Form Of Vascular Dementia Research Articles

Computational imaging for rapid detection of grade-I cerebral small vessel disease (cSVD)

An early identification and subsequent management of cerebral small vessel disease (cSVD) grade 1 can delay progression into grades II and III. Machine learning algorithms have shown considerable promise in medical image interpretation automation. An experimental cross-sectional study aimed to develop an automated computer-aided diagnostic system based on AI (artificial intelligence) tools to detect grade 1-cSVD with improved accuracy. Patients with Fazekas grade 1 cSVD on Non-Contrast Magnetic Resonance Imaging (MRI) Brain of age >40 years of both genders were included. The dataset was pre-processed to be fed into a 3D convolutional neural network (CNN) model. A 3D stack with the shape (120, 128, 128, 1) containing axial slices from the brain magnetic resonance image was created. The model was created from scratch and contained four convolutional and three fully connected (FC) layers. The dataset was preprocessed by making a 3D stack, and normalizing, resizing, and completing the stack was performed. A 3D-CNN model architecture was designed to train and test preprocessed images. We achieved an accuracy of 93.12 % when 2D axial slices were used. When the 2D slices of a patient were stacked to form a 3D image, an accuracy of 85.71 % was achieved on the test set. Overall, the 3D-CNN model performed very well on the test set. The earliest and the most accurate diagnosis from computational imaging methods can help reduce the huge burden of cSVD and its associated morbidity in the form of vascular dementia.

Innate Sleep Apnea in Spontaneously Hypertensive Rats Is Associated With Microvascular Rarefaction and Neuronal Loss in the preBötzinger Complex.

Sleep apnea (SA) is a major threat to physical health and carries a significant economic burden. These impacts are worsened by its interaction with, and induction of, its comorbidities. SA holds a bidirectional relationship with hypertension, which drives atherosclerosis/arteriolosclerosis, ultimately culminating in vascular dementia. To enable a better understanding of these sequelae of events, we investigated innate SA and its effects on cognition in adult-aged spontaneously hypertensive rats, which have a range of cardiovascular disorders: plethysmography and electroencephalographic/electromyographic recordings were used to assess sleep-wake state, breathing parameters, and sleep-disordered breathing; immunocytochemistry was used to assess vascular and neural health; the forced alteration Y maze and Barnes maze were used to assess short- and long-term memories, respectively; and an anesthetized preparation was used to assess baroreflex sensitivity. Spontaneously hypertensive rats displayed a higher degree of sleep-disordered breathing, which emanates from poor vascular health leading to a loss of preBötzinger Complex neurons. These rats also display small vessel white matter disease, a form of vascular dementia, which may be exacerbated by the SA-induced neuroinflammation in the hippocampus to worsen the related deficits in both long- and short-term memories. Therefore, we postulate that hypertension induces SA through vascular damage in the respiratory column, culminating in neuronal loss in the inspiratory oscillator. This induction of SA, which, in turn, will independently exacerbate hypertension and neural inflammation, increases the rate of vascular dementia.

H2S- and NO-Signaling Pathways in Alzheimer's Amyloid Vasculopathy: Synergism or Antagonism?

Alzheimer's type of neurodegeneration dramatically affects H2S and NO synthesis and interactions in the brain, which results in dysregulated vasomotor function, brain tissue hypoperfusion and hypoxia, development of perivascular inflammation, promotion of Aβ deposition, and impairment of neurogenesis/angiogenesis. H2S- and NO-signaling pathways have been described to offer protection against Alzheimer's amyloid vasculopathy and neurodegeneration. This review describes recent developments of the increasing relevance of H2S and NO in Alzheimer's disease (AD). More studies are however needed to fully determine their potential use as therapeutic targets in Alzheimer's and other forms of vascular dementia.

Synaptic protein levels altered in vascular dementia.

