Comparative effects of almitrine and raubasine, singly and in combination, on electroencephalographic activity in young and old rats.

A new method for quantification of electroencephalographic (EEG) signals was used to study the effects of almitrine and raubasine, alone and in combination, in two groups of six unanesthetized rats, aged 8 months (young) and 22 months (old). Coadministration of almitrine (7.5 mg/kg-1 i.p.) and raubasine (2.5 mg/kg-1 i.p.) induced an increased EEG power from 7 to 30 Hz; the frequencies concerned were identical in young and old rats, but the degree of their power variations was more marked in old rats. Almitrine induced a 20 to 50% increase in EEG power in young rats on nearly all spectral components. The effects of almitrine were only seen in the low-frequency range in old rats. Raubasine increased the EEG power in the 10 to 20 Hz frequency range; these effects were significantly greater in old rats. In both age groups, the effects on EEG power observed with coadministration of almitrine and raubasine were significantly different from those expected if raubasine and almitrine add their individual effects. These results show that a) almitrine and raubasine modify cortical electrical activity in a different manner as a function of age; b) the modification of the EEG activity induced by the coadministration is suggestive of an interaction between the cortical effects of each drug; and c) the modification of EEG power induced by the coadministration is qualitatively identical in young and old rats but quantitatively more marked in old rats.

Age-related variation of EEG responses to clonidine, prazosin and yohimbine in rats.

The EEG-effects induced by intraperitoneal administration of clonidine, prazosin and yohimbine to 8 and 22 month old rats were compared. Clonidine (0.01 mg/kg) and prazosin (1 mg/kg) increased spectral powers, yohimbine (0.5 mg/kg) decreased them. In the older rats, EEG variations were smaller for prazosin and yohimbine, but larger for clonidine. These findings show that alpha receptor mediated influences on EEG are changed during aging and show that quantified EEG gives a picture of age related changes in the functional state of the neurotransmitter systems.

[Auricular fibrillation in the elderly. Indicators of risk and cerebral prognosis]. / La fibrillation auriculaire chez la personne agée. Indicateurs de risque et pronostic cérébral.

Cardiovascular anomalies contributing to development of atrial fibrillation (AF) and subsequent cerebral repercussion have been studied by analysis of clinical, electrocardiographic and anatomicopathological data for 131 elderly (85.16 +/- 6.7 years) medium- and long-term hospital patients. AF was seen in 22.14% of cases and seems more frequent in the ninth decade than in the eight. Predisposing factors were coronary alterations of repolarization (p less than 0.001), myocardial hypertrophy (less than 0.01), hypertension with cardiac repercussions (p less than 0.01), intraventricular conduction disorders, left anterior hemiblock excepted (p less than 0.05) and mitral valvulopathy. AF developed in 12% of cases without apparent cardiopathy. The risk of cerebral infarct was marginally greater in the presence of AF than in its absence; the risk was clear for paroxysmal forms and nil when AF developed in a healthy heart. In contrast, intellectual deterioration and cerebral hypotrophy were significantly more marked (p less than 0.01) in patients presenting AF. This affirmation is evidence for long-term hemodynamic repercussions of arrhythmia affecting cerebral blood flow and constitutes an argument for re-establishment of sinusal rhythm.

Laminar distribution of neocortical senile plaques in senile dementia of the Alzheimer type.

A prospective longitudinal study was undertaken in a geriatric hospital on women over 75 years of age, clinically diagnosed as either intellectually normal or having senile dementia of the Alzheimer type (SDAT) of varying degrees of severity. Mental impairment was assessed prospectively. Fifteen brains from this population were studied to evaluate quantitatively the distribution of senile plaques (SP) in relation to cortical lamination. SP density in four neocortical areas (first temporal gyrus; supramarginal gyrus calcarine area; precentral gyrus) was significantly correlated with the degree of mental impairment. SP distribution in the cortical layers was evaluated by an indirect method and appeared to be fairly constant from one case to another. Significantly higher SP densities were observed in layers II and III of the temporal and occipital samples, while minimal values were noted in layer I. Lower densities of SP were found in layers V and IV of the occipital and temporal lobes. These data suggest a selective vulnerability of some areas of cortical projections in SDAT.

[Neuropathological study of 12 centenarians: the incidence of Alzheimer type senile dementia is not particularly increased in this group of very old patients]. / Etude neuropathologique de 12 centenaires: la fréquence de la démence sénile de type Alzheimer n'est pas particulièrement élevée dans ce groupe de personnes très âgées.

