Alzheimer Disease: Gavrilova SI

Gavrilova SI, Zharikov GA. · No affiliation provided · Zh Nevrol Psikhiatr Im S S Korsakova. · Pubmed #14763262 No free full text.

This publication has no abstract.

Gavrilova SI, Zharikov GA. · No affiliation provided · Vestn Ross Akad Med Nauk. · Pubmed #11523421 No free full text.

Abstract: This is a review of the data available in the literature and the authors' own findings on pathogenetical rationale for the use and clinical study of current treatments for Alzheimer's disease (AD) (synonym: Alzheimer-type dementia). In the past decade many attempts have been made at targeting different links of the pathogenesis of a neurodegenerative process that underlie AD. Several areas of pathogenetical therapy for AD have been developed on the basis of experimental studies and pilot clinical tests. The most developed areas are as follows: various compensatory (replacement) treatments aimed at overcoming neurotransmitter deficit in different neuronal systems that are damaged in AD to a greater or lesser extent; neuroprotective therapy promoting increased viability (survival) of neurons and their plasticity, and vasoactive therapy. Rather new directions of AD pathogenetic therapy, such as antiinflammatory and hormonal therapy along with antiamyloid therapeutic strategies are still under study.

Gavrilova SI, Bratsun AL. · No affiliation provided · Vestn Ross Akad Med Nauk. · Pubmed #10078062 No free full text.

Abstract: Alzheimer's disease or dementia of the Alzheimer's type (AD/DAT) is one of the most common dementia conditions and it amounts to over 40-90% of dementia cases among elderly and old patients. Epidemiological studies in this area make a great contribution to the study of the etiology and risk factors of AD/DAT). The collaborative reanalysis of AD/DAT prevalence and incidence in EEC countries ("EURODERM" programme) shows that the overall European age-specific prevalence of AD does not differ greatly. There was an exponential increase in age-specific AD/DAT prevalence was found with age, as evidenced by the studies made in Russia. Sex-specific prevalence and incidence of AD/DAT are unclear since the fact that the condition more often occurs in elderly women than in men of the same age has not been confirmed. The data on risk factors obtained in cohort and case-control studies of AD/DAT have been analyzed. Progress in molecular genetics has identified 3 genes that are responsible for the occurrence of familial forms of the disease. The gene of apolipoprotein E on chromosome 19 is recognized to be the major genetic risk factor of late AD/DAT. The role of gene mutations in the trigger mechanisms of sporadic BA/DAT is also discussed. The environmental risk factors of AD/DAT include brain injury, viral infections, neutroxic chemicals, various immunological and hormonal disorders. The protective role of such factors as long-term use of nonsteroid antiinflammatory agents and estrogens is discussed. The involvement of nicotine dependence in the pathogenesis and the role of smoking as a possible protective factor are the subject of discussion. Such factors as education levels, occupation, stresses are widely discussed, although their role is considered to be controversial. The Russian study revealed the influence of chronic stress on AD development. The authors consider that chronic stress may play an important role in AD/DAT progression.

Selezneva ND, Gavrilova SI, Kalyn IaB, Kolykhalov IV, Fedorova IaB. · No affiliation provided · Zh Nevrol Psikhiatr Im S S Korsakova. · Pubmed #18833116 No free full text.

Abstract: To study efficacy and safety of cholinergic therapy in patients with Alzheimer's disease or combined Alzheimer's and vascular dementia and marked somatic pathology, 30 patients, aged from 54-85 years, with mild or moderate dementia have been studied. Patients were treated with rivastigmine (exelon) in dosage 3-12 mg daily during 3 months. The safety of the drug for patients with comorbid somatic pathology has been shown: during the treatment no severe aversive effects or strengthening of diseases of visceral organs were observed. The improvement of global clinical state as well as reduction of cognitive and behavioral disorders indicate the high effectiveness of exelon. The recommendations allowing to improve the tolerability of treatment with exelon of patients with comorbid pathology of visceral organs are worked out.

Iakhno NN, Zakharov VV, Lokshina AB, Gavrilova SI, Fedorova IaB, Gustov AV, Korshunova IuA, Dziak LA, Miziakina EV, Odinak MM, Emelin AIu, PilipenkoP I, Vostrikova EV. · No affiliation provided · Zh Nevrol Psikhiatr Im S S Korsakova. · Pubmed #17274394 No free full text.

