Cognitive impairment is correlated with insulin resistance degree: the "PA-NICO-study".

Several epidemiological studies have shown that Diabetes Mellitus (DM) or Insulin Resistance (IR) increases the risk of dementia. Besides, some authors suggested that poor glucose control to be associated with worse cognitive function. We aimed to assess cognitive functions and IR-degree over time in diabetic. We also evaluated whether a greater magnitude of cognitive decline could be related with their IR degree. We enrolled 335 diabetic patients and 142 non-diabetic subjects; participants were subdivided into three groups in accordance with their IRdegree assessed by Homa-Index (HI): Normal-HI (non-diabetic NHI < 2,6), Moderate-HI (MHI > 2,6 < 10) and High-HI (HHI > 10). Metabolic status and a comprehensive neuropsycological test battery (MMSE, ADAS-Cog, ACDS-ADL) were assessed at baseline and every 12-months during the follow-up (6,8 years). At the end of the study, the average MMSE decreased significantly in patients of HHI group (P = .001) compared to baseline. MMSE scores were also reduced both in MHI group and in controls, but the difference between two groups was not significant. In HHI group, similar effects were observed for the ADAS-Cog score compared to baseline (P = 0.001); instead, when ACDS-ADL was evaluated, no differences was observed among the three groups. These results remained unchanged also after adjustment for confounding variables (i.e. APOε-status, sex, BMI, education level, heart diseases and HbA1c). We suggest that higher IR-degree is associated with greater cognitive decline in diabetic patients; so we hypothesize that IR degree, more than IR status itself, could be related to the severity of cognitive impairment.

Serum calcium level is related to both intima-media thickness and carotid atherosclerosis: a neglect risk factor in obese/overweight subjects.

BACKGROUND: Experimental studies suggested that high serum calcium may be important in the pathogenesis of vascular diseases. Since calcium seems to affect specifically the cerebrovascular district, aim of this study was to determine the relation between serum calcium levels, within normal range, and subclinical atherosclerosis in the carotid arteries, in a population of obese/overweight subjects. METHODS: In our retrospective study we included 472 subjects (59% female) with body mass index equal to or more than 25 kg/m2. They underwent a physical examination, a biochemical assessment (including calcium evaluation) and a B-mode ultrasonography of the extracranial carotid arteries to detect carotid atherosclerosis presence and to measure intima-media thickness. RESULTS: Mean age of the population was 50 ±12 years. Prevalence of the Carotid atherosclerosis was 40%. Mean carotid intima-media thickness was 0,66 ± 0,18 mm. The univariate and multivariate analysis showed an association between calcium and carotid intima-media thickness (p = 0,035). We divided the population in serum calcium tertiles. We found an higher carotid atherosclerosis prevalence in the III tertile in comparison to that of the I tertile (p = 0,039). CONCLUSIONS: In this study we found a positive relation between serum calcium levels, within normal range, and subclinical atherosclerosis in the carotid arteries, in a population of obese/overweight subjects. It is important to consider the impact of the serum calcium levels in the overall risk assessment of patients, at least in obese subjects.

Palinopsia in patients with migraine: a case-control study.

OBJECTIVES: This study was aimed at investigating the frequency of the visual phenomenon of palinopsia (visual perseveration) in patients with migraine. METHODS: We interviewed 63 patients with migraine with aura (MwA), 137 patients with migraine without aura (MwoA) and 226 sex-age-matched healthy control subjects using an ad hoc structured interview/questionnaire. The interview was divided into four classes of variables for statistical testing. RESULTS: Palinopsia occurred in 19/200 patients (9.5%); of them 10/63 had MwA and 9/137 MwoA (14.2% vs 6.6%, chi = 9.7, degrees of freedom = 1, p = 0.002). Patients with palinopsia had a significantly lower migraine attack frequency than those without this visual phenomenon (4.3 ± 0.3 vs 14.4 ± 0.2, z = 7.1, p < 0.0001). No healthy control subjects complained of palinopsia according to the structured interview/questionnaire. DISCUSSION: Palinopsia is probably under-diagnosed in patients with migraine. Further investigations are needed to assess whether migraineurs are particularly susceptible to the development of recurrent episodes of visual perseveration.

Effects of safinamide on REM sleep behavior disorder in Parkinson disease: A randomized, longitudinal, cross-over pilot study.

