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In this randomized double-blind, placebo controlled, multicentre study on 108 elderly patients with mild to moderate mental deterioration of vascular origin, idebenone - a benzoquinone derivative with a hydroxyalkyl side chain - proved to be therapeutically effective in the treatment of multi-infarct dementia. The oral administration of idebenone 45 mg/day b.i.d. for 120 days significantly improved the scores of the following test in comparison with placebo: Mini Mental State, Randt Memory Test, Gottfries Rating Scale, Token Test, Toulouse Piéron Test, indicating improvements in memory attention and cognitivity. The drug was well tolerated and effective in patients with multi-infarct dementia. No changes in laboratory parameters were observed either before or after treatment.

Autoantibodies against glial fibrillary acidic protein (GFAP) were investigated by ELISA test in sera of patients suffering from senile dementias and in healthy aging people. One hundred eight subjects divided into control, vascular dementia (VD), presenile Alzheimer's disease (AD), and senile Alzheimer's disease (SDAT) groups were included in the study. VD patients showed the highest antibody titers when compared to controls, whereas AD had the lowest titers when compared to the other groups. These results do not support the utility of anti-GFAP antibodies as useful markers of Alzheimer's disease, suggesting that their presence is a secondary phenomenon to blood-brain barrier disruption.

Platelet MAO-B activity, serum vitamin B12 levels, and plasma folate were measured in patients suffering from presenile (AD) and senile (SDAT) dementia of Alzheimer-type, and vascular dementia (VD). MAO-B was higher in the SDAT group than in AD and controls. An inverse relationship between MAO-B activity and vit. B12 levels was documented in the whole group and in each category studied; furthermore, MAO-B was positively related to age. All the patients were then divided into two groups, according to vit. B12 levels (Group I: less than 200 pg/mL; Group II: greater than or equal to 200 pg/mL); Group I showed a significantly higher MAO-B activity with respect to Group II. The results indicate the existence of a negative association between platelet MAO-B activity and serum levels of vitamin B12 and confirm the existence of biological differences between presenile and senile dementia of Alzheimer type.

Cerebrospinal Fluid (CSF) levels of the main metabolites of monoamines (MHPG, 5-HIAA, and HVA) were measured in patients with early onset (AD) and late-onset (SDAT) Alzheimer's disease, vascular dementia (VD), and elderly controls. Psychobehavioral assessment was carried out by means of MMSE and GBS. Mean MHPG levels did not differ from controls; 5-HIAA was lower in VD when compared to both controls and SDAT. HVA was decreased in AD, SDAT, and VD with respect to controls. Significant correlations between HVA and psycho-behavioral parameters were observed in SDAT and VD groups, whereas no relationship was documented in AD. The SDAT group was divided in SDAT-A (age at onset: greater than 65 less than or equal to 80 yr) and SDAT-B (age at onset: greater than 80 yr). SDAT-A had significantly lower CSF HVA values than SDAT-B (165 +/- 64 vs 235.7 +/- 85). SDAT-B HVA levels were similar to those observed in controls. Correlation analysis between HVA and neuropsychological variables was significant in SDAT-A, but not in SDAT-B. These results might support the evidence of SDAT heterogeneity.

Acetyl-L-carnitine (ALC), a physiological component of the L-carnitine family, has been proposed for treating Alzheimer's disease in pharmacological doses. As this condition requires prolonged therapy, its kinetics has been examined after a multiple dose regimen, involving different routes of administration, in 11 patients suffering from Senile Dementia of Alzheimer Type. The study design comprised a 3-day basal observation period, sham treatment with repeated blood sampling; treatment with 30 mg.kg-1 i.v. [corrected] for 10 days (plasma kinetics was studied on the 7th day), and 50 days of 1.5 g/day [corrected] p.o. given in three daily doses. Total acid soluble L-carnitine, L-carnitine and acetyl-L-carnitine in plasma and CSF were evaluated using an enantioselective radioenzyme assay. Short chain L-carnitine esters were calculated as the difference between total and free-L-carnitine. The plasma concentrations of individual components of the L-carnitine family did not change during the three days of the basal period, nor were they affected during the sham therapy period. Following the i.v. bolus injections, the plasma concentrations showed a biphasic curve, with average t1/2 of 0.073 h and 1.73 h, respectively. At the end of oral treatment, plasma acetyl-L-carnitine and L-carnitine short chain esters were significantly higher than during the run-in phase. The CSF concentrations paralleled those in plasma, suggesting that ALC easily crosses the blood-brain barrier. It is concluded that i.v. and oral administration of multiple doses of ALC can increase its plasma and CSF concentration in patients suffering from Alzheimer's disease.

