Use of Memantine (akatinol) for the Correction of Cognitive Impairments in Parkinson’s Disease Complicated by Dementia

This study addresses the effects of 52 weeks of treatment with the NMDA glutamate receptor antagonist memantine on motor, cognitive, and mental disorders in patients with Parkinson’s disease complicated by dementia, as compared with a control group of patients not treated with memantine. Patients of the experimental group (32 subjects) received memantine (20 mg/day), while patients in the control group continued on antiparkinsonism treatment alone. Cognitive, psychiatric, and motor symptoms were assessed before the study and then at the ends of weeks 12, 24, and 52, using clinical assessment, rating scales, and neuropsychological tests. Plasma homocysteine levels were measured by HPLC. Patients treated with memantine had better measures on the MMSE (p < 0.05), ADAS-cog (p < 0.05), clock drawing test (p < 0.05), and FAB (p < 0.01) as compared with the control group by the end of study week 24. Members of the group of patients with high homocysteine levels mounted significantly better responses with memantine treatment, as compared with patients of the control group with high homocysteine levels but not receiving memantine, at the ends of study weeks 24 and 52, in terms of all rating scales (UPDRS, MMSE, ADAS-cog, D-KEFS Verbal Fluency Test, FAB. NPI, and DAD, p < 0.05). By the end of week 52, significant changes in points scores on the NPI-12 scale from baseline were in favor of patients receiving memantine, this applying to the disinhibition (p = 0.006), irritability (p = 0.04), anxiety (p = 0.04), and hallucinations (p = 0.048) subscales. The presence of hyperhomocysteinemia may indicate faster progression of both motor and cognitive impairments in Parkinson’s disease. Prolonged memantine treatment of patients with Parkinson’s disease complicated by dementia leads to improvements in cognitive functions, stabilization of motor impairments, and decreases in the severity of mental disorders, especially in patients with hyperhomocysteinemia.     

Comparative Analysis of Cognitive Impairments in Lewy Body Dementia and Alzheimer's Disease

Neuropsychological studies of 50 patients with Lewy body dementia (LBD) and 50 patients with Alzheimer's disease (AD) were performed to assess the characteristics of the cognitive impairments in these diseases. In patients with dementias of similar severities, patients with LBD showed greater impairment of executive and visuospatial functions and had more marked neurodynamic dysfunction. Patients with AD showed more profound memory disorders. __________ Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 105, No. 1, pp. 20–24, January, 2005.     

Use of the dopamine receptor agonist Mirapex in the treatment of Parkinson’s disease

We present a review of the literature on dopamine receptor agonists along with our own data on the treatment of Parkinson’s disease (PD) with Mirapex, which was used in 30 patients (mean age 61.8 ± 7.7 years, duration of disease 8.4 ± 1.3 years). Mirapex was used at a dose of 3.5 ± 1.1 mg/day on the background of treatment with levodopa preparations. The efficacy of Mirapex was assessed using quantitative scales. Improvements were demonstrated in general state, motor activity, daily activities, and the quality of life. Attention is drawn to a decrease in the severity of motor fluctuations and dyskinesias and in anxiety and depression, and to improvements in cognitive functions. The significance of the combination of the high efficacy and good tolerance of this agent is emphasized. __________ Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 106, No. 6, pp. 26–33, June, 2006.     

Use of Noben (idebenone) in the Treatment of Dementia and Memory Impairments without Dementia

Noben (idebenone) at a dose of 120 mg per day for six months was used in the treatment of 35 patients aged 60–86 years with Alzheimer’s-type dementia, mixed dementia, and memory impairments not reaching the stage of dementia. Patients were assessed on the basis of data from somatic, neurological, and psychiatric investigations, as well as neuropsychological testing and a series of psychometric and other scales and tests, before and after treatment. Significant improvements in patients’ conditions on the MMSE were seen in patients with mild and moderate dementia. Improvements in daily activities were obtained in 27% of patients. Neuropsychological investigations demonstrated improvements in short-term and long-term memory and attention, with improvements in speech functions, performance of kinesthetic, spatial, and dynamic praxis tests, and in visuospatial gnosis, thought, and writing. On the CGI scale, positive treatment effects were obtained in 37% of patients, while 48% of patients remained in a stable state. Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 108, No. 4, pp. 27–32, April, 2008.     

