Binswanger's Disease Research Articles

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 …

Neuropathology of frontotemporal dementia

Frontotemporal dementia (FTD) is a clinical phenotype of dementia, characterized by complex of clinical symptoms, including disinhibition, character change, increased appetite, sexual misconduct and language problems. Frontotemporal lobar degeneration (FTLD) is a pathological classification of neurodegenerative disorder and its core consists of Pick's disease (PiD). Historically, PiD was morphologically subclassified into three types, but recent immunocytochemical investigations defined type I as PiD with Pick bodies (three repeat tauopathy), type II as corticobasal degeneration (CBD, four repeat tauopathy) and type III as FTLD with ubiquitinated inclusions (FTLD-U). The recent progress provided an evidence that the majority of FTLD-U represented primary TDP 43 proteionopathy. Three major clinical phenotypes of FTLD consist of FTD, semantic dementia (SD) and progressive non-fluent aphasia (PNFA). Clinical and pathological correlative studies demonstrated that majority of the background pathology of FTD is PiD with Pick bodies, that of SD is FTLD-U and that of PNFA is CBD, although there are too many exceptions. Although FTD is one of the major clinical manifestations of FTLD, the most frequent pathological background of FTD is Alzheimer disease (AD). The degenerative processes causing FTD symptoms include dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and argyrophilic grain disease. Moreover, vascular process such as Binswanger disease and inflammatory process such as neurosyphilis could also present with FTD symptoms. Since FTD requires special clinical care distinct from AD, clinical diagnosis of FTD is quite important. But for the fundamental treatment based on background pathological processes, surrogate biomarkers, including structural and functional neuroimages and findings of cerebrospinal fluid, blood and urine, should be pursued for future progress in FTD research.

Apoptosis in Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

To test the hypothesis that an apoptotic process plays a role in the pathogenesis of cerebral lesions in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), we examined samples from frontal, temporal, insular, and occipital regions, basal ganglia, and cerebellum from 4 patients with CADASIL, 2 with Binswanger disease, and 3 controls. Apoptotic cells were identified using in situ end labeling and activated caspase 3 immunostaining. Immunolabeling for Notch3, the beta-amyloid protein precursor, and phosphorylated neurofilament protein was performed on successive sections. Apoptosis of vascular cells was markedly increased in status cribrosus in CADASIL, both in basal ganglia and subcortical white matter, suggesting that concomitantly with Notch3 deposition it may play a causative role in the dilatation of Virchow-Robin spaces. Neuronal apoptosis was found in CADASIL, mostly in cortical layers 3 and 5. Its severity correlated semiquantitatively with the extent of ischemic lesions and axonal damage in the underlying white matter. It was more severe in demented patients. Only occasional apoptotic neurons were found in the Binswanger cases and none in the controls. This supports the view that neuronal apoptosis may contribute to cortical atrophy and cognitive impairment in patients with CADASIL and that it may, at least partly, result from axonal damage in the underlying white matter.

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.

Comparison of regional cerebral blood flow in two subsets of subcortical ischemic vascular dementia: Statistical parametric mapping analysis of SPECT

Background The brain imaging criteria for subcortical ischemic vascular dementia (SIVD), as proposed by Erkinjuntti, incorporated two clinical entities, the lacunar state and Binswanger's disease. However it has not been proven whether these two subtypes of SIVD have common pathophysiological features. This study investigated the changes of regional cerebral blood flow (CBF) in the two subsets of SIVD to establish whether these two subtypes could be incorporated into the same group for the purpose of conducting clinical trials. Methods Twelve SIVD patients with predominant white matter lesions, 13 patients with predominant lacunar infarctions and 17 controls were evaluated. Single photon emission computed tomography (SPECT) was performed to measure the regional CBF, and statistical parametric mapping (SPM) was applied to the analysis of the SPECT data. Results The normalized CBF (nCBF) in the bilateral thalami, the anterior cingulate gyri, the superior temporal gyri, the caudate heads and the left parahippocampal gyrus was significantly decreased in the SIVD patients compared to the controls. This pattern of nCBF reduction was same in both the two subtypes of SIVD patients. Conclusion Our study suggests that the two subsets of SIVD may have a common nCBF abnormality, and Erkinjuntti's criteria offer a solution for researchers to identify the more homogeneous group of vascular dementia patients.

