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.

The novel PSEN1 M84V mutation associated to frontal dysexecutive syndrome, spastic paraparesis, and cerebellar atrophy in a dominant Alzheimer's disease family.

We identified the novel PSEN1 pathogenic mutation M84V in 3 patients belonging to a large kindred affected by autosomal dominant Alzheimer's disease (AD). The clinical phenotype was characterized by early onset dementia in 14 affected subjects over 3 generations. Detailed clinical, imaging and genetic assessment was performed. We highlighted the presence of unusual symptoms such as frontal executive syndrome, psychosis and spastic paraparesis in these patients. Spastic paraparesis has been reported in other PSEN1 mutations in adjacent codons, suggesting that the position of the genetic defect may affect the clinical expression, although this phenotype can occur in mutations throughout the whole PSEN1 gene. Brain magnetic resonance imaging showed diffuse cortical atrophy, but also atrophy of cerebellar lobules, mainly involving Crus I, in 2 patients without cerebellar motor deficits. These neuroimaging results were consistent with recent findings about the association between sporadic AD and distinct and circumscribed cerebellar atrophy. The present work acknowledged the novel PSEN1 pathogenic mutation M84V and might contribute to the ongoing debate about the involvement of cerebellum in AD.

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.

Role of impaired glucose metabolism in the postherpetic neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is one of the most common and debilitating sequela of herpes zoster. The etiology of PHN is not completely understood. Several studies showed that diabetes mellitus may increase the risk of infectious diseases, including herpes zoster. Instead, the relationship between PHN and prediabetes has never been described. OBJECTIVE: To evaluate glucose metabolism abnormalities in patients with PHN. METHODS: We studied 87 consecutive patients with PHN and normal fasting glycemia and 108 pain-free controls. In both groups we evaluated glucose and insulin levels after a 2-hour oral glucose tolerance test and insulin resistance. In addition, in all patients we performed skin thoracic biopsy to exclude a small fiber neuropathy. RESULTS: After a 2-hour oral glucose tolerance test, the prevalence of glucose metabolism abnormalities was significantly higher in patients than in controls (P<0.001): impaired glucose tolerance was found in 36 (38%) patients and in 16 (15%) controls, whereas a newly diagnosed diabetes mellitus was found in 9 (9%) patients and in 6 (5%) controls. The insulin resistance showed no significant differences between patients and controls. CONCLUSIONS: Our study suggests that PHN may be a marker for impaired glucose tolerance. A glucose tolerance test should be considered in patients presenting with PHN.

Insulin resistance possible risk factor for cognitive impairment in fibromialgic patients.

To evaluate glucose metabolism and/or insulin resistance (IR) in 96 patients with Fibromyalgia (FM), associated or not to cognitive impairment. We investigated glucose metabolism in 96 FM patients. Enrolled patients were divided into two groups: 48 patients with memory deficit (group A) and 48 without memory deficit (control group). We evaluated glucose and insulin levels after a 2 h-Oral-Glucose-Tolerance-Test (2 h-OGTT) and insulin resistance (IR) by the homeostasis model assessment formula (HOMA). Body Mass Index (BMI), waist-to-hip-ratio (WHR), anxiety level, fasting plasma insulin and Non-Steroidal Anti-Inflammatory agents use were higher in patients with FM with memory impairment; while age, sex, waist circumference, education level, fasting plasma glucose, glycate hemoglobin, triglycerides, blood lipid profile, C- Reactivity-Protein (CRP), blood pressure and smoking habits were similar in both groups. Following OGTT the prevalence of glucose metabolism abnormalities was significantly higher in group A. IR was present in 79% patients, of whom 23% had also impaired glucose tolerance, 4% newly diagnosed diabetes mellitus and 52% IR only. Obesity and overweight prevailed in group A. IR, but not BMI or WHR was associated to an increased risk of memory impairment (OR = 2,6; 95% CI: 1,22-3,7). The results of this study suggest that IR may represent a risk factor for memory impairment in fibromialgic patients.

