Effect of galantamine on platelet functions in healthy elderly people.

BACKGROUND & OBJECTIVES: Galantamine, a centrally-acting cholinesterase inhibitor, has been used in the treatment of mild-to-moderate dementia of Alzheimer disease. Increased mortality, mainly due to cardiovascular events, was observed in placebo-controlled trials of galantamine. Several studies have evaluated the efficacy of galantamine in dementia, it is not clear whether it has an effect on platelet function. It is important to clarify this effect, because it may be related to thrombotic tendency or bleeding diathesis. This study was aimed to investigate the effect of galantamine on platelet aggregation in whole blood from healthy, elderly subjects. METHODS: Fifteen healthy (mean age 76.8 ± 7.2 yr) volunteers were included in the study. Three concentrations of galantamine solution (20, 40 and 80 ng/µl) were prepared. Each concentration of galantamine solution and control diluent without galantamine were incubated with whole blood. After incubation, aggregation responses were evaluated with ADP (5 µM) and collagen (2 µg/ml) in platelet-rich plasma. RESULTS: Compared to control, pre-incubation with all dilutions of galantamine had no detectable effect on platelet aggregation response induced by ADP and collagen. Galantamine also had no detectable effect on platelet aggregation in a dose-dependent manner. INTERPRETATION & CONCLUSIONS: This in vitro study suggested that galantamine administration had no effect on platelet aggregation in the clinically relevant doses.

The comparative effects of valsartan and amlodipine on vWf levels and N/L ratio in patients with newly diagnosed hypertension.

High levels of circulating Von Willebrand factor (vWf) and increased neutrophil to lymphocyte (N/L) ratio may reflect vascular inflammation in hypertensive patients. In present study, we aimed to investigate the effects of valsartan as an angiotensin II receptor antagonist and amlodipine as a calcium channel blocker on the vWf levels and N/L ratio in patients with essential hypertension. Patients were randomized to one of the following intervention protocols: calcium channel blocker (amlodipine, 5-10 mg/day) as group A (n = 20 mean age = 51.85 ± 11.32 y) and angiotensine II receptor blocker (valsartan, 80-320 mg/day) as group B (n = 26 mean age = 49.12 ± 14.12 y). Endothelial dysfunction and vascular inflammation were evaluated with vWf levels and N/L ratio in hypertensive patients before treatment and after treatment in the 12th week. No statistically significant differences were found among the groups in terms of age, sex, and body mass index (BMI). There was a significant decrease in vWf levels (P < .001) and N/L ratio after treatment (P = .04, P < .001, respectively) in both the groups. Von Willebrand factor levels and N/L ratio are very important markers having a role in vascular inflammation and antihypertensive treatment with amlodipine and valsartan may improve cardiovascular outcomes by decreasing these biomarkers.

Amlodipine increases vitamin D levels more than valsartan in newly diagnosed hypertensive patients: pointing to an additional effect on bone metabolism or a novel marker of inflammation?

Hypertension is a major challenge for public health. Appropriate antihypertensive treatment seem to provide a better life with lower morbidity and mortality rates. Another pathologic condition, osteoporosis, mainly affects postmenouposal women, and constitutes a growing body of risks after a particular age. As bone is a dynamic organ system that is directly related to calcium and phosphor metabolism, imbalance in these two parameters upon aging or menopause finally may lead to osteoporosis. Today, both osteoporosis and high blood pressure are major morbidities, especially in the elderly population. There are some intriguing results on the effects of antihypertensive agents on bone metabolism in the literature. In this study, we aimed to investigate the effects of widely used antihypertensive agents, valsartan and amlodipine on vitamin D levels in newly diagnosed hypertensive population. We found that amlodipine increased vitamin D levels significantly in patients with a newly diagnosed hypertension on a 12-week treatment duration compared to valsartan.

An elderly diabetic case of ochronosis with depression and chronic pain.

Alkaptonuria (ochronosis) is a rare autosomal recessive disorder featuring a genetic error in the amino acid metabolism. A defect in the tyrosine metabolism results in the accumulation and deposition of homogentisic acid in connective tissue, causing a blue-black discolouration. Degenerative arthropathy of the spine, knee, and hip are common signs of ochronosis in older age. An association between ochronosis and depression has not previously been discussed in the literature. This case report describes a 69 year-old woman with diabetes mellitus, ochronosis, depression and chronic pain.

Effect of low-intensity versus high-intensity resistance training on the functioning of the institutionalized frail elderly.