One hundred and nine elderly patients suffering from mild to moderate cognitive impairment fulfilling NINCDS-ADRDA criteria for probable dementia of the Alzheimer type were treated for 6 months with a new nootropic drug, aniracetam (Ro 13-5057) in a double-blind randomized study versus placebo. The two treatment groups were comparable at baseline for demographic and behaviourial parameters and symptomatology. Patients underwent clinical, behaviourial and psychometric evaluation every other month. The aniracetam group differed significantly from the placebo group by the end of the study and also showed a statistically significant improvement versus baseline in the psychobehavioural parameters, while in the placebo group a steady deterioration was observed. Tolerability to aniracetam was excellent.

The presence of a dense appearance of the horizontal part of the middle cerebral artery (the "dense middle cerebral artery sign") was looked for on CT scans taken on admission in 90 consecutive patients with ischemic stroke in the carotid artery distribution. The outcome of the 14 patients with the sign was poorer than that of 76 patients without the sign (Odds ratio 4.3). We suggest that this sign could be a useful prognostic variable in the acute phase of an ischemic stroke.

This double-blind pilot study observed the effects of a twenty-one day oral ticlopidine treatment (250 mg/twice daily) on the neurologic outcome and the hemorheologic pattern of 15 patients and 15 placebo-treated controls. Patients and controls (age range sixty-six to eighty-six years) were included in the study within twelve hours of the onset of ischemic stroke, confirmed clinically and by computerized tomography. Scores on Hachinski's Scale and the following hemorheologic parameters were monitored weekly for twenty-one days: fibrinogen levels, the whole blood, unfractionated white and red blood cell filterability rates (through 5-micron-pore-diameter filters using a constant-flow positive-pressure system), and the leukocyte count and activation (by microscopic observation). The results showed treatment with ticlopidine improved the neurologic outcome (Hachinski's Score +36%, p less than 0.03) slightly but significantly (p less than 0.001) increased the average values of the whole blood (+19%) and red cell (+17%) filterability rates and decreased fibrinogen levels (-17%).

The purpose of the study was to determine whether oxiracetam crosses the human blood-brain barrier and to evaluate its comparative kinetics in serum and in cerebro-spinal fluid (CSF). Six DAT patients, undergoing CSF collection for diagnostic purposes, received 2 g oxiracetam daily, by a 60 min i.v. infusion, for 7 days. On the last day, in four patients blood samples were collected at time 0, 30, 60 and 120 min, and lumbar drainage was performed at the end of infusion: at this time mean CSF concentration was 3.5 micrograms/ml, i.e. 4.0% of the serum one, demonstrating that oxiracetam crosses the blood-brain barrier. In two patients, blood samples were collected at time 0, 60, 120 and 240 min, and lumbar drainage was performed 60 min after the end of infusion: at this time mean CSF concentration was 2.8 micrograms/ml, i.e. 5.3% of the serum one, indicating a persistence of oxiracetam within this deep compartment. These results provide the first evidence in humans that oxiracetam penetrates the central nervous system and contribute to the understanding of its long-lasting pharmacodynamic effect in man.

It has been hypothesized that acetyl-L-carnitine has a cholinomimetic action. It is for this reason that it has been used in the therapy of Alzheimer's type senile dementia impairment. In the present controlled double-blind study the authors followed two randomized homogeneous groups of both sexes of 30 patients each, aged over 65 years and suffering from mild mental impairment. One group of patients underwent therapy with acetyl-L-carnitine, 2 g/day for three months, while the other group was treated with a placebo. The statistical evaluation of the results was carried-out using non-parametric methods (Friedman-Nemenyi two-way ANOVA). It was possible to affirm that the acetyl-L-carnitine treated patients showed statistically significant improvement in the behavioural scales, in the memory tests, in the attention barrage test and in the Verbal Fluency test. These satisfactory results confirm the therapeutic importance of acetyl-L-carnitine in the treatment of elderly patients with mental impairment, which could be related principally to acetylcholine defects.

