Evaluation of Peripheral Neuropathy in Rat Models of Metabolic Syndrome and Diabetes Mellitus.

The dynamics of nephropathy development in rats with type 2 diabetes mellitus, caused by a high-fat diet and the streptozotocin administration (25 mg/kg), and metabolic syndrome, caused by addition of 20% fructose solution to the diet, was evaluated during the experiment. Models with moderate severity of metabolic changes without significant changes in body weight were obtained after 24 weeks. To study neuropathy severity, the method of electroneuromyography was used; the velocities of motor and sensory excitation propagation along the caudal nerve fibers were measured. In modeled diabetes mellitus against the background of hyperglycemia, a marked decrease in motor and sensory propagation rates was observed, and an increase in the response durations was noted from week 12 to week 24, indicating pronounced neuropathy. In the fructose model, the motor response duration increased from week 12, which possibly indicates the development of peripheral neuropathy.

Comparison of Metabolic Changes after 6 Months of High-Carbohydrate Diet or High-Fat Diet with Low Dose Streptozotocin Injection in Rats.

We compared 2 models of metabolic syndrome in rats: high-fat diet (58% calories) with single streptozotocin injection at a dose of 25 mg/kg and replacement of water with 20% fructose solution. The model with fructose solution did not cause the main signs of metabolic syndrome over 24 weeks: concentrations of glucose, triglycerides, cholesterol, weight, and BP did not significantly differ from the control group (standard diet). At the same time, single streptozotocin administration was followed by the development of persistent hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and signs of visceral obesity. High-fat diet combined with injection of streptozotocin in a low dose can be considered a more representative model of metabolic syndrome in humans.

[Features of the conflict adaptation effect in mild cognitive decline.]

Conflict adaptation effect in interference control tasks (like Stroop task or flanker task) consists in better interference suppression in incongruent trials following an incongruent trial. In a flanker task is shown that in normal cognitive aging there is a null conflict adaptation effect and that in mild cognitive impairment there is a reversed (negative) conflict adaptation effect. Using the drift diffusion model of reaction time, it is shown that the change in conflict adaptation effect in mild cognitive impairment is associated with the absence of adaptive increase in processing speed in the presence of distractors. This can be interpreted as the rigidity of perceptual control mechanisms, which are responsible for strategic distribution of attention in older age and in pathological aging, in particular. The conclusion is drawn that reversed conflict adaptation effect may be an early marker of pathological cognitive aging.

[The use of extractive freezing-out at the stage of preliminary preparation of bioprobes in GC-MS chemico-toxicological analysis]. / Primenenie ékstraktsionnogo vymorazhivaniia na étape predvaritel'noi podgotovki bioprob v GKh-MS khimiko- toksikologicheskom analize.

The authors propose a new express method of low-temperature sample preparation based on the use of extractive freezing-out combined with a sample centrifugation as a stage of a preliminary preparation of a biological object (cadaveric liver, kidneys). The method made it possible to minimize sufficiently the so-called chemical noise of endogenous coextractive substances and to improve sufficiently the conditions of the GC-MS method.

Inducible NO Synthase mRNA Expression and Infiltration of Rats Myocardium with Inflammatory Cells in 2-4 Hours after Modeled Permanent Ischemia or Ischemia/Reperfusion.

Expression of inducible NO-synthase mRNA and myocardial infiltration with neutrophils were studied in rats with modeled permanent ischemia and ischemia/reperfusion models. Expression of inducible NO synthase mRNA in the ischemic region increased significantly in 3, 3.5, and 4 h in modeled ischemia/reperfusion and in 3.5 and 4 h in permanent ischemia. Myocardial infiltration with neutrophils was significantly higher than in intact controls throughout the experiment without significant intergroup differences. In non-ischemic myocardium, enhanced expression of inducible NO synthase mRNA and moderate neutrophilic-lymphocytic myocardial infiltration were also observed in 3.5, and 4 h after ischemia.

