vessels might possibly lead to both clinical symptoms and white matter lesions through the breakdown of the blood-brain barrier and resultant vasogenic edema. Although cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was suspected, neither NOTCH3 mutation nor granular osmiphilic material (GOM) in the arteriole walls were detected. Further accumulation of similar cases is necessary to establish the possibility of a new familial leukoencephalopathy.

VITA study: white matter hyperintensities of vascular and degenerative origin in the elderly.

The etiology of white matter hyperintensities (WMH) seen on T2-weighted cranial magnetic resonance images is a matter of debate. We investigated deep and periventricular WMH in the brains of a community-based cohort of 532 subjects aged 75-76 years. The objective of this study was to determine whether WMH at age of 75 years were associated rather with vascular factors than with degenerative factors. Arterial hypertension treated with antihypertensive drugs favored WMH, and WMH were found more frequently in subjects with focal vascular lesions. Additionally, we found significant associations between both, deep white matter and periventricular hyperintensities, and focal atrophy of medial temporal lobe structures. The odds ratio for deep WMH in subjects with more severe medial temporal atrophy was 4.4 (95%-CI: 1.9-9.8) that for periventricular hyperintensities was 3.9 (95%-CI: 1.7-8.8). These findings might indicate that not only vascular factors alone but also degenerative factors favor the occurrence of WMH after the age of 75 years.

Protective effects of Nicotiflorin on reducing memory dysfunction, energy metabolism failure and oxidative stress in multi-infarct dementia model rats.

The present study aimed to determine whether Nicotiflorin, a natural flavonoid extracted from coronal of Carthamus tinctorius, has a protective effect on cerebral multi-infarct dementia in rats. The multi-infarct dementia model rats were prepared by injecting man-made micro-thrombi into the right hemisphere. The administration groups were treated once daily with 30, 60 and 120 mg/kg Nicotiflorin (i.g.) from 5 days before ischemia operation to 3 days after the operation for biochemical examination, 10 days for Morris water maze study and morphological observations and 20 days for eight-arm radial maze task. 2,3,5-triphenyltetrazolium chloride (TTC) staining showed that infarct volume of each Nicotiflorin administration group was much smaller than that of vehicle-treated multi-infarct dementia group, and hematoxylin and eosin (HE) staining showed that histopathological abnormalities of each Nicotiflorin group were also much lighter than that of vehicle-treated multi-infarct dementia group. Each Nicotiflorin group showed much better spatial memory performance in Morris water maze tests and eight-arm radial maze task compared with the vehicle-treated multi-infarct dementia group, significantly attenuated the elevation of lactic acid and malondialdehyde (MDA) contents and the decrease in lactate dehydrogenase (LDH), Na(+)K(+)ATPase, Ca(2+)Mg(2+)ATPase and superoxide dismutase (SOD) activity in the brain tissue which was composed of striatum, cortex and hippocampus of the ischemia hemisphere at day 3 after ischemia operation. These results suggest that Nicotiflorin has protective effects on reducing memory dysfunction, energy metabolism failure and oxidative stress in multi-infarct dementia model rats.

Hereditary multi-infarct dementia of the Swedish type is a novel disorder different from NOTCH3 causing CADASIL.

Several hereditary small vessel diseases (SVDs) of the brain have been reported in recent years. In 1977, Sourander and Wålinder described hereditary multi-infarct dementia (MID) in a Swedish family. In the same year, Stevens and colleagues reported chronic familial vascular encephalopathy in an English family bearing a similar phenotype. These disorders have invariably been suggested to be cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) but their genetic identities remain unknown. We used molecular, radiological and neuropathological methods to characterize these disorders. Direct DNA sequencing unexpectedly confirmed that affected members of the English family carried the R141C mutation in the NOTCH3 gene diagnostic of CADASIL. However, we did not detect any pathogenic mutations in the entire 8091 bp reading frame of NOTCH3 or find clear evidence for NOTCH3 gene linkage in the Swedish DNA. This was consistent with the lack of hyperintense signals in the anterior temporal pole and external capsule in Swedish subjects upon magnetic resonance imaging. We further found no evidence for granular osmiophilic material in skin biopsy or post-mortem brain samples of affected members in the Swedish family. In addition, there was distinct lack of NOTCH3 N-terminal fragments in the cerebral microvasculature of the Swedish hereditary MID subjects compared to the intense accumulation in the English family afflicted with CADASIL. Several differences in arteriosclerotic changes in both the grey and white matter were also noted between the disorders. The sclerotic index values, density of collagen IV immunoreactivity in the microvasculature and number of perivascular macrophages were greater in the English CADASIL samples compared to those from the Swedish brains. Multiple approaches suggest that the Swedish family with hereditary MID suspected to be CADASIL has a different novel disorder with dissimilar pathological features and belongs to the growing number of genetically uncharacterized familial SVDs.

[Multi-infarct disorder presenting as corticobasal degeneration (DCB): vascular pseudo-corticobasal degeneration?]. / Infarctus cérébraux multiples se présentant comme une dégénérescence cortico-basale: pseudo dégénérescence cortico-basale vasculaire?

