Vincenzo Marigliano

Effect of aerobic training on the cognitive performance of elderly patients with senile dementia of alzheimer type

The importance of physical activity to maintain a healthy psychological functions is widely known. The present study involved 15 males affected by senile dementia of Alzheimer type (SDAT) and assessed their functional capabilities by means of the following neuropsychological tests: test of attentional matrix, verbal span test, supraverbal span test, mini mental state examination. After an exercise training program of 3 months, patients were assessed again by the same psychological tests which demonstrated a significant improvement.

Abnormal passive head-up tilt test in subjects with symptoms of anxiety power spectral analysis study of heart rate and blood pressure

Previous reports that subjects with anxiety symptoms are at higher risk of sudden death may imply that anxiety induces stable sympathetic hyperactivity. To address this subject, in persons with and without anxiety symptoms, we evaluated autonomic nervous system activity by power spectral analysis of heart-rate and arterial-pressure variability at baseline (rest) and after sympathetic stress (tilt). The 117 subjects selected (56 men and 61 women, age range 23-87 years) were subdivided by questionnaire into three groups: 49 subjects (mean age 55.8+/-2.8 years) had no anxiety symptoms; 36 (mean age 56.8+/-3.6 years) had one anxiety symptom; and 32 (mean age 55.0+/-2.9 years) had two or more anxiety symptoms. Power spectral analysis recognizes three main components: high frequency (HF), chiefly reflecting vagal efferent activity; low frequency (LF), reflecting sympathetic activity; and very-low-frequency (VLF). The ratio of low- to high-frequency powers (LF:HF) of heart rate variability provides a measure of sympathovagal balance. Power spectral analysis showed that subjects with two or more anxiety symptoms had significantly lower resting values for all power spectral components of heart rate variability: total power (TP), VLF, LF, and HF than did symptomless controls (P<0.05). The highest anxiety-score groups also had a higher baseline LF:HF than the other two groups (P<0.05). Their resting LF:HF ratio correlated positively with anxiety symptom scores (r=0.72, P<0.0001). Tilt induced opposite results: the highest anxiety-score groups had a significantly lower LF:HF ratio; the ratio correlated inversely with their anxiety scores (r=-0.69; P<0.0001). Recordings of resting systolic arterial pressure variability showed that the group with two or more anxiety symptoms had significantly higher LF power (P<0.05) than symptomless controls. Our findings suggest that persons with high anxiety scores have baseline cardiac sympathetic hyperactivity. They also have low heart-rate variability, possibly explaining their susceptibility to sudden cardiac death.

AGING AND RED BLOOD CELL MEMBRANE : A STUDY OF CENTENARIANS

Successful aging, characterized by little or no loss in physiological functions, should be the usual aging process in centenarians. It is known that well-preserved physiological functions depend on the proper functioning of cell systems. In this article we focus on cell membrane integrity and study the red blood cell membrane to evaluate the effect of physiological aging in centenarians. Fifteen healthy, self-sufficient centenarians, mean age 103 years, were examined by assessing hemocytometric values and some relevant characteristics of the erythrocyte membrane, i.e., the cholesterol/phospholipid molar ratio, the distribution of phospholipid classes and their fatty acid composition, the integral and skeletal protein profiles. The centenarians showed a significant decrease in the red blood cell count (p < 0.0002), hemoglobin (p < 0.0002), and hematocrit (p < 0.0005). The red blood cell membrane showed a significantly increased cholesterol/phospholipid molar ratio (p < 0.01), with a concomitant increase in polyunsaturated fatty acids in phosphatidylcholine (p < 0.001) and, to a lesser extent, in phosphatidylethanolamine. The electrophoretic pattern of membrane proteins was qualitatively normal compared to controls but the densitometric analysis showed a significant increase in the integral protein band 4.2 (p < 0.05) and in the skeletal protein actin (p < 0.001). Extreme longevity seems to be associated with a substantial integrity of the erythrocyte membrane. Moreover, the evident increase in polyunsaturated fatty acids and in actin are likely to improve the membrane fluidity and to strengthen the membrane structure.

Nimodipine in the treatment of old age dementias

1. In a multicenter, placebo-controlled, double-blind clinical study in 178 elderly patients with cognitive decline, nimodipine, a calcium antagonist was found to be a therapeutically effective agent in the treatment of old age dementias. 2. Treatment with 90 mg of nimodipine administered orally in divided doses for 12 weeks was significantly superior to an inactive placebo on all outcome measures including the Wechsler Memory Scale, the Mini Mental State Examination, the Global Deterioration Scale, the Sandoz Clinical Assessment Geriatric Scale, the Plutchik Geriatric Rating Scale, the Severity of Illness and Global Improvement Scales of Clinical Global Impression, and the Hamilton Psychiatric Rating Scale for Depression. 3. Adverse effects with nimodipine were few and mild. The drug was equally well tolerated and equally effective in the two major dementias of old age, i.e., primary degenerative and multi-infarct. The number of abnormal laboratory test readings remained essentially unchanged from pre-treatment to post-treatment.

