Severe Vascular Dementia Research Articles

Multi-center open comparative randomized study of efficacy and safety of Akatinol Memantine 20 mg (single-doses) vs Akatinol Memantine 10 mg (double-doses) in patients with vascular dementia

Evaluation of the efficacy and safety of the drug Acatinol Memantine, 20 mg (once daily) in comparison with the drug Acatinol Memantine, 10 mg (twice daily) in patients with moderate to moderate severe vascular dementia. The study included 130 patients aged 50-85 years of both sexes with instrumentally and clinically confirmed vascular dementia. The patients were randomized into 2 groups. Group I consisted of 65 patients receiving Akatinol Memantine, 20 mg once daily, group II - 65 patients receiving Akatinol Memantine, 10 mg twice daily for 24 weeks. Clinical, parametric and statistical research methods were used. The Alzheimer's disease assessment scale, the cognitive subscale (ADAS-cog), the short mental Status Assessment Scale (MMSE) and the general clinical impression scale for patients condition and illness severity (CGI-C and CGI-S) and the Hamilton Depression Rating scale (HAM-D) were used. Adverse events were collected and analyzed. At week 24, both groups showed statistically significant positive change in ADAS-cog total score: in group I the total score was 27.2±8.76 points (absolute difference from baseline 3.5 points; p<0.01), and in group II - 26.1±7.86 points (absolute difference from baseline 2.5 points; p<0.01) with no statistically significant differences between groups. Evaluation of secondary efficacy criteria (change in ADAS-cog total score at week 12 and MMSE at weeks 4, 12, and 24) also revealed statistically significant benefit in both groups compared to baseline with no significant differences between groups. Statistically significant improvement was noticed on CGI-S and CGI-C scales in both groups. Akatinol Memantine was safe and well tolerated in both groups. The study showed no lesser efficacy and safety of Akatinol Memantine, 20 mg (once daily) compared to Akatinol Memantine, 10 mg (twice daily) in patients with moderate and moderately severe vascular dementia.

Blood pressure-lowering treatment for prevention of recurrent stroke, severe vascular events and dementia in patients with stroke or transient ischemic attack in the past history

Blood pressure-lowering treatment for prevention of recurrent stroke, severe vascular events and dementia in patients with stroke or transient ischemic attack in the past history

Clinical-psychopathological structure of hallucinator-paranoid disorders during vascular dementia of heavy direction of expression

The purpose of this study is to determine the clinical and psychopathological features of hallucinatory-paranoid disorders in severe vascular dementia. The clinical and psychopathological structure of hallucinatory and paranoid disorders in patients with severe vascular dementia was studied in a group of 34 patients with mixed cortical-subcortical dysfunction with hallucinatory-paranoid symptoms — F01.3 (1-2), which consisted the main group. As a control group, the study involved 29 patients with severe vascular dementia (F01.3), without by hallucinatory-paranoid disorders. To achieve the goal and objectives of the study, a set of research methods was used, including the clinical and psychopathological method, supplemented by the Behavioral Disorders Scale (Bahav-AD), neuropsychiatric questionnaire (NPI), non-cognitive sections of the AD assessment scale (ADAS-Non Cog) and methods of statistical data processing. According to the results of the study, the following symptoms were revealed in the structure of hallucinatory-paranoid disorders in patients with severe vascular dementia: the prevalence of hallucinatory disorders over paranoid and paranoid disorders; the dominance in disorders of perception of frequent visual, auditory and tactile hallucinations of moderate severity; the prevalence of delusional beliefs that “the house is not his house” and the spouse/caretaker is impostors; the predominance of non-deployed, unsystematized and sketchy crazy ideas, that do not tend to expand; a combination of hallucinatory and paranoid disorders with frequent aimless activity of moderately strong severity; frequent generalized anxiety of moderate to severe severity; frequent sleep/wake rhythm disturbances of moderate severity; periodic moderate swagger; pronounced distractibility. The data obtained should be taken into account when conducting differential diagnosis of patients with hallucinatory-paranoid disorders in severe vascular dementia.

Stereological Quantification of Plaques and Tangles in Neocortex from Alzheimer's Disease Patients.

