[Effects of Tongluo Xingnao effervescent tablets on blood rheology, iNOS, VEGF and LDH-5 in MID rats].

The study was to explore effects of Tongluo Xingnao effervescent tablets on the blood rheology, iNOS, VEGF and LDH-5 in multi-infarct dementia(MID) model rats. Establish MID model rats were induced by microthrombosis, from which 50 successful model rats were randomly divided into five groups, such as the model control group, the dihydroergotoxine mesylate tablets(hydergine) group(0.7 mg•kg⁻¹), Tongluo Xingnao effervescent tablets high-dose, medium-dose and low-dose groups(7.56, 3.78, 1.89 g•kg⁻¹). Another ten rats in the sham group were randomly selected as the parallel control group. Each group was orally administered with drugs for 90 days. The learning and memory ability was evaluated with the Morris water maze test, while the whole blood viscosity and the erythrocyte aggregation index derived from abdominal aorta were measured in different shear rates. In addition, the levels of VEGF and iNOS in the serum were determined by ELISA kits. The expression of LDH-5 in hippocampus of rats was measured with immunohistochemistry and image quantitative analysis. The result showed that Tongluo Xingnao effervescent tablets notably decreased the escape latency of MID model rats, increased times of entering into the escape platform and prolonged retention time in medium ring, meanwhile the whole blood viscosity in MID model rats was also notably reduced in four shear rates, i.e. 1, 5, 30, 200 S⁻¹, erythrocyte aggregation index, serum VEGF and iNOS, and average optical density value of LDH-5, with a statistically significant differences compared with the model control group (P<0.05). In conclusion, Tongluo Xingnao effervescent tablets could improve the ability of learning and memory of MID model rats and the blood rheology, reduce the level of iNOS, VEGF and the expression of LDH-5, and then improved the brain energy supply.

[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.

Prediction of incident dementia: impact of impairment in instrumental activities of daily living and mild cognitive impairment-results from the German study on ageing, cognition, and dementia in primary care patients.

OBJECTIVES: There is an increasing call for a stronger consideration of impairment in instrumental activities of daily living (IADL) in the diagnostic criteria of Mild Cognitive Impairment (MCI) to improve the prediction of dementia. Thus, the aim of the study was to determine the predictive capability of MCI and IADL impairment for incident dementia. DESIGN: Longitudinal cohort study with four assessments at 1.5-year intervals over a period of 4.5 years. SETTING: : Primary care medical record registry sample. PARTICIPANTS: As part of the German Study on Ageing, Cognition, and Dementia in Primary Care Patients, a sample of 3,327 patients from general practitioners, aged 75 years and older, was assessed. MEASUREMENTS: The predictive capability of MCI and IADL impairment for incident dementia was analysed using receiver operating characteristics, Kaplan-Meier survival analyses, and Cox proportional hazards models. RESULTS: MCI and IADL impairment were found to be significantly associated with higher conversion to, shorter time to, and better predictive power for future dementia. Regarding IADL, a significant impact was particularly found for impairment in responsibility for one's own medication, shopping, and housekeeping, and in the ability to use public transport. CONCLUSIONS: Combining MCI with IADL impairment significantly improves the prediction of future dementia. Even though information on a set of risk factors is required to achieve a predictive accuracy for dementia in subjects with MCI being clinically useful, IADL impairment should be a very important element of such a risk factor set.

Intelligence impairment, personality features and psychopathology disturbances in a family affected with CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small-vessel disease of the brain that is characterized by headache, recurring lacunar strokes, mood changes and progressive cognitive deterioration. The disease is transmitted with an autosomal dominant pattern and usually starts during midadulthood (at 30-50 years of age). Cognitive deficits in patients with CADASIL develop slowly. The dementia causes frontal-like symptoms and it typically develops after a history of recurrent stroke. We describe three patients from one Spanish family affected by this disease. All three cases underwent comprehensive clinical and neuropsychological examination, and were monitored for seven years. The results obtained in this study describe a) a significant loss of the intelligence quotient (IQ) and noticeable damage to abstract ability (g factor), b) mood and psychopathological disturbances (major depression and dysthymia), and c) a personality with neurotic features.

[Biography and dementia. Origin of challenging behavior in patients with multi-infarct dementia or senile dementia of the Alzheimer type in long term care with reference the biographical level]. / Biografie und Demenz. Entstehung von herausforderndem Verhalten bei Menschen mit einer Multi-Infarkt-Demenz oder einer senilen Demenz vom Alzheimer Typ in der Langzeitversorgung auf biografischer Ebene.