The brains of 12 patients aged more than 100 years were studied neuropathologically. These were all women who had been long-stay patients at the Charles Foix Hospital, Ivry. On the basis of a retrospective examination of the clinical records the patients were classified as demented or non-demented. No attempt was made to evaluate their mental status more precisely because of the prevalence of deafness (in 10) and blindness (in 7) and also because of the difficulty in assessing mild cognitive changes in institutionalized patients. Three patients were considered to have been demented according to the criteria of the DSM3 (1980). In the brain of one demented case the pathology was that of Alzheimer's disease, in one there were multiple infarcts and in the third there were both senile and vascular changes. The findings in this study are in accordance with the reports of others and indicate that the incidence of senile dementia of the Alzheimer type is not increased in people of very advanced age. Neuropathological findings included reduced brain weight; neurofibrillary tangles in hippocampal neurons of every case as well as in neocortical neurons (absent from neurons of the substantia innominata in only 1 case); senile (neuritic) plaques were found commonly in the hippocampus, less so in neocortical areas (senile plaques totally absent in only one case); granulovacuolar degeneration in hippocampal neurons in every case; amyloid angiopathy present in 9 and mineralization of vessels in 10 cases; hyaline change in vessel walls and abundant lipofuscin in neurons and astrocytes were constant findings. No Lewy bodies were seen.

[Longitudinal study of the relation between environmental conditions and the health of patients in a long-stay hospital]. / Etude longitudinale sur les relations entre les conditions d'environnement et la santé des pensionnaires d'un hôpital de long séjour.

A longitudinal survey has been conducted for a 30-month period in the long-term care hospital of Ivry, in Paris urban area. 1500 people were medically monitored daily by the doctors who were in charge of each unit of the hospital; each individual pathological event was exactly recorded, with complete development. This follow-up permitted to report 6300 acute illnesses. Environmental physical parameters (NOx, SO2, particulates, temperature, humidity, atmospheric pressure) were recorded indoors and outdoors during the whole period. The relation of environmental conditions to health has been studied with the cross-correlations method, applied to respiratory disease incidence rates and physical parameters series. It appeared that only NOx was significantly related to an increase of respiratory disease incidence rates.

Cortical atrophy in senile dementia of the Alzheimer type is mainly due to a decrease in cortical length.

A prospective study was undertaken to select mentally normal old subjects and patients with senile dementia of the Alzheimer type (SDAT). The test score of Blessed et al. (1968) (BTS) was used to determine the severity of mental impairment. A pathologic study confirmed the diagnosis of either SDAT or normal brain aging at postmortem examination in 12 cases. The cortical area and the cortical perimeter of the different cerebral lobes were measured on 1-cm-thick coronal sections using a semiautomatic image analyzer. Cortical length and thickness were calculated using perimeter and area values. BTS was significantly correlated with both the area (r = 0.7695, P = 0.003) and the length (r = 0.7421, P = 0.006) of the temporal cortex. There was no significant correlation between BTS and thickness of the temporal cortex (r = 0.559, P = 0.059). These results show that reduction of length is one of the major determinants of cortical atrophy. Although this has to be confirmed by histological study, they favor the hypothesis of a column-selective atrophy in SDAT which should be considered in the interpretation of the microscopic data.

The role of the left ventricle in the shape of the arterial pressure wave as affected by age.

The role of the heart and its working conditions on the shape of aortic pressure curves was studied by analysis of pressure signals produced at the input of an artificial ejection circuit by 25 isolated working hearts of rats aged 4-22 months. The hearts were paced at five successive heart rates and three levels were imposed for the left auricular perfusion pressure (LAPP). With ageing of the myocardium, increased LAPP and low heart rates, there was an alteration of the pressure wave visual aspect towards a tele-systolic maximum. This modification was regularly associated with significant differences in the harmonic content of the pressure signal. More precisely, there was a bigger increase in the first harmonic amplitude than in the second and third harmonic amplitudes. Because of the physical linearity of the artificial ejection circuit and the controlled working conditions for the heart, it is possible to explain these changes in the pressure wave shape. Lowering of the heart rate is associated with an involvement of a more left part of the circuit impedance curve. Ageing of the myocardium and increased LAPP change the pressure wave shape because they were associated with an increase in left ventricular ejection time.

[Pressure wave morphology and cardiovascular aging]. / Morphologie de l'onde de pression et vieillissement cardio-vasculaire.

The effects of age, pre-load and heart rate on the juxta-aortic pressure wave form in an artificial ejection circuit were studied in 25 isolated perfused rat hearts beating at a controlled rate. The hearts were taken from male Wistar rats aged 4, 8, 12, 16 and 22 months. Each heart was submitted to 3 pre-loads by adjusting the level of left atrium perfusion to 15, 20, 25 cm H2O. Five different heart rates (300, 240, 198, 174 and 150/min) were imposed at each level of pre-load by pacing the interatrial septum after destroying the sinoatrial node. Age, increasing pre-load and bradycardia produced similar changes in the systolic part of the wave characterised by a delayed peak. The effects of these three factors were significant and independent and corresponded to significant changes of the harmonic composition of the pressure wave. In these three conditions, the amplitude of the first harmonic of the pressure increased significantly compared with the second, third and fourth harmonics. The predominance of the amplitude of the first harmonic is characteristic of pressure waves with delayed systolic summits . The linear character of the physical properties of the circuit was tested experimentally. A change in the wave form at a fixed rate is explained by a modification of ventricular ejection which is therefore necessarily present when pre-load is increased and the age of the heart varies. On the other hand, the effect of rate changes on the wave form are explained essentially by the interplay of different zones of the impedence curve of the circuit.(ABSTRACT TRUNCATED AT 250 WORDS)

[Viewpoints on the therapeutic trials in senile cerebral insufficiency]. / Points de vue sur les essais thérapeutiques de l'insuffisance cérébrale sénile.

