My Mind Project: the effects of cognitive training for elderly-the study protocol of a prospective randomized intervention study.

BACKGROUND: Cognitive decline and dementia represent a key problem for public health as they heavily impair social functioning and independent living. The development of new strategies to support recommendations for patients and their caregivers may represent an outstanding step forward. AIMS: To describe the study protocol and methods of "My Mind Project: the effect of cognitive training for elderly" (Grant No. 154/GR-2009-1584108), which investigates, by the use of a multidisciplinary approach, the effects of a comprehensive cognitive training programme on performances in aged subjects with mild-moderate Alzheimer's disease, mild cognitive impairment and normal cognitive functioning. METHODS: The study is a prospective randomized intervention for the assessment of cognitive training effects in three groups of elderly subjects with different cognitive status. A total of 321 elderly people were enrolled in Marche Region, Italy. Each subject was randomly assigned to an experimental group or to a control group. Cognitive performances and biochemical blood markers have also been analysed before cognitive training (baseline), immediately after termination (follow-up 1), after 6 months (follow-up 2) and after 2 years (follow-up 3). DISCUSSION: The results will be useful to identify some efficient programmes for the enhancement of cognitive performance in elderly with and without cognitive decline. CONCLUSION: The application of a non-pharmacological approach in the treatment of elderly with cognitive disorders could have a profound impact on National Health Service.

Protective effect of treatment with nicardipine on cerebrovascular tree of spontaneously hypertensive rats.

The effect of an eight-week treatment with the Ca2+ channel blocker nicardipine on different-sized pial arteries and intracerebral arteries was assessed in spontaneously hypertensive rats (SHR) by microanatomical techniques. Normotensive Wistar-Kyoto (WKY) rats were used as normotensive reference animals. In SHR a significant increase of systolic blood pressure (SBP) in comparison with WKY rats was noticeable. An increased thickness of tunica media and luminal narrowing were also seen in medium- and small-sized pial arteries, and in intracerebral arteries of SHR in comparison with WKY rats. The media-to-lumen ratio was also increased in medium (diameter between 150 and 50 microm) and small-sized (diameter < than 50 microm) pial and intracerebral arteries. Treatment with nicardipine significantly reduced SBP, the thickness of tunica media, media-to-lumen ratio and increased luminal area of medium- and small-sized pial arteries and of intracerebral arteries. These findings demonstrate that treatment of SHR with nicardipine induces a moderate vasodilatation of both pial and intracerebral arteries regulating cerebrovascular resistance. This property may be useful in avoiding generalized or exaggerated cerebrovascular dilatation in hypertension which could be accompanied by impaired brain perfusion.

Effect of nicardipine treatment on the expression of neurofilament 200 KDa immunoreactivity in the brain of spontaneously hypertensive rats.

Neurofilaments (NFP) are components of neuronal cytoskeleton involved primarily in axonal transport and in the regulation of dynamic activities of nerve cells. NFP consist of three subunits denominated high- (200 kDa, NFP-H), intermediate- (160 kDa, NFP-I), and low-molecular weight (68 kDa, NFP-L) neurofilament proteins. Their function and polymerization depends on phosphorylation status, and is regulated by Ca2+ influx. Ca2+ overload enhances degradation of NFP and may compromise axonal transport. An increased susceptibility to ischemia occurs in hypertension, which is also a cause of brain damage. In this study, the expression of phosphorylated NFP (P-NFP) was investigated in the brain of spontaneously hypertensive rats (SHR) using immunohistochemical techniques with antibodies against the phosphorylated epitope of NFP RT-97. Microanatomical analysis included frontal cortex, occipital cortex, hippocampus and cerebellar cortex. The effect of long-term treatment with the dihydropyridine-type Ca2+ antagonist nicardipine on the expression of P-NFP was investigated as well. In hypertension a decreased P-NFP immunoreactivity was observed in frontal and occipital cortex, in the CA1 subfield of hippocampus and in the dentate gyrus, but not in the CA3 subfield of hippocampus or in the cerebellar cortex. Treatment with a daily dose of 3 mg/kg of nicardipine and 10 mg/kg of hydralazine significantly reduced systolic pressure in SHR. The above dose of nicardipine and to a lesser extent a non-hypotensive dose of the compound (0.1 mg/kg/day), but not hydralazine, increased P-NFP immunoreactivity in the cerebral cortex and hippocampus, except the CA3 subfield. The possibility that rescued P-NFP immunoreactivity by treatment with nicardipine depends on improved brain perfusion caused by the compound and/or by countering neuronal Ca2+ overload is discussed.

