Neurophysiological predictors of death

The neurophysiological study of aging is closely related to the analysis of age-dependent characteristics. There are a huge number of physiological indicators, the age dynamics of which have been studied in elderly and old people. Obviously, the aging process is associated with calendar age, but this relationship is non-linear, if aging is understood to mean an increase in the likelihood of death in old age. Gompertz’s well-known pattern relates the age of a person to the exponential increase in the probability of death, starting from the period of maturity . The age-related dynamics of many neurophysiological indicators do not always directly reflect the process of increasing the likelihood of death, in particular due to the exposure of these characteristics to the influence of many external and internal factors that are independent of the aging process. Therefore, those neurophysiological indicators that are most closely associated with an age-related increase in mortality are of particular interest.

Aging, the development of diseases and death are inseparable from the syndrome of non-specific adaptation (stress). This syndrome develops when the requirements for maintaining homeostasis exceed the currently available adaptive capabilities of the body (see section 6.6 “Changes in cerebral energy metabolism under stress”). The main stages of the syndrome: anxiety (activation), training and exhaustion. The terminal and close periods of aging, regardless of the characteristics associated with diseases, correspond to the stage of depletion due to a lack of, first of all, energy resources . Apparently, neurophysiological indicators reflecting energy-consuming processes are those characteristics that may be associated with the likelihood of death in older people .

The study was carried out by us on 310 healthy subjects of both sexes aged 2 to 92 years. The subjects included 32 women 73 – 92 years old, who were in 1983 in a boarding school for the elderly, whose survival time was monitored. All subjects underwent a neurological and psychiatric examination. Women died 2-12 years after the examination. In 28 of them, the cause of death was coronary heart disease, in one – tumor intoxication, two women were hospitalized in a psychiatric clinic with an unknown diagnosis.

SCP was recorded in 17 areas of the head in accordance with the International Scheme 10-20, and the reference electrode was located on the wrist of the right hand. When calculating the relationship between age, mortality, and AMR dynamics, we used statistical data taken from the Moscow City Statistics Committee as an example of the urban population of Moscow residents for 1995. The total population of Moscow as of December 31, 1995 amounted to 8572394 people, while in 1995 146666 people died. Mortality was determined for people of different ages grouped at five-year intervals, starting at two years. Mortality was calculated as the ratio of the number of deaths per thousand living for each age interval. The increment of mortality was also determined as the difference in mortality in two adjacent age intervals. For further calculations, we considered it expedient to use not mortality, but the increment of mortality with age, as an indicator that more closely correlates with the aging process.

The age of a person is highly reliably associated with an increase in mortality: in men, the correlation coefficient r = 0.81, in women 0.63 with p <0.01 in a time interval from 2 to 95 years. Under 17 years, mortality decreases with age. If we calculate the correlation coefficient of the increment of mortality with age in men and women after 17 years, then its value is 0.82, 0.80. With the logarithm of the increment in mortality, this indicator is even higher and amounts to 0.94 and 0.95, respectively, which is consistent with the Gompertz law.

A high correlation was found between the increment in mortality and the magnitude of local SCP in the frontal and, especially, in the left temporal leads . In this part of the table, correlation coefficients were calculated for the entire set of healthy subjects aged 2 to 92 years using the information of the Moscow City Statistics Committee on mortality in different age groups. Data on mortality and AMR were averaged over five-year age intervals, which made it possible to better identify the stable nature of their relationship.

Coefficients correlation of indicators of the level of constant potential of the brain with increment of mortality and age of survival

# – local SCP, * – significance level p <0.01, other correlation coefficients ( r ) are significant at p <0.05. In brackets in Latin letters accepted in encephalography, the areas of SCP are indicated: Ts – left temporal, Fp – lower frontal sagittal, Cs – left central, Fd and Fs – right and left frontal, Os – left occipital. Square brackets indicate that the soft starter value is taken modulo.

In group A, the data of the Moscow City Statistics Committee on mortality in different age groups and the characteristics of AMR for the entire population of healthy subjects aged 2 to 92 years were used to calculate correlations; mortality and AMR data were averaged over five-year age intervals. To calculate the correlations in group B, the AMR parameters and mortality rates for women 73–92 years old were used.