We estimated by stereological methods the neocortical volume occupied by plaques and tangles in females dying with severe Alzheimer's disease (AD), age-matched female subjects with severe vascular dementia (VaD), and normal control brains. Stereological investigations include a uniform sampling of the tissue in the whole of neocortex and its subdivisions. Resultant volume estimates provide information about the overall burden of these two pathological changes and their volume fractions and allow for correlational studies between the pathological changes and factors such as the total neocortical neuronal cell numbers, dementia test scores, and age. We estimated the volume of plaques and tangles in the entire neocortex and frontal-, temporal-, parietal-, and occipital cortex in nine female AD brains, four female patients dying with VaD, and six neurologically normal female control brains using point-counting in uniform samples of neocortex. The volume occupied by plaques comprised approximately 1% of neocortex, while the neocortical tangles made up approximately 0.1% of neocortex of AD patients but were scarcely present in the other study groups. The individual tangle and plaque volumes did not correlate to the ultimate dementia score of the AD subjects, despite correlating with reduced neocortical volume. In neocortex of AD patients, the burden of plaques and tangles is much higher than that in patients with severe vascular dementia or normal older women but only occupy a small fraction of the neocortical volume.

A Pilot Longitudinal Study on Cerebrospinal Fluid (CSF) Tau Protein in Alzheimer's Disease and Vascular Dementia.

BackgroundAlzheimer’s disease (AD) has high a prevalence rate, high medical costs, and care difficulties, and has become a serious social and economic problem in our aging society. So far, there has not been a reliable and objective diagnostic criteria for AD found. In recent years, there have been many domestic and foreign studies on the biological markers of cerebrospinal fluid in the patients with AD, and high levels of the T-tau, P-tau found in cerebrospinal fluid (CSF) is at this point an indisputable fact. However, the relationship between these markers and the severity of dementia, as well as the development of the disease, should be further studied.ObjectiveCompare the CSF level of total tau (T-tau) and phosphorylated tau at threonine 231 (P-tau231) between patients with moderate to severe Alzheimer’s disease (AD) and those with vascular dementia (VD) at baseline, and 6 month follow-up. Observe the differences between patients with AD and control group, as well as the changes as the disease develops.MethodsThere were 11 patients with moderate AD (10 ≤ MMSE ≤ 20), 10 patients with severe AD (MMSE ≤ 9), and 7 age-matched patients with severe VD at baseline, among which 7 AD patients and 6 VD patients completed the 6 months follow-up. CSF levels of T-tau, P-tau231 were measured with sandwich ELISA.ResultAt baseline, the concentrations of the CSF level of T-tau were 470.08 (263.58) pg/mL in the AD group and 208.76 (42.24) pg/mL in the VD group. This difference was statistically significant (Z= -3.369, p <0.001). The concentrations of CSF level of P-tau231 were 90.94 (49.86) pg/mL in the AD group and 42.96 (13.10) pg/mL in the VD group. This difference was also statistically significant (Z = -3.237, p <0.001). Compared to patients with severe VD, the concentration of CSF T-tau in patients with severe AD was significantly higher (Z= -2.830, p = 0.005), as well as the concentration of CSF P-tau231 (Z = -2.392, p = 0.017). The concentration of CSF P-tau231 in the patients with moderate AD was significantly higher than that in the patients with severe VD (Z = -2.605, p = 0.009). At the 6 months follow-up, there were no statistically significant differences in the changes of CSF T-tau and CSF P-tau231 concentrations between the AD group and VD group.ConclusionThe CSF level of T-tau and P-tau231 in the AD patients was significantly higher than that in the VD patients. The concentration of CSF P-tau231 in the moderate AD patients was significantly higher than that in the patients with severe AD. During the 6 months follow-up, the changes of the CSF concentrations of T-tau and P-tau231 between AD group and VD group were not statistically significant.

Eosinophilic syndrome with life-threatening end-organ damage

Introduction: Neuroleptic malignant syndrome (NMs) is a life-threatening disease more often considered than truly diagnosed. the NMs is a life-threatening neurologic emergency associated with the use of antipsychotic drugs and characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia. case report: A 69-year-old wheel chair bound male with past medical history of severe vascular dementia with behavioral problems, schizoaffective disorder referred from nursing home due to fever for 1 day. According to his room-mate, his baseline mental status use to be drowsy and disoriented. Vitals showed temperature 102°F (38.8°c), tachycardia, high blood pressure 140/90 mmHg, tachypnea and low oxygen saturation of 87% on room air. Arterial blood gases showed hypoxia and respiratory alkalosis with high A-a gradient. Also suspected infection due to leukocytosis with neutrophilia. However, we kept neuroleptic malignant syndrome (NMs) in mind since patient was taking haloperidol for episodic agitation although haloperidol dose was unchanged and no new drugs were added. When total creatine kinase came back as 3142 IU/L, he was managed successfully with dantrolene and amantadine.

