[Potential developments in gerontology and geriatrics from a cognitive point of view].
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Biomedical subjects
Publications and source records attributed to J Jolles.
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Government, scientists and health care workers show an increasing interest in dementia and memory defects. It is unclear, however, whether the general public has acquired more access to the increased knowledge in this field. This is important to know because many people seem to worry about memory dysfunctions or about a possible dementia. An analysis of newspaper articles over a period of 3 years (March 1987 until March 1990) shows that the number of newspaper articles on memory has decreased. On the other hand, the average number of articles on dementia has increased from 11 per month in the first year to 25 and 28 in the second and third year. In these articles, most attention is given to research on dementia and to health care services for dementia patients. The number of articles on general aspects of dementia remained practically unchanged, although these articles in particular have an important informative function. In national newspapers, the attention for the six different themes is unequally divided. The themes 'general aspects of dementia', 'health care services' and 'research on dementia' have a relatively high impact. Finally, it appears that the same headline of an article can evoke different emotional reactions in a group of judges. Taking the results of this research into account, the authors argue that more health education activities should be directed at memory defects and dementia. Furthermore they conclude that a more systematic evaluation of these activities is necessary.
It is hardly known to what extent consensus criteria for dementia are adhered to in clinical practice. An inquiry was held among the participants of the Dutch consensus meeting on dementia to investigate this point. 85 clinicians diagnosed the case descriptions of 10 patients with cognitive dysfunctions. The inquiry was split into two parts, i.e. before and after the meeting. There was no difference between the two parts in the level of consensus. There was not difference between the disciplines in syndrome diagnoses. However, with regard to etiology, significant differences existed between the specialties. Furthermore, the agreement increased with the severity of the cognitive disturbances. In cases where depressive symptoms coexisted, the diagnosis was more often in error. The nature of the diagnoses appeared to be dependent on the discipline of the diagnostician. This study underlines the necessity of a multidisciplinary diagnostic approach based on well accepted criteria.
Acetyl-l-carnitine (ALCAR) exerts antiaging effects with study we evaluated the effect of a chronic treatment with ALCAR (6 weeks, 50 mg/kg/day) on the open field behavior of 5-month-old and 26-month-old male Wistar rats. Old rats defecated more, made fewer crossings, and spent more time in the corner squares. However, it is difficult to interpret these findings in terms of an increase in emotional reactivity with age because locomotor performance generally has been found to be impaired in old rats. Consequently, treatment effects were analysed within age groups. ALCAR had no effect in young rats, but the old ALCAR-treated rats ambulated less and spent more time in the corner squares than the old control rats. We have interpreted this in terms of an enhanced emotional reactivity of old ALCAR-treated rats.
The after-effects of fatigue or stress on the performance of cognitive tests have been particularly difficult to demonstrate. In this study we examined whether salivary cortisol, used as an index of stress evoked by the continuous performance of mental tasks, reflected individual differences in cognitive performance. In a within-subject experiment in which 24 subjects were exposed to 4 hours of continuous mental activity and to a control session, significantly higher cortisol levels were found during the continuous task session. Cognitive performance was assessed before and after each session. The relevant test parameters involved aspects of verbal memory, concept shifting and divided attention. When subjects were divided into two groups based on the magnitude of individual cortisol responses to the continuous tasks, it was found that the subgroup with higher cortisol responses decreased in attention compared with their attention after the control session. In contrast, the performance of the subgroup with no or lower cortisol responses did not differ between the two sessions. There was no evidence of similar effects on verbal memory or concept shifting.
EVINCE-I is a desktop expert system for the differential diagnosis of dementia, implemented on a personal computer. It is intended to assess the effectiveness of this new technology in modeling a psychiatrist who uses international guidelines for diagnosing dementia. EVINCE-I was tested in diagnosing 19 patients with varying stages of dementia and 10 patients showing other disorders except dementia. EVINCE-I and the human expert were in perfect agreement on the diagnosis of dementia and correlated highly on the diagnosis of dementia of the Alzheimer type and multiple infarct dementia. EVINCE-I thus offers important possibilities as a tool in investigating the data and procedures used by the human expert.