Age-adjusted normal confidence intervals for heart rate variability in healthy subjects during head-up tilt

PURPOSE Aging leads to a decline in autonomic nervous system function. In this study, designed to assess the influence of age on neuroautonomic regulation of cardiac activity, heart rate variability was measured by power spectral analysis and normal ranges were determined in a population of healthy subjects. PATIENTS AND METHODS In 83 healthy volunteers (42 men and 41 women; age range 25-85 years) autonomic nervous system function was assessed by autoregressive spectral analysis of heart rate variability in clinostatism and after passive orthostatic load (head-up tilt). The analysis considered two spectral components relevant to the study of the autonomic nervous system--high-frequency power (approximately 0.05 Hz) and low-frequency power (approximately 0.10 Hz)--and the ratio between them. Low-frequency spectral components, in particular the ratio between low- and high-frequency spectra, reflect sympathetic activity; high-frequency components reflect parasympathetic activity. RESULTS For data comparison, the study group was subdivided into three age groups: 25 subjects (12 men and 13 women) under 44 years of age; 28 (15 men and 13 women) aged 44-64 years; and 30 (15 men and 15 women) over 64 years of age. The natural logarithms and normalized units of low- and high-frequency power, and the low-to-high power ratio were used to calculate 95% confidence intervals. Power spectral analysis at baseline and after postural tilt showed significantly higher low-frequency power of heart rate variability (P < 0.05), natural logarithm of power (P < 0.001) and normalized units (P < 0.001) in the two younger groups than in the oldest group. The two younger age-groups also had significantly increased high-frequency power (P < 0.05) and natural logarithm of power (P < 0.05). The oldest age group had significantly increased high-frequency power analyzed in normalized units (P < 0.001). CONCLUSION The age-related lowering observed in nearly all the spectral frequency components of heart rate variability confirms in healthy subjects that autonomic nervous system function declines with age.

Exaggerated morning blood pressure surge and cardiovascular events. A 5-year longitudinal study in normotensive and well-controlled hypertensive elderly

Cardiovascular events (CE) occur most frequently in the morning hours in hypertensive subjects. We studied the association between the morning blood pressure (BP) surge and CE in prognosis of 10 normotensive and 32 well-controlled hypertensive elderly, in whom ambulatory BP monitoring was performed and who were followed prospectively for 5 years. The morning surge (MS) of BP was calculated as mean systolic BP during 2h after awakening--mean systolic BP during 1h that included the lowest sleep BP. During an average of 60 months, five CE occurred. When the patients were divided into two groups according to MS, those in the top terzile (MS group; MS> or =34 mmHg, n=14) had a higher prevalence of CE (5 versus 0, p=0.001) during the follow-up period, than the others (non-MS group; MS<34 mmHg, n=28). The logistic regression analysis showed the MS sleep-trough surge as predictive variable of CE (odds ratio, OR=0.794, p=0.022). In conclusion, in older normotensives and well-controlled hypertensives, a higher BP MS is associated with vascular risk independently of clinical and ambulatory BP. Reduction of the MS could thus be a therapeutic target for preventing vascular events also in non-hypertensive patients.

Heart Rate and Blood Pressure Variabilities in Salt-Sensitive Hypertension

In salt-sensitive hypertension, a high sodium intake causes plasma catecholamines to rise and pulmonary baroreceptor plasticity to fall. In salt-sensitive and salt-resistant hypertensive subjects during low and high sodium intakes, we studied autonomic nervous system activity by power spectral analysis of heart rate and arterial pressure variabilities and baroreceptor sensitivity. In all subjects, high sodium intake significantly enhanced the low-frequency power of heart rate and arterial pressures at rest and after sympathetic stress. It also increased heart rate and arterial pressure variabilities. During high sodium intake, salt-sensitive hypertensive subjects had significantly higher low-frequency powers of systolic arterial pressure (7.5 mm Hg2, P < .05) and of heart rate at rest (59.2 +/- 2.4 normalized units [NU], P < .001) than salt-resistant subjects (6.6 +/- 0.3 mm Hg2, 55.0 +/- 3.2 NU) and normotensive control subjects (5.1 +/- 0.5 mm Hg2, 41.6 +/- 2.9 NU). In salt-sensitive subjects, low sodium intake significantly reduced low-frequency normalized units (P < .001) and the ratio of low- to high-power frequency (P < .001). High-sodium intake significantly increased baroreflex sensitivity in control subjects (from 10.0 +/- 0.7 to 17.5 +/- 0.7 ms/mm Hg, P < .001) and salt-resistant subjects (from 6.9 +/- 0.7 to 13.9 +/- 0.9, P < .05) but not in salt-sensitive subjects (7.4 +/- 0.3 to 7.9 +/- 0.4). In conclusion, a high sodium intake markedly enhances cardiac sympathetic activity in salt-sensitive and salt-resistant hypertension. In contrast, although reduced sodium intake lowers arterial pressure and sympathetic activity, it does so only in salt-sensitive subjects. Hence, in salt-resistant subjects, neither arterial pressure nor sympathetic activity depends on salt intake. During a high sodium intake in normotensive subjects and salt-resistant hypertensive subjects, increased sympathetic activity is probably compensated by enhanced baroreflex sensitivity.

