Cognitive complaints after breast cancer treatments: examining the relationship with neuropsychological test performance.

BACKGROUND: Cognitive complaints are reported frequently after breast cancer treatments. Their association with neuropsychological (NP) test performance is not well-established. METHODS: Early-stage, posttreatment breast cancer patients were enrolled in a prospective, longitudinal, cohort study prior to starting endocrine therapy. Evaluation included an NP test battery and self-report questionnaires assessing symptoms, including cognitive complaints. Multivariable regression models assessed associations among cognitive complaints, mood, treatment exposures, and NP test performance. RESULTS: One hundred eighty-nine breast cancer patients, aged 21-65 years, completed the evaluation; 23.3% endorsed higher memory complaints and 19.0% reported higher executive function complaints (>1 SD above the mean for healthy control sample). Regression modeling demonstrated a statistically significant association of higher memory complaints with combined chemotherapy and radiation treatments (P = .01), poorer NP verbal memory performance (P = .02), and higher depressive symptoms (P < .001), controlling for age and IQ. For executive functioning complaints, multivariable modeling controlling for age, IQ, and other confounds demonstrated statistically significant associations with better NP visual memory performance (P = .03) and higher depressive symptoms (P < .001), whereas combined chemotherapy and radiation treatment (P = .05) approached statistical significance. CONCLUSIONS: About one in five post-adjuvant treatment breast cancer patients had elevated memory and/or executive function complaints that were statistically significantly associated with domain-specific NP test performances and depressive symptoms; combined chemotherapy and radiation treatment was also statistically significantly associated with memory complaints. These results and other emerging studies suggest that subjective cognitive complaints in part reflect objective NP performance, although their etiology and biology appear to be multifactorial, motivating further transdisciplinary research.

[The problems of studying the effects of far long-duration space mission factors on the higher nervous activity in model experiments with animals].

The article presents the analysis of difficulty with studying the CNS functional changes caused by ionizing radiations solely and in combination with the other spaceflight factors, and discusses optional methods of modeling the basic elements of operator's work in experiments with animals, primates specifically, as well as of data extrapolation on humans.

[Peculiarities of modifying influence of the factors forming the functional status of the central nervous system on dynamics of the rat higher nervous activity disturbances totally exposed to electron and gamma-radiation at a dose of 100 Gy].

The dynamics of using a stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after the total influence of high energy electrons and gamma-rays at a dose of 100 Gy and a modifying influence of the two most important factors forming the functional status of the central nervous system: the stage of the conditioned reflex consolidation and typological peculiarities of the higher nervous activity have been investigated. The influence of both types of ionizing radiation has been shown to cause far more profound disturbances of non consolidated conditioned reflexes in comparison with the automatized conditioned reflexes and provoke an inverted picture of disturbances in the animals with opposed peculiarities of the higher nervous activity. The qualitative picture of the dynamics of disturbances that are caused by these types of radiation is identical. In summary, the studied conditions that form the functional status of the central nervous system determine the nature of neuroradiation syndrome to a greater extent than differences in the effectiveness of these types of radiation.

[The dynamics of the rats higher nervous activity disturbances after total influence of electrons and gamma-rays in doses 5-100 Gy].

The dynamics of using of stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after total influence of high energy electrons and of gamma-rays in doses 5-100 Gy were investigated. The quality structure of higher nervous activity disturbances after the influence of these kinds of ionizing radiation was identical. Therefore the tendency to disturbances aggravating after the electron radiation influence in the periods of the initial depression and of relatively normalization was revealed, especially after the irradiation in dose 50 Gy. The effective compensation of the functional disturbances in the central nervous system at the first 5-10 min after irradiation was after influence of electron radiation in doses about 30 Gy and after the influence of gamma-radiation in doses about 50 Gy. The irradiation of rats in doses 10 Gy and 5 Gy caused qualitative different dynamics of radiation disturbances in rats higher nervous activity. The differences in rats higher nervous activity after influence of electron and of gamma-radiation in these doses did not manifest distinctly.

