The safety, tolerability, and efficacy of once-daily memantine (28 mg): A multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe alzheimers disease taking cholinesterase inhibitors
Grossberg G.T.,Saint Louis University |
Manes F.,Institute Neurologia Cognitiva INECO |
Allegri R.F.,Institute Investigaciones Neurologicas Raul Carrea FLENI |
Gutierrez-Robledo L.M.,Institute Geriatria |
And 7 more authors.
CNS Drugs | Year: 2013
Introduction: Immediate-release memantine (10 mg, twice daily) is approved in the USA for moderate-to-severe Alzheimer's disease (AD). This study evaluated the efficacy, safety, and tolerability of a higher-dose, once-daily, extended-release formulation in patients with moderate-to-severe AD concurrently taking cholinesterase inhibitors. Methods: In this 24-week, double-blind, multinational study (NCT00322153), outpatients with AD (Mini-Mental State Examination scores of 3-14) were randomized to receive once-daily, 28-mg, extended-release memantine or placebo. Co-primary efficacy parameters were the baseline-to-endpoint score change on the Severe Impairment Battery (SIB) and the endpoint score on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus). The secondary efficacy parameter was the baseline-to-endpoint score change on the 19-item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19); additional parameters included the baseline-to-endpoint score changes on the Neuropsychiatric Inventory (NPI) and verbal fluency test. Data were analyzed using a two-way analysis of covariance model, except for CIBIC-Plus (Cochran-Mantel-Haenszel test). Safety and tolerability were assessed through adverse events and physical and laboratory examinations. Results: A total of 677 patients were randomized to receive extended-release memantine (n = 342) or placebo (n = 335); completion rates were 79.8 and 81.2 %, respectively. At endpoint (week 24, last observation carried forward), memantine-treated patients significantly outperformed placebo-treated patients on the SIB (least squares mean difference [95 % CI] 2.6 [1.0, 4.2]; p = 0.001), CIBIC-Plus (p = 0.008), NPI (p = 0.005), and verbal fluency test (p = 0.004); the effect did not achieve significance on ADCS-ADL19 (p = 0.177). Adverse events with a frequency of ≥5.0 % that were more prevalent in the memantine group were headache (5.6 vs. 5.1 %) and diarrhea (5.0 vs. 3.9 %). Conclusion: Extended-release memantine was efficacious, safe, and well tolerated in this population. © 2013 The Author(s).
Gutierrez-Robledo L.M.,Institute Geriatria
European Geriatric Medicine | Year: 2012
Sarcopenia is an increasingly recognized problem in the elderly. Recently an algorithm to detect this condition was developed. The aim of our study was to determine the prevalence of sarcopenia in a group of elderly in Mexico City, using the European Wording Group on Sarcopenia in Older People (EWGSOP) algorithm. A cross-sectional assessment of community dwelling elderly was performed in a sample of 345 subjects, who were 70 years or older, during the year of 2008. The data was gathered by a group of standardized interviewers. In order to determine sarcopenia, muscle mass, muscle strength and physical performance were obtained from database. Muscle mass was measured by means of calf circumference, muscle strength by grip strength and physical performance by gait speed. Cut-points suggested in the EWGSOP algorithm of sarcopenia detection (ASD) were used. A total number of 116 (33.6%) subjects were detected as sarcopenic, 75 (48.5%) women and 41 (27.4%) men; with a greater prevalence in 80-year or older subjects (50.4%). Sarcopenic obesity was found in five subjects (1.4%), moderate sarcopenia in 21 subjects (6%) and severe sarcopenia in 94 subjects (27.2%). The ASD of the EWGSOP is a useful tool for detecting sarcopenia prevalence; the frequency in our population was similar to other reports using other methodology. © 2012 Published by Elsevier Masson SAS.
Arango-Lopera V.E.,Institute Geriatria |
Arroyo P.,Institute Geriatria |
Gutierrez-Robledo L.M.,Institute Geriatria Periferico sur |
Perez-Zepeda M.U.,Institute Geriatria
Journal of Nutrition, Health and Aging | Year: 2013
Sarcopenia has an important impact in elderly. Recently the European Working Group on Sarcopenia in Older People (EWGSOP) defined sarcopenia as the loss of muscle mass plus low muscle strength or low physical performance. Lack of clinical sounding outcomes (ie external validity), is one of the flaws of this algorithm. The aim of our study was to determine the association of sarcopenia and mortality in a group of Mexican elderly. A total of 345 elderly were recruited in Mexico City, and followed up for three years. The EWGSOP algorithm was integrated by: gait speed, grip strength and calf circumference. Other covariates were assessed in order to test the independent association of sarcopenia with mortality. Of the 345 subjects, 53.3% were women; with a mean age of 78.5 (SD 7) years. During the three year follow-up a total of 43 (12.4%) subjects died. Age, cognition, ADL, IADL, health self-perception, ischemic heart disease and sarcopenia were associated in the bivariate analysis with survival. Negative predictive value for sarcopenia regarding mortality was of 90%. Kaplan-Meier curves along with their respective log-rank test were significant for sarcopenia. The components of the final Cox-regression multivariate model were age, ischemic heart disease, ADL and sarcopenia. Adjusted HR for age was 3.24 (CI 95% 1.55-6.78 p 0.002), IHD 5.07 (CI 95% 1.89-13.59 p 0.001), health self-perception 5.07 (CI 95% 1.9-13.6 p 0.001), ADL 0.75 (CI 95% 0.56-0.99 p 0.048) and sarcopenia 2.39 (CI 95% 1.05-5.43 p 0.037). © 2012 Serdi and Springer-Verlag France.