Cognitive Impairments in Progression of Parkinson’s Disease

A total of 88 patients with progression of Parkinson’s disease (PD) were studied. Cognitive impairments (CI) in PD were in most cases progressive in nature, predominantly because of increases in the severity of dysregulatory and neurodynamic disorders, impairments to visuospatial functions, and, in some cases, deficits in nominative speech function. A high frequency of transformation of moderate cognitive impairments to dementia was demonstrated over periods of 2–5 years. Predictors of the progression of CI in PD were identified: elderly age, later onset of disease, and the severity of PD. The greatest rate of progression of CI was seen in patients with initially more severe impairments of regulatory and visuospatial functions.     

Neuropsychological functioning of dementia patients with psychosis.

The current research sought to test the hypothesis that psychotic symptoms in patients with dementia might be due to relatively greater executive control and visuoperceptual deficits. Twenty-four dementia patients with psychosis and 24 outpatients without psychosis diagnosed with either probable Alzheimer's disease (AD) or possible/probable Ischemic Vascular Dementia (IVD) were studied. Groups did not differ with respect to age, education, severity of dementia, or depression. Presence and severity of psychosis was measured with a modification of the Neuropsychiatric Inventory (NPI; Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gorbein, J. (1994). The neuropsychiatric inventory: Comprehensive assessment of psychopathology in dementia. Neurology, 44, 2308-2314). Between-group and regression analyses found a consistent relationship such that patients with psychosis obtained low scores on the Boston Revision Wechsler Memory Scale-Mental Control subtest (WMS-MC subtest), a test of executive control. On some analyses patients with psychosis also made more perceptual errors on tests of naming and obtained higher scores on tests of delayed recognition memory. However, the relationship between severity of psychosis and performance on visuoperceptual and memory measures was considerably less robust. These data suggest a strong relationship between severity of psychosis and poor performance on executive control. Less evidence was obtained to support our contention that psychotic symptoms in dementia may arise from an interaction of neuropsychological deficits involving greater impairment in executive and visuoperceptual functioning.     

Use of Coaxil (tianeptine) in elderly patients with combined mild cognitive and depressive-anxiety disorders

The studies reported here addressed 20 patients aged 60–69 years whose clinical picture combined the manifestations of mild dementia with those of mild depression and anxiety. Patients were treated with Coaxil (tianeptine) for 60 days at a dose of 37.5 mg/day. Patients were assessed by clinical-psychological investigations with addition of the Hamilton scales and neuropsychological testing by the Luriya method. Coaxil was found to be highly effective in relation to all psychopathological components. Recommendations for the use of Coaxil in elderly patients with cognitive and depressive-anxiety disorders are formulated. Translated from Zhurnal Nevrologii i Psikhatrii imeni S. S. Korsakova, Vol. 108, No. 1, pp. 36–39, January, 2008.     

Treatment of Motor and Cognitive Disorders in Patients during the Residual Period of Stroke

The efficacy and safety of Axamon were studied in patients aged 65–88 years with motor and cognitive disorders during the residual period of stroke: 25 patients received basal treatment and Axamon prescribed for 12 weeks at a dose of 20 mg three times daily, while 25 patients of the control group received basal treatment only. Along with neurological studies, assessment of the efficacy and safety of complex therapy was performed using neuropsychological tests and scales. Decreases in the severity of cognitive and motor disorders were seen in patients given Axamon. Axamon promoted optimization of the rehabilitation potential of patients during the residual period of stroke.     

Cholinergic Treatment of Alzheimer’s Disease and Its Influence on Health and the Quality of Life of Carers

The efficacy and safety of four-month courses of rivastigmine and changes in measures of carer burden were studied in a non-randomized group of 25 patients with Alzheimer’s disease (AD). All patients received p.o. rivastigmine and 22 patients received antipsychotic therapy along with rivastigmine on admission. Treatment was continued for 16 weeks (12 weeks in hospital and four weeks in out-patient conditions). These studies showed that the use of rivastigmine in AD patients with behavioral and psychotic disorders at the stage of moderately severe dementia not only improved the patients’ cognitive functions, but also had positive effects in terms of decreasing psychotic and behavioral disorders. Inclusion of rivastigmine in the complex treatment of AD patients led to significant decreases in the need for psychotherapeutic agents, and in some patients to complete withdrawal of all antipsychotics. It is extremely important to emphasize that the use of rivastigmine in patients with moderately severe AD and behavioral disorders led to significant (up to 30%) decreases in the time spent on the care and supervision of the patients, along with decreases in the level of stress and improvements in the health of carers, indicating increases in the quality of life of both patients and their families.     

