Delusion symptoms are associated with ApoE epsilon4 allelic variant at the early stage of Alzheimer's disease with late onset.

Alzheimer's disease (AD) is a neurodegenerative disorder with mixed cognitive and behavioural clinical manifestations. The possession of apolipoprotein-E (ApoE) epsilon4 allelic variant is one of the most important risk factors for developing late-onset AD (LOAD). In this study we analysed the relationship between the entire range of behavioural symptoms, cognitive deficit, and sociodemographic characteristics and ApoE epsilon4 allele possession with multivariate logistic regression models in LOAD patients. Patients included (n = 171) were consecutively admitted in a memory clinic for the first diagnostic visit. Levels of behaviour and cognition within the last month were assessed by the Neuropsychiatric Inventory and Mini Mental State Examination. Presence of clinically significant psychosis, delusions and hallucinations at the early stage of the illness, from the onset to the first visit, was measured with diagnostic criteria. ApoE epsilon4 allele possession was associated with increased levels of delusions within the last month from the first visit (OR 1.23; 95% CI 1.01-1.50; P < 0.05) and with the presence of categorical delusions at the early stage until the first visit (OR 3.11; 95% CI 1.21-8.01; P < 0.02). In this study, which considers the entire range of behavioural expressions in LOAD patients at the early stage of the illness, the relationship between behaviour and ApoE epsilon4 allele is confirmed for delusions only.

Effects of switching from an AChE inhibitor to a dual AChE-BuChE inhibitor in patients with Alzheimer's disease.

OBJECTIVE: Cholinesterase (ChE) inhibitors are the only medications approved for the treatment of Alzheimer's disease (AD). The features of ChE inhibitors differ considerably. In addition to acetylcholinesterase (AChE) inhibition, rivastigmine also inhibits butrylcholinesterase (BuChE), providing dual AChE and BuChE inhibition. An observational study was performed to determine the response in routine clinical practice to switching AD patients to rivastigmine from a selective AChE inhibitor when that treatment no longer delivered a satisfactory clinical response. RESEARCH DESIGN AND METHODS: A prospective, multicentre, 3-month observational trial in patients with mild to moderately severe AD (adjusted Mini Mental State Examination [MMSE] score 10-26) deteriorating (at least 2 adjusted MMSE points in last 6 months) on selective AChE inhibitor treatment. Adjusted MMSE, activities of daily living (ADL) and instrumental activities of daily living (IADL), the Zarit caregiver burden and global function (short Clinical Global Impression of Change, CGIC) scores were noted before the switch and 3 months after the switch. RESULTS: 225 patients entered the study. The switches made were from donepezil to rivastigmine in (D-R) in 188 patients, galantamine to rivastigmine (G-R) in 33 patients and donepezil to galantamine (D-G) in four patients. Ten patients discontinued due to adverse events and eight for other reasons. More than half of the switches were within 36 hours of a patient's first treatment visit. In the D-R and G-R groups, 67.7% and 66.7% of patients responded (CGIC score < or = 4), respectively. In non-responders, worsening (CGIC score 5-7) was mild in approximately 80% or more of patients. Adjusted MMSE improved after the switch from both donepezil and galantamine to rivastigmine (+0.69 +/- 3.2, p = 0.008 and +0.6 +/- 1.6, p = 0.05, respectively). Mean ADL, IADL, and Zarit scores remained stable. The proportion of patients on concomitant antipsychotic therapy diminished by 30.5% and benzodiazepines were discontinued in all patients, except one. CONCLUSIONS: AD patients deteriorating on selective AChE inhibitor treatment can benefit from switching to a dual AChE-BuChE inhibitor, such as rivastigmine, in terms of stabilization of disease, improvement in cognitive function and reduction in the burden of concomitant psychoactive treatment. The switch was well tolerated. Confirmation of these results is required in a controlled study.

Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally.

We measured, by RIA methods, ictal and interictal levels of substance P (SP), calcitonin-gene related peptide (CGRP) and neurokinin A (NKA) in the plasma of 30 young migraine patients with aura (MPA) and 45 migraine patients without aura (MWA), and compared the results with those of 30 age-matched controls. There were no significant differences between the levels of these vasoactive peptides in the control group and the levels in both migraine groups studied in headache-free periods. An elevation of CGRP levels in plasma was found during attacks in MPA and, to a lesser extent, in MWA (p < 0.03 and p < 0.05, respectively). A significant increase in NKA levels was also demonstrated in the MPA and MWA groups (p < 0.02 and p < 0.04, respectively). These data suggest, although indirectly, that CGRP and NKA could be involved in the pathogenesis of migraine attacks in juvenile migraine patients.

Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids.

