RU2719667C1 - Method for diagnosing chronic cerebral ischemia at the stage of moderate cognitive disorders with accompanying anxiety-depressive disorders - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to medicine, namely to neurology, neuropsychology and occupational pathology, and can be used for diagnosis of chronic cerebrovascular ischemia (CCVI) of vascular origin at the stage of moderate cognitive disorders in patients with concomitant anxiety-depressive disorders. A patient with clinically diagnosed syndrome of moderate cognitive disorders is followed by background recording of EEG for 6 minutes with closed eyes, followed by 6 minutes with open eyes and 4 minutes with closed eyes. Then, four tests are verbally suggested: "Words" test, "What is common?" test, "Plants" test and "Count" test. EEG is recorded with open eyes, the beginning and the end of each fragment and test are marked on the record by the "Background CE", "Background OE", "Background CE", "Words", "What is common?", "Plants" and "Count". Spectral characteristics of the areas marked off by markers are analyzed, relative values of power of each rhythm of each lead, obtained from the table in Encephalan program, are substituted into values of declared discriminant functions. Values of these functions are calculated. Obtained values are compared with control intervals of values of discriminant functions. If values of discriminant functions of tests "Count", "Plants", "Common", "Words", fragments "Background OE" and "Background CE" in all six cases fall into intervals Ffrom 82.6 to 193.5; Ffrom 15.5 to 92.5; Ffrom 27.2 to 54.6; Ffrom -70.02 to -23.1; Ffrom -23.4 to 58.8; Ffrom -198.3 to -148.7 – diagnosing chronic cerebrovascular ischemia of vascular genesis with moderate cognitive impairments accompanied by anxiety-depressive disorders. If these conditions are not met, cognitive impairments of a different origin are detected: cerebral diseases of neurodegenerative genesis, for example, Alzheimer's disease, diabetic encephalopathy, toxic encephalopathy.EFFECT: method enables the accurate and effective diagnosis of CCVI vascular origin at the stage of moderate cognitive disorders in the patients with accompanying anxiety-depressive disorders by evaluating the complex of the most significant indicators.1 cl, 3 dwg, 1 tbl, 3 ex

Description

The invention relates to medicine, namely to neurology, neuropsychology and occupational pathology, and can be used for the diagnosis of chronic cerebral ischemia (HIGM) of vascular origin at the stage of moderate cognitive impairment in patients with concomitant anxiety-depressive disorders.

The problem of cognitive impairment leading to dementia is acquiring an increasingly relevant social significance, in connection with an increase in the proportion of elderly people in the population. Therefore, early diagnosis of cognitive impairment at the pre-dementive stages is extremely important, which will delay or slow the clinical outcome in dementia. The frequency of occurrence of dementia increases with age: from 2-3% in the population up to 65 years and up to 20-30% at the age of 80 years and older [Damulin I.V. The use of nimodipine (nimotope) for vascular cognitive impairment. Review Neurological journal. No. 3, 2012]. According to forecasts of the World Health Organization (WHO), the total number of people with dementia will almost double every 20 years and amount to 65.7 million in 2030 and 115.4 million in 2050 [Dementia: public health priority / WHO. 2013].

The study of pre-dementive cognitive impairment (CI) intermediate between age-related changes in cognitive function and dementia has become relevant. For their characterization, the term “moderate cognitive impairment” (UKI) was proposed [Petersen R., Smith G., Waring S. et al. "Mild cognitive impairment: clinical charactirization and outcome. Arch. Neurol, 56 (3), 303-308, 1999].

Cerebrovascular diseases can also cause mild cognitive impairment and are one of the most common causes, especially in the elderly. The severity of cognitive impairment is variable: from the minimum in its manifestations of disorders of higher brain functions to the degree of dementia. Moreover, moderate cognitive impairment is one of the serious complications of a stroke [Petersen R.S., Touchon J. Consensus on mild cognitive impairment. Res Pract Alzheimer's Dis 2005; 10: 24-32. 2005]. Vascular UKN occurs in 10% of people aged 70 to 90 years and accounts for about a third of all cases of cognitive impairment in the elderly, not reaching the degree of dementia. They increase mortality, disability and medical expenses due to the increasing number of older people in the population, reducing quality and life expectancy. However, in practice, this variant of vascular cognitive impairment is often not recognized. Recent data indicate that vascular RBM is potentially reversible, therefore, the importance of their early detection in individuals with cognitive disorders who do not reach the stage of dementia is undeniable. Their timely diagnosis expands the potential for secondary prevention and therapeutic intervention, which can delay or even prevent the onset of professional and social maladaptation.