Disorders of higher mental function due to single infarctions in the thalamus and in the area of the thalamofrontal tracts

Nine patients (five female and four male, mean age 58 years) with small infarcts in the thalamus (TH) or in the region of the thalamofrontal tracts and producing acute mental disturbances which in the acute phase of insult consisted of dementia in seven cases and mild cognitive disturbances in two cases. The complex of mental changes was similar to that seen in “frontal syndrome” and was characterized largely by lack of spontaneity, adynamia, disorientation, loss of attention and memory, slowing of all mental processes, and lack of criticality and adequacy. Accompanying focal neurological symptoms were mild in seven patients and moderate or pronounced in two. In five patients, the severity of mental disturbances decreased with time. Computer tomography demonstrated small infarcts in the anterior or medial parts of the TH in seven patients and in the posteromedial parts of the anterior limb of the internal capsule, i.e., the thalmofrontal tracts, in two cases. In five cases, infarcts were located in the dominant hemisphere, with lesions in the non-dominant hemisphere in three and in both hemispheres in one. The positions of all foci corresponded to structures traversed by pathways connecting the TH and the lower part of the reticular formation to the frontal lobes. It is suggested that disconnection of these pathways leads to cognitive lesions or dementia because of functional inactivation of the frontal cortex. Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 98, No. 6, pp. 8–13, June, 1998.     

Characteristics of neurological and cognitive status in patients with multiple sclerosis in relation to the location and volumes of demyelination foci and the severity of brain atrophy

A total of 65 patients with clinically significant diagnoses of remitting multiple sclerosis in the stage of remission were studied. Neurological status was investigated with assessment on the FS and EDSS scales, with neuropsychological testing, and MRI scans (1.5 T). The severity of brain atrophy (in terms of the parenchyma volume) and the total volume of foci on T2 images were assessed as proportions of intracerebral volume. The severity of neurological deficit depended on the volume of intratentorial focal lesions and the level of brain atrophy. Cognitive disorders were identified in 89% of patients, and the severity of these was associated with the level of atrophy and the volume of foci on T2 images in the dominant hemisphere. Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Multiple Sclerosis, Supplement, No. 4, pp. 46–49, 2007.     

Coaxil (tianeptine) in the treatment of depression in Parkinson’s disease

An open, non-comparative clinical study was performed to assess the efficacy and safety of tianeptine (Coaxil) in Parkinson’s disease (PD). A total of 18 patients with PD were used whose clinical state increased moderately severe and more profound depression (assessed on the Hamilton and Beck scales). After three months of treatment, depression on the Hamilton depression scale was decreased by 34% and on the Beck scale by 31% compared with baseline data (_p < 0.05). Improvements in mental status were noted in 14 of 18 patients (77%); eight patients (44%) showed more than 50% reductions on the Hamilton scale. Analysis of the structure of depressive symptomatology showed that improvement occurred because of decreases in anxiety and the severity of somatoform symptoms and, to a lesser extent, in melancholy and sleep disturbance. There was no significant change in apathy. The decrease in the severity of depression was accompanied by an improvement in the quality of life. The efficacy of Coaxil was greater in patients with less marked depressive and motor symptoms, shorter durations of illness, and less marked cognitive impairments. Coaxil was well tolerated by the patients. The data obtained here provide grounds for recommending the use of Coaxil in the treatment of depression in PD. __________ Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 106, No. 3, pp. 20–25, March, 2006.     

Dose–response relationship in music therapy for people with serious mental disorders: Systematic review and meta-analysis

Serious mental disorders have considerable individual and societal impact, and traditional treatments may show limited effects. Music therapy may be beneficial in psychosis and depression, including treatment-resistant cases. The aim of this review was to examine the benefits of music therapy for people with serious mental disorders. All existing prospective studies were combined using mixed-effects meta-analysis models, allowing to examine the influence of study design (RCT vs. CCT vs. pre-post study), type of disorder (psychotic vs. non-psychotic), and number of sessions. Results showed that music therapy, when added to standard care, has strong and significant effects on global state, general symptoms, negative symptoms, depression, anxiety, functioning, and musical engagement. Significant dose–effect relationships were identified for general, negative, and depressive symptoms, as well as functioning, with explained variance ranging from 73% to 78%. Small effect sizes for these outcomes are achieved after 3 to 10, large effects after 16 to 51 sessions. The findings suggest that music therapy is an effective treatment which helps people with psychotic and non-psychotic severe mental disorders to improve global state, symptoms, and functioning. Slight improvements can be seen with a few therapy sessions, but longer courses or more frequent sessions are needed to achieve more substantial benefits.     