Abstract: Mild Cognitive Impairment (MCI) means cognitive deterioration not yet causing disability or dementia. Aged patients with MCI constitute a group of high risk for Alzheimer disease and other types of dementia. Currently, there is no generally adopted approach to MCI management but medications with neuroprotective properties are presumed to be the most perspective. Presented are the results of a multicentral open-label clinical trial of vascular and neuroprotective drug tanakan (EGb 761). The study has shown the decrease of cognitive impairment, which was both clinically and statistically significant, in patients at early stages of vascular and neurodegenerative pathological process. Probable efficacy of long-term tanakan treatment in prevention of dementia is discussed.

Gavrilova SI, Kolykhalov IV, Korovaĭtseva GI, Zharikov GA, Kalyn IaB, Selezneva ND. · No affiliation provided · Zh Nevrol Psikhiatr Im S S Korsakova. · Pubmed #15880838 No free full text.

Abstract: Correlation association between an ApoE4 genotype in patients with mild-moderate Alzheimer's disease and efficacy of neurotrophic (cerebrolysin) and cholinergic (exelon) therapy was studied in the groups of patients formed using case-control method. A 4-month treatment has shown that both types of therapy had a significant clinical effect, however clinical effect proved to be more higher and stable in patients treated with cerebrolysin. A number of responders in the cerebrolysin group was 1.7-fold higher comparing to that in the exelon group. Patients with the ApoE4(+) genotype did not differ in response to either drug but in those with genotype ApoE4(-) the number of responders was 3-fold higher in the group treated with cerebrolysin compared to the group given exelon. A follow-up estimation of cognitive impairment in ApoE4(-) patients revealed that long-term clinical effect of cerebrolysin treatment was 6.5 times higher than that of exelon.

Roshchina IF, Gavrilova SI, Zharikov GA, Kalyn IaB, Kolykhalov IV, Selezneva ND. · No affiliation provided · Zh Nevrol Psikhiatr Im S S Korsakova. · Pubmed #15704485 No free full text.

Abstract: An open comparative randomized clinico-neuropsychological study of 4 cerebrolysin treatment courses was conducted during 19 months. The differences in long-term effects of different medication dosages (10 and 30 ml) were revealed. The higher cerebrolysin dose was more effictive for cognitive functioning of patients. In patients receiving a dosage of 10 ml, the disease progress was significantly more pronounced. The results obtained indicate that a course of cerebrolysin treatment in higher dosages significantly inhibited neurodegenerative process.

Shcherbatykh TV, Kiryanov SA, Korovaitseva GI, Selezneva ND, Voskresenskaya NI, Golimbet VE, Farrer L, Gavrilova SI, Rogaev EI. · Scientific Center for Mental Health, Russian Academy of Medical Sciences, Moscow. · Neurosci Behav Physiol. · Pubmed #11388371 No free full text.

This publication has no abstract.

Roshchina IF, Kolykhalov IV, Selezneva ND, Zharikov GA, Gerasimov NP, Gavrilova SI. · No affiliation provided · Zh Nevrol Psikhiatr Im S S Korsakova. · Pubmed #10629930 No free full text.

Abstract: The paper presents a study concerning an influence of cerebrolysin on the efficiency of subsequent therapy with amiridin in patients with mild and moderate dementia of Altzheimer's type (DAT). A study included 2 groups of patients similar in terms of clinical and demographic parameters. The patients of group 1 (23 cases) were treated by amiridin in daily dose of 80 mg during 10 weeks. In group 2 (26 patients) a session of 20 intravenous infusions of cerebrolysin (30 ml in 150 ml of physiologic solution during 4 weeks) preceded the same therapy with amiridin. The neuropsychological assessment was made according to Luria's method with a quantitative estimation of the regulatory and operational components of mental activity. Comparison of the results of neuropsychologic examination both before and after the therapy showed a more pronounced improvement in the states of all regulatory and separate operational components of mental activity in combined therapy with cerebrolysin and amiridin versus monotherapy with amiridin. In patients of group 2 with disturbances of higher mental functions the pathological symptomatology connected with anterior frontal and deep structures of brain was significantly decreased as compared with the patients from group 1.

Gavrilova SI, Fedorova IaB, Kolykhalov IV, Odinak MM, Emelin AIu, Kashin AV, Selezneva ND, Kalyn IaB, Roshchina IF. · No affiliation provided · Zh Nevrol Psikhiatr Im S S Korsakova. · Pubmed #18833104 No free full text.

