MRI evaluation of vascular dementia

OBJECTIVE: To explain the association between vascular dementia and the cranial MRI manifestations, and recognize the value of cranial MRI in the early diagnosis of vascular dementia and the assessment of disease conditions. DATA SOURCES: Pubmed database was searched to identify articles about the cranial MRI manifestations of patients with vascular dementia published in English from January 1992 to June 2006 by using the of "MRI, vascular dementia". Others were collected by searching the name of journals and title of articles in the Chinese full-text journal database. STUDY SELECTION: The collected articles were primarily checked, those correlated with the cranial MRI manifestations of patients with vascular dementia were selected, while the obviously irrelative ones were excluded, and the rest were retrieved manually, the full-texts were searched. DATA EXTRACTION: Totally 255 articles were collected, 41 of them were involved, and the other 214 were excluded. DATA SYNTHESIS: MRI can be taken as one of the effective methods for the early diagnosis and disease evaluation of vascular dementia. White matter lesions are the important risk factors of vascular dementia. Vascular dementia is accompanied by the atrophy of related brain sites, but further confirmation is needed to investigate whether there is significant difference. MRI can be used to quantitatively investigate the infarcted sites and sizes of patients with vascular dementia after infarction, but there is still lack of systematic investigation on the association of the infarcted sites and sizes with the cognitive function of patients with vascular dementia. CONCLUSION: Cranial MRI can detect the symptoms of vascular dementia at early period, so that corresponding measures can be adopted to prevent and treat vascular dementia in time.     

Towards a prevention of dementia?

Many studies have shown that high blood pressure and, to a lesser extent, other vascular risk factors could be the target of interventions aiming to reduce the incidence of dementia. Two large controlled trials have demonstrated that blood pressure lowering drugs have a significant effect on the risk of dementia including Alzheimer's disease. On another hand, large epidemiological studies have shown associations between different vascular factors and dementia. Overall, these data suggest that interventions aiming to reduce the level of vascular risk factors might prevent dementia. The expected benefit of these interventions could be estimated from data provided by epidemiological studies, but large population-based controlled studies are needed to demonstrate the efficacy of preventive interventions.     

Alzheimer's dementia or cerebral toxoplasmosis? Case study of dementia following toxoplasmosis infection

Cerebral toxoplasmosis can lead to dementia in AIDS and in immunodeficient patients. We present a case study in which cerebral toxoplasmosis was associated with a dementia of Alzheimer type. Half a year to one year before the cognitive impairment began, the patient suffered a subacute infection of toxoplasmosis at the age of 56. Neuropsychological examination as well as MRI suggested a diagnosis of dementia with infectious genesis. However, serological tests showed only little evidence of infection. Since the results of the PET examination indicated changes in the glucose metabolism typical of Alzheimer's disease, we infer a comorbidity of cerebral toxoplasmosis and dementia of Alzheimer type.     

Is dementia with Lewy bodies the second most common cause of dementia?

Lewy bodies were originally described in isolated brainstem nuclei in persons with Parkinson's disease. They have since been recognized as a widespread and common neuropathologic finding in individuals with dementia. Dementia with Lewy bodies (DLB) is the preferred term for the dementia syndrome associated with Lewy bodies. Although DLB is acknowledged as the second most common degenerative dementia, trailing only Alzheimer's disease, its ranking with respect to vascular dementia remains controversial. Large, community-based studies of DLB with postmortem confirmation are lacking. Available data suggest that DLB is more common than pure vascular dementia but not more common than any vascular contribution to dementia.     

Frontotemporal dementia: Pathology of gait?

The main diagnostic criteria of the behavioural variant of frontotemporal degeneration (bvFTD) include neurobehavioral and dysexecutive syndromes, but not specific gait characteristics although strong relationship between gait and prefrontal functions are increasingly recognized. Accordingly, we tested the hypothesis that patients with bvFTD would have more gait changes than older healthy controls and demented patients with Alzheimer's disease (AD). Sixty subjects were included in the study: 19 with bvFTD, 19 with AD and 22 healthy controls. Mean values and coefficients of variation (CV) of stride time while just walking (i.e., single tasking) and while walking with backward counting (i.e., dual tasking) were measured using the SMTEC®‐footswitch system. Stride time, mean value, and CV were significantly increased in both patient groups compared with healthy controls during single task or walking alone (P < 0.001) and during dual tasking (P < 0.001). After adjusting for age, Mini‐mental examination, psychoactive drugs, gender, and history of previous fall, only the patients with bvFTD group was associated with an increase of CV of stride time during single walking (P < 0.001) and dual tasking (P < 0.001). These data suggest that gait instability during single and dual tasking could represent a supportive argument for bvFTD. In clinical practice, such a diagnosis should be at least considered in any demented patient with gait instability. © 2010 Movement Disorder Society     

Treatment of dementia: anything new?