Oxidative Status in Different Areas of the Cerebral Cortex of Wistar Rats during Focal Ischemia and Its Modulation with Carnosine.

Oxidative status was assessed in different areas of the cerebral cortex of male Wistar rats under normal condition and during permanent 24-h focal ischemia. In intact animals, the level of lipid hydroperoxides in the frontal lobes of both hemispheres was by 36% higher than in other cortical areas, while total antioxidant activity was by 25% higher than in other areas. During ischemia, changes in oxidative status were localized only in the ischemic focus and penumbra zone and did not involve other cortical areas. We demonstrated for the first time a neuroprotective effect of therapeutic administration of carnosine in low doses (50 mg/kg) on parameters of the oxidative status under conditions of focal ischemia comparable to its effect of high doses (500 mg/kg) as well as its local effect in the penumbra zone. A dose-dependent effect of carnosine on antioxidant activity in the penumbra zone during ischemia was also demonstrated. These findings confirm effectiveness of not only preventive carnosine administration, but also its application in the postischemic period of the stroke.

Changes in Sympathetic Innervation of the Heart in Rats with Experimental Myocardial Infarction. Effect of Semax.

The effect of peptide Semax on remodeling of cardiac sympathetic innervation was examined in rats with experimental myocardial infarction. In 28 days after ischemia/reperfusion injury, Semax diminished the growth of sympathetic innervation of ventricular septum, although it produced no effect on the density of ß1 and ß2 adrenoceptors.

[The determination of pyrovaleron in the urine by gas chromatography in the combination with the method of extractive chilling-out and centrifugation]. / Gazokhromatograficheskoe opredelenie pirovalerona v moche metodom ékstraktsionnogo vymorazhivaniia v sochetanii s tsentrifugirovaniem.

The express-method for the determination of pyrovaleron in the urine based on the combination with the method of extractive freezing-out and centrifugation of the samples as the preliminary stage of the preparation of a biological object for the analysis. The identification and quantitative determination of the substance of interest were performed using gas chromatography with nitrogen-selective detection. The preparation of the samples was carried out as a single-step procedure no longer than 30 min in duration. The limit of alpha-pyrovaleron detection in the urine was estimated at 1 mcg/ml. Its concentration after extraction from the urine increased by a factor of more than nine.

Changes in Sympathetic Innervation of Rat Caudal Artery in Experimental Myocardial Infarction. Effect of Semax Peptide.

Activation of the sympathetic nervous system aggravates the course of myocardial infarction. Semax peptide moderated the degree of this activation and prevented the increase in the density of sympathetic endings in rat caudal artery in 28 days after ischemia or ischemia/reperfusion. The peptide reduced the density of α-adrenoreceptors in the caudal artery of rats with myocardial infarction. Semax produced no effect on ß-adrenoreceptors in both experimental models. The experiments on isolated segments of the caudal artery revealed reduced vascular responsiveness to electrical stimulation and norepinephrine infusion in rats treated with Semax after ischemia/reperfusion injury.

[THE ROLE OF INFLAMMATION IN THE DEVELOPMENT OF PROLIFERATIVE VITREORETINOPATHY].

This paper focuses on the risk factors of primay and secondary proliferative vitreoretinopathy, modern views of pathophysiology of this disease, and the role of inflammation in its development. Special attention is given to the involvement of pigment epithelial cells, macrophages, hyalocytes, gliocytes, supporting fibers (Muller's cells), mediators of inflammation, such as cytokines, chemokines, and growth factors, with reference to their interaction in the processes of proliferation and development of retinal membranes.

Efficacy and safety of Ginkgo biloba extract EGb 761 in mild cognitive impairment with neuropsychiatric symptoms: a randomized, placebo-controlled, double-blind, multi-center trial.