Ramadori G.,University of Texas Southwestern Medical Center |
Fujikawa T.,University of Texas Southwestern Medical Center |
Anderson J.,University of Texas Southwestern Medical Center |
Berglund E.D.,University of Texas Southwestern Medical Center |
And 8 more authors.
Cell Metabolism | Year: 2011
Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions. Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance. Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure. Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle. Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone leptin. Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity. Our results unveil important protective roles of SIRT1 in SF1 neurons against dietary metabolic imbalance. © 2011 Elsevier Inc.
Mejia-Arango S.,Colegio de Mexico |
Gutierrez L.M.,Institute Geriatria
Journal of Aging and Health | Year: 2011
Objective: To estimate the prevalence and incidence of dementia and cognitive impairment without dementia (CIND) in the Mexican population. Method: The MHAS study is a prospective panel study of health and aging in Mexico with 7,000 elders that represent eight million participants nationally. Using measurements of cognition and activities of daily living of dementia cases and CIND were identified at baseline and follow-up. Overall incidence rates and specific rates for sex, age, and education were calculated. Results: Prevalence was 6.1% and 28.7% for dementia and CIND, respectively. Incidence rates were 27.3 per 1,000 person-years for dementia and 223 per 1,000 persons-year for CIND. Rates of dementia and CIND increased with advancing age and decreased with higher educational level; sex had a differential effect depending on the age strata. Hypertension, diabetes, and depression were risk factors for dementia but not for CIND. Discussion: These data provide estimates of prevalence and incidence of dementia and cognitive impairment in the Mexican population for projection of future burden. © 2011 SAGE Publications.
Tovar-y-Romo L.B.,National Autonomous University of Mexico |
Tovar-y-Romo L.B.,Institute Geriatria |
Tapia R.,National Autonomous University of Mexico
Journal of Neurochemistry | Year: 2010
Vascular endothelial growth factor (VEGF) protects spinal motor neurons in models of familial amyotrophic lateral sclerosis. We previously demonstrated that VEGF also prevents motor neuron death and hindlimb paralysis in rats subjected to α-amino-3-hydroxy-5-isoxazolepropionate (AMPA)-induced chronic excitotoxic motor neuron degeneration. Here, we show that tyrosine kinase receptor-2 for VEGF (VEGFR2) is expressed in spinal motor neurons of the adult rat, and that its blockade impedes the VEGF-mediated protection against motor neuron death and paralysis. In addition, inhibition of phosphatidyl-inositol-3-kinase, which is activated by VEGFR2, completely prevented this protection, whereas blockade of mitogen-activated protein kinase kinases resulted only in a partial prevention. We show as well that AMPA induces an increased p38 mitogen-activated protein kinase (p38MAPK) phosphorylation and that VEGF blocks this effect. Furthermore, inhibition of p38MAPK prevents the paralysis induced by AMPA. These results shed light into the mechanisms of the protective effect of VEGF against excitotoxic motor neuron death in vivo and suggest that VEGFR2 and activation of phosphatidyl-inositol-3-kinase or inhibition of p38MAPK might be important therapeutic targets for amyotrophic lateral sclerosis. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.
Quiroz-Baez R.,National Autonomous University of Mexico |
Quiroz-Baez R.,Institute Geriatria |
Flores-Dominguez D.,National Autonomous University of Mexico |
Arias C.,National Autonomous University of Mexico
Current Alzheimer Research | Year: 2013
Synaptic loss is the major neuropathological correlate of memory decline as a result of Alzheimer's Disease (AD). Synaptic failure appears to depend on the toxic actions of small and soluble amyloid-β (Aβ) oligomers. However, few studies have addressed the mechanism by which aging makes synapses more vulnerable to Aβ toxicity. In the present study we analyzed mitochondrial function and morphology and markers of oxidative stress in isolated presynaptic nerve endings from the hippocampus that were exposed to Aβ peptide at different ages. We found an age-related decline in mitochondrial activity, reduced antioxidant contents and increased oxidative stress markers in resting and depolarized synaptic terminals. Ultrastructural changes including an increase in mitochondrial size and a significant reduction of synaptic vesicles contents were also observed. In addition, synaptosomes obtained from 24 month old rats were more sensitive to Aβ toxicity. These data provide evidence of morphological and biochemical synaptic changes associated with aging that may contribute to exacerbate the damaging effects of Aβ. © 2013 Bentham Science Publishers.