Abstract: A potential of prolonged 2-years course of cerebrolysin therapy with courses repeated every 6 months to slow down or prevent the transition of the syndrome of mild cognitive impairment, amnestic type, to clinically relevant dementia has been studied in the open comparative study of 73 patients divided into 2 groups, one of which included patients treated with cerebrolysin and another one those who did not receive this drug. The effect of the 2-years course therapy with cerebrolysin suggested by the authors has been proven. Such therapy allows to prevent the progression of cognitive deficit and development of dementia of Alzheimer's type. The results obtained give grounds to recommend this course therapy for prevention of dementia in elderly patients with mild cognitive impairment.

Doody RS, Gavrilova SI, Sano M, Thomas RG, Aisen PS, Bachurin SO, Seely L, Hung D, Anonymous00052. · Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA. · Lancet. · Pubmed #18640457 No free full text.

Abstract: BACKGROUND: Although treatments for Alzheimer's disease sometimes improve cognition, functional ability, or behaviour compared with baseline levels, such improvements are inconsistent across studies and measures, and effects diminish over time. More effective treatments are needed. We assessed the safety, tolerability, and efficacy of dimebon in the treatment of patients with mild-to-moderate Alzheimer's disease. METHODS: We enrolled 183 patients with mild-to-moderate Alzheimer's disease (mini-mental state examination [MMSE] scores 10-24) at 11 sites in Russia. Patients were randomly assigned by a computer-generated randomisation scheme to receive oral dimebon, 20 mg three times a day (60 mg/day [n=89]), or matched placebo (n=94). Other antidementia drugs were not allowed. The primary outcome measure assessed cognition, the difference in mean change from baseline to week 26, or last completed observation on the cognitive subscale of the Alzheimer's disease assessment scale (ADAS-cog). All patients and study personnel were blinded throughout the study. We compared dimebon with placebo with an intention-to-treat analysis, with last observation carried forward (ITT-LOCF) imputation. Analyses were repeated on the fully evaluable population, defined as all patients in the intention-to-treat population who had an ADAS-cog at week 26 and at least 80% compliance. 134 patients (68 in dimebon group, 66 in placebo group) enrolled in the 6-month blinded extension phase of the study. This trial is registered with Clinicaltrials.gov, number NCT00377715. FINDINGS: 155 (85%) patients completed the trial (78 [88%] in dimebon group, 77 [82%] in placebo group). Treatment with dimebon resulted in significant benefits in ADAS-cog compared with placebo (ITT-LOCF) at week 26 (mean drug-placebo difference -4.0 [95% CI -5.73 to -2.28]; p<0.0001). Results of the ITT-LOCF and the evaluable population analyses were much the same for all measures. Patients given dimebon were significantly improved over baseline for ADAS-cog (mean difference -1.9 [-2.92 to -0.85]; p=0.0005). Dimebon was well tolerated: dry mouth and depressed mood or depression were the most common adverse events associated with dimebon (12 [14%] patients for each symptom by week 26). The percentage of patients who had adverse events in the two groups did not differ. INTERPRETATION: Dimebon was safe, well tolerated, and significantly improved the clinical course of patients with mild-to-moderate Alzheimer's disease.

Gavrilova SI. · No affiliation provided · Vestn Ross Akad Med Nauk. · Pubmed #17111921 No free full text.

Abstract: The role of apolipoprotein E (ApoE) genotype in the forming of response to various kinds of pathogenetic therapy of Alzheimer's disease (AD) was studied in two samples of patients receiving cholinergic or neurotrophic therapy during four months. The samples were formed by pair control method according to the following parameters: clinical type of AD (presenile or senile) and the severity of dementia (mild or moderate). The average scores according to cognitive scales (MMSE and ADAS-cog) and to the scale which evaluates the everyday activity of patients (IADL) were practically identical. Patients in group I were treated with exelon (rivastigmine) in maximal individually tolerable doses (76.7% of the patients were receiving > or = 6 mg/ day). Patients in group II received two courses of cerebrolysin (20 i.v. injections of 30.0 ml of the drug in 100 ml of normal saline) with an 8-week break. Both treatments had a significant therapeutic effect, but the proportion of responders to different kinds of therapy depended on ApoE genotype. Among ApoEepsilon4(+) patients the proportion of responders was practically equal in both treatment groups (30.8% and 31.2%), while among ApoEepsilon4(-) patients the proportion of responders to cerebrolysin was three times as big as the proportion of responders to exelon (47.0 and 14.3%, respectively). In the cerebrolysin group the proportion of responders was 1.5 times bigger among ApoEepsilon4(-)patients, while in the exelon group, on the contrary, the proportion of responders was twice bigger among ApoEepsilon4(+) patients (31.2% and 14.3%, respectively). Long-term effects of cerebrolysin (two months after the end of the treatment) in ApoEepsilon4(-) patients were also higher than those in ApoEepsilon4(+) patients, while in exelon patients long-term effects did not depend on ApoEepsilon4. The study demonstrates the significance of the detection of ApoEepsilon4 genotype for the choice of a therapeutic approach in patients with mild or moderate dementia caused by AD.