Leukoaraiosis and Ischemia

See related article, pages 1391–1398 Although Alois Alzheimer had described in 1902 a baffling extensive and severe degeneration of the cerebral white matter (misnamed Binswanger disease), over half a century of regular examination of brains by histological techniques failed to recognize the common occurrence of bilateral, patchy or confluent, white matter lesions revealed first as hypodense areas by computed tomography and later with much improved definition as hyperintensities in T2 and FLAIR sequences in magnetic resonance.1 Even in retrospect, it is hard to identify on histological sections the exact location of lesions so brightly demonstrated on magnetic resonance images. The name leukoaraiosis will be used in this editorial to designate these white matter lesions, as opposed to others related to demyelinating, infectious, toxic, or metabolic processes.2 Having named the finding we were left with an existentialist lesion in search of significance. As a marker, leukoaraiosis is a prognostic factor for stroke and myocardial infarction.3,4 Its consequences, even in samples restricted to nondisabled elderly, include impaired cognitive function,5,6 mediated by deterioration in information processing speed and executive functions,7 as well as reduced motor function,8 and possibly late onset-depression.9 But how are the lesions produced? Epidemiological studies suggest association with aging and vascular risk factors such …

Ischemic demyelination

White matter lesions representing ischemic demyelination have evolved in terms of our understanding of their pathogenesis and potential clinical significance. Low density lesions on CT brain scan, most commonly seen in the periventricular region, also frequently seen in the centrum semiovale, have been termed 'leukoaraiosis'. In the past years, it was not uncommon at all to hear the term 'Binswanger's disease' used in an attempt to define the neurological sequelae of such lesions. Further refinement came with the advent of magnetic resonance imaging (MRI) brain scan which is particularly sensitive to such white matter areas of increased signal intensity, which tend to be seen particularly well on T2-weighted and fluid attenuation inversion recovery (FLAIR) scans.The major challenge has been to correlate the clinical attributes with such relatively frequent findings in the elderly population. Recent studies have looked at lesion load in a fashion analogous to that seen with multiple sclerosis. A particularly relevant clinical model for white matter disease is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) which combines the potential components of small vessel disease, resulting in progressive neurological deficit, with a common association with migraine which can also be associated with white matter lesions. However, the most common pathogenic factor associated with the microangiopathy, which appears to be at the heart of ischemic demyelination, continues to be hypertension. How well we are able to tie in the various pathological mechanisms associated with this end organ damage of the brain will determine how well we can arrive at effective interventions for a common contributor to neurological deficits in the elderly.

Small Artery Dementia in Japan: Radiological Differences between CADASIL, Leukoaraiosis and Binswanger’s Disease

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a hereditary small artery disease which is phenotypically similar to Binswanger’s disease (BD), a nonhereditary form of small artery disease. Recent studies have indicated that lesions in the temporopolar, medial frontopolar areas and external capsule are frequently seen in Caucasian patients with CADASIL. However, it remains unclear whether magnetic resonance (MR) imaging findings are helpful in diagnosing small artery disease outside countries with Caucasian populations, since CADASIL is rare despite the high prevalence of small artery disease in Japan. We examined 58 patients with small artery disease, all of whom were devoid of major vessel occlusion or severe stenosis. These patients included 7 patients from 3 families with CADASIL, 27 nondemented patients with extensive leukoaraiosis (LA) and 24 patients with BD. On T₂-weighted MR images, hyperintensities in the temporopolar areas were observed in all 7 patients with CADASIL, whereas these lesions were observed in only 1 subject from each of the nondemented LA and BD groups. Hyperintensities in the medial frontopolar areas were seen in 4 of the 7 patients with CADASIL (57%) and in 14 of the 24 patients with BD (58%), and were more frequent than in the nondemented LA group (4 of the 27 patients; 15%). In contrast, hyperintensities in the external capsule were frequently observed in all groups. Therefore, temporopolar lesions can also serve as diagnostic markers for CADASIL in non-Caucasian patients.