To demonstrate the influence of n-3 PUFA supplementation on cytokine and eicosanoid production in peripheral blood mononuclear cells (PBMCs) of MS patients (MSP), we investigated the impact of a 6-month dietary supplementation with these fatty acids on the levels of interleukin-1 beta (IL-1 beta), IL-2, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the supernatants of stimulated PBMCs and serum soluble IL-2 receptors in a group of 20 relapsing-remitting (R-R) MSP and a group of 15 age-matched control individuals (CI). The production of PGE2 and LTB4 in the stimulated PBMCs was also assessed in patient and control groups supplemented with n-3 PUFAs. In both groups, n-3 PUFA supplementation led to a significant decrease in the levels of IL-1 beta and TNF-alpha, and this reduction was more pronounced in the 3rd and 6th month of supplementation. An analogous decrease was observed in the levels of IL-2 and IFN-gamma produced by stimulated PBMCs, and in the levels of serum soluble IL-2 receptors. n-3 PUFA supplementation also appeared to significantly affect prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production in PBMCs, both in MSP and the control group. The reduced production of these proinflammatory eicosanoids, and the decrease of some cytokines with an immunohenancing effect as a consequence of n-3 PUFA supplementation, could modulate some immune functions which have been demonstrated to be altered in MSP.

Neuropeptide Y plasma levels and serum dopamine-beta-hydroxylase activity in MS patients with and without abnormal cardiovascular reflexes.

An impairment in the autonomic function has been demonstrated in patients with multiple sclerosis (MS) using electrophysiological, pupillary and biochemical tests. Particularly evident were alterations in the cardiovascular reflexes, cutaneous sympathetic response and lymphomonocyte adrenergic binding. Electrophysiological and biochemical findings in MS patients have only occasionally been compared. Among the peripheral markers of the autonomic system, Neuropeptide Y (NPY) and dopamine-beta-hydroxylase (DBH) have been singled out as reliable indices of sympathetic function. The former is a peptide with a strong vasoconstrictive action, which is released from adrenergic endings together with noradrenaline following sympathetic activation. The latter is the enzyme which catalyses the conversion of dopamine to norepinephrine. It is located both in sympathetic endings and the chromaffin granules of adrenal medulla. To verify a failure in autonomic function in the course of MS, a battery of cardiovascular tests (assessing sympathetic and parasympathetic functions) was performed on 25 MS patients. The results were compared with a group of 20 age- and sex-matched control individuals. The plasma levels of NPY and the serum DBH activity were also determined in both groups. 52% of patients showed an impairment in sympathetic function in one or more tests (sustained handgrip, postural hypotension, cold face test). 48% of the patients had abnormal values in deep breathing test, indicating a failure of the parasympathetic function. 44% of patients showed also a paroxysmal tachycardia after cold face test, indicating an abnormal function of the vagal-cardiac and sympathetic-vascular smooth muscle pathways of the trigeminal nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropeptide Y in juvenile migraine and tension-type headache.

Neuropeptide Y (NPY) is widely distributed throughout sympathetic nerve endings where it is co-stored and co-secreted with noradrenaline. It is considered a marker of noradrenergic function. To determine the role of NPY in the pathogenesis of juvenile headache, we determined its plasma levels in two groups of young migraine patients (with and without aura), in a group of episodic tension-type headache patients and in a group of age and sex-matched healthy subjects. Significantly lower plasma levels of NPY were evident in the migraine patients with aura (P < 0.001) and, to a lesser extent, in the migraine patients without aura (P < 0.02), both assessed in the interictal period, with respect to the control group. Plasma NPY levels tended to significantly increase during attacks in migraine patients with aura (P < 0.0009). A less evident, though significant increase was also present during attacks in migraine patients without aura (P < 0.02). No significant variations were observed between headache-free periods and attacks in tension-type headache patients. Reduced NPY levels in the interictal period can be considered further evidence of the derangement of the sympathetic function in the course of migraine, particularly that with aura. The increase in NPY levels during migraine attacks could be an expression of sympathetic activation, even though the functional status of this system is less efficient.

A dedicated MRI apparatus for medical and industrial applications.

So far, one of the major obstacles to the development of special purpose MRI imaging apparatus has been the lack of a magnetic technology that could cater to the need for a light, compact and efficient magnet, capable of providing the required field uniformity at a reasonable cost. Today, recent advances in magnet design permit attaining, with the use solely of ferrite, low-cost, small-scale scanners, which can open up new areas of application of MRI, in both medical and industrial fields. A novel apparatus (ARTOSCAN) is described and some examples of applications in different fields are shown. The apparatus has been designed specifically for the imaging of extremities, but possible applications on the industrial side are numerous and not yet all identified. Such a device could be used, for example, in the agricultural, food, and oil industries, where some of the needs for nondestructive quality-control devices could be fulfilled. Some tests have been performed that demonstrate the potential of the apparatus in the study of rock properties, of the drying process of pasta and wood, and to display flaws that could be present in ceramic materials before firing.

Endothelin 1 in migraine and tension-type headache.