Diffuse and multifocal damage to the brain in CGI with the predominant involvement of its deep parts lead to a violation ("disconnection") of the connection between the cortical and subcortical departments and the development of secondary dysfunction of the frontal lobes. The phenomenon of "separation" underlies the clinical manifestations of HIGM: emotional (anxiety, depression), cognitive (from mild to moderate to dementia), as well as motor and autonomic disorders [Yakhno N.N., Lokshina AB, Zakharov V. AT. Mild and moderate cognitive impairment in discirculatory encephalopathy // Clinical gerontology. 2005.V. 11., S. 38 - 39 .; Levin O.S. Discirculatory encephalopathy: current understanding of developmental mechanisms and treatment // Consilium medicum. 2006.V. 8, No. 8. S. 72 - 79].

Anxiety disorders in general medical practice are observed in 10% of patients diagnosed with CGI, and subclinical conditions can occur in 76% of patients [Starostina, E.G. Generalized anxiety disorder and anxiety symptoms in general medical practice. / E.G. Starostina // Russian Medical Journal. - 2004. - No. 22. - 1277-83]. Differential diagnosis of these diseases is complicated by the lack of objective markers for making a diagnosis, which is based today on subjective complaints that patients present to specialists and are identified using various scales. Due to the fact that the prevailing symptoms of a depressive or anxious nature can alternate in the same patient, it is necessary to search for more objective and stable markers for the selection of reasonable therapy for affective disorders.

From the existing level of technology there is a method for determining the effectiveness of anti-dementia therapy of Alzheimer's disease, described Voznesenskaya T., Medvedeva A. (RF patent No. 2414856, March 27, 2011), characterized in that patients from 10 to 13 hours are tested for memorizing 12 words and fluency of speech, the spectral power of the EEG delta and theta ranges is examined before and after a 20-minute load for fatigue with a character-digital substitution test and Bourdon's corrective breakdown before and after 3-month therapy and with a decrease in spectral power in the frontal and central leads by more than 14% and an increase in scores of 2 or more in tests for memorizing 12 words and fluency after speech fatigue load compared to therapy, conclude its effectiveness.

The disadvantages of this method include the fact that the EEG study is carried out before and after the cognitive load, and not in the process of completing tasks, and this method is also applicable only to patients with Alzheimer's disease.

A known method for the diagnosis of cognitive impairment of vascular origin in chronic cerebral ischemia, described by Efremov V.V., Bakuzova D.V., Kizhevatova E.A., Omelchenko V.P. (RF patent No. 2584651, 05/20/2016), characterized in that a patient with a clinically identified syndrome of moderate cognitive impairment undergoes background recording of EEG for 3 minutes with open and closed eyes, then verbally present tests: the “Words” test, including verbal presentation 5 words that the patient repeats immediately and 30 seconds after their presentation, and the “Plants” test, which includes the patient listing for 30 seconds the maximum number of plant names, while recording EEG with open eyes, the beginning and end The performance of each fragment and test is marked on the record with the markers “Von OG”, “Von ZG”, “Slovo”, “Plants” manually, after that they analyze the spectral characteristics of the areas highlighted by the markers, the relative values of the power of each rhythm obtained by spectral analysis the leads taken from the table in the Encephalan program are substituted into the values of the discriminant functions, respectively, and the values of these functions are calculated, and if the values of the discriminant functions of the tests are “Plants”, “Words”, fragments of “Background OG” and “Von ЗГ” in all four cases fall into the intervals F of the _plant from -2743.1 to -2676.6, F _words from 261.2 to 316.6, F _{background ОГ} from 73.7 to 156.3, F _{background MH} from 52.4 to 91.5 - they diagnose cognitive disorders of vascular origin and the patient is assigned to the group of people with chronic cerebral ischemia, if these conditions are not met, they will be diagnosed with cognitive disorders of a different origin.