Rehabilitation nursing 68 patients with binswanger disease combined psychosis

皮质下动脉硬化性脑病(binswanger disease,BD)是由于脑动脉硬化引起的脑白质广泛性脱髓鞘疾病,临床表现为进行性智能障碍、亚急性运动迟缓,累及神经体征及局灶性神经功能障碍.随着CT和MRI的广泛应用,BD越来越多地在中、老年人中被发现[1].住院精神病患者由于长期大量地使用精神药物,导致全身处于高凝状态,同时日常活动少,成为BD的高发人群[2].为改善患者的神经功能,提高生活质量,2000年1月-2005年6月我院对住院精神病伴发BD的68例患者进行综合康复护理,患者日常生活能力显著改善,智能障碍程度明显降低,现报道如下。

Upregulated Expression of 14-3-3 Proteins in Astrocytes From Human Cerebrovascular Ischemic Lesions

Several types of chaperone proteins, such as heat shock proteins, have been reported to be associated with brain ischemia. The purpose of this study was to investigate whether an abnormal expression of 14-3-3 proteins, a novel type of molecular chaperones, occurs in human gray and white matter ischemic lesions. We prepared formalin-fixed, paraffin-embedded sections from 33 autopsied brains, consisting of 7 normal controls, 4 cases with cerebral thrombosis, 5 cases with cerebral embolism, 8 cases with multiple lacunar infarctions, and 9 cases with Binswanger disease. Deparaffinized sections from all cases were immunostained with anti-14-3-3 antibodies using the avidin-biotin-peroxidase complex method, and some sections were also double-immunostained for 14-3-3 and glial markers. In the normal control brains, 14-3-3 immunoreactivity was mainly localized to the neuronal somata and processes. Strongly 14-3-3-immunopositive astrocytes were distributed in the infarct lesions and were particularly abundant in infarcts at the chronic stage. Intensely 14-3-3-immunolabeled astrocytes were also observed in the ischemic white matter lesions, and in the severely affected white matter lesions from patients with Binswanger disease, dense 14-3-3 immunoreactivity was found in clasmatodendritic astroglia as well as in reactive astrocytes. Our results suggest that 14-3-3 proteins may be induced mainly in astrocytes from human cerebrovascular ischemic lesions, and that the upregulated expression of 14-3-3 proteins in astrocytes may be involved in the formation of astrogliosis.

White Matter Changes in Elderly People: MR-pathologic Correlations

Magnetic resonance (MR) imaging features of white matter lesions, often seen in the elderly, are correlated with histologic findings. Dilatation of perivascular spaces is seen, especially in the frontal and/or parietal subcortical white matter; the spaces are less than 3 mm in diameter and have sharp margins with no perifocal abnormality. Old lacunar infarcts are larger than 3 mm in diameter and are irregularly shaped and accompanied by perifocal myelin pallor and gliosis. Periventricular hyperintensity, including cap and rim, histologically shows myelin pallor, dilatation of perivascular spaces, discontinuity of the ependymal lining, and subependymal gliosis. Deep and subcortical white matter hyperintensity reflects myelin pallor and dilatation of perivascular spaces. Diffuse white matter lesion, seen in Binswanger's disease, shows myelin pallor and tissue rarefaction associated with loss of myelin and axons. U-fibers are usually well preserved. Severe arteriosclerosis and arteriolosclerosis are usually seen in the white matter. Knowledge of the pathologic features of incidental changes in white matter helps in understanding MR imaging findings.

Binswanger's disease: clinical and computed tomography neuroradiological study of seven cases