The presence of a highly reliable correlation of individual AMR indicators with an increase in mortality in men and women suggests that these indicators can be used to assess the likely survival periods of specific people. Survival means the period from the registration of SCP to death. To verify this assumption, we evaluated the correlation of various AMR indicators with the terms of survival and increment of mortality among women 73 – 92 years .

In the group of women examined, a reliable correlation coefficient was found between the time of survival and the values ​​of local SCP in the left occipital lead (Os #), i.e., a decrease in SCP in the left occipital region is accompanied by a decrease in survival time. These data confirm the logical relationship between a decrease in left brain hemisphere energy exchange and an increase in mortality detected in the entire population (see above). The age of the subjects correlated with the survival time negatively .

Given in the table. 5.2 data indicate a reliable correlation of mortality characteristics with AMR indicators in the left hemisphere. At the same time, age correlated with SCP parameters of the right hemisphere. Thus, in the group of examined women of senile age, a significant correlation was observed between SCP in the right frontal region and age , and in the entire sample of people from 2 to 92 years old, correlated with SCP in the right temporal region. Interhemispheric characteristics of AMR are related to the age of death and the duration of survival . In the work devoted to interhemispheric asymmetry, it was suggested that the right hemisphere is more connected with the events of the past, and the left hemisphere with the events of the future. The data obtained by us do not contradict these provisions, and, moreover, supplement them with ideas about a possible prognosis of life expectancy associated with the energy exchange of the left, dominant, hemisphere.

An increase in the increment in mortality from about 70 – 75 years old is accompanied by significant shifts in local SCP in these parts of the brain, which change by 10 – 12 mV over 10 – 15 years. The SCP values ​​in the lower frontal lead become more positive, and in the left temporal region more negative. These indicators are changing friendly with the mortality rate .

The abscissa is the age in years; on the ordinate axis for AMR – the scale in mV, for the increment of mortality – conventional units.

The relationship between a decrease in local SCP in the left temporal region and an increase in mortality is understandable. The decrease in AMR reflects a relative increase in pH and a decrease in energy metabolism, which is naturally observed during aging in the left hemisphere . Low energy exchange in the left hemisphere becomes insufficient to ensure its activities necessary for reliable adaptation. This condition is incompatible with life.

In the frontal region, with an increase in mortality, on the contrary, an abnormal increase in local SCP is correlated, which indicates a decrease in pH in this part of the brain. The acidification of the brain is probably a consequence of the transition to glycolysis and other alternative ways of generating energy, which may be associated with neurodegeneration. It is in the frontal region that there is a maximum decrease in local cerebral blood flow and with aging . An increase in frontal SCP in old people adversely affects psychophysiological parameters . Such changes in the brain decrease life expectancy.

In addition to the above, using the one-way analysis of variance, it was possible to reveal the following regularity: regardless of the age of the subjects at the time of registration, those who had a small interhemispheric difference in the frontal and occipital regions, as well as those who had the parameters of the SCP in the lower frontal region did not go beyond 6 to 16 mV .

Od-Os is the difference of the SCP between the right and left occipital regions, Fp is the lower frontal abduction along the sagittal line, Fd- Fs is the difference of the SCP between the right and left frontal areas. The differences between the survival time represented by white and black bars are statistically significant ( p <0.05)

It can be concluded that a significant indicator for predicting life expectancy is the absence of very high or low values ​​of SCP, since they indicate a violation of cerebral CSR and energy homeostasis.

The spatial synchronization of SCP is important for predicting life expectancy. To evaluate it, a correlation matrix was calculated for each monopolar lead with each monopolar lead. It turned out that in the group of people with a life expectancy of more than two years, there was a highly reliable positive correlation between the values ​​of SCP in many monopolar leads, correlation was absent with SCP in all central, parietal and occipital areas. Living after examination for 2 years or less correlation