Myagkova MA, Gavrilova SI, Lermontova NN, Kalyn YB, Selezneva ND, Zharikov GA, Kolykhalov IV, Abramenko TV, Serkova TP, Bachurin SO. · Department of Biochemical Assays, Institute of Physiologically Active Substances, Russian Academy of Sciences, Chernogolovka. · Bull Exp Biol Med. · Pubmed #14534609 No free full text.

Abstract: We measured serum content of autoantibodies to beta-amyloid protein Abeta(1-42), its neurotoxic fragment Abeta(25-35), vasopressin, bradykinin, thrombin, antithrombin III, alpha(2)-macroglobulin, and angiotensin II in patients with various forms of Alzheimer's dementias, including presenile and senile dementias of the Alzheimer type. The ratio of antibradykinin and anti-Abeta(1-42) autoantibody contents differed by 39% in these patients. Our results can be used for the development of a new biochemical method for differential diagnostics of dementias of the Alzheimer type.

Iznak AF, Gorbachevskaia NL, Zhigul'skaia SE, Grigor'eva NV, Grachev VV, Vasil'eva AG, Chaianov NV, Gavrilova SI, Roshchina IF, Kolykhalov IV, Bashina VM, Simashkova NV. · No affiliation provided · Vestn Ross Akad Med Nauk. · Pubmed #11523430 No free full text.

Abstract: Increased central-parietal EEG theta-2 activity (about 6.5 per sec) was found in children with cognitive disorders (in Rett's syndrome, fragile X-syndrome, infantile autism) and in elderly patients with Alzheimer-type dementia (with prevalence of neuropsychological "frontal" disorders) in the presence of suppressed alpha rhythm. This theta-activity was closely associated with cognitive deficits and possessed a specific functional topography, namely it focused in the parietal region and suppressed by both visual stimulation and motor tests. The similar EEG pattern was observed in some patients treated with neuroleptics and/or during hyperventilation. By taking into account the data available in the literature on motor, oculomotor, regional cerebral blood flow and the probability prediction in frontal lobar dysfunction, it is suggested that the theta-activity described appears in the visuomanual coordination system and is a physiological correlate of decreased functional status of frontal lobes.

Braginskaya FI, Zorina M, Pal'mina NP, Gaintseva VD, Burlakova EB, Selezneva ND, Kolykhalov IV, Gavrilova SI. · Institute of Biochemical Physics, Russian Academy of Sciences, Moscow. · Neurosci Behav Physiol. · Pubmed #11508499 No free full text.

Abstract: Acetylcholinesterase (ACE) activity and lipid peroxidation (LPO) parameters were measured in the blood of patients with Alzheimer's disease (AD) during treatment with amiridine and gliatiline. Treatment was accompanied by inhibition of ACE. There was a statistically significant relationship between clinical efficacy and changes in ACE activity. AD was charactefized by significant changes in LPO parameters, with a three-fold increase in the level of primary oxidation products on the background of a sharp (seven-fold) increase in total lipid desaturatedness. There was a statistically significant relationship between ACE activity and the levels of primary oxidation products in the RBC of patients with AD before and after treatment with amiridine and gliatiline.

Korovaĭtseva GI, Shcherbatykh TV, Selezneva NV, Gavrilova SI, Golimbet VE, Voskresenskaia NI, Rogaev EI. · Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, 113152 Russia. · Genetika. · Pubmed #11421127 No free full text.

