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We investigated the relationship of metabolic syndrome (MetS) and its individual components with incidence of mild cognitive impairment (MCI) and its progression to dementia in a large longitudinal Italian population-based sample with a 3.5-year follow-up. A total of 2097 participants from a sample of 5632 65-84-year-old subjects from the Italian Longitudinal Study on Aging were evaluated. MetS was defined according to the Third Adults Treatment Panel of the National Cholesterol Education Program criteria. MCI, dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were classified using current published criteria. Among MCI patients those with MetS (N=49) had a higher risk of progression to dementia (HR, 4.40; 95% CI, 1.30-14.82) compared with those without MetS (N=72). After a multivariate adjustment, the risk in MCI patients with MetS approximately doubled (multivariate adjusted HR, 7.80, 95% CI 1.29-47.20) compared with those MCI without MetS. Finally, among non-cognitively impaired individuals there were no significant differences in risks of developing MCI in those who were affected by MetS (N=608) in comparison with those without MetS (N=837), as well as excluding those individuals with undernutrition or low inflammatory status with or without undernutrition. In our population, among MCI patients the presence of MetS independently predicted an increased risk of progression to dementia over 3.5 years of follow-up.

Background Functional cerebral asymmetries (FCAs) are known to fluctuate across the menstrual cycle. The visual line-bisection task administered to normally cycling women showed different patterns of the interhemispheric interactions during menses and the midluteal cycle phase. However, the contribution of estrogens and progestins hormones to this phenomenon is still unclear. Study Design The aim of our study was to show a variation of FCAs in women administered oral contraceptives (OCs) using the visual line-bisection task. Visual line-bisection task with three horizontal lines was administered to 36 healthy women taking a 21-day OC. Twenty-nine patients were right handed. The task was administered during OC intake (day 10) and at the end of the pill-free period. Results The right-handed women showed a significant leftward bias of veridical center on the first and third lines during OC intake compared with an opposite rightward bias during the pill-free period. The same phenomenon of contralateral deviation was observed in left-handed women on day 10 of OC intake. Conclusions The results of this study confirm a hormonal modulation on interhemispheric interaction and suggest that OCs may improve the interhemispheric interaction reducing FCAs compared with the low hormone level period. This opens new insights in OC prescription and choice of administration schedule in order to improve cognitive performances.

The role of adrenergic mechanisms in the modulation of the immune response is well established [1], and several lines of evidence point to their involvement in immunemediated diseases of the nervous system such as multiple sclerosis (MS) [2]. Adrenoceptor ligands such as the b-adrenoceptor agonists terbutaline and isoproterenol [3] and the a-adrenoceptor antagonist prazosin [4] produce beneficial results in rats with experimental allergic encephalomyelitis (EAE), an established animal model of MS. Nonetheless, the rational basis for a therapeutic role of adrenoceptor ligands in MS has been hampered by the limited comprehension of the contribution of such mechanisms to human disease. The interesting article by De Keyser and co-workers, published recently inTiPS [5], discussed the involvement of b2-adrenoceptors expressed on astrocytes in inflammatory demyelinationandaxonaldegeneration inMS,andprovides novel insights into this intriguing topic. In this regard, we would like to add further points for consideration. First, noradrenaline acting on b2-adrenoceptors on astrocytes might be derived not only from noradrenergic nerve endings but also from activated lymphocytes infiltrating the CNS. Human peripheral lymphocytes express, following their activation, tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines, and subsequently increase their intracellular content of dopamine, noradrenaline and adrenaline by up to 20–40-fold basal levels [6]. Intracellular catecholamines that accumulate in activated lymphocytes appear to be involved in the modulation of activationinduced apoptosis [7]. In addition, they provide these cells with a supply of mediators to be released following appropriate stimulation. Interestingly, interferon b (IFN-b), which is at least partially beneficial in MS, appears to be a strong inducer of catecholamine production and release from activated lymphocytes [8]. Although the relevance of this in vitro effect for the in vivo activity of IFN-b remains to be established, it cannot be excluded that this might contribute to a ‘restorative’ effect by IFN-b of the astrocyte–lymphocyte crosstalk. It would therefore be of interest to investigate the effects of IFN-b on b-adrenoceptor expression on astrocytes. Second, human lymphocytes express adrenoceptors, which might represent additional targets for noradrenaline, either released by nerve endings or derived from immune cells. In patients with MS, b2-adrenoceptor expression on lymphocytes: (i) is increased; (ii) correlates withmagnetic resonance imaging (MRI) disease activity in primary progressive MS; and (iii) also occurs in the secondary progressive form of MS (although no relationship withMRI disease activity has been demonstrated) [9]. Increased production of cAMP has been detected in resting, but not activated, lymphocytes from MS patients following stimulation in vitro with b2-adrenoceptor agonists [10]. However, despite this phenomenon, reduced immunological responses to b2-adrenoceptor agonists appear to characterize lymphocytes from MS patients and from mice affected by EAE [11,12]. Biochemical deficiencies downstream of cAMP might therefore account for the aberrant signalling through b2-adrenoceptors in MS and EAE diseases, although these remain to be clearly elucidated [12]. The observation that IFN-b counteracts activation-induced reduction of b-adrenoceptor agonistinduced cAMP accumulation in human lymphocytes [13] might have interesting implications. It can therefore be proposed that in MS b2-adrenoceptor-dependent cAMP signalling might play a role not only in astrocytes, as pointed out by De Keyser and co-workers [5], but also in lymphocytes. In addition to b2-adrenoceptors, lymphocytes express a wide array of other G-proteincoupled receptors that, following stimulation, might Corresponding author: Marco Cosentino (marco.cosentino@uninsubria.it). Available online 8 May 2004 Update TRENDS in Pharmacological Sciences Vol.25 No.7 July 2004 350