The aim of this study was to explore the connection between the nature of agitated behaviour and meaningful biographical experiences within two types of dementia in a moderate stadium. The two dementia types included Alzheimer Disease (SDAT) and Multi-infarction aphrenia (MID). Biographical narrative interviews with 26 nursing home residents suffering from dementia have been concluded. Topics were their first thirty years of life (based on a foreign anamnesis). The challenging behaviour has been observed systematically in nursing situations. The data has been evaluated with the comparative casuistics method (Jüttemann, 1990). The behaviour has been measured with the CMAI-scale before and also after having moved to a nursing home. Residents behaviour patterns can be divided into three biographical central characters: Life as finding, life as emotional disorder and life as struggle. Institutional characteristics: Loss of near rhythms of life, losing control over the personal area, experience of social isolation and certain characteristics from nurses: staff detractions and the exercise of nursing actions which appears threats contribute to the phenomena. A disparity is shown between the types of dementia in terms of patterns of demonstrated behaviour. In addition gender differences could be shown. The recognition of the phenomena by means of the CMAI-scale elucidate that the phenomena appears for the first time or is stronger after the resettlement to a nursing home. These findings can improve nurses' understanding of the phenomena within long-term care.

Vascular cognitive impairment in small vessel disease: clinical and neuropsychological features of lacunar state and Binswanger's disease.

BACKGROUND: ischaemic cerebrovascular small vessel disease (SVD) is a prevalent and under-diagnosed condition that triggers vascular cognitive impairment (VCI). OBJECTIVE: to describe the neuropsychological and clinical profiles in SVD (Binswanger's disease, BD; lacunar state, LS) from the clinician's perspective at the VCI stage. METHODS: a total of 1257 patients admitted to a tertiary center with a diagnosis of stroke, neuroradiological vascular disease, cognitive impairment/dementia, during a 13-year period were investigated. We prospectively assessed cognition in a subset of 141 patients with VCI (LS n = 28, BD n = 69, large vessel disease-LVD-n = 44) with MMSE, CAMDEX-H, WAIS-R, EXIT-25 and Trail making test. RESULTS: executive dysfunction (ECD) (n = 89, 91.7% versus n = 10, 22.7%; P < 0.001) and gait disturbances (n = 74, 76.3% versus n = 15, 34.1%; P < 0.001) characterized SVD. Prior strokes (n = 9, 9.3% versus n = 23, 52.3%; P < 0.001) and embologenous cardiopathy (n = 39, 40.2% versus n = 28, 63.6%; P < 0.04) featured LVD cases. BD was defined by hypertension (n = 52, 75.4% versus n = 30, 44.1%; P < 0.001), ECD (n = 65, 94.2% versus n = 34, 47.2%; P < 0.001) and VCI onset with cognitive impairment but not strokes (n = 44, 63.8% versus n = 34, 50%; P < 0.01). CONCLUSIONS: ECD and a frontal gait are SVD's clinical landmarks in our sample. LS and BD cases share a similar cognitive profile.

Is the clock drawing test appropriate for screening for mild cognitive impairment?--Results of the German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe).

BACKGROUND: Individuals with mild cognitive impairment (MCI) are at high risk of developing dementia and are a target group for preventive interventions. Therefore, research aims at diagnosing MCI at an early stage with short, simple and easily administrable screening tests. Due to the fact that the Clock Drawing Test (CDT) is widely used to screen for dementia, it is questionable whether it is suited to screen for MCI. METHODS: 3,198 primary care patients aged 75+ were divided into two groups according to their cognitive status, assessed by comprehensive neuropsychological testing: individuals without MCI and individuals with MCI. The CDT scores, evaluated by the scoring system of Sunderland et al. [J Am Geriatr Soc 1989;37:725-729], of both groups were compared. Multivariate analyses were calculated and the sensitivity and specificity of the CDT to screen for MCI were reported. RESULTS: Significant differences were found for CDT results: MCI patients obtained worse results than cognitively unimpaired subjects. CDT has a significant impact on the diagnosis of MCI. However, sensitivity and specificity as well as receiver operating characteristic analyses are not adequate, meaning that the CDT could not be named as an exact screening tool. LIMITATIONS: Applying different CDT versions of administration and scoring could yield different results. CONCLUSIONS: CDT does not achieve the quality to screen individuals for MCI.