A 3-yr follow-up study on the trend of memory performance in 9 elderly subjects with selective memory defects, which was carried out in an attempt to clarify the evolution of the disorder, revealed marked worsening of sensory visual memory, retention capacity and recent memory. No other mental function was compromised. The results of this study suggest that the onset of a selective memory defect in the elderly is not necessarily the expression of a demential amnestic syndrome, but rather the manifestation of a senile brain deterioration limited to the anatomo-functional memory system.

This study was carried out to define the effects of both long-term hypertension and hypotension on the cerebral functioning of the elderly, comparing them to the effects of normotension. Ninety-eight subjects of both sexes, between 70 and 82 years of age, were divided into three groups on the basis of their mean blood pressure: 33 normotensives, 36 hypotensives and 29 hypertensives. They underwent a neuropsychological assessment, a haemorrheological evaluation and an EEG monitoring while awake. The results show that the three parameters were almost always within normal limits in the normotensives, while EEG alterations, lower neurophysiological scores and blood hyperviscosity were noted in both the hypertensives and hypotensives. Our results would seem to confirm that long-term hypertension may induce alterations in the cerebral electrogenesis and intellectual functions of the elderly and that also long-term hypotension might negatively interfere with some functional aspects of the aging brain.

A two-year follow-up on 118 atherosclerotic lesions of the extracranial carotid tract observed in 70 patients was carried out using real-time high-resolution echotomography. The following plaque characteristics were monitored: the echogenic patterns (soft, intermediate, hard, and mixed), the surface aspects, and the degree of stenosis. The aim of the study was to evaluate plaque evolution, in relation both to the degree of vessel stenosis produced and to the echostructural characteristics of the lesion. After two years 68% of the lesions remained unchanged while the degree of vessel stenosis increased in 32%; no case of regression was observed. Intrinsic factors appearing to condition an increase in degree of stenosis were "mixed" and "hard" echogenic pattern, an irregular lesion surface, and an initial degree of stenosis of more than 50%. A modification in the echogenic pattern, which generally tended to progress toward more highly reflecting echogenic levels was observed in 27% of the lesions studied.

Clinical and hemorheologic data were recorded in a homogeneous group of 72 patients (age range sixty-one to seventy years), suffering from ischemic stroke with an onset of less than eight hours, confirmed clinically and by computerized tomography. A quantitative neurologic analysis and the following hemorheologic parameters were monitored for twenty weeks following the acute episode: fibrinogen, total proteins, albumin, hematocrit, leukocyte and platelet counts, whole blood filterability (WBF), red blood cell deformability (RBCD), and blood plasma, and serum viscosity. The results show a significant decrease in hematocrit values parallel to the clinical neurologic improvement and a significant increase in RBCD in the patients with the better clinical recovery. These data confirm the role of hemorheologic parameters in the clinical follow-up of cerebrovascular disorders.

Plasma lipoprotein changes were evaluated in 65 type II patients undergoing sequential 4-week dietary treatments with: (I) standard low-lipid diet; (II) low-lipid diet with total replacement of animal proteins with textured soy proteins containing 6% of lecithin (L-TVP); (III) standard low-lipid diet; (IV) low-lipid diet with a 50% substitution of animal proteins with L-TVP. Total cholesterolemia was significantly reduced in both periods of L-TVP administration: -18.6% during phase II (total replacement) and -13.2% during phase IV (partial replacement). High-density lipoprotein (HDL) cholesterol levels tended to increase during L-TVP administration. However, only patients in the mid- and low tertiles for HDL cholesterolemia showed a significant increase of HDL levels during L-TVP. This 'normalizing' activity of L-TVP on plasma lipoproteins, even when administered as a partial dietary substituent, may be of clinical interest for subgroups of patients at high vascular risk.