OBJECTIVE: The study was conducted to explore the effects of EGb 761 (Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany) on neuropsychiatric symptoms (NPS) and cognition in patients with mild cognitive impairment (MCI). METHODS: One hundred and sixty patients with MCI who scored at least 6 on the 12-item Neuropsychiatric Inventory (NPI) were enrolled in this double-blind, multi-center trial and randomized to receive 240 mg EGb 761 daily or placebo for a period of 24 weeks. Effects on NPS were assessed using the NPI, the state sub-score of the State-Trait Anxiety Inventory and the Geriatric Depression Scale. Further outcome measures were the Trail-Making Test (A/B) for cognition and global ratings of change. Statistical analyses followed the intention-to-treat principle. RESULTS: The NPI composite score decreased by 7.0 ± 4.5 (mean, standard deviation) points in the EGb 761-treated group and by 5.5 ± 5.2 in the placebo group (p = 0.001). Improvement by at least 4 points was found in 78.8% of patients treated with EGb 761 and in 55.7% of those receiving placebo (p = 0.002). Superiority of EGb 761 over placebo (p < 0.05) was also found for the State-Trait Anxiety Inventory score, the informants' global impression of change, and both Trail-Making Test scores. There were statistical trends favoring EGb 761 in the Geriatric Depression Scale and the patients' global impression of change. Adverse events (all non-serious) were reported by 37 patients taking EGb 761 and 36 patients receiving placebo. CONCLUSIONS: EGb 761 improved NPS and cognitive performance in patients with MCI. The drug was safe and well tolerated.

Effects of activated protein C on the size of modeled ischemic focus and morphometric parameters of neurons and neuroglia in its perifocal zone.

The effects of activated protein C (APC) on the quantitative parameters of neurons and neuroglia in the perifocal zone of infarction induced in the left hemispheric cortex were studied in two groups of rats. Group 1 animals served as control (control infarction). Group 2 rats were injected with APC (50 µg/kg) in the right lateral cerebral ventricle 3 h after infarction was induced, and after 72 h the infarction size was evaluated and the neurons and neuroglia in the perifocal zone were counted. APC reduced the infarction size 2.5 times in comparison with the control and reduced by 16% the neuronal death in the perifocal zone layer V, causing no appreciable changes in layer III, and did not change the size of neuronal bodies but increased (by 11%) the size of neuronal nuclei in layer III. The protein maintained the sharply increased count of gliocytes in the perifocal zone of infarction and promoted their growth. Hence, APC protected the neurons from death in the ischemic focus by increasing the gliocyte count and stimulating the compensatory reparative processes.

[Cerebrolysin in the preventive therapy of dementia in elderly patients with mild cognitive impairment: a three-year prospective comparative study]. / Tserebrolizin v preventivnoi terapii dementsii u pozhilykh patsientov s sindromom myagkogo kognitivnogo snizheniya: rezul'taty trekhletnego prospektivnogo sravnitel'nogo issledovaniya.

OBJECTIVE: To study the efficacy and safety of long-term (3 years) course Cerebrolysin therapy in an open comparative study as a means potentially capable of slowing or preventing the transition of MCI into dementia, as well as to analyze the possibility of Cerebrolysin preventive effect predicting based on clinical and biological parameters. MATERIAL AND METHODS: In total, 100 patients with aMCI were included in the study, randomly assigned to 2 groups: patients of group 1 (n=50) received annual course therapy with Cerebrolysin for 3 years (20 intravenous infusions of Cerebrolysin 20 ml in 100 ml of saline solution for 4 weeks). Group 2 patients underwent annual clinical examination, but did not receive therapy. All patients were monitored on an outpatient basis and were examined once a year. Clinical and psychopathological, psychometric, immunological, catamnestic, molecular genetic, and statistical methods were used. RESULTS: A comparative three-year prospective study conducted in a group of aMCI patients treated with annual course therapy with Cerebrolysin and those who did not receive therapy showed a lower progression of cognitive deficits and a significantly lower conversion rate to dementia in patients who received annual courses for 3 years Cerebrolysin therapy compared with the comparison group. CONCLUSION: The data obtained indicate the presence of a disease-modifying effect in the annual course of Cerebrolysin and the possibility of using this drug in programs of dementia preventive therapy in people with a high risk of cognitive deficits progression and the dementia development in elderly patients with aMCI.

