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1.  Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy 
Introduction
Memantine and cholinesterase inhibitors potentially offer additional benefits in Alzheimer's disease (AD) when used together. This study assessed the efficacy and safety of combination treatment with memantine added to stable donepezil in patients with moderate to severe AD, and in a subset with moderate AD.
Methods
Post hoc meta-analyses of data combined from two 24-week, randomised, double-blind, placebo-controlled trials of memantine 20 mg/day versus placebo, added to a stable cholinesterase inhibitor, were conducted. Data were included for all patients receiving donepezil 10 mg/day with Mini-Mental State Examination (MMSE) scores < 20 (n = 510). Efficacy was assessed using measures of cognition, function, and global status. Furthermore, marked clinical worsening, defined as concurrent deterioration from baseline in the three main efficacy domains, and safety, measured by treatment-emergent adverse events, were assessed. Analyses were performed for patients with moderate to severe AD (MMSE 5-19; MOD-SEV subgroup), and also for patients with moderate AD (MMSE 10-19; MOD subgroup; n = 367).
Results
At week 24, in the MOD-SEV subgroup, patients receiving memantine added to donepezil significantly outperformed those receiving placebo added to donepezil in measures of cognition (P < 0.0001), function (P = 0.02), and global status (P = 0.010), with standardised mean differences (SMDs) of 0.36, 0.21, and 0.23, respectively (all last observation carried forward). Similarly, in the MOD subgroup, significant benefits were observed for cognition (P = 0.008), function (P = 0.04) and global status (P = 0.008), with SMDs of 0.28, 0.21, and 0.28, respectively. Significantly fewer patients receiving memantine added to donepezil showed marked clinical worsening than those receiving placebo added to donepezil, in both subgroups (MOD-SEV: 8.7% versus 20.4%, P = 0.0002; MOD: 5.9% versus 15.0%, P = 0.006). The incidence of adverse events was similar between treatment groups.
Conclusions
These results support and extend previous evidence that combination treatment with memantine added to stable donepezil in patients with moderate AD, and in those with moderate to severe AD, is associated with significant benefits in reducing 24-week decline in cognition, function and global status. Combination treatment produces substantially reduced rates of marked clinical worsening, has good safety and tolerability, and generates effect sizes that are both statistically significant and clinically meaningful.
doi:10.1186/alzrt160
PMCID: PMC3580327  PMID: 23336974
2.  A web-based normative calculator for the uniform data set (UDS) neuropsychological test battery 
Introduction
With the recent publication of new criteria for the diagnosis of preclinical Alzheimer's disease (AD), there is a need for neuropsychological tools that take premorbid functioning into account in order to detect subtle cognitive decline. Using demographic adjustments is one method for increasing the sensitivity of commonly used measures. We sought to provide a useful online z-score calculator that yields estimates of percentile ranges and adjusts individual performance based on sex, age and/or education for each of the neuropsychological tests of the National Alzheimer's Coordinating Center Uniform Data Set (NACC, UDS). In addition, we aimed to provide an easily accessible method of creating norms for other clinical researchers for their own, unique data sets.
Methods
Data from 3,268 clinically cognitively-normal older UDS subjects from a cohort reported by Weintraub and colleagues (2009) were included. For all neuropsychological tests, z-scores were estimated by subtracting the raw score from the predicted mean and then dividing this difference score by the root mean squared error term (RMSE) for a given linear regression model.
Results
For each neuropsychological test, an estimated z-score was calculated for any raw score based on five different models that adjust for the demographic predictors of SEX, AGE and EDUCATION, either concurrently, individually or without covariates. The interactive online calculator allows the entry of a raw score and provides five corresponding estimated z-scores based on predictions from each corresponding linear regression model. The calculator produces percentile ranks and graphical output.
Conclusions
An interactive, regression-based, normative score online calculator was created to serve as an additional resource for UDS clinical researchers, especially in guiding interpretation of individual performances that appear to fall in borderline realms and may be of particular utility for operationalizing subtle cognitive impairment present according to the newly proposed criteria for Stage 3 preclinical Alzheimer's disease.
doi:10.1186/alzrt94
PMCID: PMC3308021  PMID: 22078663
Alzheimer's disease; cognitive aging; MCI; memory; norms

Results 1-2 (2)