Cardiac and Blood Pressure Safety of Transdermal Rivastigmine in Elderly Patients With Dementia With Lewy Bodies.

BACKGROUND: Dementia with Lewy bodies (DLB) is the second most common dementia. Features of DLB include postganglionic cardiac sympathetic denervation and autonomic instability. Rivastigmine therapy, an acetylcholinesterase inhibitor, is widely used in the primary treatment of DLB; however, the cardiovascular safety and tolerability of transdermal rivastigmine needs to be reviewed. OBJECTIVE: To evaluate whether transdermal rivastigmine has an effect on blood pressure, heart rate, and electrocardiography measurements. MATERIALS AND METHODS: A total of 722 patients diagnosed with dementia were retrospectively screened. Fifty-seven of 98 DLB patients who received transdermal rivastigmine treatment with available serial electrocardiography and blood pressure measurements were included in the study. Baseline and follow-up measurements were compared for patients on the 9.5 to 13.3 mg/d rivastigmine dose for at least 4 weeks. RESULTS: The mean age of the patients was 80.77±6.04, and the majority were women (63%). A total of 8 cases with bradycardia and 5 with orthostatic hypotension were detected during follow-up, and rivastigmine patch was stopped in one of those 8 patients due to symptomatic bradycardia. Nonetheless, there was no difference between baseline and follow-up measurements of the patients, including heart rate, cardiac rhythm, electrocardiographic intervals, blood pressure, pulse pressure, and postural blood pressure changes. CONCLUSIONS: Transdermal rivastigmine therapy is not associated with arrhythmogenic or hypotensive effects in the elderly patients with DLB. However, when prescribing transdermal rivastigmine, physicians should pay attention to newly emerging orthostatic hypotension during the follow-up in these patients.

Triple test, a diagnostic observation, can detect cognitive impairment in older adults.

BACKGROUND: A simple, quick, and efficient screening tool for detecting mild cognitive impairment (MCI) and Alzheimer's disease (AD) is essential, especially in the primary care setting. In this study, we examined the neuropsychological profiles of elderly patients and aimed to assess the diagnostic value of the triple test, comprised of the attended alone sign (AAS), head-turning sign, and applause sign (AS), for detecting MCI and AD. METHOD: Comprehensive geriatric assessment was performed in 354 elderly outpatients, and the presence or absence of AS, AAS and HTS was investigated. RESULTS: Of the 354 patients, 93 patients were considered to be cognitively impaired (MCI: 30; AD: 63); the remaining 261 were cognitively healthy. Relative to those without AS, patients with AS had significantly lower scores on the Mini-Mental State Examination, the clock-drawing test, Instrumental Activities of Daily Living Scale, and Basic Activities of Daily Living Scale (P < 0.001, for each). Similar significant differences were found between patients who were positive and negative for the HTS (P < 0.001) and between those who attended the clinic alone and those who were accompanied (P < 0.001). The sensitivity of the triple test for identifying cognitively impairment (CI), MCI, and AD was 0.61, 0.30, and 0.72, respectively; the specificity was 0.85, 0.68, and 0.83, respectively; and the positive and negative predictive values were 0.69, 0.09, and 0.59, respectively, and 0.79, 0.90, and 0.89, respectively. CONCLUSIONS: The present study suggests that the triple test is a simple, quick, and efficient screening tool for detecting cognitive impairment, and the results may reflect deterioration in patients' activities of daily living. Additionally, it could be advantageous in clinical practice because educational level does not affect the test outcome. Therefore, it may be an appropriate test to screen for cognitive impairment in the elderly, both as a bedside diagnostic test and in daily clinical practice, especially in the primary care setting.

COST: Cognitive State Test, a brief screening battery for Alzheimer disease in illiterate and literate patients.

BACKGROUND: The aim was to develop a brief screening battery, Cognitive State Test (COST), for detecting the presence of dementia in both illiterate and literate patients and to assess its validity and reliability. METHODS: COST is a cognitive screening tool that consists of almost all cognitive domains. It takes 5-7 minutes to administer, and has a maximum score of 30. Data were obtained from 114 healthy volunteers and 74 Alzheimer dementia (AD) patients. Subjects' age divided into two groups: A1: <65 years; and A2: ≥65 years and their education level divided into three groups: E1: illiterate; E2: 1-5 years; and E3: ≥6 years. For assessing concurrent validity, total COST score was compared to the Clinical Dementia Rating (CDR), the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and Basic Activities of Daily Living (BADL). Sensitivity and specificity were determined through a discriminant analysis using the Receiver Operating Characteristic (ROC) curves. Internal consistency was measured using Cronbach's coefficient α. RESULTS: For normal and AD subjects, mean age was 64.9±9.8 years (50 women and 64 men) and 67.2±13.2 years (55 women and 19 men), respectively. Schooling ranged from 0-15 years (mean 5.7±4.2 and 3.3±3.8 years, respectively), and 21 and 37 subjects were illiterate, respectively. The COST significantly and positively correlated with MMSE and MoCA, and significantly and inversely correlated with CDR, the Geriatric Depression Scale (GDS), and BADL. In the E1, E2, and E3 education groups, the optimal cut-off points of COST chosen for diagnosis of AD were 23/24 (sensitivity: 81%, specificity: 99%), 24/25 (sensitivity: 75%, specificity: 86%), and 26/27 (sensitivity: 77%, specificity: 84%), respectively. When illiterate and literate subjects were then pooled, the optimal cut-off score of COST was 24/25, which yielded a sensitivity of 81% and a specificity of 87%. Reliability of the COST was good (0.86). CONCLUSION: The COST is a valid and reliable screening battery for detection of dementia both in the illiterate and the literate Alzheimer patients.