Neuropsychiatric symptoms in patients with vascular dementia in mainland China.

BackgroundNeuropsychiatric deficits can induce marked disability in patients with dementia and increase caregiver distress. Several studies have found that neuropsychiatric symptoms are common both in patients with Alzheimer’s disease (AD) and patients with vascular dementia (VaD). However, there are few studies of the neuropsychiatric disturbances in large clinical samples of patients with mixed (cortical - subcortical) VaD from mainland China. This study aimed to investigate the neuropsychiatric symptoms in VaD patients in mainland China.MethodsEighty patients with mixed VaD for over 6 months duration, and their caregivers (VaD group), were recruited for interview in Zhongnan Hospital of Wuhan University, from June 2010 to June 2012. Eighty age- and sex-matched normal volunteers (control group) were interviewed at the same time. The Mini Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI) were administered to the VaD patients, their caregivers, and normal volunteers. Group differences were analyzed using the unpaired t-test.ResultsThe total mean scores of the NPI in the VaD group were higher than in the control group (P < 0.01). The subscale scores of NPI, including delusions, hallucinations, depression, apathy, irritability, agitation, aberrant motor behavior, and change in appetite were significantly higher in the VaD group than in the control group (P < 0.05–0.01). Compared with the mild VaD subgroup, the NPI subscale scores of apathy, irritability and total scores were significantly higher in the moderate VaD subgroup (P < 0.05–0.01); the NPI subscale scores of anxiety, apathy, irritability, and total scores were significantly higher in the severe VaD subgroup (P < 0.01). Compared with the moderate VaD subgroup, the NPI subscale scores of anxiety and apathy were significantly higher in the severe VaD subgroup (P < 0.05–0.01).ConclusionsNeuropsychiatric symptoms, such as hallucination, anxiety, apathy, irritability and aberrant action behavior, are common in patients with mixed VaD from mainland China; anxiety and apathy were more pronounced in the subgroup of severe VaD patients.

1162 – Vascular factor in the etiology and pathogenesis of alzheimer’s disease

Introduction Vascular factor is very important in the development of AD. The research investigates the changes in the cerebral angioarchitectonics at various AD stages. Methods The research included 92 patients of which: Test Group: 47 aged 34–79 suffering from AD different stages including: • 4 with preclinical stages or high risk of disease development (TDR-0); • 15 with mild dementia (TDR-1); • 20 with moderate dementia (TDR-2); • 8 with severe dementia (TDR-3). Control Group: 45 aged 28–78 with various types of brain lesions accompanied by dementia but without Alzheimer’s disease including: • 15 with chronic cerebrovascular insufficiency of atherosclerotic genesis and moderate dementia; • 12 with severe vascular dementia; • 14 with atherosclerotic parkinsonism; • 4 with Parkinson’s disease. Each patient underwent MRI, CT, SG, REG, MUGA. Results At AD different stages, changes in angioarchitectonics and microcirculation show themselves in: • lack of expressed atherosclerotic lesions of intracranial vessels - 47 (100%) patients, • reduction of capillary bed in the temporal and frontoparietal regions - 47 (100%), • development of multiple arteriovenous shunts in the same areas - 47 (100%), • corresponding early venous shunts - 47 (100%), • abnormal development of venous trunks receiving blood from arteriovenous shunts - 42 (89.4%), • venous congestion at frontal and parietal region border - 43 (91.5%), • increased loop fromation of intracranial arteries - 37 (78.7%). Control group patients had no combination of such changes. Conclusions We named the vascular factor in AD “the discirculatory angiopathy of Alzheimer’s type” (DAAT).

A change on an electrocardiogram not to be missed

An 80 year old woman with a history of severe vascular dementia presented to the acute surgical unit. A collateral history given by staff at her nursing home stated she had had seven days of abdominal pain associated with vomiting. She had not opened her bowels for many days. Medical history included stroke and hypertension. She had no surgical history. At the time she was taking aspirin, ramipril, and simvastatin. On examination her pulse rate was regular at 98 beats/min, blood pressure was 132/84 mm Hg, respiratory rate was 12 breaths/min, she had a temperature of 37.1°C, and her oxygen saturations were 96% on room air. Her abdomen was visibly distended and felt firm on palpation, but neither guarding nor organomegaly was detected. A plain abdominal radiograph showed dilated bowel loops. A computed tomography scan did not show evidence of mechanical bowel obstruction. She was treated for pseudo-obstruction with a nasogastric tube and intravenous fluids. After conservative management, an electrolyte abnormality was noted from the blood test results. Arterial blood …