MMPI profiles among neuropsychology patients

Examined MMPI profiles in a sample of 345 patients who were referred for neuropsychological evaluation because of known or suspected brain damage in an effort to determine how these profiles compare to MMPI profiles among general mental health outpatients. The relationship between the severity of brain damage as determined by the neuropsychological evaluation and the severity of emotional problems as reflected by the MMPI also was examined. A third part of the study focused on two MMPI “organic” codes (“29” and “139”) to determine whether these code types reflect brain disorders at greater than chance level. Results indicate that a large majority of neuropsychology patients exhibit significant emotional problems as evidenced by one or more scale elevations on the MMPI. These patients differ considerably from general outpatients in terms of the scales most frequently elevated. In contrast to earlier findings, present results suggest only a low relationship between the severity of emotional problems and the severity of brain damage with much of this relationship reflected in SC scale elevations.     

Pharmacological treatments for psychotic symptoms in dementia: A systematic review with pairwise and network meta-analysis

Psychotic symptoms of dementia are highly prevalent and lead to poor medical outcomes and substantial dysfunction. To date, which drug to use remains controversial without a summary of all direct or indirect comparisons of pharmacotherapy. Therefore, we conducted a systematic review with pairwise and network meta-analysis to examine efficacy and tolerability outcomes of pharmacological treatments in dementia patients. MEDLINE, Cochrane Library, EMBASE, and PubMed were searched systematically up to August 31, 2020. We included trials of cholinesterase inhibitors (ChEIs), memantine, antipsychotics, antidepressants, and mood stabilizers, with final approval from the U.S. Food and Drug Administration. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities. This analysis is based on 34 trials, which included 10,415 patients randomly assigned to 15 commonly used drug regimens. Donepezil (standardized mean difference [SMD] −0.30, 95% credible interval [CrI] −0.50 to −0.12; SUCRA, 0.85), memantine (SMD −0.20, 95%CrI −0.34 to −0.07; SUCRA, 0.68) and aripiprazole (SMD −0.17, 95% CrI −0.32 to −0.02; SUCRA, 0.62) showed greater benefit than placebo, and with relatively good tolerability in network meta-analyses. Risperidone was also found to be more efficacious than placebo (SMD −0.16, 95% CrI −0.28 to −0.05; SUCRA, 0.60), but with poor tolerability (odds ratios [OR] 1.50, 95% CrI 1.06–2.26). Donepezil, memantine, haloperidol, aripiprazole and risperidone were more efficacious than quetiapine (SMDs ranged from −0.36 to −0.22). Besides, donepezil, memantine and mirtazapine were more efficacious than sertraline (SMDs ranged from −0.47 to −0.36). Most of the results were rated as “low” to “very low”. Several effective treatment choices for psychotic symptoms are available across drug classes. Donepezil, memantine and aripiprazole are probably the appropriate options to consider when a pharmacological treatment is indicated. Given the limitations of the meta-analytic approach and the low methodological quality of the majority of studies, our results should be cautiously interpreted.     

Clinicopathologic and genetic features of multiple system atrophy with Lewy body disease

Background: Abnormal aggregates of α‐synuclein are pathologic hallmarks of multiple system atrophy (MSA) and Lewy body disease (LBD). LBD sometimes coexists with MSA, but the impact of co‐pathology, particularly diffuse LBD, on presentation of MSA has not been studied. We aimed to determine the frequency and clinicopathologic features of MSA with LBD (MSA+LBD). Methods: Using hematoxylin & eosin and α‐synuclein‐immunostained slides, we assessed the distribution and severity of LBD in 230 autopsy‐confirmed MSA patients collected from 1998 to 2018. Alzheimer‐type pathology was assessed to assign the likelihood of clinical presentations of dementia with Lewy body (DLB) using the consensus criteria for DLB. We reviewed medical records to characterize clinicopathologic features of MSA+LBD. Genetic risk factors for LBD, including APOE ε4 allele and mutations in GBA, SNCA, LRRK2, and VPS35, were analyzed. Results: LBD was observed in 11 MSA patients (5%); seven were brainstem type, three were transitional type, and one was diffuse type. The latter four had an intermediate or high likelihood of DLB. Three of the four had an antemortem diagnosis of Parkinson’s disease with dementia (PDD) or clinically probable DLB. Two patients had neuronal loss in the substantia nigra, but not in striatal or olivocerebellar systems with widespread glial cytoplasmic inclusions, consistent with minimal change MSA. In these cases, LBD was considered the primary pathology, and MSA was considered coincidental. APOE ε4 allele frequency was not different between MSA+LBD and MSA without LBD. Two of nine MSA+LBD patients had a risk variant of GBA (p.T408M and p.E365K). Conclusions: Although rare, MSA with transitional or diffuse LBD can develop clinical features of PDD or DLB. Minimal change MSA can be interpreted as a coincidental, but distinct, α‐synucleinopathy in a subset of patients with diffuse LBD.     

