Hallucinations and sleep-wake cycle in Alzheimer's disease: a questionnaire-based study in 218 patients.

The aim was to evaluate the relationship between hallucinations and the sleep-wake cycle in a sample of Alzheimer's disease (AD) patients in the early-moderate stage. Two hundred and eighteen AD patients (66 males, 152 females, mean age 74.3+/-6.85) were administered a sleep questionnaire in the presence of a care-giver. Twenty-six out of 218 (12%) reported the occurrence of hallucinations, mainly visual. In 18/28 (69%) hallucinations occurred when the patient was awake and in 8 (31%) hallucinations were reported to occur close to a specific phase of the sleep-wake cycle. Vivid dreams were reported in 25/218 (11%) and violent sleep-related and dream-related behaviours (probable REM behaviour episodes) in 22/218 (10%). Both REM phenomena were more frequent in AD hallucinators than in AD non-hallucinators (26.9% vs. 9.3%, and 26.9% vs. 7.8%, p<0.007). Our data indicate a lower incidence of hallucinations and presumable REM behaviour disorder (RBD) in AD, at least in the early-moderate phase, than that observed in synucleinopathies. However, the higher occurrence of vivid dreams and RBD in AD patients with hallucinations compared to those without hallucinations indicates a potential role of disordered REM sleep in influencing the occurrence of hallucinations in AD, similar to what has been observed in synucleinopathies.

Cognitive disturbances in non-demented subjects: heterogeneity of neuropsychological pictures.

The aim of this study was to individuate different clinical and cognitive pictures among non-demented subjects reporting cognitive disturbances. We evaluated 75 subjects referring to Alzheimer's Disease Assessment Unit of IRCCS C. Mondino, Pavia, who complained memory disturbances in absence of impairment in every day activities, not fitting DSM-IV criteria for dementia (MMSE>24). The subjects underwent neurological examination, blood chemistry and neuroimaging. The neuropsychological evaluation included tests exploring language, short- and long-term memories, logical abilities, attentive and visuo-constructional functions. Fifty-two patients fitted the criteria for mild cognitive impairment (MCI); twenty-three subjects had a neuropsychological evaluation within normal range for age and schooling; they were significantly younger and better educated and presented higher scores at scale for depression and anxiety than the MCI patients. In the MCI group, on the basis of cognitive profile and neuroimaging, different subtypes could be distinguished. Subjective cognitive complaints represent a heterogeneous condition, which can develop into different clinical pictures. It is, therefore, important to individuate specific clinic and neuropsychological profiles, possible predictive of different evolution.

Influence of losartan and atenolol on memory function in very elderly hypertensive patients.

The aim of this study was to compare the effect of the beta-adrenergic blocker atenolol and the Angiotensin II type 1 (AT1) receptor antagonist losartan on cognitive function in very elderly hypertensive patients. A total of 120 mild to moderate essential hypertensive (DBP >90 and <105 mmHg) patients, aged 75-89 years, were studied. After a 4-week wash-out period on placebo, they were randomized to receive atenolol 50 mg or losartan 50 mg for 24 weeks according to a parallel arm design. At the end of the placebo period and of each active treatment period, BP was measured (by mercury sphygmomanometer, Korotkoff I and V) and cognitive function was evaluated through three different tests (word list memory, word list recall and word list fluency). Both atenolol and losartan were equally effective in reducing SBP (-22.1 and -23.1 mmHg, respectively, P< 0.01 vs baseline) and DBP (-10.3 and -11.2 mmHg, respectively, P< 0.01 vs baseline). Atenolol treatment did not induce significant changes in any test score, whereas losartan significantly increased the score of both the word list memory (+2.2, P<0.05 vs baseline) and the word list recall test (+2.1, P<0.05 vs baseline). The comparison between losartan and atenolol was significant (P<0.05) for both memory tests. These data suggest that in very elderly hypertensive patients, chronic AT1 receptor blockade by losartan could improve cognitive function, in particular immediate and delayed memory.