90 was significantly less, especially with SCP in all lower frontal and temporal leads. In clinical practice, various markers, including electrophysiological ones, are often used to predict survival and longevity in somatic and neuropsychiatric diseases. On the whole, this approach paid off: the validity of many markers was proven follow-up . In the present work, an attempt is made to approach the problem of predicting life expectancy in clinically healthy people. An increase in mortality and a short survival time turned out to be associated with low AMR and, accordingly, reduced energy metabolism in the left hemisphere, which is more sensitive to aging processes. The prognosis of survival is best described by the indicators of SCP, recorded either in the occipital leads or in the frontal. SCP in the occipital lead reflects the activity of brain structures in the pool of the vertebral artery, including stem centers, which provide for the regulation of vital vegetative functions. Low values ​​of SCP in this lead indicate a violation of energy homeostasis in the pool of the vertebral artery. Indicators of SCP in the frontal areas are also significant for the survival period. With aging, these parts of the brain are primarily prone to atrophy, the development of which increases the likelihood of death. The increase in SCP in the frontal leads may indirectly indicate a subclinical stage of the atrophic process, since it is accompanied by an increase in the acidity of brain tissue and an increase in SCP. Certain interhemispheric relationships are also important for predicting life expectancy. Exceeding the optimal level of interhemispheric differences indicates the development of stress or dysfunction of one of the hemispheres, which adversely affects life expectancy.

In childhood, a friendly, although not always simultaneous, maturation of systems that provide cerebral energy metabolism occurs. In newborns, BBB functions are mainly formed, but cerebral blood flow and glucose metabolism are reduced compared to adults, and glucose metabolism is higher in phylogenetically older parts of the brain. Ketone bodies are used as an energy substrate along with glucose. In newborns, the nerve cells have half the mitochondria and 2 to 3 times lower activity of the respiratory chain enzymes than in adults. Regional differences in glucose consumption are formed by the year, but quantitatively, energy metabolism continues to increase up to 8 – 10 years, and then decreases almost twice in the second decade of life.

Glucose is used as a source of energy metabolism, while pH depends on the accumulation of the final acidic products of energy exchange. Nonetheless, changes in SMG and AMR parameters reflecting CRR during brain maturation, in general, occur in parallel.

In children aged 2 to 7 years, quite high values ​​of SCP indicate intense energy metabolism. The topography of the SCP is mainly formed, except for interhemispheric differences, which are established later. The highest cerebral energy metabolism, according to AMR, as well as according to the results of glucose studies, is detected at the age of 8 – 10 years. At this time, interhemispheric differences in SCP with higher energy metabolism in the left temporal region, characteristic of adults, are formed in comparison with the symmetric division of the right hemisphere. In the second decade of life, the energy exchange of the brain decreases. In the future, the process of reducing cerebral energy metabolism slows down.

In adulthood, SCP is higher in the left temporal region than in the right. According to PET data, in the corresponding areas of the left hemisphere there is also a higher glucose consumption compared to the symmetric parts of the right hemisphere. Interhemispheric differences in adulthood are better expressed in men than in women.

With aging, rearrangements in the energy metabolism of the brain occur. Starting from 40 – 50 years, local cerebral blood flow decreases, oxygen consumption by the brain decreases, and more significantly in the left hemisphere. Glucose metabolism decreases mainly in the frontal parts, while there is an increase in glucose metabolism in the basal ganglia and a number of other parts of the brain. The functions of mitochondria are disrupted both as a result of primary damage in the mitochondrial genome, and as a result of secondary changes due to intra-neuronal acidosis.

In old age, in most areas of the brain, SCP decreases due to a decrease in cerebral energy metabolism. However, a secondary increase in SCP is observed in the frontal region, apparently due to acidification of the brain due to a decrease in cerebral blood flow and the use of anaerobic metabolic pathways. Acidification disrupts the respiratory chain of mitochondria, causing an increase in free-radical oxidation. Regional, including interhemispheric, AMR differences are smoothed out.

Characteristics of AMR in the elderly and senile age allow predicting the upcoming life expectancy. Great informativeness for predicting the terms of survival have the parameters of the SCP of the left hemisphere. The probability of death increases with a decrease in SCP in the left temporal region, with very high or low values ​​of SCP in the frontal region, an increase in interhemispheric differences in SCP, as well as with a decrease in spatial synchronization of parameters of SCP in different areas.

local_offerevent_note September 17, 2019

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