Sixty elderly patients suffering from initial mental deterioration (less than 6 months) were divided at random into two groups, homogeneous for age, sex and life habits. For 28 weeks Group I was given a placebo and Group II was given 400 mg pentoxifylline ('Trental' 400) 3-times daily for two 3-month periods interrupted by a 4-week wash-out period. Neuropsychological performance and haemorheological parameters were evaluated at the beginning and at the end of each phase of the study. The results showed that pentoxifylline medication significantly improved the psycho-intellectual performance, decreased whole blood viscosity and increased red cell filterability. The results indicate a need to concentrate further study on haemorheological factors in the clinical aspects of the ageing brain, also with a view to allowing for sufficiently long treatment periods.

High-resolution real-time echotomography was used in a longitudinal study on 118 atherosclerotic plaques of the extracranial carotid tract with the aim of identifying those most likely to cause a cerebrovascular event. Seventy patients (average age 61 +/- 7 years), referred to our Clinical Vascular Laboratory because suffering from transient cerebral ischemic attacks (TIA), coronary heart disease (CHD, peripheral artery disease (PAD), or cervical bruits (CB), were followed up for two years. Medical treatment remained that of the referring physician. Ten patients suffered from clinical events caused by stroke, TIA, and/or carotid occlusion during the follow-up. The echostructural profile of the lesions most often correlated with the clinical event was characterized by a mixed or hard echogenic pattern, and irregular surface, and an initial vascular stenosis of more than 50%.

The animal proteins in a low-lipid, low-cholesterol diet were substituted with a textured soybean preparation for 127 outpatients with stable type II hyperlipoproteinaemia selected from eight Italian and one Swiss lipid clinics. Eight weeks of the modified diet reduced plasma cholesterol by 23.1% in the 67 participating male patients and by 25.3% in the 60 females. No significant changes in plasma triglycerides, high-density lipoprotein cholesterol, and body weight were recorded. Better reductions in plasma cholesterol occurred in non-familial cases and in very young male patients. The acceptable taste of the soybean preparation used in this study, and its easy handling, indicate that this type of dietary treatment may be suitable for outpatients.

A group of 80 elderly subjects affected with recent onset (less than 6 mth) slight to moderate mental deterioration was observed before and after oral drug treatment for a period of 28 wk. The study consisted of four randomized groups of subjects homogeneous for age, sex and life habits. The first group received a placebo, the second group received piracetam (1600 mg 3 times a day), the third group received pentoxifylline (400 mg 3 times a day), and the fourth group received a combination of piracetam and pentoxifylline. At the beginning and end of each phase of the study, neuropsychological and haemorheological parameters were evaluated in all subjects. The results show that the most evident improvement in psycho-intellectual performance, associated with an increase of whole blood filtration values, was obtained in the group treated with the two-drug combination.

Although it is universally accepted that the grade of reduction of district blood flow in PVD is directly correlated to alteration of the haemorheological pattern, there is still no uniformity of opinion regarding the existence of a specific rheological alteration in PVD. The scope of our study was to discover the existence of possible PVD-specific markers; we thus carried out a comparative evaluation of the rheological characteristics in blood of controls and patients affected with PVD. Eighty-nine males between the ages of 50 and 65 years (median 58 +/- 1 SE) were studied, all with a stage II vascular pathology with clinical onset of less than three months. Exclusion criteria were: diabetes mellitus, hyperlipaemia, stable hypertension, presence of vascular disease in other districts, cardio-circulatory problems and serious medical or surgical pathologies, previous vascular surgery, a history of acute thrombo-embolic episodes, and chronic alcoholism. Each patient, after a drug wash-out of 20 days, was monitored for haemorheological parameters. At the same time, the above parameters were measured in a group of 50 male controls of the same age range. All 139 subjects were smokers (10-15 cigarettes average per day). Our results indicate that modification in the bio-humoral (fibrinogen and plasma globulins) parameters, a reduced red blood cell filterability and a relative increase in the number of activated polymorphonucleate cells are probably specific haemorheological markers of the clinical onset of PVD.