The disadvantages of this invention is the impossibility of its use in individuals with concomitant emotional disorders, which will not allow for the early diagnosis of cognitive impairment in this category of patients.

A known method for the diagnosis of anxiety and depressive disorders described Kichuk I.V., Chausovoy S.V., Olympieva S.P. (RF patent No. 2689886, 05.29.2019), consisting in conducting electroencephalographic studies using leads "10-20" and ear ipsilateral electrodes as reference, with subsequent spectral and coherent analysis, characterized in that they determine the spectral power in the frequency range 2-4 Hz on leads T6-A2 and T5-A1, indicators of the square of the coherence module C2 between leads O1-P3 in the range of 20-21 Hz; between T5-P3 leads in the range of 7-8 Hz; between F7-F3 leads in the range of 14-15 Hz; between T3-C3 leads in the range of 9.5-11 Hz; between assignments of P4-F7 in the range of 24.5-26 Hz; normalized coherence (NC) indices are calculated by the formula NC = Ln (C2 / (l-C2)), then the Y index is calculated by the formula Y = -A + 1,6B + 0,69C-0,63D-0,32E + 0,097 F + 1.5; Where

A - NK between leads O1-P3 in the range of 20-21 Hz;

B - Ln (P (R) / P (L)),

where P (R) is the spectral power in the range of 2-4 Hz at lead T6; P (L) - on lead T5;

With - NK between assignments of T5-P3 in the range of 7-8 Hz;

D - NC between leads F7-F3 in the range of 14-15 Hz;

E - NK between the T3-C3 leads in the range of 9.5-11 Hz;

F - NC between leads P4-F7 in the range of 24.5-26 Hz;

and with values of Y equal to or greater than zero, a depressive affective disorder is diagnosed, with Y less than zero, anxiety affective disorder is diagnosed.

The disadvantages of this method include the fact that an EEG study is carried out without cognitive load, not in the process of completing tasks, and this method is applicable only to patients with clinically manifested anxiety-depressive disorders.

Thus, the known methods do not allow differentiating CID from other cognitive impairments, provided that there are simultaneous cognitive disorders of vascular origin and emotional disturbances, which limits the use of methods in this category of patients.

The prototype of the claimed invention, we have chosen "A method for the diagnosis of cognitive impairment of vascular origin in chronic brain ischemia" (RF patent No. 2584651, 05.20.2016.). The disadvantages of the prototype are eliminated in the claimed technical solution.

The task to which the invention is directed is to increase the efficiency of early diagnosis of chronic cerebral ischemia at the stage of moderate cognitive impairment in patients with concomitant anxiety-depressive disorders.

The problem is solved by conducting verbal tests and studying the spectral power of the EEG: a patient with a clinically identified syndrome of moderate cognitive impairment is given background recording of EEG with eyes closed (6 minutes), then with open eyes (6 minutes) and again with eyes closed (4 minutes), then they propose four verbal tests “Words” (a modification of the “5 words test” B. Dubois, 2002), “What is common? / General” (a fragment of the Montreal scale for assessing cognitive functions (MOCA) -Z.Nasreddine MD2004), “Count” ( test modification Battery frontal dysfunction and - Frontal Assessment Batter - FAB, B. Dubois et al., 1999) and “Plants” (Addenbrook cognitive scale (ACE-R), E. Mioshi, 2006, fragment of the subscale “Speech activity”) with open eyes and record EEG , the beginning and end of each epoch and test is marked on the record with the markers “Von ZG”, “Von OG”, “Von ZG”, “Words”, “General”, “Account” and “Plants” manually, after which they analyze the spectral characteristics of the areas highlighted by markers obtained by spectral analysis of the relative power values of each rhythm of each lead, taken from the table Encephalan program, substitute the values of the discriminant functions, respectively, and calculate the values of these functions, and if the values of the discriminant functions of the tests are “General”, “Count”, “Plants”, “Words” of the fragments “Von OG” and “Von ZG” in all six cases fall into the intervals F _score from 82.6 to 193.5, F _plants from 15.5 to 92.5, F _total from 27.2 to 54.6, F _words from -70.02 to -23.1 , F _{von exhaust} from -23.4 to 58.8, F _{von MO} from -198.3 to -148.7 - diagnose cognitive impairment of vascular origin and the patient referred to a group of people with chronic cerebral ischemia in stages mild cognitive impairment associated with anxiety and depressive disorders, If these conditions are diagnosed with cognitive disorders of other origin (cerebral neurodegenerative disease genesis, e.g., Alzheimer's disease, diabetic encephalopathy, toxic encephalopathy).