PURPOSE OF REVIEW: The aim of this article is to discuss new data on presently approved drugs for dementia, such as cholinesterase inhibitors and memantine, and concerns regarding the use of antipsychotics for treating neuropsychiatric symptoms, as well as to summarize some relevant studies recently published on emerging therapies with potential disease-modifying effects. RECENT FINDINGS: The main focuses of recent studies of cholinesterase inhibitors and memantine have been on efficacy and safety aspects in extended clinical trials, combined treatments or comparative analysis between agents, and also on potential neuroprotective effects and new indications. Other publications have assessed the evidence of efficacy and the increased risk of cerebrovascular events, rapid cognitive decline, and mortality with the use of antipsychotics in dementia, providing important information in relation to the controversy surrounding its use. Although more studies are warranted, a sizable literature on novel treatment options under investigation is currently available as a result of a better understanding of pathogenesis of dementia. SUMMARY: So far, there is no established method to predict better responders or long-term benefits with currently approved drugs for treatment of dementia. Recent systematic reviews and new research on current treatment, however, provide valuable information for clinicians, and novel drugs under investigation reveal promising new therapeutic strategies.     

Stigma and GPs’ perceptions of dementia

Objectives: General practitioners (GPs) are crucial to improving timely diagnosis, but little is reported about how they perceive dementia, and whether their perceptions display any elements of stigma. The aim of this study was to explore how GPs’ perceptions of dementia map onto current conceptualizations of stigma and whether GPs feel that stigma affects timely diagnosis.

Methods: Twenty-three GPs from England were interviewed by telephone. Data were analyzed by means of content analysis. This involved open coding followed by the application of a coding framework derived from the literature to explore how and to what extent their perceptions relate to stigma as well as the unique nature of their perceptions.

Results: Three themes emerged from the analysis: (1) ‘making sense of dementia’, (2) ‘relating perceptions of dementia to oneself’ and (3) ‘considering the consequences of dementia’. GPs’ perceptions of dementia mapped onto current conceptualizations of stigma. Perceptions about dementia that were linked to their own existential anxiety and to a perceived similarity between people with dementia and themselves were particularly salient. GPs perceived dementia as a stigma which was gradually being overcome but that stigma still hindered timely diagnosis. They provided examples of structural discrimination within the health service, including lack of time for patients and shortcomings in training that were to the detriment of people with dementia.

Conclusion: Measures to involve GPs in tackling stigma should include training and opportunities to explore how they perceive dementia, as well as support to address structural discrimination.     

Polymorphism of apolipoprotein E gene and post-stroke vascular dementia

INTRODUCTIONRecent researches indicate that the incidence rate of vascular de- mentia after stroke is about 25%[1]. Though vascular dimension can be caused by various factors, such as the site, number and size of stroke, etc. [2], there are arguments in t…     

Executive function: the core feature of dementia?

Links between Alzheimer's disease (AD) and vascular dementia (VaD) have been examined, and this paper investigates the role of executive control function (ECF) within the dementia syndrome. 307 AD patients, 168 VaD patients and 208 controls were compared on tests of cognitive function. Results indicated that controls outperformed both patient groups (p < 0.001) on all tests. AD patients performed more poorly than VaD patients on 11 of the 18 cognitive tests (p < 0.05). Factor analysis of patient data indicated the existence of 3 factors generated from the battery of tests, relating to episodic memory, ECF and face recognition. It was primarily on tests of ECF that the AD and VaD groups did not differ significantly. It is concluded that ECF is a feature of cognition shared by the two pathologies, giving rise to an obligation to reconsider the current understanding of the core cognitive feature of dementia.     

Is the immobility of advanced dementia a form of lorazepam-responsive catatonia?

Patients with end-stage dementia typically are very immobilized. Could this state actually be a form of lorazepam-responsive catatonia? Catatonia has been documented following cerebrovascular accidents, head injury, HIV encephalitis, brain tumors, and multiple sclerosis. Identified anatomical substrates include frontal lobes, parietal lobes, limbic system, diencephalon, and basal ganglia. Given that Alzheimer's disease, vascular dementia, Lewy body dementia, corticobasal degeneration, frontotemporal dementia, and Parkinsonian dementia often have degeneration in some of the same areas, dramatic awakenings might be possible by giving lorazepam challenges to locked-in dementia patients. If even a small percentage were lorazepam responders, the impact worldwide would be tremendous. Serious consideration should be given to undertaking large-scale clinical trials.     

Utility of the Mattis dementia rating scale to assess the efficacy of rivastigmine in dementia associated with Parkinson’s disease