BACKGROUND: Rapid Eye Movement sleep behavior disorder (RBD) is characterized by dream enactment and loss of muscle atonia during REM-sleep. RBD as a premotor feature occurred souvent in patients who develop Parkinson's disease. The glutamatergic, glycinergic, and GABA-ergic systems appear to play a crucial role in the pathogenesis of RBD. METHODS: The present exploratory longitudinal cross-over study aimed to observe the effect of safinamide on RBD symptoms. Thirty patients with PD and RBD were randomized into two groups (15 subjects each), those that received for a period of 3-months safinamide (50 mg/die) in addition (Group A + ) or in absence (Group B - ) to the usual antiparkinsonian therapy. Patients exploring the clinical and video-polysomnographic changes occurred during this pharmacological therapy. RESULTS: Twenty-two of 30 patients reported clear improvement in symptoms during safinamide treatment, and 16 were absolutely free from clinical RBD-symptoms at the end of the treatment. Eight patients reported slight improvement in RBD-symptoms. In 6/30 patients no substantial improvement was recorded about clinical RBD-symptoms had frightening dreams or from the bed after 1-week of treatment. In addition, after safinamide, the mean UPDRS-II and III scores decreased, while PDSS-2 score indicating an improvement in both motor symptoms and nocturnal sleep features. A significant reduction of sleep behavior disorder by questionnaire-Hong Kong-score (RBDQ-HS), mainly for two individual RBDQ-HK-items (dream related movements and failing out of bed) was registered. CONCLUSIONS: This pilot study indicated that safinamide is well tolerated and improves RBD-symptom in parkinsonian.

Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs.

PURPOSE: Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels. METHODS: Patients 18-50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B(12), and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control. RESULTS: Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 microm; physiologic range 5-13 microm] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) microm, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) microm]. DISCUSSION: Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy.

Hyperhomocysteinemia in patients with epilepsy: does it play a role in the pathogenesis of brain atrophy? A preliminary report.

PURPOSE: Brain atrophy (BA) is observed in 20-50% of patients with epilepsy. Hyper-total-homocysteinemia (hyper-tHcy), which occurs in 10-40% of patients, is considered to be a risk factor for cardiovascular diseases and BA. The present study was aimed at investigating the possible association of hyper-tHcy with BA in a population of patients with epilepsy. METHODS: Fifty-eight patients (33 M/25 F, 43.5 +/- 13.1 years of age) chronically treated with antiepileptic drugs (AEDs) and 60 controls matched for age and sex were enrolled. All participants underwent determination of plasma tHcy, folate, vitamin B(12), and C677T methylene-tetrahydrofolate-reductase (MTHFR) polymorphism genotyping, and brain magnetic resonance imaging (MRI). RESULTS: Patients exhibited significantly higher tHcy and lower folate levels than controls; hyper-tHcy was significantly associated with the variables group (patients vs. controls), MTHFR genotype, and their interaction terms. BA was observed in 30.1% of patients and was significantly associated with hyper-tHcy (beta = 0.45, p = 0.003) and polytherapy (beta = 0.31, p < 0.001). DISCUSSION: Our investigation suggests that hyper-tHcy plays a role in the development of BA in patients with epilepsy. Although the real origin of this phenomenon is not yet fully elucidated, experimental data support the hypothesis of a link of the neuronal Hcy-mediated damage with oxidative stress and excitotoxicity.

Association between pulse pressure and subclinical carotid atherosclerosis in normotensive and hypertensive post-menopausal women.

Pulse pressure, the difference between systolic blood pressure and diastolic blood pressure, is associated with cardiovascular diseases. Several studies showed that a large pulse pressure is an independent predictor of cardiovascular mortality since the increased stiffness augment ascending aortic pulse pressure that, in turn, produce wall stress and development of atherosclerosis. A sample of 252 post-menopausal women underwent a clinical evaluation and carotid artery ultrasound examinations. We measured carotid intimal media thickness--a well-known atherosclerosis marker. For statistical analysis an unpaired student-test and a one-way ANOVA to compare means between the groups and a chi-square test to compare the prevalence of variables among the groups were used. Multivariate linear regression analysis was used to adjust for confounding variables. The carotid intimal media thickness (IMT) was significantly associated to pulse pressure in post-menopausal women. The statistically significant association was confirmed after adjustment for age, blood pressure, cholesterol, and trygliceride levels. Indeed, after subdivision in tertiles of pulse pressure, the IMT in the third pulse pressure tertile was significantly higher than in the first tertile. A large pulse pressure is an independent risk factor for carotid atherosclerosis in post-menopausal women. The pulse pressure could predispose to atherosclerosis influencing the nitrix oxide (NO) release or representing an injury to the arterial wall. Clinical trials are requested to assess whether a treatment aimed at reducing the pulse pressure could better prevent cardiovascular and cerebrovascular disease in these subjects.