Comparative effects of ramipril and nitrendipine on albuminuria in hypertensive patients with non-insulin-dependent diabetes mellitus and impaired renal function.

The purpose of this study was to compare the effects of ramipril and nitrendipine on urinary albumin excretion (UAE) in hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM) and impaired renal function. Forty patients with mild hypertension with NIDDM and persistent albuminuria (> 300 mg/24h) were studied. After a 3-week run-in period on placebo, patients were randomly treated with ramipril 5 mg once daily or nitrendipine 20 mg once daily for 6 months, according to a double-blind design. Blood pressure (BP), UAE, creatinine clearance and glycosilated haemoglobin were evaluated at the end of the placebo period and after 1,3 and 6 months of active treatment. Both ramipril and nitrendipine significantly lowered BP values without affecting glucose homeostasis and renal function. Despite equivalent BP control, only ramipril afforded a significant reduction in UAE, thus suggesting that the antiproteinuric effect of ramipril is at least partially independent of its anti-hypertensive effect.

[Efficacy and tolerability of nicardipine retard and captopril in hypertension in the aged. Results of a multicenter study]. / Efficacia e tollerabilità della nicardipina retard e del captopril nell'ipertensione dell'anziano. Risultati di uno studio multicentrico.

The efficacy and tolerability of nicardipine retard and captopril were assessed in 174 over-60-year-olds suffering from slight or moderate essential hypertension. After 2-3 weeks of wash out the patients were randomly assigned to calcium antagonist (40 mg twice a day) or ace-inhibitor (25 mg twice a day) treatment which continued for 180 days. Monotherapy was combined with hydrochlorothiazide (12.5 mg/day) after 2 months in the event of an unsatisfactory reduction of arterial pressure in relation to basal values. Systolic and diastolic blood pressure was measured (1st and 5th Korotkoff's tone) at monthly intervals while lying and standing; heart rate was also measured using a palpatory method. Both nicardipine retard (no. 86) and captopril (no. 88) caused a significant reduction of clino- and orthostatic systolic and diastolic arterial pressure during the first two months of treatment. Respectively 70% and 51% of patients responded to treatment and the blood pressure reductions achieved using monotherapy remained unchanged during the course of the study. The association of hydrochlorothiazide resulted in a significant decrease in arterial pressure in non-responders, an effect which was observed with both nicardipine retard and captopril. No significant variation in heart rate was recorded between the two groups. Twenty-one patients in the nicardipine retard group and 16 in the captopril group suffered from slight to moderate side effects. Six patients dropped out of the nicardipine retard group and 15 patients out of the captopril group, an event for which side-effects were responsible in 1 and 3 cases respectively. In conclusion, nicardipine retard and captopril represent an efficacious form of treatment for geriatric hypertension and possess a satisfactory level of tolerability.

Comparison of bisoprolol and diazepam in the treatment of cardiac neurosis.

In order to compare the beta blockers bisoprolol and diazepam in the treatment of cardiac neurosis, 40 patients (16 males and 24 females, mean age: 39 +/- 11 years) were examined in a double-blind, crossover study. Following a 4-week placebo period, patients were randomized to receive either bisoprolol 10 mg daily or diazepam 5 mg twice daily for 4 weeks. After a second 4-week washout period on placebo, patients were switched to the alternative regimen for a further 4 weeks. At the end of the placebo periods and during each phase of treatment, the following parameters were evaluated: somatic symptoms by self-assessment questionnaire, anxiety state by Hamilton rating scale, reaction time to both acoustic and visual stimuli, blood pressure, and heart rate. Both treatments were effective in reducing somatic symptoms of cardiac neurosis, but bisoprolol was significantly more effective than diazepam (p less than 0.01). On the contrary, diazepam was superior to bisoprolol in improving the Hamilton scale related to psychic symptoms. Only diazepam prolonged reaction times. Both treatments were well tolerated; however, 12 patients complained of drowsiness and nine of sedation under diazepam. In conclusion, bisoprolol appeared to be as effective as diazepam in the treatment of cardiac neurosis, but with better effects on somatic symptoms and without affecting patients' psychomotor performance.