[Dynamics of the rats higher nervous activity disturbances after partial influence of high energy electrons in high doses].

The dynamics of the disturbances of stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after total and partial (the head or body irradiated) influence of high energy electrons in dose 100 Gy was investigated. The head irradiation, the same way as total irradiation, provoked the early effects of disturbances of higher nervous activity, specifically, initial shock-like effect--the "early transient incapacitation" (ETI). The head shielding, on the contrary, prevents these disturbances. At the same times the body irradiation in dose 10 Gy (this dose don't provoke ETI effect) provoked practically the same disturbances of higher nervous activity as the total irradiation. Consequently, in animals irradiated in super-lethal doses the early disturbances of higher nervous activity provoked of direct influence of ionizing radiation to the brain. In animals irradiated in lesser doses these disturbances caused of non direct effects basically.

[Antioxidant modification of ionizing irradiation and additional stress effects on higher nervous activity in rats].

The aim of this study was to investigate the oxidative effect of the low-level radiation upon the higher nervous activity. Behavioral (shuttle-box) and statistical methods were used. The effect of the ionizing radiation (0.05 Gy) upon the indices of rats behavioral reaction as well as ability of some antioxidants (alpha-tocopherol, ascorbic acid, beta-carotene) used separately and in complex to diminish exposure effects on the indices studied have been investigated Beta-carotene demonstrated the largest protective effect alone and as a component in complex compound. Alpha-tocopherol used in animal exposured to the dose of 0.05 Gy, could case decline of the rats behavior reactions indices; this suggest that use of antioxidant therapy demands certain cautiousness. The results obtained suggest dominant role of the oxidant stress during ionizing radiation at least in dose of 0.05 Gy.

[The neurotropic effects of low-intensity electromagnetic waves in rats with different typological characteristics of higher nervous activity]. / Nekotorye neirotropnye éffekty élektromagnitnykh voln maloi intensivnosti u krys s raznymi tipologicheskimi osobennostiami vysshei nervnoi deiatel'nosti.

The effects of the ultralow-intensity electromagnetic fields (EMF, frequency of 4200 and 970 MHz, modulated by a quasistochastic signal in the range of 20-20,000 Hz, power density 15 microW/cm2, specific body absorption rate up to 4.5 mJ/kg) on the reactions of the central nervous system (CNS) of rats with different types of behavior were studied. Some neurochemical and behavioral mechanisms of rats' reactions were investigated. It was shown that the EMF produce pronounced changes in the state and activity of monoaminergic brain systems. These changes, on the whole, correspond to the alterations at the integrative level (predominantly, of the inhibitory character).

[Postradiation changes in the brain asymmetry and higher mental functions of right- and left-handed subjects (the sequelae of the accident at the Chernobyl Atomic Electric Power Station)]. / Postradiatsionnye izmeneniia asimmetrii mozga i vysshikh psikhicheskikh funktsii prevshei i levshei (posledstviia avarii na Chernobyl'skoi AES).

The present study was aimed at comparative electrophysiological, clinical, and neurophysiological assessment of the brain functional state in dextrals (50 men) and sinistrals (5 men), who participated in the Chernobyl clean. The patients were observed over the course of 10 years (from 1990 to 1999). The results of examination of healthy persons (20 dextrals and 10 sinistrals) were used as a control. The clinical examination revealed the earlier manifestation and more severe development of paroxysmal and epileptic seizures in sinistrals than in dextrals. Electrophysiological study showed a progressive decrease in interhemispheric asymmetry of the EEG coherence characteristic for a healthy brain to inversion of its sign. These changes were more pronounced in sinistrals. In the remote terms after radiation, the interhemispheric EEG coherence decreased over the whole cortex, especially, in the frontal and central areas in both groups of patients. Neurophysiological study revealed a progressive impairment of voluntary motor activity and tactile sensibility, especially, in the left hand. These defects were more expressed in sinistrals than in dextrals. The results of complex and longitudinal examination suggest that the observed changes in brain asymmetry and interhemispheric interaction can be not only a result of a dysfunction of subcortical limbic-reticular and mediobasal brain structures but also a result of the white matter damage including corpus callosum. More expressed impairments in sinistrals than in dextrals can be explained by specific morphofunctional organization of the brain in persons with different sensor and motor asymmetries.