Frailty has emerged as an important risk factor for disability. Age-related declines in physical and physiological function lead to increased risk of loss of independence and poor quality of life. Recent evidence has shown the effectiveness of physical exercise programmes in preventing or reversing frailty. The aim of this study was to evaluate changes in the functioning of frail elderly individuals after undergoing resistance training for 3 days a week for 8 weeks. The effectiveness of exercise training was investigated in 48 frail elderly individuals who were randomly assigned to the following intervention groups: high-intensity (HI; n=16; age: 69-96 years) or low-intensity (LI; n=16; age: 77-93 years) strength training groups or a control group (n=16; age: 76-93 years) with no specific exercise programme. Participants were assessed for muscle strength, physical function, activities of daily living, depression and quality of life. The HI group had significantly better results (P<0.05) on the Short Physical Performance Test than the LI group; however, the LI group did show a significant improvement in those scores, whereas the scores of the control group worsened. Results for the other evaluations were similarly favourable in both exercise groups (P>0.05). The study showed that LI exercise was as effective as HI exercise for most parameters tested. Exercise training is useful for the prevention or treatment of frailty, as it improves functioning by contributing positively to muscle strength, gait, balance and quality of life.

Assessment of geriatric predictors of adherence to Zoledronic acid treatment for osteoporosis: a prospective follow-up study.

Objectives Discontinuation of bisphosphonate treatment remains high even with the long acting parenteral options. Whether there are some unidentified causes of noncompliance more specific to aged individuals is unknown. The aim of this study was to investigate baseline predictors of adherence to Zoledronic acid (ZOL) infusions among non-demented older adults with osteoporosis. Methods Patients aged ≥ 65 years who received a first ever ZOL infusion for osteoporosis were prospectively enrolled. Risk factors for osteoporosis and fractures, comorbidities, geriatric assessment measures, including depression, and anticholinergic burden were determined at baseline. Adherence was defined as taking the next ZOL infusion at 12 months. Results A total of 187 participants were included (mean age: 75.7 ± 6.3 years, female: 77.5%). Adherence to the next ZOL infusion was 66.8% (n = 125). Non-adherent participants (n = 62, 33.2%) had significantly higher frequency of historical height decrease and depression at baseline. Poor adherence was associated with height decrease, presence of depression, and higher anticholinergic burden in univariate analysis. After adjustment for relevant confounders, fragility fracture history (OR: 0.38, 95%CI: 0.17-0.86, p = 0.020), depression (OR: 0.32, 95%CI: 0.12-0.82, p = 0.018), and higher anticholinergic burden (OR: 0.67, 95%CI: 0.49-0.93, p = 0.017) were the predictors of lower adherence to ZOL infusion. Conclusions The rate of adherence to the next ZOL infusion was still suboptimal among older women and men in this study. Past osteoporotic fractures, depression, and higher anticholinergic drug burden predicted poor ZOL adherence. It was a novel finding that drug-related anticholinergic side effects adversely influenced adherence to another medication without anticholinergic properties.

Undetected Peripheral Arterial Disease Among Older Adults With Alzheimer's Disease and Other Dementias.

BACKGROUND: Peripheral arterial disease (PAD) was reported to increase the risk of dementia(s) even more than stroke. We assessed the prevalence of PAD in a group with definite diagnosis of dementia. METHODS: Patients aged 65 years or older with Alzheimer's disease (AD), vascular dementia (VaD), or AD-VaD were enrolled (n = 162, mean age: 78.87 [6.05] years). An age- and gender-matched control group was also included (n = 190). Peripheral arterial disease was diagnosed by the ankle-brachial index. RESULTS: Frequency of PAD among patients with and without dementia was 35.2% and 16.3%, respectively ( P < .001), being similar among different types of dementia. After adjustment for covariates, dementia (odds ratio: 2.41, 95% confidence interval: 1.34-4.32; P = .003) was among the predictors of PAD diagnosis along with older age, female gender, and diabetes. CONCLUSIONS: The prevalence of PAD was more than double in patients with dementia, with no difference among AD, VaD, and AD-VaD types.

Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance.

