ISSN 2079-0570, Advances in Gerontology, 2017, Vol. 7, No. 3, pp. 241–245. © Pleiades Publishing, Ltd., 2017. Original Russian Text © I.N. Deryabina, Yu.S. Dzhos, 2017, published in Uspekhi Gerontologii, 2017, Vol. 30, No. 1, pp. 103–108.
Characteristics of the Cognitive Evoked Potentials in Elderly People with Cognitive Decline I. N. Deryabina* and Yu. S. Dzhos Institute of Medical and Biological Research of Northern (Arctic) Federal University, Arkhangelsk, 163045 Russia *e-mail:
[email protected] Abstract—Results of research of cognitive visual evoked potentials in elderly women with various level of cognitive decline are shown in the article. Both relevance of the early diagnostics of cognitive disorders and expedience of use of methods of functional neurovisualization to reveal higher cortical dysfunctions are also shown. To appraise cognitive functions, we applied an express-method of evaluating of cognitive functions during normal aging. According to results of this test, two groups were created: the first were women without cognitive disorders and the second were women with mild cognitive impairment. The evoked potentials were registered for all participants using a 128-channel GES-300 system. Latency of P300-wave and reaction time were calculated. According to temporary characteristics of a P300-wave, it has been revealed that the group with cognitive decline differed in longer latent period in centro-temporo-parietal area of the left hemisphere, and also longer reaction time. However, latency of P300 in central-parietal areas of the right hemisphere was less than one in persons of the control group. These changes reflect dysfunction of structures of a medial temporal lobe, which is expressed mainly by memory disorders. Keywords: cognitive visual evoked potentials, P300, cognitive decline, mild cognitive impairment, advanced age DOI: 10.1134/S2079057017030067
INTRODUCTION One of the most frequent manifestations of aging of the central nervous system is a decline in cognitive functions, which is expressed, mainly, in memory impairment. Indeed, with age, a number of regular changes occur in the brain, which are predisposing to the deterioration of cognitive functions. Thus, in the process of aging, the brain mass decreases, neuronal plasticity declines, non-rough periventricular leukoaraiosis, predominantly of anterior localization may form, and mild neurotransmitter failure develops [5, 8, 17]. According to the Prometheus All-Russia Epidemiological Study, cognitive impairment was detected in approximately 70% of patients over 60 years of age who consulted a neurologist, and it reached significant levels in 25% [4]. The increase in the proportion of elderly and senile people in the population makes the problem of cognitive impairment extremely urgent [2, 9]. Many of the diseases that cause the occurrence of cognitive disorders (vascular, neurodegenerative, demyelinating, etc.) can be corrected in the case of timely diagnosis. Obviously, an earlier detection of cognitive disorders at the stage of noncognitive impairment is relevant for effective therapy [11]. Timely diagnosis of cognitive impairment, before the formation of the dementia syndrome, contributes to the earlier prescription of pathogenetic therapy and to
slowing or halting the progression of cognitive disorders. To assess cognitive functions, mainly psychological tests are used in modern studies. However, these methods are rather subjective. In connection with this, more and more use in the diagnosis of the functional organization of cognitive functions is obtained by methods for evaluating the bioelectric activity of the brain, including evoked potentials. The P300 cognitive evoked potential reflects the state of the brain integrative processes underlying the realization of higher cortical functions, the neuronal processes associated with nonspecific activating reticulotalamic systems, and limbic and neocortical mechanisms of directed attention and short-term memory [3]. According to existing ideas, any evoked potential reflects sensory processes of information reception (early short-latency components of the response) and processes of processing, storing information, and deciding on an action (late long-latency response components). Analysis of the parameters of longlatency responses is of great importance for assessing the state of cognitive functions associated with the perception and processing of information. The use of the P300 cognitive evoked potentials makes it possible to detect cognitive disorders in elderly people in the early stages, which, in turn, allows the early prescription of specific pathogenetic and stabilizing therapies,