Stroke unit: a cardio-cerebral approach.

Stroke units are special units where stroke patients receive, simultaneously, medical and physical treatment. Compared to general neurological and medical wards, stroke units show a significant reduction of short- and long-time mortality, and an improvement of long-term quality of life. Nevertheless, mortality in these units is still high (1-year mortality approximately 32%; 5-year mortality degrees 60%), and consequently, new approaches are needed to control stroke parameters during the acute phase, with the goal to reduce mortality rates. The philosophy of our stroke unit in Fermo (Italy), is to establish a strong association between heart and brain care by approaching each stroke patient as a cardiocerebral patient. In particular, we perform 12-lead Holter ECG monitoring, to prevent the vicious cycle affecting correct cerebral and cardiac functions, and to react to cardiac complications, mostly arrhythmias, that can worsen cerebral damage. Holter ECG monitoring allows a fast physiotherapeutic approach, a better evaluation of metabolic parameters, and collectively, a better global evaluation of the patient during the acute phase of disease. In two years of activity, 80 patients that were admitted to our stroke unit during 1998, and treated as cardio-cerebral patients, were followed-up. This combined treatment decreased the 1-year mortality rate by about 30%, in comparison with the 22% mortality rate reported in the literature. These results confirm the validity of stroke units, as well as of our approach based on cardio-cerebral control of each stroke patient.

Superoxide dismutase activity levels in a Spanish population 50-93 years.

Reports dealing with the free radical theory of aging have focused on the possibility that aging may be accelerated in elderly individuals due to lowering of antioxidant defenses. Accordingly, free radical processes involving oxygen continously damage cells and tissues in the body, leading to degeneration and aging. Scavenging enzymes represent one of the several natural defense mechanisms against free radical-induced damage. These enzymes include superoxide dismutase. To investigate the role of this enzyme in aging, its activity was measured in 126 individuals 50-93 years of age. Cu/Zn superoxide dismutase (SOD(1)) was measured in red blood cells using the Minami and Yoshikawa method. The results were compared with those observed in a population between 18 and 65 years of age. SOD(1) activity in males remains constant or slightly decreases with age, whereas in females SOD(1) activity shows a significant increase in individuals between 68 and 93 years. Am. J. Hum. Biol. 11:45-47, 1999. Copyright 1999 Wiley-Liss, Inc.

Free radicals: important cause of pathologies refer to ageing.

Free radical are highly reactive chemical species with an unpaired electron in an atomic or molecular orbital. In biological systems, the most important free radicals are superoxide anion and hydrogen peroxide; in the presence of transition metals such as iron, copper and manganese both these free radicals produce hydroxyl radicals. Free radicals attack proteins, nuclei acids and membranes containing large quantities of polyunsaturated fatty acids. Because of their toxicity, the organism has developed ways to deactivate them. The superoxide dismutase enzyme (SOD) catalyzes dismutation of the superoxide radical into hydrogen peroxide and oxygen hydrogen peroxide is in turn reduced to water and oxygen by peroxidase glutathione and catalase enzymes. The production of radicals in the brain is due to catecholamine metabolism such as dopamine and norepinephrine and is increased by the presence of transition metals and by a deficiency of antioxidant agents such as vitamin E. Two main groups of dementia exist in older age: the multi-infarctual dementias, caused by cerebrovascular disorders and the primary degenerative disorders such as Alzheimer, where no vascular disease is evident. Free radicals play an important role in Parkinson's disease, in Alzheimer's disease and in stroke. The value of SOD and CAT activity following the above mentioned degenerative diseases differ among the various studies carried out. In Alzheimer's disease, the value of SOD activity probably increases in the neuropathologically involved areas. In stroke, the SOD value does not vary either in the ischemic area or in the peri-infarctual one during the first 24 hrs after lesion, while the CAT value decreases.