INTRODUCTION: The severe, cortical, cholinergic depletion accompanying Parkinson's disease (PD) is considered as a highly probable correlate of cognitive and behavioural dysfunction. Recent studies have demonstrated that cholinesterase inhibitors (notably rivastigmine) are beneficial in patients suffering from dementia associated with PD (PDD). However, the primary efficacy variables used in such work came from scales designed for Alzheimer's disease (AD), even though the cognitive symptoms in PD and AD dementia do not overlap completely. The aim of the present study (a double-blind, placebo-controlled clinical trial) was to determine the utility of the Mattis dementia rating scale - the most commonly used scale in PD patients - to assess the efficacy of a 24-week rivastigmine treatment. METHODS: Twenty-eight patients with PD, who constituted a subgroup of patients enrolled to the EXPRESS study (Emre et al, N Engl J Med 2004) participated in this study. They suffered from mild to moderately severe dementia (MMSE scores above 10 and below 24), with an onset of cognitive symptoms occurring at least two years after the diagnosis of PD. Patients were randomly assigned to treatment with rivastigmine (3 to 12 mg per day) or placebo. The Mattis dementia rating scale was administered to patients from six centres in France at the baseline and end-point visits. RESULTS: Compared with placebo, a 24-week rivastigmine treatment led to a significant improvement in the overall score on the Mattis dementia rating scale (p = 0.031), with a trend towards a significant improvement in the "Attention" subscale score (p = 0.061). Correlation analysis showed that in the rivastigmine group, performance on the Mattis "Attention" and "Initiation" subscales appeared to contribute heavily to the improvement in the overall score. Moreover, the latter was also related to an improvement in activities of daily living and a reduction in behavioural disturbances. DISCUSSION: By using the Mattis dementia rating scale (which comprises items that are sensitive to executive dysfunction), the present study confirmed that rivastigmine has a beneficial effect on cognitive function in PDD. Despite our study's small sample size, the Mattis scale was able to detect this improvement and could thus be considered as an interesting outcome measure in further work.     

Atrophy of the cholinergic basal forebrain in dementia with Lewy bodies and Alzheimer’s disease dementia

Similar to Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) is characterized by a profound degeneration of cortically-projecting cholinergic neurons of the basal forebrain (BF) and associated depletion of cortical cholinergic activity. We aimed to investigate subregional atrophy of the BF in DLB in vivo and compare it to the pattern of BF atrophy in AD. Structural MRI scans of 11 patients with DLB, 11 patients with Alzheimer’s disease, and 22 healthy controls were analysed using a recently developed technique for automated BF morphometry based on high-dimensional image warping and cytoarchitectonic maps of BF cholinergic nuclei. For comparison, hippocampus volume was assessed within the same morphometric framework using recently published consensus criteria for the definition of hippocampus outlines on MRI. The DLB group demonstrated pronounced and subregion-specific atrophy of the BF which was comparable to BF atrophy in AD: volume of the nucleus basalis Meynert was significantly reduced by 20–25 %, whereas rostral BF nuclei were only marginally affected. By contrast, hippocampus volume was markedly less affected in DLB compared to AD. Global cognition as determined by MMSE score was associated with BF volume in AD, but not in DLB, whereas visuoperceptual function as determined by the trail making test was associated with BF volume in DLB, but not in AD. DLB may be characterized by a more selective degeneration of the cholinergic BF compared to AD, which may be related to the differential cognitive profiles in both conditions.     

Supporting family dementia caregivers: testing the efficacy of dementia care management on multifaceted caregivers’ burden

ABSTRACT

Objectives: Current research suggests that dementia care management (DCM) can decrease burden and associated health impairments of caregivers. The objective of this secondary analysis is to investigate the impact of DCM on multifaceted caregivers’ burden dimensions by differentiating between objective and subjective burden.

Methods: A sample of n = 317 dyads of caregivers and community-dwelling people with dementia (PwD) participated in a general practitioner-based, cluster-randomized intervention trial (Identifier:NCT01401582) with two arms and comprehensive data assessment at baseline and 12-month follow-up. Data provided by the caregiver included an inventory with 88 items in 20 different dimensions.

Results: Caregivers in the intervention ‘DCM’ group showed decreased caregiver burden, especially in caregivers’ objective burden due to caring (i.e. emotional support), caregivers’ subjective burden due to behavior change (i.e. cognition, aggression and resistance, depression, late symptoms) and caregivers’ subjective burden due to perceived conflicts between needs and responsibilities to care (i.e. financial losses) compared to caregivers in the control ‘care as usual’ group, which showed significant increased caregiver burden after 12 months.

Conclusion: Our findings support evidence for the effectiveness of DCM to lower family dementia caregivers' burden in multifaceted dimensions.     

HIV—dementia

Brain-derived neurotrophic factor (BDNF) is a promising candidate for the gene therapy of neurological disease. To deliver BDNF to neurons of the central nervous system (CNS), a nucleotide sequence encoding the mature peptide of BDNF was inserted into the genome of poliovirus, a neurotropic virus that is known to replicate mainly in motor neurons of the spinal cord of the CNS. Thus, the recombinant poliovirus constructed was replication-competent. The expression of BDNF in cultured cells infected with the recombinant poliovirus was evident when the cells were analyzed using an immunofluorescence assay and Western blotting. When the recombinant viruses were injected intramuscularly into transgenic mice that carry the human poliovirus receptor gene, the antigens of poliovirus and BDNF were detected in the motor neurons of the spinal cord at 3 days postinfection, and had disappeared by 7 days postinfection. This study suggests that poliovirus can be used as a virus vector for the delivery of neurotrophic factors to the motor neurons of the central nervous system and may provide a new approach for the treatment of motor neuron diseases.