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The results of the present study show that subjects who received an overnight infusion of isotonic fluid did significantly less well at particular neuropsychological tests than controls who did not receive such an infusion. The relevant test parameters involved aspects of word list learning, and concept shifting on a complex speed task. Potentially biasing factors such as anxiety, disturbed sleep, education and age could be discarded. With respect to the physiological mechanism involved, the results suggest that a relatively expanded extracellular volume without dilutional hyponatremia might underlie the diminished performance. The experimental group did not lose weight overnight, and the hemoglobin and haematocrit level of the experimental group were significantly different from those of the control group; the blood pressure, plasma electrolytes and osmolality were not different. The present results provide evidence that disturbances in fluid homeostasis may affect cognitive performance.
EVINCE-I is an expert system for neuropsychiatric diagnostics implemented on a personal computer. It is developed to assess the possibilities of an expert system which models the procedures used for medical decision taking and data analysis by a neuro-psychiatrist when making a differential diagnosis in the domain of dementia syndromes. The knowledge of the system centers around detection of Alzheimer's disease, multi-infarct dementia and depression-induced dementia. EVINCE-I and the human expert were compared in their ability to diagnose 29 patients, i.e. 19 patients with early stages of dementia and 10 patients showing varying disorders except dementia. It is shown that EVINCE-I is able to detect dementia and its main causes, and produce diagnoses that agree with those of the human expert.
Much confusion exists about the definition of the term dementia and about diagnostic criteria of dementing diseases. This confusion not only forms an impediment in the progress of scientific research, but is also potentially harmful for patient care. Recently, considerable improvements are made by consensus conferences in designing operational diagnostic criteria. However, application of these in daily practice is still not optimal. In this publication, differences in meaning of the concept of dementia and Alzheimer's Disease are discussed. A proposal is made how to overcome misunderstandings in daily practice.
Limited proteolysis with trypsin has been used to study the domain structure of the dihydrolipoyltransacetylase (E2) component of the pyruvate dehydrogenase complex of Azotobacter vinelandii. Two stable end products were obtained and identified as the N-terminal lipoyl domain and the C-terminal catalytic domain. By performing proteolysis of E2, which was covalently attached via its lipoyl groups to an activated thiol-Sepharose matrix, a separation was obtained between the catalytic domain and the covalently attached lipoyl domain. The latter was removed from the column after reduction of the S-S bond and purified by ultrafiltration. The lipoyl domain is monomeric with a mass of 32.6 kDa. It is an elongated structure with f/fo = 1.62. Circulair dichroic studies indicates little secondary structure. The catalytic domain is polymeric with S20.w = 17 S and mass = 530 kDa. It is a compact structure with f/fo = 1.24 and shows 40% of the secondary structure of E2. The cubic structure of the native E2 is retained by this fragment as observed by electron microscopy. Ultracentrifugation in 6 M guanidine hydrochloride in the presence of 2 mM dithiothreitol yields a mass of 15.8 kDa. An N-terminal sequence of 36 amino acids is homologous with residues 370-406 of Escherichia coli E2. The catalytic domain possesses the catalytic site, but in contrast to the E. coli subunit binding domain the pyruvate dehydrogenase (E1) and lipoamide dehydrogenase (E3) binding sites are lost during proteolysis. From comparison with the E. coli E2 sequence a model is presented in which the several functions, such as lipoyl domain, the E3 binding site, the catalytic site, the E2/E2 interaction sites, and the E1 binding site, are indicated.
The memory scanning performance of both unipolar and bipolar depressives and patients with anxiety states was compared with that of control subjects. Four versions of Sternberg's memory comparison task were used. Unipolar depressives showed impaired memory scanning in 3 of the tasks compared with controls, and in one task compared with patients with anxiety states. They were also slower than the other patients and controls in the non-scanning processing stages. They seemed to adopt a less efficient search strategy, and showed more controlled processing as opposed to automatic detection in a paper-and-pencil version of the task.