AbstractBackground: Binswanger's disease is a special type of vascular dementia, which requires further reappraisal and redefinition. In a geriatric psychiatry hospital (with 207 beds), we treated several patients who probably had this disease, and tried to establish a basis for making a clinical diagnosis.Methods: From 2001 to 2005, we treated seven inpatients with noteworthy symptoms, who had been under observation in hospital wards for between 4 and 19 months. Here, for these patients, we examine the history of the illness, the condition of the patients at admission, the clinical course, and serial computed tomography (CT) findings.Results: Characteristic features of the clinical courses and symptoms of these patients were: (i) onset occurred late in life (patients were aged in their 70s and 80s); (ii) vascular events were atypical and transient, leaving few permanent neurological sequelae; (iii) progression of dementia and other somatic or neurologic symptoms was continuous and fast in four patients, and rather gradual in three patients; (iv) there was an alternating or changing pattern in all patients’ state of consciousness, mood, behavior, or manner of respiration; symptoms such as mutism, lack of facial expression, and apparent indifference were counterbalanced with such behaviors as occasional unexpected smiles, pertinent verbal responses, and sincere gazes; (v) significant negative symptoms were a lack of dysarthria, lack of dysphagia, lack of involuntary movement, and occasional lack of muscle rigidity. The primary CT findings were: (i) moderate to severe generalized (involving whole of centrum semiovale), diffuse and homogeneous (except one patient) leukoaraiosis of the hemispheric white matter, including the temporal lobe (except one patient), all (except one patient) frontal and parietal dominant, with the corpus callosum involved in one case; (ii) diffuse and generalized atrophy of the pallium, most marked in the frontal and parietal lobes, restricted to the frontal and parietal lobes in three patients, and to the frontal, parietal and temporal lobes in four patients; (iii) atrophy of the medial temporal lobe was inconstant and, when present, ambiguous in degree; (iv) slight to moderate enlargement of the bilateral lateral and third ventricles; (v) a few small lacunae in the basal ganglia and thalamus in one patient, inhomogeneous macular changes of density in the basal ganglia and thalamus in two patients, and no such findings in the remaining four patients.Conclusion: We have described a group of patients with dementia characterized by a clinical course with episodes of rather transient vascular intervention, psychopathology characteristic of organic dementia, fluctuating psychotic symptoms in combination, and intensive extensive homogeneous leukoaraiosis of the hemispheric white matter on CT. These clinical and CT neuroradiological findings seem to warrant the clinical diagnosis of Binswanger's disease, which should be reconfirmed at autopsy. Early research on this disease by Binswanger, Alzheimer, Nissl and others is reviewed. Some points of differential diagnosis in serial neuroradiology are discussed in relation to multilacunar dementia.

Uncommon causes of cerebrovascular dementia

The concept of Binswanger's disease (BD) remains unclear and may not constitute a useful diagnostic category. However, cognitive decline may be present in a proportion of patients with subarachnoid hemorrhages (SAH) or subdural hematomas (SH). We provide a critical review of the concept of BD and summarize the main findings on the association between SAH, SH and cognitive decline. BD was originally identified as a type of dementia different from neurosyphilis and with characteristic white matter atrophy. The phenomenology of BD is currently construed around the concept of frontosubcortical dementia, but the validity of this construct is unclear. Patients with SAH frequently develop a variety of cognitive and behavioral problems that usually result in poor psychosocial adjustment and poor quality of life. SH is a rare cause of progressive cognitive impairment. A proportion of patients (particularly functionally impaired old individuals) are at a high risk for cognitive deficits after surgical drainage of the hematoma.

C-Reactive Protein and Cerebral Small-Vessel Disease

Stroke places a large burden on healthcare and social services resources in the older adult population. Because the incidence of stroke increases with advancing age, and the population is aging, the number of patients affected by stroke is increasing. See p 900 The burden of stroke goes well beyond those cases that are clinically recognized. Imaging techniques of the brain have revealed a remarkably high prevalence of white matter lesions (WML) and silent brain lacunar infarcts (SBLI). In the National Heart, Lung, and Blood Institute–sponsored Cardiovascular Health Study, SBLI ≥3 mm were found in 31% of all subjects.1 Fewer than 15% of patients with such lesions had a clinical history of stroke. The prevalence of SBLI increased with advancing age; 22% of subjects 65 to 69 years old had SBLI, as compared with 43% in subjects ≥80 years old. WML involving in particular the centrum ovale are a subject of great interest. Partly this is because modern neuroimaging methods detect subcortical WM changes with increasing frequency in people >60 years old and also because these abnormalities may be associated with specific neurobehavioral deficits, including dementing syndromes.2 The descriptive term leukoaraiosis (LA), frequently applied to these neuroimaging abnormalities of the WM, refers to bilateral and either patchy or diffuse areas of hypodensity on CT or hyperintensity on T2-weighted MRI.3 In this issue of Circulation , van Dijk and colleagues4 explore the relationship of C-reactive protein (CRP), a well-known systemic marker of inflammation, with the severity and progression of cerebral WML/LA on MRI scans. The investigators examined the prevalence and incidence of brain WML/LA and SBLI in the prospective cohort of 1033 older adult participants of the population-based Rotterdam Scan study. They confirmed a relationship between inflammation and the severity and progression of cerebral WML/LA and SBLI independent …