IntroductionCerebral ischaemia is the defining pathophysiological abnormality in most forms of vascular dementia (VAD), but the pathogenesis of the dementia remains poorly understood. In Alzheimer's disease (AD), there is early loss of synaptic proteins, but these have been little studied in VAD.Materials and MethodsWe measured synaptophysin, postsynaptic density protein 95 (PSD-95), drebrin, synaptosomal-associated protein 25 (SNAP-25) and vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assays in superior temporal cortex from 11 patients with VAD and, initially, 11 non-dementia controls. We corrected for neuronal content by measurement of neuron-specific enolase. A further 11 controls were subsequently used in a validation study. Simulation of post-mortem delay found that PSD-95 was stable at 4°C but declined slightly at RT. SNAP-25 and drebrin showed good post-mortem stability. Previous studies had shown good post-mortem preservation of synaptophysin and VEGF.ResultsThe VAD cases had lower synaptophysin (but P > 0.05 in initial study), significantly lower SNAP-25 (P = 0.024) and significantly higher drebrin (P = 0.020). On comparison with the second control group, the reduction in synaptophysin was significant (P = 0.008), and the other results were confirmed.ConclusionThere is probably a reduction in presynaptic proteins in the temporal cortex in VAD, although not as marked as in AD. In VAD, there is also an increase in drebrin, which may be a response to reduced synaptic input.

A Report of Accelerated Coronary Artery Disease Associated with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common heritable form of vascular dementia and it is caused by mutations in the NOTCH3 gene. The neurologic manifestations of CADASIL syndrome have been well characterized; however, here we report one of the first de novo cases of CADASIL-associated coronary artery disease. A 45-year-old woman with a history of CADASIL and remote tobacco use presented with unstable angina. She was found to have diffuse and irregular narrowing of the left anterior descending artery and a drug eluting stent was deployed. Months later, she developed two subsequent episodes of unstable angina, requiring stent placement in the distal left anterior descending artery and the right coronary artery. Though the neurologic manifestations of CADASIL have been well described, these patients may also be predisposed to developing premature coronary artery disease. Patients with CADASIL and their physicians should be aware of this possible association because these patients may not be identified as high risk by traditional cardiovascular risk estimators. These patients may benefit from more aggressive interventions to reduce cardiac risk.

Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers—The VMCI-Tuscany Study: Rationale, Design, and Methodology

Dementia is one of the most disabling conditions. Alzheimer's disease and vascular dementia (VaD) are the most frequent causes. Subcortical VaD is consequent to deep-brain small vessel disease (SVD) and is the most frequent form of VaD. Its pathological hallmarks are ischemic white matter changes and lacunar infarcts. Degenerative and vascular changes often coexist, but mechanisms of interaction are incompletely understood. The term mild cognitive impairment defines a transitional state between normal ageing and dementia. Pre-dementia stages of VaD are also acknowledged (vascular mild cognitive impairment, VMCI). Progression relates mostly to the subcortical VaD type, but determinants of such transition are unknown. Variability of phenotypic expression is not fully explained by severity grade of lesions, as depicted by conventional MRI that is not sensitive to microstructural and metabolic alterations. Advanced neuroimaging techniques seem able to achieve this. Beside hypoperfusion, blood-brain-barrier dysfunction has been also demonstrated in subcortical VaD. The aim of the Vascular Mild Cognitive Impairment Tuscany Study is to expand knowledge about determinants of transition from mild cognitive impairment to dementia in patients with cerebral SVD. This paper summarizes the main aims and methodological aspects of this multicenter, ongoing, observational study enrolling patients affected by VMCI with SVD.