Treatment of hypertension in the elderly: effects on blood pressure, heart rate, and physical fitness.

The subjects were 36 hypertensive patients aged 61 to 79 years (mean, 66 years). After a placebo run-in period of one month, each patient was randomly assigned to two months of treatment with 100 mg of metoprolol, 50 mg of captopril, or 25 mg of hydrochlorothiazide plus 2.5 mg of amiloride daily, or placebo. The doses were doubled if diastolic pressure was above 95 mm Hg after one month of treatment. Blood pressure, heart rate, and physical fitness (endurance during a standard cycle ergometer exercise) were measured and side effects assessed after each two-month treatment period. Mean blood pressures were significantly lower after treatment with metoprolol (154/92 mm Hg), captopril (157/92 mm Hg), and hydrochlorothiazide-amiloride (152/91 mm Hg) than after placebo (170/101 mm Hg). Heart rate was significantly lower after treatment with metoprolol (64 beats/minute) than after placebo (77 beats/minute). Exercise endurance was lower after treatment with metoprolol (498 seconds) and hydrochlorothiazide-amiloride (519 seconds) than after placebo (529 seconds) and higher after captopril (541 seconds). More patients reached the target exercise work load after captopril than after the other treatments. No patients withdrew from treatment because of side effects or abnormal laboratory test results. All three active treatments benefited the elderly hypertensive patients and did not lower their physical fitness. Captopril appeared to be more effective than the other two treatments.

The effect of celiprolol on the blood lipid profile in hypertensive patients with high cholesterol levels.

The aim of this study was to compare the effects of chronic antihypertensive therapy with either celiprolol or atenolol on plasma lipids in patients with hypercholesterolemia. Forty-six patients with essential hypertension and a total cholesterol (TC) concentration greater than 220 mg/dl were studied. After 1 month on placebo, patients were stratified into five classes on the basis of their plasma TC levels and then randomized to receive atenolol 100 mg/day or celiprolol 400 mg/day for 1 year. Blood pressure (BP), heart rate (HR), and blood samples for evaluation of TC, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglycerides (TG) were taken before and after the placebo period, and every 6 months from the beginning of the active treatment. Celiprolol and atenolol caused similar reduction in BP. Both atenolol and celiprolol decreased TC. Atenolol significantly reduced HDL-C, while celiprolol increased it (p less than 0.01 at 12 months), and the difference between the two drugs was statistically significant in this regard. LDL-C levels were not significantly affected by atenolol, but were progressively reduced by celiprolol (p less than 0.05 at 6 months, p less than 0.01 at 12 months). TG rose under atenolol but was reduced by celiprolol (p less than 0.05). The results of this study show that the celiprolol-induced changes in plasma lipids may be favorable and suggest that, in hypertensive patients with high cholesterol levels, beta-blocker therapy with celiprolol may be effective in lowering BP without worsening the lipid profile.

Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. The Studio della Ticlopidina nell'Angina Instabile Group.