Effects of pioglitazone and retinoic acid in a rotenone model of Parkinson's disease.

Parkinson's disease (PD) is a late-onset, progressive and neurodegenerative disorder of unknown etiology. Besides the other therapeutic approaches, new drug options in pharmacotherapy of PD are important. The aim of the present study was to investigate the effects of pioglitazone and retinoic acid, antioxidant and neuroprotective agents, on rotenone-induced model of PD in rats. Adult male Wistar rats (260-373 g) were subjects. Rotenone (2.5mg/kg, sc) was injected to rats for 70 days. At the end of rotenone administration, rats were treated with pioglitazone (10mg/kg, ip) and retinoic acid (1mg/kg, ip) or vehicles for 15 days. Then, rats were tested for evaluation of Parkinson signs by measurement of locomotor activity. In addition, dopamine levels were detected in striatum, hippocampus and hypothalamus in individual groups of control, rotenone and pioglitazone or retinoic acid-treated rats. Rotenone significantly reduced locomotor activity of the rats. It also significantly reduced dopamine levels in striatum and hippocampus, but not hypothalamus. Pioglitazone and retinoic acid reversed in reduction of locomotor activity significantly. Pioglitazone, but not retinoic acid, significantly reversed the reduced striatal dopamine level. Both drugs were ineffective on reduced levels of dopamine in hippocampus. Our results suggest that pioglitazone and retinoic acid have some beneficial effects on rotenone-induced model of PD in rats. Pioglitazone seems to be more effective than retinoic acid. These agents may be helpful for preventing or controlling of some signs of PD.

Acinar cell ultrastructure after taurine treatment in rat acute necrotizing pancreatitis.

OBJECTIVE: To evaluate the organelle-based changes in acinar cells in experimental acute necrotizing pancreatitis (ANP) after taurine treatment and the association of electron microscopic findings with histopathological changes and oxidative stress markers. METHODS: The study was performed in February 2005 at Gulhane School of Medicine and Hecettepe University, Turkey. Forty-five rats were divided into 3 groups. Acute necrotizing pancreatitis was induced in groups II and III. Groups I and II were treated with saline and Group III with taurine 1000 mg/kg/day, i.p, for 48 hours. Histopathological and ultrastructural examinations were determined using one-way analysis of variance and Kruskal-Wallis tests. RESULTS: Histopathologic findings improved significantly after taurine treatment. Degree of injury in rough and smooth endoplasmic reticulums, Golgi apparatus, mitochondria and nucleus of acinar cells also decreased with taurine in correlation with biochemical and histological results. CONCLUSION: Taurine improves acinar cell organelle structure, and ultrastructural recovery in ANP reflects histological improvement.

Rat liver fibrosis regresses better with pegylated interferon alpha2b and ursodeoxycholic acid treatments than spontaneous recovery.

BACKGROUND/AIMS: Fibrosis and cirrhosis are common complications of chronic liver diseases. An imbalance between fibrogenesis and fibrolysis results in scarring of the liver parenchyma. We aimed to investigate the possible antifibrotic effectiveness of a newly modified interferon molecule peginterferon alpha2b (PEG-IFNalpha2b) which has better antiviral activity, and ursodeoxycholic acid (UDCA). METHODOLOGY: Liver fibrosis was established on 60 male Sprague Dawley rats with CCl4 in 12 weeks. After cessation of CCl4 Group I was left for spontaneous recovery. Group II was treated with PEG-IFN 1.5 microg/kg/week, Group III with UDCA 25 mg/kg/day and Group IV with combination of both drugs. All rats were killed at week 16. Histopathologic fibrosis scores, tissue hydroxyproline, TIMP-1 and MMP-13 levels were determined. Hepatic stellate cell apoptosis was detected by dual staining with TUNEL technique and anti-alpha smooth muscle actin. RESULTS: Fibrosis scores were lower in Group II, III and IV than Group I (p<0.05 for group I vs. II and III; p<0.01 for group I vs. IV). Tissue hydroxyproline levels were significantly decreased in Group II, III and IV when compared to Group I (p<0.05 for group I vs. II, p<0.01 for group I vs. III and IV). Lower liver TIMP-1 and higher MMP-13 levels were measured in Group II, III, and Group IV than Group I (p<0.01 for TIMP-1 and p<0.01, for MMP). Activated HSC apoptosis was significantly increased in Group II, III and IV when compared to Group I (p<0.01, for all). There was significantly higher apoptosis in Group II than Group III and IV (p<0.01). CONCLUSION: Treatment with both PEG-IFNalpha2b and UDCA improved CCl4 induced rat liver fibrosis. Significantly higher effects were obtained using these agents in combination.