Quantitative analysis of hemodynamic and metabolic changes in subcortical vascular dementia using simultaneous near-infrared spectroscopy and fMRI measurements

Subcortical vascular dementia (SVD) is a form of vascular dementia from small vessel disease with white matter lesions and lacunes. We hypothesized that hemodynamic and metabolic changes in the cortex during a simple motor task may reflect the impaired neurovascular coupling in SVD. We used fMRI and near-infrared spectroscopy (NIRS) simultaneously, which together provided multiple hemodynamic responses as well as a robust estimation of the cerebral metabolic rate of oxygen (CMRO2). During the task periods, the oxy-hemoglobin, total-hemoglobin, blood oxygenation level-dependent (BOLD) response, cerebral blood flow (CBF), and CMRO2 decreased statistically significantly in the primary motor and somatosensory cortices of SVD patients, whereas the oxygen extraction fraction increased when compared with controls. Notably, the flow–metabolism coupling ratio, n representing the ratio of oxygen supply to its utilization, showed a robust reduction in the SVD patient group (nControl=1.99±0.23; nSVD=1.08±0.24), which implies a loss of metabolic reserve. These results support the pathological small vessel compromise, including an increased vessel stiffness, impaired vascular reactivity, and impaired neurovascular coupling in SVD. In conclusion, simultaneous measurement by NIRS and fMRI can reveal various hemodynamic and metabolic changes and may be used for as an early detection or monitoring of SVD.

CADASIL: A HEREDITARY CEREBROVASCULAR DISEASE AS MODEL FOR COMMON VASCULAR ISCHEMIC DEMENTIA

Together with Alzheimer’s disease, vascular dementia (VD) is the most frequent cause of progressive cognitive deterioration. The most common form of VD, subcortical vascular ischemic disease of the brain (SVIDB), affects elderly subjects who generally have a medical history of common vascular risk factors, especially hypertension. The clinical picture is generally progressive or stepwise due to recurrent stroke, and besides cognitive deterioration includes depression and problems with walking, swallowing and sphincter control. Magnetic resonance imaging (MRI), which is crucial in the diagnosis and follow-up of SVIDB, shows small subcortical infarcts (ischemic lacunae) and diffuse vascular damage in the

Leukoaraiosis: From an Ancient Term to an Actual Marker of Poor Prognosis

See related article, pages 1409–1413. The term leukoaraiosis (from the Greek leuko , white, and araiosis , rarefaction) was introduced in 1986 by Hachinski, Potter and Merskey to designate bilateral and symmetrical areas in the periventricular and centrum semiovale white matter that appeared hypodense on CT scans and hyperintense on T2-weighted MRI.1,2 Leukoaraiosis was supposed to be “a neutral term, exact enough to define white-matter changes, sufficient as a description or label, and demanding enough to require precise clinical and imaging descriptions.”1,2 It was clear in Hachinski and coworkers’ proposal the aim of contrasting the tendency to immediately identify a radiological aspect with a clinical picture. At that time, changes or lesions of the white matter were recognized with increasing frequency on the brain CT scans of elderly patients,3 and some authors had begun to attribute a clinical significance to these radiological findings, particularly interpreting them as a correlate of cognitive decline. According to some, the introduction of CT had made possible the identification in vivo of subcortical arteriosclerotic encephalopathy (or Binswanger disease), a form of vascular dementia with only few cases reported on pathological grounds until the eighties.4,5 The issue became even more complex after the introduction of MRI in neurological clinical practice because it was soon apparent …

Capillary loss precedes the cognitive impairment induced by fractionated whole-brain irradiation: A potential rat model of vascular dementia

Brain tumor patients who are long-term survivors after whole-brain irradiation (WBI) often suffer cognitive impairment, including dementia. Although the pathogenic mechanisms remain poorly understood, our studies suggest that radiation-induced cognitive impairment may be a form of vascular dementia. We used a fractionated dose of γ-rays that is biologically similar to that given to brain tumor patients. The brains of adult rats were irradiated with 40 Gy, in eight 5 Gy fractions over 4 weeks. Cognitive function was assessed prior to WBI and up to 9 months post-irradiation using a partially-baited radial arm maze. A significant increase in working memory errors was found in the irradiated rats by two-way ANOVA ( p = 0.0042). The increased errors occurred primarily at 6 and 9 months ( p < 0.05, student's t-test). Vessel density was quantified using a stereology method with computerized image processing and analysis. Vessel density was unchanged 24 h after the last dose, but significantly decreased ( p = 0.002), by approximately 30%, from 10 weeks to 52 weeks. Thus, cognitive impairment arose after brain capillary loss in irradiated rats that show no other gross brain pathology. Capillary loss may play an important role in radiation-induced dementia and this may be a model of vascular dementia.