We conducted a controlled multicenter trial with central randomization and evaluation of events under blind conditions involving 652 patients with unstable angina. Patients were treated either with conventional therapy alone (group C) (n = 338) or with conventional therapy combined with an inhibitor of platelet aggregation, ticlopidine 250 mg b.i.d. (group C + T) (n = 314). Patients were assigned randomly within 48 hours of admission and followed up for 6 months. With the "intention-to-treat" approach, the primary end points, vascular death and nonfatal myocardial infarction, were observed in 13.6% of the patients in group C and in 7.3% of the patients in group C + T, which is a reduction in risk of 46.3% (p = 0.009). Vascular mortality was 4.7% in patients in group C and 2.5% in patients in group C + T, which is a reduction in risk of 46.8% (p = 0.139). The risk of nonfatal myocardial infarction was reduced by 46.1% (p = 0.039), with a frequency of 8.9% in patients in group C and 4.8% in patients in group C + T. New Q wave myocardial infarction occurred with a frequency of 6.8% in patients in group C and 3.8% in patients in group C + T, which is a reduction in risk of 44.1% (p = 0.091). Fatal and nonfatal myocardial infarction was 10.9% in patients in group C and 5.1% in patients in group C + T, which is a reduction in risk of 53.2% (p = 0.006). These findings confirm the importance of platelets in the pathogenesis of unstable angina and the usefulness of antiplatelet treatment for the prevention of cardiovascular events.

Ketanserin in chronic treatment of hypertension in type 2 diabetes mellitus.

This study was performed in order to evaluate the effects of ketanserin monotherapy on blood pressure and glucose metabolism in essential hypertensives with type 2 diabetes. Twenty-nine patients, 17 males and 12 females, aged 45 to 78 years, with mild hypertension (DBP greater than or equal to 95 and less than or equal to 105 mmHg) and type 2 diabetes were studied. After a 4 week run-in period on placebo, each patient received ketanserin 20 mg b.i.d. for 6 months, with no modification in previous antidiabetic therapy. SBP, DBP, HR, fasting and post-prandial glycemia were monitored monthly. An oral glucose tolerance test (OGTT), glycosilated hemoglobin (HbA1c), urinary C-peptide, serum electrolytes, creatinine, uric acid, total cholesterol and 24 h protein and glucose urinary excretion were evaluated before and after 3 and 6 months of treatment. Ketanserin significantly reduced both SBP and DBP (p less than 0.005) with no changes in HR. No significant modifications of fasting and post-prandial glycemia, HbA1c and C-peptide were observed. Besides, ketanserin did not affect glucose tolerance, the levels of glucose during the OGTT were not significantly different before and after treatment. None of the patients required any change in antidiabetic therapy. In conclusion, ketanserin was effective in the treatment of mild hypertension in patients with type 2 diabetes. The absence of effects on glucose metabolism makes it an especially interesting drug in such patients.

Beta-blocker effects on plasma lipids in antihypertensive therapy: importance of the duration of treatment and the lipid status before treatment.

The aim of this study was to evaluate the effects of long-term monotherapy with four beta-blockers provided with different pharmacological properties on plasma lipids in both normocholesterolemic and hypercholesterolemic hypertensive patients. After a 1-month run-in period on placebo, 70 hypertensive patients with basal total cholesterol (TC) < or = 220 mg/dl were treated for 3 years with propranolol 160 mg/day or atenolol 100 mg/day or bisoprolol 10 mg/day or mepindolol 10 mg/day, while 59 hypertensive patients with basal TC > 220 mg/dl were given the same beta-blockers at the same dosage for 6 months. In both normocholesterolemic and hypercholesterolemic hypertensive patients. HDL-C and triglyceride (TG) levels showed significant changes that appeared to be related to the type of beta-blocker used and to the duration of therapy. Nonselective, non-ISA (intrinsic sympathomimetic activity) propranolol caused the most pronounced changes, decreasing HDL-C and increasing TG concentrations; beta1-selective atenolol and bisoprolol had similar, but less remarkable effects; even more discrete changes were observed on mepindolol (with ISA). The variations in HDL-C and TG values reached their peak in 6-12 months of beta-blocker therapy; then, after a plateau phase, they showed a progressive trend toward pretreatment levels. In hypercholesterolemic patients, the percent change in both HDL-C and TG values was lower compared to normocholesterolemic patients.

Antihypertensive efficacy and influence on physical activity of three different treatments in elderly hypertensive patients.