The experience acquired and a better understanding of the pathogenesis of cerebral impairment in elderly subjects have enabled the authors to propose certain rules for therapeutic trials in such patients. The patient population should be homogeneous with regard to the severity of cerebral impairment. A clear-cut distinction should be made between at least two categories of patients: those at home and those in institutions. Impairments due to different causes (arteriopathy, parkinsonism, traumas, chronic intoxication, idiopathic) require different trials. Criteria of assessment should intervene at recruitment to homogenize the degrees of severity. They should be consistent with the purpose of the trial (pragmatic or explicative) and with its duration and the number of subjects involved. In pragmatic trials assessment should be based on changes in social and affective relationships or even changes in the likelihood of admission to an institution. Assessment scales using psychometric, clinical and socio-affective criteria may be used provided the importance of each criterion is weighed beforehand and the results concern overall changes rather than changes of any particular item. Such trials are necessarily protracted and involve a large number of patients. Psychometric and neurophysiological tests seem to be best suited to explicative trials, as they are reproducible and easily performed. While they may demonstrate the effects of the drug on memory, mood, alertness, etc., or merely show an impact on the central nervous system, this does not necessarily mean that they are of interest in senile cerebral impairment. Explicative trials, which are shorter and require less patients, help to select the drugs suitable for long-term trials. Finally concerning the three topics constantly debated when organizing such trials, viz, maximum age of the subjects, use of a cross-over method and association of psychotropic drugs, the authors' opinion is: (a) there is no reason for an upper age limit; (b) cross-over studies should be avoided, and (c) psychotropic drugs must be banned in short-term trials but are unavoidable in long-term trials.

[Comparison of the effects of almitrine, raubasine and 5023 SE on arterial oxygen desaturation during exercise]. / Comparaison des effets de l'almitrine, de la raubasine et du 5023 SE sur la désaturation artérielle en oxygène lors de l'exercice.

The effects of almitrine (60 mg/24 h), raubasine (20 mg/24 h) and Duxil administered orally were compared in 30 elderly subjects (mean age: 60 years) who showed a decrease in oxygen saturation during maximum exercise. After 1 month of treatment, raubasine proved ineffective whereas almitrine and Duxil significantly reduced this decrease. The effect of Duxil was significantly more pronounced than that of almitrine.

[Demonstration of the therapeutic activity of 5023 SE on intellectual and psychomotor efficacy in elderly impaired patients. Double-blind controlled study versus placebo]. / Mise en évidence de l'activité thérapeutique du 5023 SE sur l'efficacité intellectuelle et psycho-motrice des sujets âgés détériorés. Etude contrôlée à double-insu contre placebo.

A controlled double-blind drug versus placebo trial was conducted in a population of mentally impaired hospital patients divided at random into two groups. In the group treated with Duxil the level of intelligence remained stable and the mental and psychomotor performances improved, as demonstrated by the response time to sounds and colours and by the number of correct answers and errors by perseveration in the Benton's test. The improvement observed under Duxil may be ascribed to a better use of the remaining intellectual capabilities.

Arterial compliance, systolic pressure and heart rate in elderly women at rest and on exercise.

In two groups of elderly women, the relationships between arterial compliance estimated by pulse wave velocity (PWV), and systolic blood pressure (SP), heart rate (HR), oxygen consumption and the time taken to run 400 m have been studies. Both at rest and with increasing levels of exercise, faster PWVs are associated with higher SPs. These is a tendency for resting HR to be higher with faster PWVs. The changes in HR and oxygen consumption from resting values are strikingly increased with faster PWVs. The time taken over 400 m rises as arterial compliance falls. Therefore, it seems that, with aging, reduced arterial compliance is a major factor affecting cardiovascular responses to exercise.

[The treatment of hypertension in the elderly using a beta-blocker: acebutolol (author's transl)]. / Traitement de l'hypertension artérielle du sujet âgé par un bêta-bloquant: l'acébutolol.

The tolerance and antihypertensive action of acebutolol, as a sole drug and in combination with a diuretic, were studied in a population of 34 female subjects aged over 65 years, with a mean of 81 years, suffering from well tolerated essential hypertension. The study was carried out in the form of double blind permutations, each subject receiving successively in an order determined by random selection each of three therapeutic phases: acebutolol, acebutolol in combination with a diuretic and a placebo. The results showed that in the elderly acebutolol had a moderate diuretic action which was remarkably potentialised by diuretics. The tolerance of this beta-blocker was excellent: no cases of cardiac failure, and no disturbances in atrioventricular conduction developed during the phases with active treatment.