Carotid atherosclerosis associated to metabolic syndrome but not BMI in healthy menopausal women.

BACKGROUND: Obesity and the metabolic syndrome (MS) frequently coexist. Both are apparently associated to cardiovascular disease. However, the contribution of obesity to cardiovascular risk, independent of the presence of the metabolic syndrome, remains controversial. The purpose of this study was to investigate whether the subclinical carotid atherosclerosis prevalence is different in obese postmenopausal women with and without the metabolic syndrome. METHODS: On the basis of consecutive recruitment, 313 postmenopausal women underwent a clinical, biochemical and ultrasound characterization. Women affected by cardiovascular disease or diabetes were excluded from the study. RESULTS: Among enrolled women the metabolic syndrome and body mass index (BMI) resulted strongly associated, but only metabolic syndrome was associated with carotid atherosclerosis, a well-known marker of cardiovascular disease. Similarly, increases in BMI unit (normal to overweight to obese) were not associated with carotid atherosclerosis whereas metabolic status (normal to metabolic syndrome) conferred an approximate three-fold adjusted odds of carotid atherosclerosis. CONCLUSIONS: The metabolic syndrome but not obesity is associated to carotid atherosclerosis in postmenopausal women. Although it remains prudent to recommend weight loss in overweight and obese women, evaluation and control of metabolic risk factors should be considered the main goal to prevent cardiovascular and cerebrovascular disease.

Endogenous testosterone and endothelial function in postmenopausal women.

OBJECTIVE: It is well known that coronary heart disease incidence increases in women after menopause. This phenomenon was related to reduced levels of female sex hormones. Estrogen decline, however, is not the only hormonal change during the postmenopausal period and estrogen administration did not protect women from cardiovascular disease. Therefore, it is justified to explore other hormonal changes. The role of androgens is still controversial. The aim of the present study was to investigate the relationship between endogenous sex hormones and endothelial function, measuring the brachial artery flow-mediated dilation. METHODS AND RESULTS: Sixty postmenopausal women were consecutively enrolled and underwent a clinical and biochemical examination. Brachial artery flow-mediated dilation was also evaluated by ultrasound. After correction for confounding variables, testosterone was positively correlated to flow-mediated dilation (beta=0.277, P=0.03). Indeed, women in the lowest testosterone tertile had a flow-mediated dilation smaller than that in the highest tertile (P=0.02). CONCLUSIONS: This result could suggest that the development of cardiovascular disease after menopause is due not only to estrogen decline but also to androgen decline. More studies are needed to evaluate the role of androgen replacement therapy on postmenopausal women with low level of this hormone.

[Lack of association between LDL-cholesterol and carotid intima-media thickness in elderly women]. / Il colesterolo LDL non è associato ad ispessimento medio-intimale carotideo nelle donne anziane.

BACKGROUND: It is known that the association between LDL-cholesterol (LDL-C) and cardiovascular morbidity and mortality in the elderly is controversial. The aim of this study was to investigate this issue using carotid intima-media thickness as a marker of cardiovascular disease. METHODS: Women aged 35-79 years were consecutively enrolled in the study. They underwent a questionnaire to assess cardiovascular disease, a clinical examination to assess blood pressure and anthropometric variables, a biochemical evaluation of lipid profile and glucose, and an ultrasound evaluation of carotid arteries. The study population was divided into two age groups (≤65 years and >65 years), and each group was then divided into two subgroups according to LDL-C level (normal and high). A Student's t-test was used to compare mean values between groups, and a chi square test was used to compare the prevalence of carotid atherosclerosis. RESULTS: A lack of association between LDL-C and carotid intima-media thickness was observed in subjects aged >65 years, with the intima-media thickness average being similar between those with and without high LDL-C. Conversely, a significant difference in carotid intima-media thickness was observed among adults with and without high LDL-C level. CONCLUSIONS: Our findings, similar to those obtained in other epidemiological studies, provide the rationale for revising the use of statins in elderly women without cardiovascular disease.