The technical result provided by the given set of features is that the claimed method allows for high accuracy in the early stages to carry out differential diagnosis of chronic cerebral ischemia of vascular origin with moderate cognitive impairment with concomitant anxiety-depressive disorders, thereby this method allows to optimize the diagnosis and therapy of appropriate patients and prevent the progression of their disease.

With concomitant anxiety-depressive disorders, the use of an objective method of EEG diagnostics simplifies the procedure for choosing the tactics for treating cognitive impairment in chronic brain ischemia.

It has been established that the bioelectric activity of the brain is a derivative of cortical processes in which cognitive activity is reflected [Polunina, A.G. Electroencephalogram indicators in the assessment of cognitive functions. / A.G. Polunin // Journal of Neurology and Psychiatry. S.S. Korsakova. - 2012. - No. 7. - S. 74-82]. Both age-related changes and cognitive decline of varying degrees of severity, as well as affective disturbances are accompanied by impaired neurodynamics (the rate of the main mental processes, their exhaustion under functional loads). Therefore, it is not neurodynamic disturbances proper that are diagnostically significant, but the degree of their severity and the nature of the disorders.

A comparative analysis of the proposed solution with the above methods revealed a difference in the scenario of presentation of cognitive loads in the process of recording EEG. Based on this, we can conclude that the proposed method meets the criterion of "inventive step".

The authors have not identified ways to use spectral and discriminant analysis of the rhythmic characteristics of EEGs with cognitive load for the diagnosis of chronic cerebral ischemia with concomitant anxiety-depressive disorders. Thus, the proposed solution meets the criteria of the invention of "novelty."

This method can be used by neurologists, psychiatrists, therapists, physiologists, neuropsychologists for the differential diagnosis of cognitive impairment, which meets the criterion of "industrial applicability".

A detailed description of the method and examples of its clinical implementation

An electroencephalographic study is carried out using an Eencephalan-131-03 electroencephalographic unit at a constant time of 0.3 seconds and a high-pass filter of 70 Hz at a sampling frequency of 125 Hz (manufactured by LLC NPKF Medicom-MTD, Taganrog). This serial device has been manufactured since 1998 and has all the registration documents: certificate of approval of the type of measuring instruments RU. S. 39.026. A No. 5608 dated 10/15/98; certificate of conformity ROSS RU. IMO2. B06321 No. 02754248 of 10/20/98; number in the State Register No. 17829-98; registration certificate of the Ministry of Health of the Russian Federation No. 29/03030698 / 0442-00 of June 23, 2000). Data processing, obtaining spectral data is carried out using the Encephalan program, on the basis of which this device works.

A patient with a clinically diagnosed syndrome of moderate cognitive impairment with concomitant anxiety-depressive disorders undergoes background recording of EEG with eyes closed (6 minutes), then with eyes open (6 minutes) and eyes closed (4 minutes), while the subject is in a relaxed state, sitting on the armchair. Then he is offered four tests with open eyes according to the developed scenario. Test “Words”: immediate and delayed reproduction of 5 words in 5 series with audio presentation (repeating words immediately after presentation, then the patient thinks about the words for 30 seconds and repeats them again at the command). Test “General” - visual presentation of 5 words, non-verbal assessment by the patient, then the patient calls a generalizing symptom for the presented group of words. Test “Account” - the patient non-verbally performs a serial subtraction of 100 digits 7, after 30 seconds calls the answer. Test "Plants": for speech activity in relation to semantically mediated associations - the patient within 30 seconds calls the maximum number of plants. Each action in the course of the script is marked manually on the EEG recording in a way convenient for the researcher, for example, with a marker.

After that, the EEG is divided into fragments “Background closed eyes”, “Background open eyes”, “Words (audio presentation)”, “General”, “Account”, “Plants”.