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which will promote active longevity and improve the quality of life [3], since, according to WHO, “there is no health without mental health” [15]. Based on this, the purpose of our study was to identify the specific features of the induced bioelectric activity of the brain in elderly people with impaired cognitive functions. MATERIALS AND METHODS The study involved 53 relatively healthy women 55–75 years old, selected on a voluntary basis and with their written consent. Exclusion criteria: history of cerebral circulatory disorders, mental illness, craniocerebral trauma, and chronic diseases in the stage of decompensation. All subjects were righthanded. To assess the level of cognitive functions, an express technique developed by N.K. Korsakova et al. was used. This method includes 12 tasks for evaluation in points of audio-verbal memory, visual-spatial activity and memory, possibility of selective actualization of various events from memory, and for evaluating the processes of verbal thinking [6]. According to its results, two groups were formed: the control group was 27 people (average age of 61) who scored 14 points or less, which corresponds to the normal state of cognitive functions; the main group was 26 people (average age of 68) with a score of 15–19, with slight cognitive impairment. Also, both groups conducted questionnaires to assess their social conditions and educational level. According to the questionnaire, the groups did not statistically significantly differ in the parameters studied. Cognitive evoked potentials to the visual stimulus were recorded using a 128-channel GES-300 system (United States) with a GSN helmet. Color images of animals with their names in contrast color in large print were used as visual stimuli. The images were displayed on a computer screen at a distance of 90 cm. In total, 100 visual signals were given. The examinees pressed the button “1” when the name of the animal coincided with its image (target stimuli) and button “2” in the opposite case. Averaging was conducted over the “target” (P300) stimuli. The stimuli were given at a frequency of one stimulus in 4 seconds. Of all the stimuli presented, the target ones were 30%. Visual stimuli were presented using the E-Prime 2.0 program, where the reaction time and the accuracy of its execution were recorded. For the analysis of cognitive evoked potentials, the data of 72 standard leads selected in accordance with the international “10–10” scheme were used. The analysis period was 1000 ms. In each lead, peak latency and amplitude P300 were calculated. EEG processing was carried out starting with filtration, and the high-frequency filter was set to 0.1 Hz, while that for low frequencies to 30 Hz. Further, as a result of segmentation, periods of 1000 ms
(100 ms before stimulus supply, 900 ms after) were allocated. Then, with the help of software, defective channels and eye blink and movement artifacts were identified and labeled. The threshold value of the difference between the maximum and minimum amplitudes for blinking was 140 μV, and that for eye movement was 100 μV. Further, the replacement of defective channels, EEG averaging, and correction of isoline were performed. The asymmetry coefficient (AC) was also calculated for delta (0.5–3.5 Hz), theta (3.5–7 Hz), alpha 1 (7–11 Hz), alpha 2 (11–13 Hz), beta 1 (13–16.5 Hz), and beta 2 (16.5–20 Hz) EEG ranges. The coefficient was calculated using the following formula: AC = (ASP of the left hemisphere – ASP of the right hemisphere)/(ASP of the left hemisphere + ASP of the right hemisphere) × 100, where AC is the asymmetry coefficient and ASP is the absolute spectral power. The positive value of the AC corresponds to the leftsided asymmetry of the rhythm index, and the negative value corresponds to the right-sided one. Statistical processing of the data was carried out using the SPSS 21.0 application software package for Windows. For each indicator studied, the distribution of features for normality was evaluated using the Shapiro–Wilk test. The distribution of the indicators did not meet the criteria for normality, and, as a result, the Mann–Whitney U test was used for two independent samples. For the descriptive statistics of the characteristics, the median (Me) and the range of values from the first (Q1) to the third (Q3) quartile were used. The critical level of significance (p) in testing the statistical hypotheses in the study was ≤0.05. RESULTS AND DISCUSSION After analyzing the data obtained by the express method of estimating cognitive functions by N.K. Korsakova, statistically significant differences between the groups were revealed in tasks aimed at examining the volume of audio-verbal and visual-spatial memory, the rate of memorization of the verbal material presented for hearing, and optico-constructive operations (tasks 1, 3, 5, 6, and 8), Table 1. Consequently, the main group was characterized by a smaller presentation volume and a lower learning rate compared to the control group. Also, people with mild cognitive impairment experienced noticeable difficulties in memorizing the spatial characteristics of information. The volume of audio-verbal memory and the rate of memorization were also reduced due to the fact that the material suggested for memorization was unorganized in meaning. This is confirmed by equally successful execution of task 10 (word memorization united by common semantic attribute) by both groups. Also, the main group was characterized by relative retention of activities related to thinking and actual-
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Table 1. Points by the express method of cognitive functions estimation by N.K. Korsakova in patients of both groups, Me (Q1–Q3) No.