Abstract: Allele epsilon 4 of the apolipoprotein E (APOE) gene is associated with higher risk of Alzheimer's disease (AD) in many, though not all, ethnic groups. The APOE allele and genotype frequency distributions were studied in 207 AD patients without cerebrovascular disorders, 62 AD patients with cerebrovascular disorders (combined AD), and 206 control individuals (ethnic Russians from the Russian population). The frequency of allele epsilon 4 in patients with early-onset and late-onset AD was three times higher than in control individuals (p < 0.000001). Compared with control people, patients with cerebrovascular disorders displayed a twofold higher frequency of allele epsilon 4; the difference between the two groups was significant (p = 0.0019). Relative risk of AD in carriers of allele epsilon 4 was five times higher than in carriers of alleles epsilon 2 and epsilon 3 (p < 0.000001). Allele epsilon 2 had a protective effect with respect to AD onset until 65 years of age (p = 0.015). Thus, APOE allele epsilon 4 proved to be a universal factor of early-onset, late-onset, and combined AD in ethnic Russians from Russia.

Myagkova MA, Gavrilova SI, Lermontova NN, Kalyn YB, Selezneva ND, Zharikov GA, Kolykhalov IV, Abramenko TV, Serkova TP, Bachurin SO. · Laboratory of Neurochemistry, Institute of Physiologically Active Substances, Russian Academy of Sciences, Chernogolovka, Moscow Region, Russia. · Bull Exp Biol Med. · Pubmed #11391392 No free full text.

Abstract: The content of autoantibodies to beta-amyloid protein Abeta(1-42), its neurotoxic fragment Abeta(25-35), and neurotransmitters were studied in the blood of patients with presenile Alzheimer's disease and senile dementia of the Alzheimer type. Significant differences in the relative content of autoantibodies to Abeta(1-42)and autoantibodies to biogenic amines were demonstrated. These results can be used for the development of a biochemical method for differential diagnosis of Alzheimer dementias.

Iznak AF, Zhigul'skaia SE, Gorbachevskaia NL, Vasil'eva AG, Chaianov NV, Gavrilova SI, Roshchina IF, Kolykhalov IV, Zharikov GA. · No affiliation provided · Fiziol Cheloveka. · Pubmed #11247513 No free full text.

This publication has no abstract.

Braginskaia FI, Zorina OM, Pal'mina NP, Gaintseva VD, Burlakova EB, Selezneva ND, Kolykhalov IV, Gavrilova SI. · No affiliation provided · Zh Nevrol Psikhiatr Im S S Korsakova. · Pubmed #10900685 No free full text.

Abstract: Acetylcholinesterase (AChE) activity and parameters of the system of regulation of lipid peroxidation (LPO) were estimated in blood of patients with Alzheimer's disease (AD) during therapy with amiridine and gliatiline. It was found that the therapy was accompanied by inhibition of AChE activity. A significant correlation was observed between clinical efficiency and changes of AChE activity. AD was characterised by essential changes in LPO parameters: the level of the primary products of oxidation was increased three times with a sharp increase (seven times) of total unsaturation of lipids. A significant correlation was found between AChE activity and the level of the primary products of oxidation in blood erythrocytes of AD patients before and after therapy with amiridine and gliatiline.

Shcherbatykh TV, Kir'ianov SA, Korovaĭtsev GI, Selezneva ND, Voskresenskaia NI, Golimbet VE, Farrr L, Gavrilova SI, Rogaev EI. · No affiliation provided · Zh Nevrol Psikhiatr Im S S Korsakova. · Pubmed #10533256 No free full text.

This publication has no abstract.

Korovaitseva GI, Premkumar S, Grigorenko A, Molyaka Y, Galimbet V, Selezneva N, Gavrilova SI, Farrer LA, Rogaev EI. · Mental Health Research Center, Russian Academy of Medical Sciences, Moscow. · Neurosci Lett. · Pubmed #10477119 No free full text.

Abstract: Alpha-2-macroglobulin (A2M) is a proteinase inhibitor that is present in senile plaques and may play a role in metabolism of amyloid beta (A beta) peptide. Recently it was reported that inheritance of the deletion allele (A2M-2) confers increased risk for late-onset Alzheimer disease (AD) with significance of this effect similar to the epsilon4 allele of apolipoprotein E (APOE). We examined the distribution of A2M genotypes and alleles in a cohort of 146 AD patients and 160 age-matched non-demented individuals. There was no evidence for association in the total sample or in subsets stratified by age or APOE epsilon4 status. These results suggest that this polymorphism is not a strong genetic risk factor for either early- or late-onset forms of the disorder. However, they do not exclude the possibility that an AD susceptibility allele is located elsewhere in A2M or a nearby gene.