精神病患者亲属情绪障碍的心理干预分析

目的:观察综合性心理干预对精神病人亲属情绪障碍的效果。方法:采用90项症状自 评量表(SCL-90)对102例精神病人亲属进行心理状况调查,并将其中的70例列入实验组进行为期一 年的综合性心理干预,另32例列入对照组与之进行比较。结果:两组精神病人亲属普遍存在着心理问 题,情绪障碍以强迫、焦虑、抑郁、人际关系不良等症状为突出。实验组病人亲属通过一年的综合性心理 干预治疗后,SCL-90评分明显下降,与对照组比较差异有显著意义(P<0.05);两组病人的年复发率 比较差异也有显著意义(P<0.05)。结论:对精神病人亲属进行综合性心理干预,有利于减轻其情绪障 碍和心理压力,提高对病人的监护水平和质量,降低病人的复发率。     

Clinical experience with risperidone and memantine in the treatment of Huntington's disease

We described a 32-year-old woman with Huntington's disease (HD) who presented with severe chorea, psychosis and cognitive abnormalities. We started risperidone at 2 mg p.o./d and increased to 4 mg p.o./d after six weeks. Psychotic and motor symptoms were markedly improved. Since there was no change in cognitive functions, we added memantine at 5 mg p.o./d and gradually increased the dose to 20 mg p.o/d after five weeks. We continued risperidone and memantine for nearly six months. The patient did not show any progression of cognitive symptoms or motor abnormalities. We did not observe any psychotic symptoms.     

Decreased oligodendrocyte nuclear diameter in Alzheimer's disease and lewy body dementia

To better understand the pathogenesis of dementia, it is important to understand histopathologic changes in neurodegenerative diseases because they might highlight key aspects of the degenerative process. In this study, the nuclear diameter of neurons and oligodendrocytes in selected temporal lobe areas were determined in autopsy tissue sections from patients with Alzheimer's disease (AD), Lewy body dementia (LBD) and controls. Our morphometric studies targeted neurons in the CA4 region of the pyramidal cell layer of the hippocampus, neurons in the granular layer of the dentate gyrus and oligodendrocytes in parahippocampal white matter. Mean neuronal nuclear diameters were not different among the studied groups. However, our studies revealed a statistically significant reduction of mean oligodendrocyte nuclear diameter in AD and LBD relative to controls. The reduction of the mean nucleus diameter of oligodendrocytes in LBD was independent of the presence of associated AD pathology in LBD. These findings for the first time identify decreased oligodendrocyte nucleus diameter as a morphologic feature of AD and LBD and may lead to a better understanding of the role of oligodendrocytes in AD and LBD pathogenesis.     

Post-Traumatic Stress Disorder in Adults with Serious Mental Illness and Substance Abuse

ABSTRACT

Post-Traumatic Stress Disorder continues to be under-diagnosed among individuals with severe mental illness and substance abuse. In a convenience sample of 64 patients with severe mental disorders being treated at an urban outpatient clinic, 24% met full criteria for PTSD based upon a comprehensive assessment protocol while only 3% were diagnosed with PTSD by clinicians in the medical record (Cochran's Q = 11.267, df 1, p <.001). In contrast, there was a high rate of diagnostic agreement for psychotic and affective illnesses as well as substance abuse. More attention needs to be given to systematically assessing PTSD among severely mentally ill and dually diagnosed individuals because even highly skilled diagnosticians miss the complex presentation of symptoms with which these patients present for treatment.