[Efficacy and safety of choline alfoscerate in the preventive therapy of dementia in elderly patients with Mild Cognitive Impairment: a three-year prospective comparative study]. / Effektivnost' i bezopasnost' kholina al'fostserata v preventivnoi terapii dementsii u pozhilykh patsientov s sindromom myagkogo kognitivnogo snizheniya: rezul'taty trekhletnego prospektivnogo sravnitel'nogo issledovaniya.

OBJECTIVE: To study the efficacy and safety of the use of annual course therapy of choline alfoscerate (CA) as a drug potentially capable of slowing or preventing the transition of amnesic type mild cognitive impairment (aMCI) into clinically pronounced dementia in a three-year open comparative study, as well as to explore the possibility of predicting the preventive effect of such therapy based on a number of clinical and biological parameters. MATERIAL AND METHODS: The study included 100 patients with aMCI, randomly divided into 2 groups: the therapeutic group consisted of 50 patients who received CA course therapy once a year for 3 years (20 intravenous infusions of 1000 mg (4 ml) in 100 ml of saline solution for 4 weeks) and a comparison group of 50 patients who underwent an annual examination at the center and did not receive therapy. Clinical and psychopathological, psychometric, immunological, follow-up, and statistical methods were used. RESULTS: A comparative three-year prospective study conducted in a group of aMCI patients treated with annual course therapy of CA for 3 years and aMCI patients who did not receive therapy with similar initial demographic, diagnostic, psychometric and immunological characteristics showed a lower progression of cognitive deficits (12.2% and 39.1%, respectively) and a lower conversion rate (8.2% and 26.1%, respectively) to dementia in the therapeutic group compared with the comparison group. The differences between the initial and final (after 1, 2 and 3 years of follow-up) cognitive functioning indicators in the therapeutic group and the comparison group were significant (p<0.05) on all scales and tests in favor of the therapeutic group throughout the entire follow-up period. CONCLUSION: The results allow us to consider CA as a possible model of preventive dementia therapy aimed at preventing the progression of cognitive deficits and the development of dementia in people at high risk of developing AD - patients with aMCI.

Dihydroquercetin-Loaded Liposomes Change Fibrous Tissue Distribution in the Bleomycin-Induced Fibrosis Model.

The effects of the antioxidant dihydroquercetin (DHQ) were studied in a model of pulmonary fibrosis. DHQ penetration into the lesion was facilitated by encapsulation into liposomes. Pulmonary fibrosis was modeled in rats by intratracheal injection of bleomycin. For the first 7 days, the rats in the treatment group received a liposomal emulsion with DHQ, while in the comparator group rats received saline. In the control group, intact rats did not receive any exposure. Thirty days after the initiation, lung function and the pathological lesion volume were assessed by 7T 1H MRI and the lungs were taken for histologic examination. The proportion of fibrous tissue was counted by Masson's trichrome staining. Both experimental groups were characterized by a significant functional pulmonary deficiency, with low mortality and a small lesion area. In the rats treated with DHQ, the distribution of fibrous tissue was significantly altered. Significantly more fibrous tissue was found in the center of the lesion, while significantly less was in the interstitial space of alveoli. Lung density at the same time was lower in the treated lungs. Dihydroquercetin encapsulated in liposomes affects the mechanisms of bleomycin-induced pulmonary fibrosis progression in rats. While accelerated fibrosis of the lesion can restrict inflammatory processes, delayed fibrosis of the interstitium can further improve the functional state of the lungs.

[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]. / Mnogotsentrovoe otkrytoe sravnitel'noe randomizirovannoe issledovanie effektivnosti i bezopasnosti primeneniya preparata Akatinol Memantin, 20 mg (odnokratnyi priem) v sravnenii s preparatom Akatinol Memantin, 10 mg (dvukratnyi priem) u patsientov s sosudistoi dementsiei.