Task
Control group
Main group
1 2
Memorizing nine words Picture of three geometric figures (triangle to the right of the circle, but to the left of the square) Serial subtraction “from 100 to 7” (five operations) Delayed retrieval of nine words Benton visual retention test (ten subtests) Arrangement of hands on a clock without a dial (time was 7:25 a.m.) Solution of an arithmetical problem Memorizing ten words (not more than five presentations) For 1 min, name as many any food items as possible Memorization of nine words having a common semantic sign Actualization of events consolidated in the past Choice of the statement corresponding to the meaning of a proverb
1 (1–1) 0 (0–1)
2 (1–2) 1 (0–1)
0 0.014
0 1 (1–1) 4 (2–6) 1 (0–2) 0 (0–1) 2 (1–3) 0 0 0 (0–1) 0
0 (0–2) 1 (1–2) 6 (5–7) 2 (1.75–3) 0 (0–1) 3 (3–3) 0 (0–0.25) 0 (0–1) 1 (0–1) 0 (0–1)
06 0.020 0 03 0.178 0 0.049 0.188 0.161 0.016
3 4 5 6 7 8 9 10 11 12
p-level
Table 2. Values of the accuracy and time of a complex hand-eye choice reaction in persons of both groups, Me (Q1–Q3) Parameter Errors, % Reaction time, ms
Control group
Main group
p-level
5.26 (2.13–8.42) 1127.6 (937–1243.3)
5.73 (2.87–9.38) 1288.7 (1118.9–1444.3)
0.838 0.019
ization of material organized in meaning from memory, where an important role is played by the thinking component (tasks 7 and 11). According to the law of Ribot, newly acquired memories are more vulnerable than memories acquired long ago [13]. Thus, persons of both groups performed tasks for memorizing new information worse than tasks for actualizing events from the past. Relatively low indices when assessing cognitive functions in persons of the main group may be due to a decrease in sensory and mnestic abilities, which is usually expressed by slowing down the rate of information processing, reducing the amount of operative memory, and a decrease in the ability to memorize new information [16]. The parameter characterizing the duration of the process of processing information is the time of the sensorimotor reaction [10]. When comparing the time of a complex sensorimotor choice reaction between the control group and the main group, statistically significant differences were obtained. Thus, in persons of the main group, the reaction time is statistically significantly higher (p = 0.019) than in the control group (Table 2). However, in the parameters of accuracy, no significant differences were found. The data obtained can be explained by the decrease in short-term memory, which is an integral part of the mental component of the complex handeye choice reaction. Disturbance of short-term memory may be due to a general decrease in the volume of perception and deterioration of selective attention, ADVANCES IN GERONTOLOGY
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which is associated with a reduced efficiency of nerve transmission and with a sensory deficit that limits a person’s ability to perceive the information required for memorization quickly and accurately [9]. The formation of the P300 wave is influenced by many factors that determine cognitive activity at a given time: the state of operative memory, the process of decision making, and the function of selective attention. There is a close correlation between the degree of lengthening of the evoked potentials and the severity of cognitive impairment [3]. Thus, the time parameters of the P300 wave differed statistically significantly depending on the level of cognitive impairment. It was found that, in persons with mild cognitive impairment, the latent period of cognitive evoked potentials in the centro-temporo-parietal regions of the left hemisphere (T7, TP7, CP5) is statistically significantly higher in comparison with the group with normal cognitive functions (Table 3). Our data are consistent with those previously described in the literature, that the latent period increases by 15–30% compared with the norm in mild cognitive impairment and mild dementia of the cortical type [1]. The changes identified in the centro-temporo-parietal region of the left hemisphere may indicate a dysfunction of the structures of the medial temporal cortex. The anterior and posterior regions of the medial temporal cortex are involved in the mechanisms of episodic and semantic memory [19]. Also, some studies have shown the involvement of hippo-
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Table 3. Values of the latent period of the P300 potential in persons of both groups, ms (Me (Q1–Q3)) Lead Control group T7 CP5 TP7 FPz C4 CP4
Main group
p-level
336 (308–368) 371 (346.25–388) 322 (304–361) 371 (329.50–394) 325 (304–373) 366.50 (315.50–392.25) 375 (338–386) 342 (314–372) 348 (317–378) 314 (302.75–350.75) 336 (314–373) 315.50 (301–340)