Visfatin, a new adipokine, facilitates adipogenesis and has insulin-mimetic properties. We aimed to investigate the plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT), who had no obesity or hypertension. Twenty-two patients with T2DM, 18 subjects with IGT and 40 healthy controls were enrolled. Visfatin levels were measured along with the BMI, blood pressure, lipids, glucose, insulin, adiponectin and hsCRP levels, and HOMA-IR indexes. Age, sex and BMI were similar in all groups. Visfatin levels were higher in the diabetic group than the controls (p=0.01). There was no significant difference in the visfatin levels between the T2DM and IGT groups as well as IGT group and healthy controls. Plasma visfatin concentrations did not differ between men and women. Visfatin levels did not correlate with BMI, blood pressure, plasma adiponectin, insulin, hsCRP, glucose and lipid levels or HOMA-IR indexes in the three groups. These results indicate that hyperglycemia causes an increase in plasma visfatin levels and, as in people with T2DM but not with IGT, this increase gets more prominent as the glucose intolerance worsens.

Combination of allopurinol and hyperbaric oxygen therapy: a new treatment in experimental acute necrotizing pancreatitis?

AIM: To investigate the individual and combined effects of allopurinol and hyperbaric oxygen (HBO) therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation (BT) in the experimental rat acute pancreatitis (AP). METHODS: Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls (sham, Group I). AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group II received saline, Group III allopurinol, Group IV allopurinol plus HBO and Group V HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS: Serum amylase levels were lower in Groups III, IV and V compared to Group II (974 +/- 110, 384 +/- 40, 851 +/- 56, and 1664 +/- 234 U/L, respectively, P < 0.05, for all). Combining the two treatment options revealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations (13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P < 0.01). Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups III, IV and V compared to Group II (54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P < 0.05 for all). CONCLUSION: The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.

Essential hypertension and hypermetropia: is there really an association?

AIM: To investigate the relationship between hypermetropia and systemic hypertension. METHODS: The study was performed on 2 groups of participants (a total of 1,162 participants). Group 1 comprised 370 patients with arterial hypertension and 205 age- and sex-matched normotensive subjects. Hypertension was defined as systolic blood pressure >or=140 mm Hg and/or diastolic blood pressure >or=90 mm Hg. Spherical equivalents between -0.50 and +0.50 dpt were regarded as emmetropia. Keratometry, anterior chamber depth (ACD) and axial length (AL) were measured with IOL Master (Zeiss, USA). Group 2 comprised 124 myopic, 206 emmetropic and 257 hypermetropic subjects. Differences for mean spherical equivalent, keratometry, ACD and AL measurements between hypertensive patients and control subjects (group 1) were compared using independent-sample t test and Mann-Whitney U test, and distributions of refractions were compared with the chi(2) test. Distributions of hypertensive and normotensive subjects (group 2) among myopic, emmetropic and hypermetropic subjects were compared with the chi(2) test. RESULTS: Mean spherical equivalents of the patients with hypertension and of control subjects were -0.03 +/- 1.63 and 0.22 +/- 1.82 dpt, respectively (p = 0.182). The differences for keratometric values, ACD and AL were not significant (p = 0.151, 0.692 and 0.548, respectively). There was also no significant difference (p = 0.143) for hypertension ratios among myopic (66.1%), emmetropic (57.8%) and hypermetropic (55.6%) subjects. CONCLUSION: There is no association between systemic arterial hypertension and hypermetropia.

Functions and oxidative stress status of leukocytes in patients with nephrotic syndrome.

This study was conducted to establish the functions and oxidative stress status in leukocytes of adult patients with nephrotic syndrome. Thirty adult patients with nephrotic syndrome and 32 controls were included. Phagocytosis ability, the killing ability of the micro-organism phagosited of polymorphonuclear leukocytes (PMNL) and monocytes, along with oxidative stress parameters of PMNLs were assessed. There was no statistically significant difference in phagocytosis function of PMNLs and monocytes of patients when compared to those of controls. PMNL burst activities of the patient and control groups also showed no difference; however, the monocyte burst activities of patients were significant (p = 0.012). The glutathione peroxidase (GSH-Px) activities in PMNLs of the patients with nephrotic syndrome were significantly higher (p = 0.026) when compared to those of controls. In comparison with those of the control subjects, the patients had also higher selenium levels in their PMNLs (p < 0.001). Although PMNL malonyldialdehyde (MDA) levels of the patients seem to be higher than those of controls, the difference had no statistical significance (p = 0.071). Conclusively, in the patients with nephrotic syndrome, PMNLs appear to be exposed to an oxidative stress as indicated by their increased GSH-Px activities and selenium content. However, PMNLs in nephrotic syndrome patients seem to be coping with the insulting oxidative stress, as suggested by their near-normal MDA productions. Furthermore, these data suggest that nephrotic syndrome appears not to have an influence on phagocytosis and killing abilities of granulocytes and monocytes as long as these cells can overcome the oxidative stress to which they are exposed in this disease.