Capillary beds are decreased in Alzheimer's disease, but not in Binswanger's disease

Morphological abnormalities of the cortical microvessels have been reported in Alzheimer's disease (AD), but not in Binswanger's disease (BD), a form of vascular dementia. Therefore, we compared the capillary beds in AD and BD brains, using a modified Gallyas silver impregnation method and immunohistochemistry for β amyloid. Eight autopsied brains with AD and seven with BD were compared with six control brains. The cortical microvessels in AD were frequently narrowed, and torn off, especially in close proximity to the senile plaques. The capillary densities in AD were significantly decreased as compared with the control brains. In contrast, there were no significant changes in the capillary densities and their morphologies in BD brains. Immunohistochemistry for β amyloid revealed numerous deposits in the vascular wall and perivascular neuropil exclusively in AD brains. Cortical microvascular changes in AD and their absence in BD may indicate a role of β amyloid for the microvessel pathology in AD.

Cross-cultural studies using a modified mini mental test for healthy subjects and patients with various forms of vascular dementia

Existing neuropsychological tests are often complex and time-consuming. We designed a modified Mini Mental Test (MMT) battery for clinical assessment of the global and regional higher cortical functions of the brain. We tested its applicability in healthy subjects with different ethnic, cultural and educational backgrounds. The usefulness of our MMT as a tool for the clinical evaluation of patients with various forms of vascular dementia was determined. The MMT comprises five subtests, including clinical evaluations of: (A) orientation (6 points); (B) attention, right–left discrimination, speech, and calculation (20); (C) immediate recall, and recent and remote memory retrieval (10); (D) praxis (10); and (E) visuospatial orientation, agnosia, hemianopsia, and visual hemineglect (14). The MMT was administered to 100 healthy subjects from two different ethnic backgrounds (Indonesian and Chinese/Taiwanese) and diverse cultural and educational backgrounds, and to 61 patients with various forms of vascular dementia. MMT scores were significantly lower in healthy subjects with a low level of education regardless of their ethnic background ( p < 0.001). Patients with vascular dementia had much lower MMT scores than did the comparable age-adjusted normal controls ( p < 0.001). Of the patients with vascular dementia, those with Binswanger’s disease had the lowest MMT scores (25.5 ± 28.9), followed by those with large cerebral infarcts (48.0 ± 7.1), cerebral haemorrhage (49.0 ± 8.5), and multiple lacunar infarctions (55.0 ± 0.5) ( P < 0.001). With a cut-off point of 33/55 (partial score/total score), the sensitivity and positive predictive value of the MMT were 0.98 and 0.94, respectively. The MMT is a simple and useful tool for clinical assessment of the cognitive functions of healthy subjects and patients with or without vascular dementia. It can be used for individuals with different ethnic, cultural and educational backgrounds.

What's Etiology Got to Do With It?

Cerebrovascular Disease, Cognitive Impairment and Dementia. John O'Brien, David Ames, Lars Gustafson, Marshal Folstein, and Edmond Chiu (Eds.). 2004. London: Martin Dunitz, 406 pp., $79.95 (HB).Cerebrovascular Disease, Cognitive Impairment and Dementiais the second edition ofCerebrovascular Disease and Dementia(2000). The new edition is over 160 pages longer than the earlier version, with several new chapters devoted to the pathophysiology of cerebrovascular disease [including provocative chapters on neurotransmitter changes in vascular dementia (VaD), the contributions of homocysteine and low vitamin B to VaD, and a good overview of hereditary forms of VaD], vascular mild cognitive impairment, noncognitive symptoms, and an expanded discussion of prevention and treatment. It is written for both clinical and scientific audiences. As in the first edition, there is a laudable comparative emphasis, with epidemiologic studies of vascular dementia in Europe, North America, Japan, and China. Indeed, the editors hail from the U.K, Australia, Sweden, and the U.S, and this affords the volume a useful global perspective. With five editors and 22 additional contributors, however, this book suffers a bit from the “too many cooks” syndrome. There is a good bit of redundancy. After the fifth or sixth description of classification criteria for vascular dementia, the reader begins to feel on the receiving end of some repetitive rehearsal therapy for her own dementia.