Lymphomatosis cerebri as a cause of white matter dementia

Primary central nervous system lymphoma most often presents as a solitary, isolated lesion in immunocompetent patients. Rarely, the disease presents as a diffuse, infiltrating condition without formation of a cohesive mass, a pattern called lymphomatosis cerebri. We present 3 immunocompetent individuals who developed rapidly progressive dementia. Magnetic resonance imaging features mimicked other disorders of white matter and prompted preoperative diagnoses of Binswanger's disease (subcortical ischemic vascular dementia), unknown leukoencephalopathy, viral infection, or infiltrating glioma. Neuropathologic examination at biopsy (Poon T, Matoso I, Tchertkoff V, Weitzner I Jr, Gade M. CT features of primary cerebral lymphoma in AIDS and non-AIDS patients. J Comput Assist Tomogr . 1989;13:6-9) and autopsy (Schwaighofer BW, Hesselink JR, Press GA, Wolf RL, Healy ME, Berthoty DP. Primary intracranial CNS lymphoma: MR manifestations. Am J Neuroradiol . 1993;10:725-9) demonstrated nonnecrotic, diffusely infiltrating, large-cell B-cell lymphoma of white matter, with relative sparing of gray matter, and without significant leptomeningeal involvement or bulky periventricular disease at autopsy. Microglial and astrocytic reactions, but only subtle myelin pallor, were evident as individual tumor cells permeated the entire brain and spinal cord, albeit with considerable variation in cell density. Individual tumor cells could be identified from the optic nerve to spinal cord, documenting the "whole-brain" nature of the disease. CD20 immunostaining was necessary to fully appreciate the extent of individual lymphoma cell percolation through the white matter. The neurobehavioral deficits manifested by these patients demonstrate that lymphomatosis cerebri is an additional neoplastic cause of white matter dementia and can be added to the growing list of disorders responsible for this syndrome.

血管性痴呆―アルツハイマー病との接点

Cerebrovascular disease and Alzheimer's disease (AD) are the most frequent causes of dementia in the elderly. Pathological backgrounds for vascular dementia (VaD) are heterogenous. Cerebral white matter is mostly involved in dementia due to small-vessel disease and Binswanger's diease. In Binswanger's disease, a quantitative electron microscopic study showed the reduction of nerve fibers, oligodendrocytes and astrocytes in the white matter. These changes are associated mainly with lipohyalinosis (angionecrosis) of small intraparechymal arteries as well as atherosclerosis of main cerebral arteries. The changes in arterioles are believed to cause blood-brain barrier impairments, activation of microglia, and increased production of cytokines and free radicals, all of which may lead to white matter damage. Clinical, pathological and neuroimaging features are different between typical cases with VaD and AD. However, recent studies have reported that VaD has also characteristic features of AD, including hippocampal atrophy, the reduction in acetylcholine concentration in the bain, and possible beneficial effect of acetylcholine esterase inhibitors. Like VaD, AD also shows carebral white matter changes and changes in cerebral blood flow and oxygen metaboloism. Epidemiological studies have reported that almost all risk factors for cerebrovascular disease increased the risk of AD. Further clinicopathological investigation will enhance our understanding of the relation of VaD to AD and our capability to prevent and treat VaD and AD.

高ホモシステイン血症と高リポ蛋白（ａ）血症

Backgrounds; We investigated the incidence and clinical significance of hyperhomocysteinemia in cerebral infarction (study 1) and dementia (study 2) in relation to the clinical findings.Subjects and Methods; Blood levels of homocysteine (HC) and related coenzymes, that is, folic acid, vitamin B12, and 136, were determined in patients with cerebral infarction in the chronic stage, dementia, and controls. Data were analyzed retrospectively (study 1; n = 145, study 2; n= 143). Grades of cerebral white matter lesions (periventricular hyperintensity and/or deep and subcortical white matter hyperintensity) were evalu-ated by using Shinohara's grading (2003). Binswanger type dementia (Binswanger's disease) was diagnosed based on the criteria by Bennett DA, et al. (1990).Results; In study 1, increased levels of HC and Lp (a) as well as decreased levels of HC-related coenzymes were observed in patients with atherothrombotic infarction or white matter lesions. In study 2, increased lev-els of HC and Lp (a), and also, decreased levels of HC-related coenzymes were observed in patients with vascular dementia, mixed dementia, and Binswanger's disease.Conclusions; HC, Lp (a), and HC-related coenzymes are involved in the pathogenesis not only of cerebral infarction but also of vascular dementia including Binswanger type.