[Superoxide dismutase and catalase levels in diseases of the aged]. / Niveles de superóxido dismutasa y catalasa en enfermedades del anciano.

UNLABELLED: Superoxide dismutase (SOD) and catalase (CAT) activities were measured in blood from 420 individuals: control population 126, males and females, age between 50 to 93 years of age without any relevant pathology. Pathological population: 294 patients, males and females, age between 50 to 93 years of age, with some disease in the cardiovascular system and in the osteoarticular system, myoma, prostatic pathologies, Chronic Obstructive Pulmonary Disease (EPOC), and Acute Cerebral Vascular Accident (ACVA). The method of Minami and Yoshikawa (SOD) and the method of Aebi (CAT) were judged the techniques of choice for a population study. STATISTICAL METHODS: ANOVA and Student's "t". 1) The results were that levels of activity for SOD and CAT were increased for women in control population, and 2) the level of activity for CAT decreases with aging. In the pathological population, we detected: 3) increased activity for SOD in cardiovascular diseases, myomas, EPOC and ACVA. 4) for CAT the level of activity decreases in cardiovascular and prostatic diseases, EPOC and ACVA. 5) while in osteoarticular diseases levels of activity for SOD and CAT were standard, but SOD level decreases with aging, for CAT in cardiovascular diseases and EPOC, too. Both enzymes work to balance the antioxidant system.

Thalassemia and G6PD deficiency in Spanish blood donors.

Our purpose was to determine the frequency of the thalassemia trait and glucose-6-phosphate dehydrogenase (G6PD) deficiency in blood donors of Madrid, composed of persons from nearly all the Spanish provinces (ranging from 21 to 65 years of age). The frequency of thalassemia and G6PD deficiency has been investigated with the following results; thalassemia 0.92% and no G6PD deficiency. The frequencies observed are compared with those found in the general (non donor) Spanish population. The value of this experiment is considered a supplement to other tests done routinely in our official blood donors.

Human aging brain disorders: role of antioxidant enzymes.

In order to investigate the role of two free radical detoxificant enzymes in patients with aging brain disorders, superoxide dismutase (SOD) and catalase (CAT) activities have been measured in blood from male and female human patients of different ages with several types of aging brain disorders. When compared with activities in the normal population, we have detected: 1) SOD and CAT activities are decreased in patients with Parkinson disease. 2) SOD activity seems to be normal and CAT activity is decreased in patients with dementia. 3) In the patients with stroke, SOD activity is normal, while CAT activity is decreased. SOD activity was measured in red blood cells using the Minami and Yoshikawa method. CAT activity was measured in hemolysates by the method of Aebi. We can conclude that SOD and CAT activities in patients with Parkinson disease are decreased.

[Atheroma plaque and Apo E alleles]. / Placca ateromasica ed alleli delle Apo E.

The authors report their experience regarding the identification of Apo-E alleles on atheroma carotid plaques in 20 patients of both sexes diagnosed as suffering from severe carotid stenosis using Doppler tests. A DNA hybridization and amplification method was used to identify Apo E-2, Apo E-3 and Apo E-4 alleles and their various phenotypical combinations. The following results were obtained in the 20 plaques examined: Apo E-3/E-4 in 114 patients (70%), 2 diabetic patients Apo E-4/E-3, one vascular demented patient Apo E-2/E-3, and 3 plaques defined as severely calcified Apo E-2/E-2. It can therefore be seen that the majority of plaques (70%), considered a risk for future stroke due to altered carotid Doppler tests, does not differ greatly by the homozygote allele Apo E-3/E-3 commonly found in the blood of the so-called "normal" population. It is difficult to draw any conclusions from the alleles found in the other 5 patients due to their scarce statistical value and the limited number of carotid plaques examined, but there appears to be some sort of correlation between calcified plaque, hyperlipidemia and the allele Apo E-2/E-2, with an interchange of position between cysteine arginine amino acids in the Apo E sequences.