Zoledronic Acid Use and Risk of Cognitive Decline among Elderly Women and Men with Osteoporosis.

OBJECTIVES: Bisphosphonates are the first line treatment options in the prevention and treatment of osteoporosis among elderly women or men. Age associated cognitive decline may increase due to adverse effects of medications. The aim of the present study was to observe the course of cognitive skills in elderly subjects treated with a bisphosphonate. MATERIALS AND METHODS: This prospective study enrolled 120 community-dwelling, non-demented women and men with osteoporosis aged 65 and older who were treated with first-ever zoledronic acid. Mini mental state examination (MMSE) was measured along with geriatric depression scale (GDS) measurement, clock drawing test (CDT), and other clinical and laboratory evaluations that could affect cognition at baseline and 12 months. The primary outcome was at least one point decrease in the final MMSE score at one year. RESULTS: Scores of MMSE (28.29±2.17 and 28.23±2.37, p=0.681), GDS (3.24±2.88 and 2.96±2.88, p=0.062) and CDT (3.69±0.68 and 3.75±0.60, p=0.268) did not change after zoledronic acid infusion at one year. Education in years and presence of newly started medicines with anticholinergic properties was independently associated with at least one point reduction in MMSE score [odds ratio: 3.07 (%95 confidence interval: 1.00-9.44)]. CONCLUSION: Among elderly woman and men with osteoporosis, cognitive functions remained stable 12 months after the administration of first-ever zoledronic acid.

Galantamine improves sleep quality in patients with dementia.

The purpose of the study was to evaluate the influences of cholinesterase inhibitors on sleep pattern and sleep disturbance. A total of 87 mild to moderate stage dementia patients who were not on cholinesterase enzyme inhibitor and memantine treatment were included in the study. The dementia patients were treated with donepezil, galantamine or rivastigmine, depending on the preference of the clinician. Fifty-five dementia patients (63.2 %) completed the study. Twenty-three elderly subjects, who had normal cognitive functions, were included in the study as the control group. The Pittsburgh Sleep Quality Index was used for evaluating the sleep quality at the beginning and at the final assessment. The improvement in sleep quality was better with regard to changes in Pittsburgh Sleep Quality Index scores with galantamine treatment compared to the donepezil and the control groups. A significant decrease in Pittsburgh Sleep Quality Index scores was detected in the galantamine group after treatment. Although statistically not significant, rivastigmine decreased and donepezil increased the Pittsburgh Sleep Quality Index scores after treatment. Dementia patients who had a poor sleep quality (n: 36), the rate of improvement in sleep disturbance was 81.8 % in the galantamine group, 75 % in the rivastigmine, and 50 % in the donepezil group. Galantamine may be the first choice of cholinesterase inhibitor in mild to moderate dementia patients in terms of improving sleep quality.

Cognitive and functional influences of vildagliptin, a DPP-4 inhibitor, added to ongoing metformin therapy in elderly with type 2 diabetes.

INTRODUCTION: Diabetes mellitus has been linked to cognitive decrement faster than usual. Medical management of diabetes can also interfere with the cognitive skills. The purpose of this study was to evaluate the effects of vildagliptin on cognition, as an add-on to metformin therapy in elderly patients with type 2 diabetes mellitus. MATERIALS AND METHODS: This was a prospective and observational investigation conducted in 10 elderly type 2 diabetes mellitus patients who were started treatment with vildagliptin 50 mg twice daily to ongoing metformin. All participants underwent detailed clinical cognitive assessment and neuropsychological testing with mini mental state examination (MMSE) and clock drawing test (CDT), along with measurement of functional parameters at entry and study completion. RESULTS: Mean follow-up time was 10.9±3.7 months. No subjects reported significant side effects during the study. At follow-up, in accordance with the clinical assessment, neither MMSE nor CDT showed significant changes after addition of vildagliptin to metformin. Basic and instrumental activities of daily living (BADL and IADL), mini nutrition assessment and geriatric depression scale scores also remained unchanged between the two evaluations. DISCUSSION: In this pilot study, addition of vildagliptin to ongoing metformin therapy in elderly with diabetes was accompanied by stable cognitive and functional performance after almost one year of follow-up.

Effect of vitamin D on insulin sensitivity in elderly patients with impaired fasting glucose.