0768 Dysexecutive syndrome in Binswanger's disease and frontal variant of frontotemporal dementia

0768 Dysexecutive syndrome in Binswanger's disease and frontal variant of frontotemporal dementia

Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia

Vascular cognitive impairment (VCI) was proposed as an umbrella term to include subjects affected with any degree of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from mild cognitive impairment (MCI) to vascular dementia. VCI may or may not exclude the host of “focal” circumscribed impairments of specialized functions such as language (aphasia), intentional gesture (apraxia), or categorical recognition (agnosia), among others, that may result from a stroke. Therefore, there are no universally accepted diagnostic criteria for VCI. We conclude that this concept could be more useful if it were to be limited to cases of vascular MCI without dementia, by analogy with the concept of amnestic MCI, currently considered the earliest clinically diagnosable stage of Alzheimer disease (AD). In agreement with our view, the Canadian Study on Health and Aging successfully implemented a restricted definition of VCI, excluding cases of dementia (i.e., vascular cognitive impairment no dementia, VCI-ND). The Canadian definition and diagnostic criteria could be utilized for future studies of VCI. This definition excludes isolated impairments of specialized cognitive functions. Vascular dementia (VaD): The main problem of this diagnostic category stems from the currently accepted definition of dementia that requires memory loss as the sine qua non for the diagnosis. This may result in over-sampling of patients with AD worsened by stroke (AD+CVD). This problem was minimized in controlled clinical trials of VaD by excluding patients with a prior diagnosis of AD, those with pre-existing memory loss before the index stroke, and those with amnestic MCI. We propose a definition of dementia in VaD based on presence of abnormal executive control function, severe enough to interfere with social or occupational functioning. Vascular cognitive disorder (VCD): This term, proposed by Sachdev [P. Sachdev, Vascular cognitive disorder. Int J Geriat Psychiatry 14 (1999) 402-403.] would become the global diagnostic category for cognitive impairment of vascular origin, ranging from VCI to VaD. It would include specific disease entities such as post-stroke VCI, post-stroke VaD, CADASIL, Binswanger disease, and AD plus CVD. This category explicitly excludes isolated cognitive dysfunctions such as those mentioned above.

Dementia associated with the antiphospholipid syndrome: clinical and radiological characteristics of 30 patients.

To analyse the clinical and radiological characteristics of patients with dementia associated with the antiphospholipid syndrome (APS). Twenty-five patients were identified by a computer-assisted (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature to locate all cases of dementia associated with APS published in English, Spanish and French from 1983 to 2003. Additionally, we included five patients from our clinics. There were 21 (70%) females and 9 (30%) males. The mean age of patients was 49+/-15 yr (range 16-79 yr). Fourteen (47%) of the patients suffered from primary APS, 9 (30%) had systemic lupus erythematosus and 7 (23%) had 'lupus-like' syndrome. Ten (33%) patients had Sneddon's syndrome and 2 (7%) had cerebral lesions described as Binswanger's disease. Other APS-related manifestations included thrombocytopenia in 12 (40%) patients, cerebrovascular accidents in 11 (37%), heart valve lesions in 8 (27%), deep vein thrombosis in 7 (28%), migraine in 7 (23%), seizures in 4 (13%); five of the 21 (24%) female patients had nine spontaneous abortions. Lupus anticoagulant was present in 21/29 (72%) patients and anticardiolipin antibodies were present in 24/29 (83%) patients. Cortical infarcts were found in 19 (63%) patients, subcortical infarcts in 9 (30%), basal ganglia infarcts in 7 (23%) and signs of cerebral atrophy in 11 (37%). Anticoagulation was used in 14/25 (56%) patients, steroids in 12/25 (48%), aspirin in 6/25 (24%) and dypiridamole in 5/25 (20%). Dementia is an unusual manifestation of APS but one which has a high disability impact in a patient's daily life. In order to prevent these consequences, an echocardiographic and cerebral CT or MRI evaluation are recommended in all patients with APS. Furthermore, ruling out APS should be recommended in the clinical approach to dementia, especially in young patients.