Searching for a marker for Alzheimer's disease-Apo-E.

The authors present their study of 10 patients affected by Alzheimer's disease and 10 patients with multinfarctual dementia, who are already part of a CNR study, senile dementia project, longitudinal study. The method adopted was that of DNA crossbreeding and amplification, so as to have a precise individualisation of alleles APo-E, Apo E-3, Apo E-4 and of their various phenotype combinations. These isoforms are evaluated and compared with the disease studied, in order to help to identify a timely-marker for senile dementia. On the results obtained we hypothesised an association between Apo E-4 and the disease of about 40% for Alzheimer's disease, which leads us to increase our number of cases, regarding associations between demential diseases either Alzheimer or vascular and the presence of Apo E-4.

Evaluation of certain immunity parameters in rheumatoid arthritis, treated with cortisone.

The authors present their study on interleukin-2 receptors (IL-2R), transferrin receptors (R-Tr), CD-4/CD-8 ratio, T-lymphocytes after therapy with a corticosteroid (125 mg/die), in 7 female geriatric patients suffering from rheumatoid arthritis. The study was performed with conjugated monoclonal antibody marking the lymphocytes with fluorescein (FITC) and phycoerythrin (PE). Using the considered parameters a depressant effect was presumed on T-lymphocytes and on the immune defences in the first 6 hours after starting therapeutic cortisone infusion. The proliferative effect on T-lymphocytes, CD4 and on the receptor state of the membrane, for IL-2R and Tr-R, was already evident in the 11-12th hour with a peak at 24 hours. It is therefore useful to follow the evolution of the immune state, even using the above parameters, in order to evaluate the correct therapeutic course.

Consideration on diminished immunologic defences in the elderly neoplastic subject.

We evaluated some useful parameters which identify immuno-depressive states in the elderly neoplastic patient, who is subject to possible associated infective diseases. Out of 27 patients followed-up over four months of chemotherapy in concomitance with an immunomodulator, it was seen that in 42.3% there was an increase in their immune defences, assessed by an increase in total lymphocytes with a lymphocyte ratio of T4/T8 and NK cells, and by checking the urinoculture for urinary infections which showed an improved performance status.

Evaluation of chemical parameters in breast cyst.

During our studies on breast diseases, the following biochemical values were measured: chlorine, sodium, potassium and albumin. We examined 153 syringe biopsies from women aged between 34 and 55 years, and an analysis of the above mentioned parameters enabled us to classify the breast cyst fluid into 2 groups: group I was definitely benign, while group II was calculated as having a risk factor two to four times greater than the control group in developing breast cancer.

[The atheromatous-fibrous plaque studied by cytofluorimetry]. / La placca ateromasica-fibrosa studiata mediante citoflorimetria.

Atherosclerosis is the most frequent disease in the majority of cardiovascular arteries. It is a complex disease with peculiar characteristics, including its principal localisation in the inner stratum of the artery (the intima). The paper examines 36 atherosclerotic lesions in elderly patients in which the presence of stenosing atherosclerotic plaque had been diagnosed. The presence of replicating DNA was demonstrated using flow cytometry together with a proliferative phenomenon within the fibrous-atherosclerotic plaque due to an hypothesised migration of smooth muscle cells inside the intima, leading to the final result, a gradual restriction of the arterial gauge and consequent alteration to blood flow. The plaques examined were localised at the bifurcation of the carotid artery, an area in which it is easier to find the physical and biochemical factors facilitating platelet adhesion, which together with other cells produce mitogenic activity since they release growth factors and create the conditions for the proliferation of fibrous tissue.