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.

Cognitive and psychiatric effects of vitamin B12 replacement in dementia with low serum B12 levels: a nursing home study.

BACKGROUND: The aim of this study is to determine whether B12 replacement would ameliorate cognitive and psychiatric symptoms in elderly subjects with dementia and low serum B12 levels. METHODS: A test group (n = 28) of nursing home residents with low serum B12 levels (<250 pg/mL) and a matched comparison group (n = 28) with normal serum B12 levels (>300 pg/mL) were evaluated by blinded raters while the test group received intramuscular (IM) B12 replacement therapy. All subjects were assessed at baseline, 8 weeks, and 16 weeks with the Dementia Rating Scale, Brief Psychiatric Rating Scale, and Geriatric Depression Scale. RESULTS: Although B12 replacement produced significant improvement in hematologic and metabolic parameters, it yielded no significant effect on cognitive or psychiatric variables. A few subjects evidenced notable individual treatment responses; however, these were not statistically more frequent than in the normal B12 group. CONCLUSIONS: These results suggest that B12 replacement is unlikely to benefit cognitive or psychiatric symptoms in the vast majority of elderly dementia patients with low serum B12 levels.

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.

Patterns of neuropsychological impairment in MCI patients with small subcortical infarcts or hippocampal atrophy.

We investigated whether MCI patients with hippocampal atrophy or multiple subcortical infarcts demonstrate neuropsychological patterns and markers considered typical of Alzheimer's disease (AD) and of vascular dementia (VD), respectively. An extensive neuropsychological battery, including tests of memory, visual-spatial and executive functions, language, attention, praxis and psychomotor speed, was administered to 36 mild cognitive impairment (MCI) patients with hippocampal atrophy and 41 MCI patients with multiple subcortical infarcts. Both groups of MCI patients were very mildly impaired and well matched in terms of MMSE scores. A clear, disproportionately severe, episodic memory disorder was observed in MCI patients with hippocampal atrophy. A less specific neuropsychological profile, consisting of impairment on an Action Naming task that is sensitive to frontal lobe lesions, was observed in MCI patients with multiple subcortical infarcts. In MCI patients, a disproportionately severe episodic memory impairment strongly points to an Alzheimer's type brain pathology, whereas the prevalence of executive deficits and other frontal lobe symptoms are a much weaker diagnostic marker of small vessel subcortical disease.

Vascular dementia.

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's dementia (AD). It is characterized by loss of executive function with milder memory loss as compared with AD and is associated with cerebral brain infarction or hemorrhage. Treatment is predominantly focused on cardiovascular risk factor reduction, but anticholinesterase inhibitors and memantine may play a role. The data is most robust for donepezil.

Different responses to rivastigmine in subcortical vascular dementia and multi-infarct dementia.

Vascular dementia (VaD) is associated with a large amount of heterogeneity, as it groups together a broad category of patients in whom various manifestations of cognitive decline are attributed to cerebrovascular or cardiovascular disease. Thus, a study was designed to determine the effects of rivastigmine on cognitive function, global daily living performance, and behavioral disorders in VaD patients versus an active control (nimodipine), stratifying patients according to the type of VaD, subcortical vascular dementia (sVAD), and multi-infarct dementia (MID). The trial was a prospective study. This study shows that long-term treatment with rivastigmine, at dosages approved for therapeutic use in Alzheimer's disease, produces significant improvement in all behavioral symptoms in 2 forms of VaD, MID and sVaD, except delusions. It also suggests that rivastigmine may enable a reduction in concomitant neuroleptics and benzodiazepines in VaD, especially in MID. The results are discussed with an overview of the literature.

Effective electroconvulsive therapy in a 92-year-old dementia patient with psychotic feature.

A 92-year-old woman who suffered from dementia with psychotic feature was admitted to a psychiatric ward. She refused to eat or take any medications. After 0.5 mg i.v. injection haloperidol, prolongation of QTc interval occurred in the electrocardiogram. Therefore two sessions of electroconvulsive therapy (ECT) were performed carefully after informed consent was obtained by her family. Almost no psychotic symptoms were observed after the first ECT. No cognitive side-effects were observed during and after the two ECT sessions. This demonstrates that ECT can be used as an alternative treatment when elderly dementia patients with psychotic feature cannot tolerate medication.

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.