Alzheimer Demenz versus vaskuläre Demenz - Dichotomie oder Interaktion?

Alzheimer's dementia (AD) and vascular dementia (VD) are the two major forms of dementia in the elderly. They have been separated categorically on the basis of pathophysiological findings and clinical operationalized criteria. However, this strict separation has to be reevaluated in the light of recent data. The risk to develop a neurodegenerative dementia in old age is determined by various susceptibility genes and correlated with aging. In AD, the current understanding of pathophysiology focuses on the amyloid cascade hypothesis as the major endpoint of the complex cellular pathology. In VD, incomplete microangiopathic infarcts due to fibrohyalinosis are regarded as the major pathophysiological event. A controversial discussion exists about the coincidence or interaction of genetically determined risk factors of AD and/or VD. Further interactions between AD and VD exist with regard to perivascular mediators and those factors which impair cerebral blood flow. Based on these and other recent neuropathological and therapeutic findings the hypothesis is proposed that the two specific etiopathologies of AD and VD interact to precipitate clinical dementia in the individual and that the individual phenomenology of these dementias is modified by vascular risk factors. Neither, a categorical separation of AD and VD nor the recent idea to regard AD as a distinct form of vascular dementia, do appear convincing.

The neuropathology of vascular dementia

Ischemic infarction is the main lesion underlying vascular dementia (VaD) but cases also occur after brain hemorrhage, as well as with hypoperfusive brain ischemia. Ischemic strokes include large-vessel cortico-subcortical strokes and lacunes resulting from small-vessel disease. Arteriolosclerosis and fibrinoid necrosis are the most common forms of small-vessel disease in the elderly. Although it was originally proposed that vascular dementia could result from repeated strokes with loss of >100 mL of brain tissue loss (multi-infarct dementia), it is currently held that the location of the stroke is probably more relevant to cognitive loss and dementia. In fact, a single, strategically located stroke may interrupt cortico-subcortical circuits important for memory and cognition. Hypoperfusive lesions include border-zone cortico-subcortical infarcts, temporal lobe sclerosis, and periventricular incomplete ischemic leukoencephalopathy. The latter two lesions are commonly seen in the elderly as a result of narrowing and tortuosity of medullary arterioles irrigating these distal territories, plus cardiac pump failure. Binswanger disease is characterized by extensive periventricular ischemic leukoencephalopathy that spares the arcuate U-fibers, and presence of lacunar strokes. CADASIL is a genetic form of vascular dementia characterized by a cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CADASIL is due to a mutation of the Notch3 gene in chromosome 19. Intracerebral hemorrhages in strategic locations may produce vascular dementia. Lesions in the basal forebrain that damage cholinergic nuclei, such as those resulting from a ruptured aneurysm of the anterior communicating artery, may produce vascular dementia. Some patients with subarachnoid hemorrhage develop normal-pressure hydrocephalus. Cerebral amyloid angiopathy (congophilic angiopathy) may cause lobar hemorrhages and dementia. Vascular lesions, in particular, microinfarcts, are frequently found in patients with a clinical diagnosis of Alzheimer disease. These mixed forms of dementia are likely to become the most common form of dementia in the elderly.