We report on five patients with a clinical presentation of corticobasal degeneration (CBD), including gradually progressive, asymmetric, L-DOPA-resistant parkinsonism associated variously with apraxia, focal action myoclonus, focal dystonia, cortical sensory loss and alien limb phenomenon. Some patients also presented an atypical CBD clinical history or signs - notably sudden onset. The disease was however not suggestive of another diagnosis. Magnetic resonance imaging of the brain revealed extensive vascular lesions. Only five similar cases have been published to our knowledge. Although we cannot exclude underlying CBD pathology, our cases illustrate the fact that multi-infarct pathology can masquerade as CBD or alter the clinical phenotype of the disease.

Morphometry of the amygdala in patients with questionable dementia and mild dementia.

The volume of the amygdala is reduced in advanced Alzheimer's disease (AD). However, there is controversy whether amygdala atrophy is present in mild AD and in the transitional phase between health and the onset of dementia. The aim of this prospective longitudinal study was to investigate whether amygdala atrophy is present in subjects with questionable dementia and mild dementia and whether amygdala volume is associated with the future rate of cognitive change, that is the annual change in the Mini Mental State Examination (MMSE). At baseline, volumes of the amygdala were measured in 97 participants aged 70-87 years (40 controls, 33 patients with questionable dementia, 24 patients with mild AD) using magnetic resonance imaging. Eighty-six participants were clinically re-examined after 2.3 years on average. At baseline, significant differences in mean amygdala volume were found between controls and participants with mild AD. There was no significant correlation between the longitudinal annual change in MMSE and the baseline amygdala volume in any of the three groups.

[The cognitive rehabilitation process in a case of bithalamic infarction]. / Proceso de rehabilitación cognitiva en un caso de infarto bitalámico.

INTRODUCTION: One of the fundamental lines followed by Neuropsychology today focuses on rehabilitation processes and their effectiveness. Cognitive rehabilitation is an eclectic process that is dependent on a number of variables. This variability makes it necessary to establish a work plan that guides the intervention carried out by professionals and also makes it clear what objectives are to be achieved, as well as the strategies and tools that must be used to reach them. The purpose of this study is to offer a practical examination of the different points that must be developed in a cognitive rehabilitation process--exemplified here in a case of bithalamic infarction. CASE REPORT: From a single case and from the specific needs of the individual, a thorough work plan is drawn up. This plan includes a description of everything from the choice of a practical framework for intervention and its underlying principles up to the different training processes, learning techniques and tools that were used and finally proved to be effective. The efficacy and safety of the different strategies and tools used are demonstrated by the short and long term results of the different neuropsychological examinations carried out, which at the same time proved the effectiveness of the work plan that was selected for application. CONCLUSIONS: A clear understanding of the value of the cognitive rehabilitation processes chosen for use helps to improve the way clinical work is carried out, with the common purpose of restoring neuropsychological deficits and increasing the individual's independence and quality of life.

N-methyl-D-aspartate receptor and apoptosis in Alzheimer's disease and multiinfarct dementia.

This study investigates the role of excitotoxicity in Alzheimer's disease and in multiinfarct dementia by examining, via immunohistochemical methods, the number of cells that are positive for N-methyl-D-aspartate (NMDA) receptor and the degree of colocalization between NMDA receptor and apoptosis markers such as TUNEL or activated caspase-3 in the frontal cortex of individuals with these two conditions, comparing the results with those from subjects who died of normal aging. We showed an increased number of NMDA receptor-positive cells and an increased number of TUNEL-labeled cells in the frontal cortex of subjects with Alzheimer's disease, especially in the deeper layers of the cortex. However, only about 10% of cells showed colocalization of NMDA receptor with the apoptosis markers studied, suggesting that NMDA-mediated excitotoxicity does not play a major role in neuronal apoptosis in Alzheimer's disease or in multiinfarct dementia.

Cognitive consequences of thalamic, basal ganglia, and deep white matter lacunes in brain aging and dementia.

BACKGROUND AND PURPOSE: Most previous studies addressed the cognitive impact of lacunar infarcts using radiologic correlations that are known to correlate poorly with neuropathological data. Moreover, absence of systematic bilateral assessment of vascular lesions and masking effects of Alzheimer disease pathology and macrovascular lesions may explain discrepancies among previous reports. To define the relative contribution of silent lacunes to cognitive decline, we performed a detailed analysis of lacunar and microvascular pathology in both cortical and subcortical areas of 72 elderly individuals without significant neurofibrillary tangle pathology or macrovascular lesions. METHODS: Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included Abeta-protein deposition staging and bilateral assessment of microvascular ischemic pathology and lacunes; statistical analysis included multivariate models controlling for age, amyloid deposits, and microvascular pathology. RESULTS: Thalamic and basal ganglia lacunes were negatively associated with CDR scores; cortical microinfarcts, periventricular and diffuse white matter demyelination also significantly affected cognition. In a multivariate model, cortical microinfarcts and thalamic and basal ganglia lacunes explained 22% of CDR variability; amyloid deposits and microvascular pathology explained 12%, and the assessment of thalamic and basal ganglia lacunes added an extra 17%. Deep white matter lacunes were not related to cognitive status in univariate and multivariate models. CONCLUSIONS: In agreement with the recently proposed concept of subcortical ischemic vascular dementia, our autopsy series provides important evidence that gray matter lacunes are independent predictors of cognitive decline in elderly individuals without concomitant dementing processes such as Alzheimer disease.