Idebenone in senile dementia of Alzheimer type: A multicentre study

Idebenone is a new cerebro-active drug, effective in dementia disorders, particularly indicated in primary degenerative dementias, i.e. Alzheimers disease. This new molecule acts as an electron trapper and a free radical scavenger protecting mitochondrial membranes from lipid peroxidation. A multicentric, double-blind trial of idebenone (45 mg twice daily orally) vs. placebo was carried out on 102 elderly patients affected by Alzheimer-type dementia of mild or moderate severity. Idebenone was administered for 4 consecutive months, 45 mg twice daily. Clinical evaluations were performed at the time of enrollment (t0) and monthly thereafter (t30, t60, t90 and t120) and at follow-up (t150 ). Tolerability to idebenone treatment was good and was associated with a statistically significant improvement of memory, attention and behaviour. It is worthwhile noting that these cognitive and behavioral findings were observed after the first month of treatment with enhancement evident in the following period.

Influence of Vitamin C on Baroreflex Sensitivity in Chronic Heart Failure

Abstract— Chronic heart failure (CHF) reduces baroreflex sensitivity. Low baroreflex sensitivity, a risk factor for sudden death, could arise partly from CHF‐dependent endothelial dysfunction. Vitamin C at high doses has a protective role against CHF‐related endothelial damage. This study was conducted to investigate the effect of vitamin C on baroreflex sensitivity in CHF. A study group of 33 subjects with CHF secondary to postischemic dilated cardiomyopathy with an ejection fraction <=35% and a control group (11 subjects) underwent assessment of baroreflex sensitivity by the phenylephrine method and an autonomic nervous system study by power spectral analysis. Variables were assessed after infusion of placebo and high doses of vitamin C (2.5 mg). In subjects with CHF, baroreflex sensitivity was significantly higher after vitamin C than after placebo infusion (placebo: 4.1±0.4 versus vitamin C: 5.3±0.5 ms/mm Hg, P <0.001). Low‐frequency of R‐R (LFRR), expressed in normalized units (NU) (P <0.05); LF/high‐frequency (HF) ratio (P <0.05), and LF of SBP (LFSBP) decreased significantly; HF power (P <0.05), and [alpha]‐HF (P <0.001) increased. Conversely, in the control group, baroreflex sensitivity and other spectral variables measured at baseline, after placebo, and after vitamin C infusion remained statistically unchanged (placebo: 10.2±0.1 versus vitamin C: 10.0±0.2 ms/mm Hg, NS). Acute administration of vitamin C at high doses improves baroreflex sensitivity and vagal sinus modulation in patients with CHF. This finding could have notable clinical and therapeutic implications. Key issues to understand are whether the beneficial effect persists during chronic administration and whether it helps to improve survival.

Effects of Long-Term Beta-Blocker (Metoprolol or Carvedilol) Therapy on QT Variability in Subjects With Chronic Heart Failure Secondary to Ischemic Cardiomyopathy

Chronic heart failure (CHF) is a risk factor for sudden death. Temporal and spatial changes in repolarization are among the most studied mechanisms for inducing fatal ventricular arrhythmias. Beta blockers effectively reduce the risk of sudden death in CHF. Our aim in this study was to investigate changes induced by metoprolol and carvedilol on the QT variability index (QTVI), a new measure reflecting the temporal heterogeneity of cardiac repolarization. A total of 82 subjects, who were in New York Heart Association functional class II or III, underwent short-term spectral analysis of RR and QT variability before and after a 1-year course of high-dose metoprolol (40 subjects) or carvedilol (42 subjects) at baseline (rest) and after sympathetic stress (head-up tilt). At rest, both drug-treated groups had lower QTVI (p <0.001) than after placebo, but during tilt patients treated with carvedilol had a lower QTVI than those treated with metoprolol (p <0.05). Although both beta-blocker treatments helped to normalize the QTVI measured in normal subjects at rest, they each differentially altered the index after tilt. Carvedilol seemed to improve the QTVI more than metoprolol.