The antihypertensive efficacy and subjective and physical tolerability of three different pharmacological treatments (metoprolol, captopril and the combination of hydrochlorothiazide + amiloride) were compared with placebo in 36 elderly hypertensives (aged 61-79 years), according to a Latin-square double-blind design. The placebo and the active treatments were administered for 2 months. Seated blood pressure was significantly reduced by all the pharmacological treatments compared with placebo, but only metoprolol significantly reduced the heart rate. No haematological or biochemical changes were observed during the study. Physical fitness, evaluated as endurance in a standard cycle ergometer exercise test, was slightly decreased after the treatment with metoprolol and the diuretic combination and slightly improved after treatment with captopril. Subjective tolerability, evaluated by a check-list of symptoms, was better during the active therapies, and in particular during the captopril treatment, than during the placebo treatment. Our results indicate that all three active treatment regimens significantly reduce blood pressure in elderly hypertensives and that captopril appears slightly better tolerated physically and subjectively.

[Effects of fructose-1,6-diphosphate in patients with chronic ischemic heart disease. Echocardiographic study]. / Impiego del fruttosio-1,6-difosfato in pazienti con cardiopatia ischemica cronica. Studio ecocardiografico.

The effects of fructose-1,6-diphosphate (FDP) on cardiac activity were studied in 20 patients with chronic ischemic heart disease. Each patient received intravenously, in two different days, a single dose of FDP 20 g and placebo, according to a cross-over study design. Immediately prior to and ten minutes following each dosing, patients underwent an echocardiographic assessment. The comparison of pre- and post-treatment readings indicates that the diasto-systolic difference of left ventricular dimension increased by 10% after FDP (p less than 0.01). Similarly the increment of interventricular septum thickness increased by 16% (p less than 0.01) and that of posterior left ventricular wall thickness by 19% (p less than 0.01). In contrast the changes recorded after placebo treatment were far from being significant. These data indicate that the acute administration of a single dose of FDP may improve the cardiac performance in patients with chronic ischemic heart disease.

Plasma lipids during chronic antihypertensive therapy with different beta-blockers.

The aim of this study was to compare the effects of long-term monotherapy with five different beta-blockers on plasma lipids in patients with essential hypertension. We studied 99 male patients, aged 35-55 years, with mild to moderate hypertension, who worked in the same community. After a 1-month placebo period, patients were assigned to receive propranolol (160 mg/day), atenolol (100 mg/day), bisoprolol (10 mg/day), mepindolol (10 mg/day), or celiprolol (400 mg/day). Therapy was continued for 2 years. Blood pressure (BP), heart rate, and blood samples for evaluation of total cholesterol (TC), LDL-cholesterol (LDL-C), triglycerides (TG) and HDL-cholesterol (HDL-C) were taken before and after the initial placebo period, and subsequently every 6 months from the beginning of active treatment. All beta-blockers caused similar reductions in BP that were maintained throughout the study. None of the beta-blockers significantly affected TC or LDL-C. Propranolol, a nonselective beta-blocker, caused the most pronounced changes in TG (+33 to 43%) and in HDL-C (-30 to -32%). Atenolol, a beta 1-selective agent, had the same quantitative effects, but to a lesser extent (TG + 23 to 30%; HDL-C -15 to -19%). Bisoprolol, more beta 1-selective than atenolol, and mepindolol, nonselective with ISA, increased TG (+20 to 28% and +14 to 25%, respectively) but did not significantly affect HDL-C. In contrast, celiprolol, a highly cardioselective beta-blocker with beta 2-partial agonism, improved lipid risk factors by significantly reducing TG (-14 to -21%) and increasing HDL-C (+8 to 14%).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of different beta-blockers on lipid metabolism in chronic therapy of hypertension.