Mémantine (Ebixa ®) : une nouvelle stratégie thérapeutique dans le traitement des formes modérément sévères à sévères de la maladie d’Alzheimer

Alzheimer's disease has definitively emerged from its ghetto and has been identified as a (priority) public health concern in view of the increasing age of the population. Considerable advances have been made in this disease over the last 15 Years, with progress in the following fields: knowledge of the underlying aetiopathogenetic, genetic and biochemical mechanisms; semiological, clinical and paraclinical approaches; creation of early diagnostic centres and multidisciplinary care networks; therapy available to patients or currently under development. The four existing acetylcholinesterase inhibitors having confirmed symptomatic action in patients with mild to moderate Alzheimer's disease have now been joined by memantine (Ebixa), a non-competitive agonist of N-methyl-D-aspartate (NMDA) receptors. One pathogenic mechanism of Alzheimer's disease appears to be hyperactivity of the glutaminergic neurons. Various preclinical studies have shown that memantine (Ebixa) inhibits glutaminergic hyperactivity in Alzheimer's disease through modulation of NMDA receptors. Since the early 1990s, several controlled clinical trials in patients with moderate to severe Alzheimer's disease (3<MMSE< or =14) have demonstrated the efficacy of memantine on cognitive criteria (cognitive evaluation of severe dementia) (Severe Impairment Battery--SIB), functional criteria (Functional Assessment Stage--FAST) and global clinical criteria (Clinician's Interview-Based Impression of Change--CIBIC-Plus). The data from these studies together with clinical experience of memantine in Germany since 1982 confirm the safety of use and good tolerability profile of this medication at the recommended dosages (10 to 30 mg/day). Treatment with memantine reduces the global costs of the disease by lightening the burden on helpers and delaying institutionalisation of patients. These different studies have resulted in approval of memantine in this particular indication by the European Medicines Agency. The efficacy of memantine in mild to moderate Alzheimer's disease is currently being assessed. The preliminary results also appear to militate in favour of the efficacy of the drug in certain forms of vascular dementia. Finally, the good safety profile of combined use of this drug with antiacetylcholinesterases opens up a realistic perspective of bitherapy in Alzheimer's disease.

Effects of transforming growth factor beta receptor 1 (TGFβ R1) on demyelination and vascular pathology in Binswanger's disease and other forms of vascular dementia

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm that usually arises in children and young adults. Typically, lesions of PXA are superficially located in the cerebral hemispheres. Herein, we report two extremely rare patients with PXA arising from suprasellar regions. One of the patients is a 29-year-old man admitted to our hospital with a history of progressive headache for 1 month. The patient’s brain MRI revealed a large tumor arising from the suprasellar cistern of the third ventricle. The second patient, a 52-year-old woman, presented with progressive dizziness and visual disturbance that had developed over the course of 1 year. The MRI revealed a well-enhanced suprasellar solid mass measuring 1.4 × 1.2 × 1.4 cm. Both patients underwent surgical removal of their tumors, and both patients showed similar microscopic structures and immunohistochemical phenotypes: the tumor cells were pleomorphic with mixtures of spindle-shaped, and multinuclear giant cells. In addition, eosinophilic granular bodies and xanthomatous cells were seen on section. Immunohistochemistry was positive for GFAP, S-100, and CD34, and was negative for IDH 1, CK, and Syn. The Ki-67 proliferation index was less than 1%. Silver impregnation revealed reticulin fibers surrounding the individual tumor cells, and small cell groups. Based on these findings, the two patients were diagnosed with PXA in the suprasellar region. To date, only five such patients have been reported in the literature. PXA should be included in the differential diagnosis for tumors arising in the sellar region.

White Matter Damage is Associated with Matrix Metalloproteinases in Binswanger’s Disease