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Cerebrolysin Treatment Reduces the Risk of Mild Cognitive Decline to Dementia in 1st-Degree Relatives of Alzheimer's Patients: A Prospective Comparative Study]. / Lechenie Tserebrolizinom snizhaet risk perekhoda sindroma myagkogo kognitivnogo snizheniya v dementsiyu u rodstvennikov 1-i stepeni rodstva patsientov s bolezn'yu Al'tsgeimera: prospektivnoe sravnitel'noe issledovanie.

OBJECTIVE: To evaluate the long-term effects of annual course therapy with Cerebrolysin on cognitive functioning and the risk of transition to dementia in relatives of patients with Alzheimer's disease (AD) with amnestic-type mild cognitive decline syndrome (aMCI) in comparison with the same group untreated relatives. MATERIAL AND METHODS: The cohort included 88 first-degree relatives of BA patients with aMCI syndrome aged 50 to 82 years (mean age 65.0±9.9 years) of which 46 people received course therapy with Cerebrolysin and 42 people were not treated. Clinical, neuropsychological, statistical methods were used. Conducted annual course therapy with Cerebrolysin (a total of 3 courses of infusion therapy: for a course of 20 intravenous infusions of 20 ml of Cerebrolysin in 100 ml of isotonic saline) followed by a follow-up study after 3 months after the end of the therapeutic period. The dynamics of cognitive functioning in the therapeutic group was compared with the corresponding dynamics in the comparison group over the same period. The assessment was carried out on day 0, by the end of 1, 14, 27 and 30 months research. RESULTS: In the therapeutic group, according to the CGI-I scale, by the end of the 3rd course of therapy, in 95.7% of cases, a pronounced or moderate improvement was achieved after each of the courses on all scales and tests. In this group, by the end of the therapeutic period, a significant improvement in the initial mean group scores was established. According to the all scales and tests, a significant improvement of the initial average group scores was found after each course of therapy (p<0.05). In the comparison group there was a significant deterioration (p<0.05) of the average group scores of most of the cognitive scales and test by the end of the observation. The annual conversion from aMCI to dementia due to probable AD was 9.5% only in the comparison group. The average group indicators of all scales and tests significantly worsened starting from the 14th month of observation in the comparison group. CONCLUSION: The absence of cases of aMCI conversion to dementia in the treated patients for 2.5 years of observation can serve as confirmation of a disease-modifying effect in Cerebrolysin. These results indicate the need for more extensive clinical studies of the preventive effects of Cerebrolysin and to explore the possibility of including such therapy in drug prevention programs for AD in people at high risk for this disease.

[Russian experience in using a combination of fixed doses of donepezil and memantine in the treatment of Alzheimer's disease as an observational non-interventional multicenter program]. / Rossiiskii opyt primeneniya kombinatsii fiksirovannykh doz donepezila i memantina v terapii bolezni Al'tsgeimera v ramkakh nablyudatel'noi neinterventsionnoi mnogotsentrovoi programmy.

OBJECTIVE: To evaluate the efficacy, safety, and compliance to therapy with Mioreol, first used as part of routine clinical practice in patients with moderate-to-severe dementia due to AD. MATERIAL AND METHODS: The study was conducted as a non-interventional observational program. The work was performed on a group of 48 patients with moderate-to-severe AD aged from 60 to 90 years (median age 74 [69; 77]). The therapeutic dose of Mioreol was 10 mg donepezil + 20 mg memantine, the drug was taken orally, once a day at the same time, regardless of meals. The duration of the course of therapy was 24 weeks. The effects of the drug were assessed using the MMSE, ADAS-Cog, NPI, and CGI scales before the start of therapy and by the end of 12 and 24 weeks of treatment. RESULTS: The use of Mioreol in six-month therapy of AD patients with moderate-to-severe dementia improved not only cognitive but also a wide range of non-cognitive mental disorders. There was an improvement in the CGI-C scale in more than 50% of included patients, positive dynamics on the ADAS-cog scale (6.5 points reduction in total score) and reduction of non-cognitive mental disorders on the NPI scale (4 points reduction in total score). CONCLUSION: Fixed-dose combination therapy with Mioreol is an effective and well-tolerated treatment option for patients with moderate-to-severe AD. A combination of fixed-dose therapeutic doses of donepezil and memantine is potentially more appropriate than the simultaneous use of two recommended drugs for the treatment of AD, which will improve treatment adherence in patients with moderate to severe AD.