The aim of this study was to evaluate the possible time-related effects of long-term monotherapy with different beta-blockers on plasma lipids in patients with essential hypertension. We studied 69 mild-moderate hypertensives, all males, aged 35-56 years belonging to the same working community. After 1-month placebo period, patients were assigned to receive propranolol 160 mg/day or atenolol 100 mg/day or bisoprolol 10 mg/day or mepindolol 10 mg/day. They were followed-up for 2 years. Blood pressure (BP), heart rate and blood samples for evaluation of total cholesterol (TC), LDL-cholesterol (LDL-C), triglycerides (TG) and HDL-cholesterol (HDL-C) were taken before and after placebo period and every 6 months from the beginning of the active treatment. All beta-blockers caused similar reduction in BP values which persisted throughout the study. None of the beta-blockers significantly affected TC and LDL-C. Propranolol caused the most pronounced changes in TG (+35-43%) and in HDL-C (-36-44%). Atenolol had the same qualitative effects but to a lesser extent (TG: +26-30%; HDL: -15-25%). Bisoprolol has more beta 1-selective than atenolol, and mepindolol, non-selective with ISA, increased TG (+15-28% and +13-23%) but did not significantly affect HDL-C. Consequently, HDL-C and TG changes appeared to be related to the ancillary properties of the different beta-blockers and, in a lesser degree, to the duration of therapy.

Effect of beta-blockers on plasma lipids.

Forty-five hypertensive patients (I-II WHO), after two weeks wash out, were randomly allocated to receive 100 mg/day atenolol, 200 mg/day metoprolol and 10 mg/day mepindolol for three months, in order to evaluate their possible effect on lipid metabolism. Plasma triglyceride levels were increased by the three drug treatments; the increase was, however, greater after mepindolol. Total cholesterol was unchanged by atenolol, increased by metoprolol and decreased by mepindolol. HDL-cholesterol was unchanged by atenolol, decreased by metoprolol and increased by mepindolol, whereas LDL-cholesterol was increased by atenolol, unchanged by metoprolol and decreased by mepindolol. Therefore, the LDL/HDL ratio was decreased by mepindolol (from 3.15 +/- 1.71 to 2.92 +/- 1.17) and increased by atenolol and metoprolol. The results show that the treatment with atenolol, metoprolol and mepindolol does not significantly affect the lipid levels suggesting that cardioselective beta-blockers as well as those with ISA have no untoward effect on lipid metabolism.

Low-dose atenolol-chlorthalidone combination for treatment of mild hypertension.

In a randomized, double-blind, within-patient study, 28 out-patients with mild to moderate hypertension were given, at the end of a 3-week placebo wash-out period, four different antihypertensive treatments for 3 weeks each. the treatments were 50 mg atenolol, 100 mg atenolol, 12.5 mg chlorthalidone and a fixed combination of 50 mg atenolol and 12.5 mg chlorthalidone. All treatments were given once daily. Visits were scheduled for the last day of each treatment period, 24-26 hours after the last dose, and there was an intermediary wash-out period between each pair of active treatments. Supine systolic/diastolic blood pressure was 165/102 on placebo, 153/93 mmHg on 50 mg atenolol, 155/91 mmHg on 100 mg atenolol, 148/93 mmHg on 12.5 mg chlorthalidone and 144/89 mmHg on the combination. All the changes in pressure were significant (p less than 0.01) versus placebo. Supine systolic blood pressure was lower on the combination than on 100 mg atenolol alone (p less than 0.05) and upright systolic pressure was lower on the combination than on 100 mg atenolol (p less than 0.05) or 50 mg atenolol (p less than 0.05) alone. The heart rate was lowered by atenolol alone or combined with chlorthalidone but did not fall below 56 bpm in any patient. Serum potassium levels were lower on 12.5 mg chlorthalidone than on placebo (3.88 mEq/l vs 4.09 mEq/l--p less than 0.05) but the difference was trivial; on the combination of atenolol-chlorthalidone there was no significant difference versus placebo (3.97 mEq/l vs 4.09 mEq/l--NS).(ABSTRACT TRUNCATED AT 250 WORDS)