The cognitive profiles of CADASIL and sporadic small vessel disease.

BACKGROUND: Interpretation of treatment trials in vascular dementia is confounded by the presence of coexistent Alzheimer disease (AD) pathology. The younger onset genetic disease cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) offers a model of pure vascular dementia, in which such confounding is unlikely. To validate CADASIL's use as a model it is important to show it results in a similar cognitive impairment. METHODS: The same neuropsychological assessment was administered to patients with CADASIL (n = 34, 14 of whom had had stroke), sporadic small vessel disease (SVD) presenting with lacunar stroke and having confluent leukoaraiosis (n = 54), and healthy controls (n = 25). RESULTS: A similar pattern of neuropsychological impairment was seen in the two diseases, with prominent early executive dysfunction. Patients with CADASIL and SVD performed worse than controls on Trails switching test (CADASIL p = 0.006; SVD p < 0.001), and on verbal fluency test (CADASIL p = 0.015; SVD p = 0.004). The SVD group also performed worse on immediate (p = 0.050) and delayed (p = 0.049) memory. When only patients with CADASIL with stroke were included in analysis with SVD subjects, all of whom had had stroke, a very similar cognitive profile was seen. The only difference was on verbal fluency, where CADASIL subjects performed worse (p = 0.044). CONCLUSION: Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and small vessel disease show a similar pattern of cognitive deficits. This suggests that CADASIL provides a model of pure vascular dementia relevant for sporadic small vessel disease vascular dementia.

Behavioral alterations and vascular dementia.

BACKGROUND: Vascular dementia is one of the most frequent forms of dementia, where behavioral and cognitive symptoms coexist. Negative signs, such as apathy, abulia, opposition, and agnosia, are badly tolerated and dramatically experienced by caregivers, even worse than the other signs of cognitive decline. REVIEW SUMMARY: We have studied 120 subjects affected by subcortical vascular dementia (group A) and 120 subjects suffering from multiinfarct dementia (group B) for 24 months. The main outcomes of the study were the global performance, the global behavioral symptoms, the caregiver stress, the depression status, and the insight in their clinical situation. CONCLUSIONS: Group A manifested a reduction of depression, agitation and suicidal ideation during follow-up, with a constant tendency to refer somatic pain, to exhibit anxiety, and an evident increase in apathy, cognitive abulia, social withdrawal, and loss of insight. On the contrary, group B showed a constant tendency to manifest depression, somatic pain, anxiety, agitation, cognitive abulia, social withdrawal, and suicide ideations; they manifested a decrease of apathy and an increase in delusions, hallucinations, craving for food, and loss of insight and awareness. Their behavioral alterations were stronger than those exhibited by group A, and that was reflected by an increment of caregivers' burden score. Even from a behavioral perspective, multiinfarct dementia is not the same as subcortical vascular dementia. This opinion must be taken into account to find more suitable and tailored therapy to specific pathologies and not to a single, generic entity.

Effect of acetaminophen on behavior, well-being, and psychotropic medication use in nursing home residents with moderate-to-severe dementia.

OBJECTIVES: To evaluate the effect of regularly scheduled administration of analgesic medication on behavior, emotional well-being, and use of as-needed psychotropic medications in nursing home residents with moderate-to-severe dementia. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial. SETTING: Nursing-home based. PARTICIPANTS: Twenty-five nursing home residents with moderate-to-severe dementia. INTERVENTION: Participants received 4 weeks of acetaminophen (3,000 mg/d) and 4 weeks of placebo. MEASUREMENTS: Behavior and emotional well-being were assessed using Dementia Care Mapping, an observational method that quantifies time spent in behaviors across 26 domains (e.g., social interaction, unattended distress) and assesses emotional state while behaviors are being observed. Agitation was measured using the Cohen-Mansfield Agitation Inventory. As-needed psychotropic medication use was aggregated from medication logs. RESULTS: Participants spent more time in social interaction, engaged with media, talking to themselves, engaged in work-like activity, and experiencing unattended distress when they received acetaminophen than they did when they received placebo. Participants also spent less time in their rooms, less time removed from the nursing home unit, and less time performing personal care activities when they received acetaminophen. There were no effects on agitation, emotional well-being, or as-needed psychotropic medication use. CONCLUSION: Untreated pain inhibits activity in nursing home residents with moderate-to-severe dementia. Pain treatment in this group may facilitate engagement with the environment.