The Effect of Lipoic Acid Therapy on Cognitive Functioning in Patients with Alzheimer's Disease.

Diabetes mellitus (DM) is an important risk factor for Alzheimer's disease (AD). Most diabetic patients have insulin resistance (IR) that is associated with compensatory hyperinsulinemia, one of the mechanisms suggested for increased AD risk in patients with DM. Alpha-lipoic acid (ALA) is a disulfide molecule with antioxidant properties that has positive effects on glucose metabolism and IR. This study evaluated the effect of ALA treatment (600 mg/day) on cognitive performances in AD patients with and without DM. One hundred and twenty-six patients with AD were divided into two groups, according to DM presence (group A) or absence (group B). Cognitive functions were assessed by MMSE, Alzheimer's Disease Assessment Scale-cognitive (ADAS-Cog), Clinician's Interview-Based Impression of Severity (CIBIC), Clinical Dementia Rating (CDR), and Alzheimer's Disease Functional and Change Scale (ADFACS). IR was assessed by HOMA index. At the end of the study, MMSE scores showed a significant improvement in 43% patients of group A (26 subjects) and 23% of group B (15 subjects), compared to baseline (P = .001). Also ADAS-Cog, CIBIC, and ADFACS scores showed a significant improvement in group A versus group B. IR was higher in group A. Our study suggests that ALA therapy could be effective in slowing cognitive decline in patients with AD and IR.

Dementia is associated with insulin resistance in patients with Parkinson's disease.

BACKGROUND: Parkinson's disease is a neurodegenerative disorder involving the basal ganglia. Type-2 Diabetes Mellitus is an important risk factor for Alzheimer disease and vascular dementia. However, the association between Parkinson's disease and Diabetes Mellitus is controversial. OBJECTIVE: To investigate glucose metabolism abnormalities in 110 Parkinson's disease patients with and without dementia. SUBJECTS AND METHODS: We evaluated Insulin Resistance, glucose and insulin levels after a 2-h-oral-glucose-tolerance-test in 53 Parkinson's disease with dementia and 57 with Parkinson's disease without dementia, with normal fasting glucose. RESULTS: BMI, waist circumference, fasting glucose and insulin values, HbA1c, triglycerides, blood lipid profile, depression rating, educational levels, levodopa-dosage and antipsychotic use were similar in both groups. Disease duration and motor impairment were higher in patients with Parkinson's disease and dementia group. After 2-h-oral-glucose-tolerance-test, the prevalence of glucose metabolism abnormalities was significantly higher in group with Parkinson's disease and dementia group (p=0.03). The insulin resistance was present in 62% patients with Parkinson's disease with dementia, of whom 30% had also impaired glucose tolerance, 5,6% newly diagnosed Diabetes Mellitus and 26% only Insulin Resistance. These percentages were significantly higher in group with Parkinson's disease and dementia, also after adjustment for disease duration and motor disability. CONCLUSIONS: Our study suggests that PD patients with dementia are two times more likely to have insulin resistance than patients with PD.

Insulin resistance increases risk of carpal tunnel syndrome: a case-control study.

Carpal tunnel syndrome (CTS) is one of the most common upper limb compression neuropathies. In only 50% of cases it is possible to identify a cause. Our objective was to determine the role of glucose metabolism abnormalities in idiopathic CTS. We identified 117 patients with idiopathic moderate or severe CTS and 128 controls. In all we evaluated glucose and insulin levels at fasting and after 2-h oral glucose tolerance test (2h-OGTT). In addition we determined insulin resistance (IR). Following OGTT the prevalence of glucose metabolism abnormalities was significantly higher in the CTS group (p = 0.001). IR was documented in 80% of patients, of whom 45% had impaired glucose tolerance, 14% newly diagnosed diabetes mellitus, and 20% IR only. Waist circumference and body mass index were also significantly increased in the CTS group. In this study, we focused on evidence that pre-diabetes may represent a risk factor for CTS. We proposed to determine IR as a rule in all patients with idiopathic CTS.