[Cognitive impairment and tactics of using the drug Cerebrolysin. Resolution of the International Council of Experts (May 12, 2023)]. / Kognitivnye narusheniya i taktika primeneniya preparata Tserebrolizin. Rezolyutsiya mezhdunarodnogo soveta ekspertov (12 maya 2023 g.).

The aging of the population and the associated increase in the share of cognitive impairments in the structure of a wide range of diseases are a serious challenge for modern healthcare. Difficulties in the treatment of cognitive disorders are determined by many factors, including the age of patients, comorbidity, forced polypragmasia and the adequacy of the dosage of drugs that restore cognitive activity. The experts discussed information about the therapeutic potential of the drug Cerebrolysin in the treatment of cognitive disorders of various origins, stated significant experience of its effective and safe use in many clinical studies in mild and moderate forms of dementia. At the same time, there was a lack of consistent and systematic data on the dosage regimen, frequency, and duration of use of the drug in different forms of cognitive impairment and the degree of their severity. The aim of the international council of experts was to determine the optimal dosage regimens of the drug Cerebrolysin in patients with various etiologies and severity of cognitive impairment. The result of the work was the approval of a unified scheme for the use of the drug Cerebrolysin, considering the severity of the disease and its duration.

[Evolution of the diagnostic frontiers of Alzheimer's disease and new therapeutic possibilities]. / Evolyutsiya diagnosticheskikh granits bolezni Al'tsgeimera i novye terapevticheskie vozmozhnosti.

Over the past three decades, the definition and diagnostic boundaries of Alzheimer's disease (AD) have been repeatedly revised due to significant progress in understanding of the pathogenesis of neurodegeneration associated with Alzheimer's disease and development of high-tech diagnostic methods. The current approach to diagnosing AD is based on the discovery of biomarkers that reflect the two main neuropathological processes involved in the development of primary neurodegeneration underlying AD-abnormal amyloidogenesis and neuronal degeneration. The currently available diagnostic tools are limited to the detection of cerebrospinal biomarkers and/or assessment of the abnormal amyloid and tau protein burden in the brain via amyloid and tau positron emission tomography ligands. Practical implementation (mostly in the research field) of the biological model of AD diagnosis has led to a significant expansion of its diagnostic boundaries with the inclusion of predementia AD stages: asymptomatic and symptomatic, the latter is clinically corresponding to amnestic mild cognitive impairment (aMCI-amnestic mild cognitive impairment). On the one hand, this approach significantly expands the possibilities to study and use preventive technologies aiming to avert or delay the progression of predementia cognitive impairment to dementia but, on the other, it is associated with a number of negative implications from both the clinical and ethical points of view. A significant limitation of purely biological diagnosis of AD based on biomarker levels is due to the low prognostic value of biomarkers, which can cause diagnostic confusion in certain circumstances. Moreover, since the future evolution of the asymptomatic stage is not yet clear and there are still no reliable ways to prevent the cognitive and behavioral symptoms associated with AD, disclosure of stressful information about this "terrifying" diagnosis to patients can cause irreversible damage by triggering depressive disorder, which is a risk factor of AD itself. The current knowledge about AD prognosis in amyloid-positive cognitively unimpaired patients is insufficient. The most adequate approach to early AD diagnostics appears to be the clinical and biological model, as recommended by the International Working Group (IWG2021), which requires a combination of the clinical AD phenotype and the detection of biomarkers specific to this disease. The article discusses the potential directions for the development of biological diagnostic methods, including those based on the so-called peripheral (plasma) biomarker technologies and promising directions for the development of biological methods of secondary AD prevention.