AIM: Recent data has shown that vitamin D increases insulin sensitivity; however, there is little evidence about the effects of this treatment on elderly people with impaired fasting glucose. The aim of the present study was to investigate the effect of vitamin D treatment on insulin sensitivity and metabolic parameters in elderly people with impaired fasting glucose. METHODS: A total of 28 elderly patients were enrolled into the vitamin D treatment group. The control group included 23 age-, sex- and body mass index-matched elderly participants. The vitamin D treatment group was treated with vitamin D(3) according to serum concentrations of 25(OH)D. RESULTS: With supplementation, 96.0% of patients achieved a mean serum 25(OH)D concentration of 123.2 ± 59.9 nmol/L. After 4.7 ± 2.5 months of treatment, there was a significant decrease in homeostasis model assessment of insulin resistance, insulin and glucose concentrations in the vitamin D treatment group (P = 0.007, P = 0.007, P = 0.037, respectively). Vitamin D treatment significantly increased high-density lipoprotein cholesterol (P = 0.037), but did not cause statistically significant differences in other lipid parameters. CONCLUSION: We found that vitamin D treatment might modify insulin sensitivity in the elderly with impaired fasting glucose.

Cardiac safety of donepezil in elderly patients with Alzheimer disease.

OBJECTIVE: Donepezil is a widely used cholinesterase inhibitor for the treatment of Alzheimer's disease (AD), however its cholinergic adverse side effects on the cardiovascular system are still unclear. In this study, we aimed to examine the adverse side effects caused by donepezil on cardiac rhythm and postural blood pressure changes in elderly patients with Alzheimer Disease. METHODS: The ECG parameters including heart rate, PR, QT, QTc interval and QRS duration and postural blood pressure changes were recorded at the baseline and at each donepezil dose level (5 and 10 mg/d). Patients Seventy-one consecutive patients who were referred by primary care centers to a Geriatric Clinic were enrolled and underwent comprehensive geriatric assessment. RESULTS: Fifty-two subjects completed the study. There were no significant changes relative to the baseline in any of the ECG parameters or arterial blood pressure at any of the investigated dosages of donepezil. CONCLUSION: It was demonstrated that donepezil was not associated with increased negative chronotropic, arrhythmogenic or hypotensive effects for elderly patients with Alzheimer's disease.

Which cholinesterase inhibitor is the safest for the heart in elderly patients with Alzheimer's disease?

OBJECTIVE: Cholinesterase inhibitors (ChEIs) are widely used for the treatment of Alzheimer's disease (AD); however, their cholinergic side effects on the cardiovascular system are still unclear. In this study, we aimed to examine the side effects caused by donepezil, rivastigmine, and galantamine on cardiac rhythm and postural blood pressure changes in elderly patients with AD. METHODS: Of 204 consecutive elderly patients who were newly diagnosed with AD, 162 were enrolled and underwent comprehensive geriatric assessments. The electrocardiographs (ECGs) and blood pressures were recorded at the baseline and 4 weeks after the dose of 10 mg/d of donepezil, 10 cm(2)/d of rivastigmine, and 24 mg/d of galantamine. RESULTS: There were no changes relative to the baseline in any of the ECG parameters or arterial blood pressure with any of the administered ChEIs. CONCLUSION: It was demonstrated that none of the 3 ChEIs were associated with increased negative chronotropic, arrhythmogenic, and hypotensive effects for the elderly patients with AD.

Vitamin B(12) and folic acid levels as therapeutic target in preserving bone mineral density (BMD) of older men.

The knowledge about vitamin B(12) and folic acid levels in preserving bone mass in older men is limited. In this retrospective study, we aimed to find out whether levels of vitamin B(12) and folic acid are related to BMD in older men. Two hundred and sixty-nine older men were included in the study. Forty-two (15.6%) of them had osteoporotic, 150 (55.8%) had osteopenic, and 77 (28.6%) had normal BMD. Vitamin B(12) and folic acid levels were categorized as indicating normal, borderline, or low vitamin statuses. Femur neck densities showed statistically significant differences in subjects having low, borderline, and normal vitamin B(12), respectively. There were no significant differences between the three tertiles of vitamin B(12) in femur total, trochanteric, and intertrochanteric densities. After adjustment for age, body mass index (BMI), alcohol, smoking, and exercise with analysis of covariance, the difference was still statistically significant between two groups for femur neck density (p=0.011). No significant difference was observed between the groups of folic acid in any femur sites. We found that the normal level of vitamin B(12) in older men may be related to a decrease of femur neck bone loss.