Then, using the Encephalan program, a spectral analysis of each fragment is carried out. By default, the program divides the spectrum into 6 ranges (delta1, delta2, theta, alpha, beta1, beta2), but you must manually select only 4 standard ranges through the program settings: delta (0.5-4 Hz) - by combining delta1 and delta2 in delta, theta (4-8 Hz), alpha (8-13 Hz) and beta (13-50 Hz) - due to the combination of beta1 and beta2 into beta. The tuning algorithm is shown in FIG. 1.

After setting the EEG ranges, they go to the "Processing" menu, the program itself builds the spectra for each fragment and calculates all spectral characteristics for all leads and rhythms, displays them in graphical and tabular form.

In FIG. 2 shows a table of absolute values of power (AZM), which is displayed first by default when switching to the mode of presentation of spectral analysis data in a table form. We need to go to the tab of the table with relative power values. The relative values of power (OZM) are important, as they reflect the representation of each rhythm in the overall structure of the EEG (Fig. 3).

These data of relative power values are substituted into the values of discriminant functions, respectively:

For the test "Words":

For the test "General":

For the test "Plants":

For the test "Account":

For the test "Background ЗГ":

For the Von OG test:

The formulas indicate the frequency ranges of the spectra in the corresponding leads.

The obtained values are compared with the control intervals of the values of discriminant functions, and if the values of the discriminant functions of the tests “Count”, “Plants”, “General”, “Words”, fragments “Von OG” and “Von ZG” in all six cases fall in the intervals F _score from 82.6 to 193.5, F _plants from 15.5 to 92.5, F _total from 27.2 to 54.6, F _words from -70.02 to -23.1, F _{background OG} from - 23.4 to 58,8, F _{MH pattern} from -198.3 to -148.7 - diagnose chronic cerebral ischemia vascular origin with mild cognitive impairment associated with anxiety and depressive disorders, with evypolnenii these conditions, cognitive disorders of other origin (cerebral neurodegenerative disease genesis (Alzheimer's disease), diabetic encephalopathy, toxic encephalopathy).

Thus, for the diagnosis of chronic cerebral ischemia of vascular origin with moderate cognitive impairment with concomitant anxiety-depressive disorders, it is necessary that the results of the diagnostic functions of the tests “Count”, “Plants”, “General”, “Words”, fragments of “Background GO” and Von ZG in all six cases belonged to the same group.

Table 1 presents the empirically obtained control intervals of the values of discriminant functions.

The clinical application of the proposed method is confirmed by the following examples.

Example 1.

Patient T-something, 76 years old, was hospitalized in the neurological department of the clinic of the Rostov State Medical University from October 21, 2016 to October 28, 2016 with a syndrome of cognitive-mnemonic spectrum disorders, syndrome of diffuse micro focal symptoms and vestibular disorders identified based on complaints, medical history, objective research. Concomitant mild affective impairment was also observed in the disease picture, which exacerbated the course of cognitive impairment. The specified syndrome required differentiation of its origin. The patient was recorded by EEG with the presentation of cognitive load according to the above method. After a spectral analysis of the rhythmic characteristics of the patient’s EEG and their substitution into the formulas, the following values were obtained: F _score = 94.8, F _plants = 77.3, F _total = 35.6, F _words = (-55.8), F _{background GO} = 29.7, F _{background GO} = (-15 1.3).

Comparing with the data in table 1, we find that according to six factors, the patient belongs to the group of patients with chronic cerebral ischemia of vascular origin with moderate cognitive impairment with concomitant anxiety-depressive disorders.

Example 2

Patient V-va, 61 years old, was hospitalized in the neurological department of the clinic of the Rostov State Medical University from 05.16.2017 to 05.24.2017 with a syndrome of moderate cognitive impairment. Neurological status: pupils: D = S, palpebral fissures: D = S, eye movements not limited, weak convergence. Tongue along the midline, pharyngeal reflexes alive. Tendon reflexes: D = S. Oral automatism reflexes are positive. Reduced memory for current events. Orientation in place, time, self is saved. In order to clarify the nature of intellectual deficiency, the patient was recorded with EEG with presentation of cognitive load using the method described above. After a spectral analysis of the rhythmic characteristics of the patient’s EEG and their substitution into the formulas, it was obtained: F _score = 133.6, F _plants = 74.2, F _total = 41.3, F _words = (-38.6), F _{background GO} = (-53.2), F _background = (-162.7). Comparing with the data in table 1, we find that according to six factors, the patient belongs to the group of patients with chronic cerebral ischemia of vascular origin with moderate cognitive impairment with concomitant anxiety-depressive disorders.