07 04 0.028 0.038 0.015 0.029
Table 4. Asymmetry coefficients of the main frequency bands in persons of both groups Band Alpha 1 Alpha 2 Beta 1 Beta 2 Theta
Control group
Main group
p-level
8.7417 8.6192 9.6685 5.7164 8.1427
7.0432 11.8073 10.9781 8.0629 4.3765
0.825 0.622 0.712 0.522 0.658
campal structures in performing tasks for visual perception [14]. Thus, we can assume the presence of dysfunction of deep sections of the temporal lobes in persons of the main group. It is possible that the reason for lengthening the latency of P300 is cerebral damage, which leads to a deterioration in the cholinergic mechanisms of information processing, since acetylcholine is a modulator that increases the amplitude and reduces the latency time [12]. In the case of selective lengthening of P300, it is possible to assess the violation of integrative processes in the cognitive zones corresponding to the proposed pattern [9]. The obtained data of the express method for assessing cognitive functions show that the main group is characterized by low indicators of performance of tasks for visual-spatial activity and memory. Such a decrease may also be due to dysfunction of the parieto-occipito-temporal regions of the cortex of the left hemisphere, which manifests itself in a violation of the understanding of spatial relationships [18]. Presumably, one of the determining factors for lengthening the latent period of P300 in the temporoparietal region of the left hemisphere is the dysfunction of the interhypocampal connections. These links ensure interhemispheric organization and stabilization of mnestic processes. Due to their destruction, the relationship between the right and left hemispheres is destabilized, the functional interhemispheric asymmetry is smoothed, and the mnestic functions are violated [9]. It was also noted that, in the main group, the P300 wave latency is statistically significantly lower in the central parietal regions of the right hemisphere in
comparison with the control group. It is known that the system-dynamic formation of the organization of mental processes has a certain direction. In particular, it tends from the right hemisphere to the left. Functions related to the work of the right hemisphere of the brain form earlier, while those related to the work of the left one form later; that is, the left hemisphere locus forms in the development process. With aging, involutive changes occur in the reverse order. Thus, a decrease in the latent period of cognitive evoked potential in the central regions of the right hemisphere may be due to the transition of the control locus to the right hemisphere. It is suggested that a decrease in asymmetry in elderly persons may be associated with a decrease in the specialization of the hemispheres and/or plastic reconstructions aimed at compensating for brain dysfunction associated with energy deficiency and loss of neurons. The asymmetry of bioelectrical indices in the motor and sensory regions of the cortex appears before all else, while that in the associative (prefrontal and parietotemporal) zones of the cerebral cortex appears later [7]. As a result of the analysis of coefficients of interhemispheric asymmetry, there were no statistically significant differences between the groups (Table 4). Perhaps this is due to the fact that the AC was calculated from EEG data, which was recorded in a resting eyes-closed state, whereas, under cognitive load conditions, the lower left hemisphere functional activity in the centro-parieto-temporal region showed a relatively high activity of the right hemisphere in the centro-parietal region in women with mild cognitive impairment. CONCLUSIONS Thus, the obtained data prove that disorders of audio-verbal and visual-spatial memory predominate in persons with mild cognitive impairment. It was found that P300 latencies in the representatives of the main group are lower in the centro-parietal regions of the right hemisphere, and that in the centro-temporalparietal regions of the left hemisphere is statistically significantly higher in comparison with those in persons with normal cognitive functions. The revealed changes in the temporal characteristics of cognitive evoked potentials may reflect changes in the structures of the medial temporal cortex responsible for episodic and semantic memory. ACKNOWLEDGMENTS The work was carried out within the framework of the project part of the state task in the field of scientific activity of the Ministry of Education and Science of the Russian Federation for 2014–2016 no. 2025 to Northern (Arctic) Federal University.
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Translated by S. Avodkova