We determined the plasma levels of ET1, both interictally and ictally, in 50 migraine patients, 20 with aura (MPA) and 30 without aura (MPWA), comparing them with the levels of 40 age-matched tension-type headache patients (20 episodic and 20 chronic) (ETTHP and CTTHP) and the levels of a group of 20 healthy control subjects (CS). No statistically significant difference was evident between the mean ET1 plasma levels of MPA and those of MPWA, assessed in headache-free periods. The mean ET1 plasma levels of MPA and MPWA, assessed interictally, were significantly higher than those of CS. However, the values of plasma ET1 in ETTP and in CTTHP did not differ statistically from those of CS. MPA and MPWA ET1 plasma levels increased significantly within 2 h from the onset of attacks (p < 0.0001) and remained significantly higher between 4 and 6 h from the onset. The ET1 plasma levels of ETTHP and CTTHP assessed during attacks did not differ statistically from those of the same patients assessed in the headache-free periods. The increase in ET1 levels in MPA and MPWA patients when assessed ictally, suggests that this peptide is involved in the haemodynamic changes and vascular tone modifications observed during migraine attacks, particularly in the first phase of the ictal period.

Role of viruses in the etiopathogenesis of multiple sclerosis.

Epidemiological studies performed to identify the possible cause of Multiple Sclerosis (MS) suggest that an environmental agent could be involved in its etiopathogenesis. For a long time it has been hypothesized that this agent was a virus, but until now no virus specific to MS has been consistently identified. Animal models indicate that the demyelination of the central nervous system can be induced by certain families of viruses, but the implication of this in the etiopathogenesis of MS has not been clearly demonstrated. Morbilliviruses were the most studied. Research on this subject arose from the observation of the similarity between the brain lesions occurring in MS and encephalitis caused by the measles virus (Subacute Sclerosing Panencephalitis). Antimeasles, antirubella, antiherpes zoster antibodies have been found in the blood and the cerebrospinal fluid of MS patients, but the relationship between this finding and the disease is not clear. It has recently been proposed that the pathogenetic immune response in the brain of MS patients might be directed predominantly towards antigens of a DNA virus, such as JCV. This preferentially infects glial cells and causes a demyelinating syndrome in immunodeficient subjects, called Progressive Multifocal Leucoencephalopathy. The target JC viral antigens in MS could be synthesized during transient viral reactivation. A recent hypothesis is that retroviruses may intervene in the etiopathogenesis of MS. Strong interest has been taken in HTLV-I after its identification in Tropical Spastic Paraparesis, a disease with certain similarities to MS. Serologic and polymerase chain reaction findings from various authors have suggested an association between this human retrovirus and MS. However more recent data are not consistent with this. Current experiments aimed at detecting retroviral particles in long-term cultured peripheral blood monocytes and cerebrospinal fluid mononuclear cells in MS could clarify whether these cells provide a reservoir for such viruses, with a latency of many years without expression at brain level.

Monocyte chemotactic and phagocytic responses in migraine and tension-type headache patients.

Monocyte chemotactic and phagocytic responses were assessed in two groups of migraine patients (with and without aura) and in two groups of tension-type headache patients (episodic and chronic). The chemotactic but not the phagocytic response, assessed interictally, is significantly lower in migraine patients (p < 0.006) and in episodic tension-type headache patients, though not so significantly in the latter (p < 0.05), than in the control individuals. The chemotactic response tends to increase significantly during attack in migraine patients both with and without aura (p < 0.008 and p < 0.007 respectively). The same was evident for the phagocytic response in both migraine patient groups (p < 0.007 and 0.0004). No modifications of monocyte functions were found during attacks neither in episodic nor chronic tension-type headache patients. These findings suggest that one or more mediators of neurogenic inflammation having phagocytic and chemotactic enhancing properties (substance P, prostaglandin E and thromboxane A2 etc.) are implicated in the modification of monocyte function. The demonstration of a defect in monocyte function during the interictal period in migraine patients confirms the results of recent research which evidenced reduced capacity of monocyte to phagocyte and kill microorganisms in the course of migraine.

Evidence for an altered dopamine beta-hydroxylase activity in migraine and tension-type headache.

Sympathetic dysfunction is often present in migraine. It has been suggested that serum dopamine-beta-hydroxylase (D beta H) can be taken as an index of peripheral sympathetic activity. We studied the serum D beta H activity in migraine with and without aura and in tension-type headache patients compared with healthy control subjects. The serum D beta H activity was significantly lower in migraine and tension-type headache patients than in the control group. No significant difference was observed among the three groups of patients studied. These findings suggest that patients with migraine and tension-type headache have a sympathetic hypofunction that may play an important role in the pathogenesis.

Supplementation of polyunsaturated fatty acids in multiple sclerosis.

For several years polyunsaturated fatty acids (PUFAs) and in particular essential fatty acids (EFAs) have been proposed for the treatment of multiple sclerosis (MS). There are contrasting data in literature regarding the effects of the n-6 and the n-3 PUFA series on different aspects of the disease, in particular on the frequency and severity of relapses and platelet function. This can be ascribed to the different criteria of patient selection in relation to the form and severity of disease at the beginning of the various studies. Till now authors have tended to consider the effect of PUFA supplementation only on some clinical aspects of the disease. Modification in the more sensitive indices (immunological or biochemical) of the disease activity should be taken into account and also the influence of dietary lipid intake by patients in relation to n-3 or n-6 EFA supplementation.