Example 3

Patient E-ko, 55 years old, was hospitalized in the neurological department of the clinic of the Rostov State Medical University from 12.12.2016 to 12.19.2016 with complaints of impaired memory and attention, asthenic syndrome, mild vestibulo-atactic syndrome , During a psychological examination on a short-term scale for assessing mental status, I scored 24 points, which corresponds to moderate cognitive impairment.

During the clock drawing test, the patient scored 7 points, the battery of tests for assessing frontal dysfunction - 13 points. In order to differential diagnosis, the patient was recorded EEG with presentation of cognitive load according to the above method. After a spectral analysis of the rhythmic characteristics of the patient’s EEG and their substitution into the formulas, the following values were obtained: F _score = (-75.4), F _plants = 7.2, F _total = 19.5, F _words = 34.3, F _{background GO} = 81.3, F _{background GO} = 11.4. When comparing the results with table 1, it is concluded that the patient belongs to the group of patients with a different pathology and he needs an additional examination. Later, after receiving additional clinical data, our assumption that the patient had a different disease was confirmed: the patient was diagnosed with Alzheimer's disease.

The method was tested on 26 volunteer patients in the neurological department of the Rostov State Medical University clinic with a diagnosis of chronic cerebral ischemia of vascular origin with mild cognitive impairment and associated anxiety-depressive disorders and 24 volunteers with chronic cerebral ischemia of vascular origin with mild cognitive impairment.

The proposed method allows to increase the accuracy of the differential diagnosis of chronic cerebral ischemia with mild cognitive impairment in the early stages, even with concomitant anxiety-depressive disorders, and to optimize the choice of treatment tactics with a minimum amount of paraclinical research methods. The method can be used by neurologists, psychiatrists, therapists, physiologists, neuropsychologists in clinical practice.

Claims (20)

A method for the diagnosis of chronic cerebral ischemia at the stage of moderate cognitive impairment in patients with concomitant anxiety-depressive disorders, including verbal tests and a study of the spectral power of EEG, characterized in that a patient with a clinically identified syndrome of moderate cognitive impairment is provided with background recording of 6-minute EEG with closed eyes, then 6 minutes with eyes open and 4 minutes with eyes closed, then they verbally offer four tests: the “Words” test, which includes rbalnoe presentation 5 words that the patient repeats immediately and after 30 seconds of their presentation; test "What is in common?" - visual presentation of 5 words, non-verbal assessment by the patient, then the patient calls a generalizing symptom for the presented group of words; “Plants” test, including a patient listing within 30 seconds of the maximum number of plant names; “Account” test - the patient non-verbally performs a serial subtraction from 100 of the number 7, after 30 seconds calls the answer, EEG is recorded with eyes open, the beginning and end of each fragment and test are marked on the recording with “Von ZG”, “Von OG” markers ”,“ Von ZG ”,“ Words ”,“ What is common? ”,“ Plants ”and“ Account ”and manually, after that they analyze the spectral characteristics of the areas highlighted by markers, the relative values of the power of each rhythm of each lead obtained by spectral analysis, taken from the table in programs "Encephalan" is substituted into the value of the discriminant functions, respectively: For the test "Words":

For the test "General":

For the test "Plants":

For the test "Account":

For the test "Background ЗГ":

For the Von OG test:

they calculate the values of these functions, compare them with the control intervals of the values of the discriminant functions, and if the values of the discriminant functions of the tests “Count”, “Plants”, “General”, “Words”, fragments “Von OG” and “Von ZG” in all six cases fall into the intervals F _score from 82.6 to 193.5, F _plants from 15.5 to 92.5, F _total from 27.2 to 54.6, F _words from -70.02 to -23.1, F _{background exhaust gas} from -23.4 to 58,8, F _{MH pattern} from -198.3 to -148.7, diagnose chronic cerebral ischemia vascular origin with mild cognitive impairment associated with anxiety-depressive dist oystvami, If these conditions cognitive disorders of different origin: brain neurodegenerative disease genesis, e.g., Alzheimer's disease, diabetic encephalopathy, toxic encephalopathy.

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