Clinical analysis of neuropsychiatric symptoms in patients with vascular dementia

Objective To analyze neuropsychiatric symptoms in patients with vascular dementia (VaD). Methods Neuropsychiatric Inventory (NPI), Mini ⁃ Mental State Examination (MMSE) and Hachinski Ischemia Score (HIS) were used to assess the neuropsychiatric symptoms in 81 cases with VaD, 35 cases with post⁃stroke non⁃dementia (PS⁃ND), 58 cases with Alzheimer's disease (AD) and 61 cases with normal elders as control group. Results Presentation of delusion, hallucination, agitation, depression and (or) dysthymia, apathy, irritability and (or) lability, aberrant action behavior, and NPI total scores in VaD group were significantly more than those in control group (P < 0.05 or P < 0.01). Delusion was more often seen in AD group than that in VaD group, and the difference was significant (P < 0.01). Hallucination, anxiety, apathy, irritability and (or) lability, and aberrant action behavior were significantly different among VaD with different severity (P < 0.05 or P < 0.01). These symptoms were all more obvious along with the patients' condition. Conclusion Various neuropsychiatric symptoms in VaD are similar to those in AD. The predominant neuropsychiatric symptoms are emotional and affective disturbance in patients with moderate and severe VaD. DOI：10.3969/j.issn.1672-6731.2010.03.013

C.15.03 Pharmacology of memantine

Until recently, acetylcholinesterase inhibitors were the only approved agents for the treatment of Alzheimer's disease (AD). These medications have also been used in the treatment of vascular dementia (VD). Memantine, the first N-methyl-d-aspartate (NMDA)—receptor antagonist to be well tolerated, has been approved for the treatment of moderate to severe AD.The aim of this study was to review the current literature on the efficacy and tolerability of memantine in the treatment of AD and VD.A MEDLINE search of the English-language literature from January 1970 to March 2004 was conducted to identify randomized, double-blind, placebo-controlled, parallel-group trials in which memantine was administered to patients with VD or AD. The search terms were memantine, NMDA inhibitor, and NMDA antagonist.Excessive glutamate, the brain's major excitatory neurotransmitter, can cause excitotoxicity by allowing too much calcium to enter neuronal cells. Moderate-affinity NMDA-receptor antagonists such as memantine block pathologic activity of glutamate while allowing physiologic activity. Use of memantine has been associated with significant improvements in measures of cognition, function, and behavior in both VD and AD. Adverse events associated with memantine have been comparable to those with placebo, with the exception of an increased incidence of dizziness, constipation, cataracts, nausea, dyspnea, confusion, headache, and urinary incontinence.Memantine seems to be promising and well tolerated in the treatment of moderate to severe VD or AD, either as monotherapy or in combination with donepezil. It appears to be particularly effective in improving cognitive, functional, and global outcomes in moderate to severe AD and in improving cognitive end points in mild to moderate VD. More research is needed on important clinical questions, including whether memantine can prolong patients' ability to provide self-care and delay institutional placement.

The serial position effect in mild and moderately severe vascular dementia.

The present study examined the serial position effect in 2 subgroups of individuals with vascular dementia (VaD). Nineteen individuals with mild VaD and 17 individuals with moderate VaD were administered the California Verbal Learning Test. Both groups were impaired on a general memory measure, and the moderately impaired group demonstrated significantly poorer recall than the mildly impaired group on the first learning trial and on total learning across trials. In addition, individuals with mild dementia demonstrated an intact primacy and recency effect, whereas individuals with moderate dementia demonstrated neither primacy nor recency effects. The latter findings are consistent with studies examining the serial position effect in other dementia populations, and suggests that the absence of primacy and recency effects in more advanced dementia may occur regardless of dementia type.

Dementia Severity and Pattern of Cognitive Performance in Vascular Dementia

We evaluated the influence of dementia severity on cognitive performance in two groups of individuals with vascular dementia (VaD). Performance on the Mini-Mental State Exam (MMSE) was used to determine dementia severity. Tests of executive function, psychomotor speed, memory, language, and visuospatial function were administered. As expected, individuals with severe VaD (MMSE< 18) performed significantly more poorly than individuals with mild VaD (MMSE ≧ 18) on most tests. More important, deficits were evident for both groups in each cognitive domain when compared to normative data. These results indicate that multiple cognitive domains are affected even in mild cases of VaD. Clinicians should be aware that although the presence of "patchy" cognitive deficits may indicate stroke, general cognitive dysfunction may occur in mild cases of VaD.