Coproporphyrinogen oxidase has been located in the cytosol of yeast cells. The enzyme was purified to homogeneity from a heme mutant strain exhibiting a high specific activity (15-20 enzyme units/mg soluble protein compared to 1-2 enzyme units/mg soluble protein of by the wild-type strain). The final preparation was homogeneous as judged by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (Mr = 35,000) and isoelectrofocusing (pI = 6.2). Gel filtration on AcA 44 gave a relative molecular mass of 70,000. N-terminal amino-acid sequence analysis revealed a single polypeptide chain. Thus the enzyme appears to be a dimer with identical subunits. Two iron atoms/molecule of native protein were detected; they could not be removed by exhaustive dialysis or gel filtration on Sephadex G-25. However the involvement of the iron atoms in the oxidative catalytic activity of the enzyme was not demonstrated. The Km value for coproporphyrinogen was 0.05 microM. The enzyme was active only when molecular oxygen was used as electron acceptor; no anaerobic activity could be detected. Thiol-directed reagents partially inhibited the enzyme, indicating that an SH group is required for activity. Yeast coproporphyrinogen oxidase was activated by phospholipids or neutral detergents as described for the bovine liver enzyme.
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Vasopressin and oxytocin exert pronounced effects on behavior by a direct action on the brain. A single injection of vasopressin results in a long-term inhibition of extinction of a conditioned avoidance response suggesting that vasopressin triggers a long-term effect on the maintenance of a learned response, probably by facilitation of memory processes. In addition vasopressin improves passive avoidance behavior, facilitates retention of sexually motivated T-maze choice behavior in male rats, delays extinction of an appetitive discrimination task, affects approach behavior to an imprinting stimulus in ducklings, delays the postcastration decline in copulatory behavior in male rats, prevents or reverses amnesia induced by electroconvulsive shock, CO2 inhalation, pentylenetetrazol or puromycin. The majority of these effects may be explained by stimulatory influences of vasopressin on memory processes. Generally oxytocin exerts effects which are opposite to those of vasopressin and it has been suggested that oxytocin may be an amnesic neuropeptide. Evidence has been obtained that endogenous vasopressin and oxytocin play a physiological role in brain processes related to memory. Various limbic system structures seem to act as the anatomical substrate for the behavioral effects of vasopressin and different neurotransmitter systems seem to be involved. It is postulated that in case vasopressin affects retrieval processes the site of action is located in the amygdala and the dentate gyrus of the hippocampal complex with dopamine and serotonin as the respective neurotransmitter systems involved.(ABSTRACT TRUNCATED AT 250 WORDS)
In animals, vasopressin and related peptides are present in specific neuronal pathways in the brain and modulate brain processes. It has been suggested that in particular memory processes, including consolidation and retrieval, short and long term memories are facilitated by vasopressin. Evidence has been presented that endogenous vasopressin is involved in these processes. But also other effects of these peptides e.g. an attenuation of acquisition of heroin self-administration have been reported. Vasopressin and related peptides have been administered to humans in a number of studies including volunteers and various patient populations with and without complaints about memory. Beneficial effects on several aspects of memory, learning, attention and concentration have been found, but not in all studies. Patients with severe deficits seem to benefit less from the peptide treatment. This may be related to the amount of brain damage. Beneficial effects of vasopressin treatment have been reported in schizophrenics and heroin addicts. In addition effects on social behavior, energy and mood of certain patients have been noted. The target patient population for vasopressin neuropeptide is thus not yet well defined. With respect to cognitive disorders, sophisticated neuropsychological test procedures, including information-processing tasks, may contribute to define such a patient population. These tasks may also be applied for treatment evaluation. It should however be kept in mind that other interesting influences of vasopressin e.g. on social behavior, mood and addictive behavior, may also appear of clinical significance. Future studies in humans may yield more detailed information in this respect.(ABSTRACT TRUNCATED AT 250 WORDS)