[A dynamic assessment of the reaction of the human brain to radiation exposure (the aftermath of the accident at the Chernobyl Atomic Electric Power Station)]. / Dinamicheskaia otsenka reaktsii mozga cheloveka na vozdeistvie radiatsii (posledstviia avarii na Chernobyl'skoi AES).

The present study was aimed at the comparative assessment of electrophysiological and clinical data in persons (155 right-handed men) who took part in the Chernobyl clean-up in different periods after radiation. Dynamic evaluation of psychoneurological disorders revealed the growth of incidence and severity of cerebrovascular disturbances accompanied by the signs of organic symptoms' aggravation and encephalopathy in longer periods after radiation. The results of neuropsychological examination also showed the deterioration of patients' state manifested as growth of fatigue, cognitive defects, and emotional impairments. Analysis of the EEG parameters, including power and coherence mapping and 3-d dipole source localization analysis demonstrated the increasing number of patients with the most severe forms of EEG pathology: the "plane" type in combination with fast paroxysmal (beta-band) and slow forms of activity from 45% in 1990-92 to 63% in 1997. The "hypersynchronization" type of EEG activity was typical for the earlier period accompanied by the dominance of the pathological forms of EEG activity in mediobasal structures of the left hemisphere, and brainstem zones vs. diencephalon and the right hemisphere. The later period was characterized by decreasing coherence in symmetrical frontal and front-temporal areas of the left hemisphere, while in the early period the hypersynchronization prevailed in symmetrical central areas and in the right hemisphere. The evidence were obtained to a disconnection between the brain hemispheres. We suppose that the progressive involvement of structures of the limbic-reticular complex (especially, brainstem, mediobasal structures, and white matter) into the pathological process occurs with time in participants of clean-up of the Chernobyl disaster consequences.

[The late sequelae of radiation exposure on the nervous system]. / Otdalennye posledstviia luchevogo vozdeistviia na nervnuiu sistemu.

Clinical, neuropsychologic, neurophysiologic as well as neuromorphologic (in legal cases) examinations of Chernobyl liquidators were performed. In addition, the study was made of the monkeys exposed to 1,5 Gy radiation. The results obtained testified to the organic character of cerebral damages. They may be characterised as chronic progressive discirculatory-hypoxic syndrome in which disorders of vascular permeability were expressed and dystrophic destructive irreversible alterations of nervous cells occurred.

[The dynamic behavioral characteristics of rats in a maze after isolated and combined exposures to ionizing radiation and psychoemotional stress]. / Osobennosti dinamiki povedeniia krys v labirinte posle izolirovannogo i kombinirovannogo vozdeistviia ioniziruiushchei radiatsii i psikhoémotsional'nogo stressa.

Rats exposed to ionizing radiation (0.5 Gy) and short-term immobilization stress displayed CNS activation accompanied by diminution of working memory when tested in radial maze. Irradiation, as compared to stress, caused exploratory activity inhibition that led to certain automatism in task fulfillment. Exposure to emotional stress after irradiation modified significantly rat performance causing CNS inhibition and long-term memory decline.

[The combined action of head-down tilt hypodynamia and gamma irradiation on higher nervous activity in rats]. / Kombinirovannoe deistvie antiortostaticheskoi gipodinamii i gamma-oblucheniia na vysshuiu nervnuiu deiatel'nost' krys.