Castrejon-Perez R.C.,National Autonomous University of Mexico |
Castrejon-Perez R.C.,Institute Geriatria |
Borges-Yanez S.A.,National Autonomous University of Mexico
Gerodontology | Year: 2012
Background and Objective: The Oral Health Impact Profile is the most frequently used and validated of the Oral Health Quality of Life instruments. Several short versions have been developed; and a validation of the OHIP-49 in Spanish has been published. The objective was to develop the short version of the Oral Health Impact Profile in Spanish (OHIP-EE-14). Methods: Cross-sectional study. One hundred and thirty-one persons aged ≥60 years attending a social centre for the elderly, residents of a nursing home and persons seeking dental care at a dental school in Mexico City were interviewed and examined. The validity of each of the 49 questions was evaluated, and, to construct the short version, 14 items were selected. The perceived need for dental treatment, number of teeth, presence of coronal caries, root caries, presence of dental plaque and utilisation of removable prosthesis were measured. Internal consistency, repeatability and discriminant validity were calculated. Results: The OHIP-EE-14 was reliable (Cronbach's-α = 0.918, ICC = 0.825). Significant associations were found between OHIP-EE-14 and the number of teeth and perceived need for dental treatment. Conclusions: The OHIP-EE-14 is a reliable and valid instrument and can be used in subjects aged 60 years and over from Mexico City. © 2012 The Gerodontology Society and John Wiley & Sons A/S.
Gonzlez-Gonzlez C.,Institute Geriatria |
Snchez-Garcia S.,Instituto Mexicano Del Seguro Social |
Jurez-Cedillo T.,Instituto Mexicano Del Seguro Social |
Rosas-Carrasco O.,Institute Geriatria |
And 2 more authors.
BMC Public Health | Year: 2011
Background: Worldwide population aging has been considered one of the most important demographic phenomena, and is frequently referred as a determinant of health costs and expenditures. These costs are an effect either of the aging process itself (social) or because of the increase that comes with older age (individual). Objective. To analyze health expenditures and its determinants in a sample of Mexican population, for three dimensions acute morbidity, ambulatory care and hospitalization focusing on different age groups, particularly the elderly. Methods. A secondary analysis of the Mexican National Health and Nutrition Survey (ENSANUT), 2006 was conducted. A descriptive analysis was performed to establish a health profile by socio-demographic characteristics. Logistic regression models were estimated to determine the relation between acute morbidity, ambulatory care, hospitalization and age group; to establish the determinants of hospitalization among the population 60 years and older; and to determine hospitalization expenditures by age. Results: Higher proportion of elderly reporting health problems was found. Average expenditures of hospitalization in households were $240.6 am dlls, whereas in households exclusively with elderly the expenditure was $308.9 am dlls, the highest among the considered age groups. The multivariate analysis showed higher probability of being hospitalized among the elderly, but not for risks for acute morbidity and ambulatory care. Among the elderly, older age, being male or living in a city or in a metro area implied a higher probability of hospitalization during the last year, with chronic diseases playing a key role in hospitalization. Conclusions: The conditions associated with age, such as chronic diseases, have higher weight than age itself; therefore, they are responsible for the higher expenditures reported. Conclusions point towards a differentiated use and intensity of health services depending on age. The projected increase in hospitalization and health care needs for this group requires immediate attention. © 2011 Gonzlez-Gonzlez et al; licensee BioMed Central Ltd.
Avila-Fematt F.M.G.,Institute Geriatria |
Montana-Alvarez M.,Institute Geriatria
Revista de Investigacion Clinica | Year: 2010
Aging is associated with an increasing prevalence of chronic diseases, including type 2 diabetes mellitus and its chronic and acute complications. With changes observed in diabetes mellitus treatment goals and the lower levels of glycosylated hemoglobin recommended, the prevalence of hypoglycemia especially in patients treated with insulin has increased. Aging and changes in the physiologic reserves generate a decreased perception of symptoms associated with hypoglycemia, increasing the risk of unawareness or severe episodes. Traditionally, age was a risk factor for hypoglycemia, but in the population over 60 years, multiple comorbidities like chronic heart failure, malnutrition and renal failure are associated with increased risk of developing this acute complication. It is necessary to train doctors and nurses from all levels of care to recognize the specific clinical manifestation of low blood glucose that allow early detection and treatment, because this complication is associated with an increased hospital and 1-year after discharge mortality, with falls and cognitive impairment that directly affect the independence and functionality of older persons.