81 BACKGROUND: Binswanger’s disease (BD) is a progressive form of vascular dementia (VaD) of the elderly associated pathologically with demyelination and clinically with disturbances of gait and intellect. It is commonly found in patients with fibrinoid and hyaline changes in brain arterioles secondary to long-standing hypertension. Because of the remodeling seen in the blood vessel wall, and the role of the matrix metalloproteinases (MMPs) in extracellular matrix injury and repair, we hypothesized that disturbances in the MMPs may be involved in the BD type of VaD. METHODS: To test the hypothesis, brain tissues from five patients with VaD of the BD or multi-infarct type were immunostained with antibodies to glial fibrillary acidic protein (GFAP), a macrophage/microglial cell marker (PG-M1), gelatinase A (MMP-2), stromelysin-1 (MMP-3), and gelatinase B (MMP-9). Control tissues were from eight elderly patients: four with strokes without dementia, and four without neurological diseases. RESULTS: Macrophage/microglia (PG-M1)-positive cells appeared around infarcts both in cases with strokes without dementia, and in those with VaD. In two of the three BD patients PG-M1 cells were prominent near damaged arterioles and scattered diffusely in white matter. MMP-2 was seen normally in perivascular macrophages and astrocytic processes near blood vessels, and was present in patients with strokes in reactive astrocytes, particularly those with a gemistocytic shape. MMP-9 was seen only in acute lesions. MMP-3 was seen in PG-M1 staining microglia/macrophage cells around the acute infarctions. In BD MMP-3 persisted in tissue macrophages, disappearing in long-standing white matter gliosis. CONCLUSIONS: These observations suggest that MMPs participate in the demyelination associated with injured blood vessels in the BD form of VaD. Chronic inflammation, which may be amenable to treatment, may be a factor in the progressive forms of VaD.

White Matter Damage is Associated with Matrix Metalloproteinases in Binswanger’s Disease

81 BACKGROUND: Binswanger’s disease (BD) is a progressive form of vascular dementia (VaD) of the elderly associated pathologically with demyelination and clinically with disturbances of gait and intellect. It is commonly found in patients with fibrinoid and hyaline changes in brain arterioles secondary to long-standing hypertension. Because of the remodeling seen in the blood vessel wall, and the role of the matrix metalloproteinases (MMPs) in extracellular matrix injury and repair, we hypothesized that disturbances in the MMPs may be involved in the BD type of VaD. METHODS: To test the hypothesis, brain tissues from five patients with VaD of the BD or multi-infarct type were immunostained with antibodies to glial fibrillary acidic protein (GFAP), a macrophage/microglial cell marker (PG-M1), gelatinase A (MMP-2), stromelysin-1 (MMP-3), and gelatinase B (MMP-9). Control tissues were from eight elderly patients: four with strokes without dementia, and four without neurological diseases. RESULTS: Macrophage/microglia (PG-M1)-positive cells appeared around infarcts both in cases with strokes without dementia, and in those with VaD. In two of the three BD patients PG-M1 cells were prominent near damaged arterioles and scattered diffusely in white matter. MMP-2 was seen normally in perivascular macrophages and astrocytic processes near blood vessels, and was present in patients with strokes in reactive astrocytes, particularly those with a gemistocytic shape. MMP-9 was seen only in acute lesions. MMP-3 was seen in PG-M1 staining microglia/macrophage cells around the acute infarctions. In BD MMP-3 persisted in tissue macrophages, disappearing in long-standing white matter gliosis. CONCLUSIONS: These observations suggest that MMPs participate in the demyelination associated with injured blood vessels in the BD form of VaD. Chronic inflammation, which may be amenable to treatment, may be a factor in the progressive forms of VaD.

Dementia with Leukoaraiosis: Clinical Differentiation by Temporoparietal Hypometabolism on 18FDG-PET Imaging

Patients with dementia and leukoaraiosis may have either Alzheimer’s disease (AD) with cerebrovascular changes or a form of vascular dementia (VaD). The presence or absence of the characteristic AD pattern of bilateral temporoparietal hypometabolism on ¹⁸FDG-PET was used to differentiate 30 patients with progressive dementia and severe leukoaraiosis. Compared to 18 patients with the typical AD pattern (group I), the remaining 12 (group II) had better recognition memory, and greater difficulty with sustained attention and serial reversals. Better recognition memory, confluent periventricular leukoaraiosis, and poorer sustained attention distinguished all group II patients from group I. Dementia patients with severe leukoaraiosis and bilateral temporoparietal hypometabolism may have predominant AD; those who lack this pattern and have confluent leukoaraiosis may have a greater contribution from VaD.