The paper deals with a combined effect of 30-day HDT and gamma radiation at a dose of 3 Gy on the higher nervous activity of the experimental rats. In the rats, the immobilization and isolation stresses induced by HDT are found to cause the development of pathologic aggressive reaction with the disorder of a species-typical pattern of an aggressive act and long-term change in animal social relations. The 30-day HDT disturbs the process of forming the motor-drinking differentiated conditioned reflex coming to a reduction of internal inhibition, generalization and sluggishness of a stimulation process. Functionally, these processes are reflected by a behavioral pattern shifting to stable stereotype impeding the formation of differentiated inhibition. Against HDT the unidirectional gamma radiation exposure increases this effect. In some cases, it leads to blocking the adaptational processes showing in the development of neurotic responses or deep, beyond the limits, inhibition.

[The status of the higher nervous activity in animals exposed to microwaves in conditions simulating the intermittent work of radiolocators]. / Sostoianie vyshei nervnoi deiatel'nosti zhivotnykh pri mikrovolnovom obluchenii v rezhimakh imitatsii vremennoi preryvistosti raboty radiolokatorov.

Impulsive microwave irradiation (3 GHz, 400 imp/sec, duration of a pulse 2 microseconds, rotary speed--3.16 and 29 rpm) leads to the CNS activation in white rats. Activation was most at the slow antenna rotation (3 rpm).

[Effect of a high-intensity radiation exposure on brain function in monkeys. Postradiation changes in central coordination of brain bioelectrical processes]. / Vliianie vysokointensivnogo radiatsionnogo vozdeistviia na funktsional'noe sostoianie golovnogo mozga obez'ian. Postradiatsionnye izmeneniia sostoianiia vnutritsentral'noi koordinatsii bioélektricheskikh protsessov golovnogo mozga.

In experiments with Macaca fascicularis exposed to high-energy electrons (45 Gy, 6.5 Gy/s) revealed were early changes in the coherent spectrum of EEG semihemispheric leads. These changes were displayed by the increased interrelation between slow-wave fluctuations and decreased coherence within the mid- and high-frequency EEG-rhythms band. The relationship was noted between the changes observed and the clinical symptoms features of early radiation response as well as the dynamics of the CNS functions of exposed animals. Postirradiation changes in the intracellular bioelectric interaction are considered as one of the manifestations of the systemic response of the brain to the harmful effect of radiation.

[A quantitative validation of the patterns determining the changes in higher nervous activity after irradiation with heavy charged particles under conditions of the influence of stress factors]. / Kolichestvennoe obosnovanie zakonomernostei, opredeliaiushchikh izmeneniia vysshei nervnoi deiatel'nosti posle oblucheniia tiazhelymi zariazhennymi chastitsami v usloviiakh vliianiia stressornykh faktorov.

The major regularities that govern the alteration of the higher nervous activities after irradiation with heavy charged particles have been grounded quantitatively. The influence of the environmental factors on the exposed organism acquires a stress nature and is accompanied by the alteration of the central-central and central-peripheric relationships in major nervous processes whose pathogenesis is determined, to some extent, by a change in the homeostatic level of the synaptic energy transfer rate that depends quantitatively on the response of the irradiated organism at different stages of the development of radiation damage. The rate of the synaptic transfer at early periods of radiation damage development is 11.6, 9.7, and 12.4 (relative units) corresponding to the stages of radiation affection by heavy charged particles which permits to compare qualitatively and quantitatively the reactions of final acceptors of various executive morphofunctional structures after irradiation with heavy charged particles.

[Behavior of rats in the labyrinth after a flight on the Cosmos-690 biosatellite]. / Povedenie krys v labirinte posle poleta na biosputnike "Kosmos-690".

Rats irradiated aboard the biosatellite Cosmos-690 and in the synchronous mockup showed deteriorated retention and recovery of the skill of traversing the maze. The rats irradiated on the Earth displayed greater changes in the parameters. The rats irradiated inflight exhibited an increased fatigue during enhanced activity. All the exposed animals showed an insignificant change in the capacity to transfer their experience.