Spatial Statistics with S-Plus

An overview is given over the S-Plus libraries and modules for statistical analysis of spatial data that are currently available at the Department of Statistics, University of Dortmund. It is believed that this includes all libraries currently available on the internet. Listings of functions show what statistical techniques are implemented, and where to find them. This facilitates the search for any particular function, and saves from re-programming of techniques that are already available. This overview may therefore also be viewed as a starting point for developing further analysis tools for spatial and spatio-temporal statistics in S-Plus

Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch

INTRODUCTION: OPtimizing Transdermal Exelon In Mild-to-moderate Alzheimer’s disease (OPTIMA) was a randomized, double-blind comparison of 13.3 mg/24 h versus 9.5 mg/24 h rivastigmine patch in patients with mild-to-moderate Alzheimer’s disease who declined despite open-label treatment with 9.5 mg/24 h patch. Over 48 weeks of double-blind treatment, high-dose patch produced greater functional and cognitive benefits compared with 9.5 mg/24 h patch. METHODS: Using OPTIMA data, a post-hoc responder analysis was performed to firstly, compare the proportion of patients demonstrating improvement or absence of decline with 13.3 mg/24 h versus 9.5 mg/24 h patch; and secondly, identify predictors of improvement or absence of decline. ‘Improvers’ were patients who improved on the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog) by ≥4 points from baseline, and did not decline on the instrumental domain of the Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale (ADCS-IADL). ‘Non-decliners’ were patients who did not decline on either scale. RESULTS: Overall, 265 patients randomized to 13.3 mg/24 h and 271 to 9.5 mg/24 h patch met the criteria for inclusion in the intention-to-treat population and were included in the analyses. Significantly more patients were ‘improvers’ with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Weeks 24 (44 (16.6%) versus 19 (7.0%); P < 0.001) and 48 (21 (7.9%) versus 10 (3.7%); P = 0.023). A significantly greater proportion of patients were ‘non-decliners’ with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Week 24 (71 (26.8%) versus 44 (16.2%); P = 0.002). At Week 48, there was a trend in favor of 13.3 mg/24 h patch. Functional and cognitive assessment scores at double-blind baseline did not consistently predict effects at Weeks 24 or 48. CONCLUSION: More patients with mild-to-moderate Alzheimer’s disease who are titrated to 13.3 mg/24 h rivastigmine patch at time of decline are ‘improvers’ or ‘non-decliners’ i.e. show responses on cognition and activities of daily living compared with patients remaining on 9.5 mg/24 h patch. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00506415; registered July 20, 2007. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-014-0088-8) contains supplementary material, which is available to authorized users

Efficacy of Higher Dose 13.3 mg/24 h Rivastigmine Patch on Instrumental Activities of Daily Living in Patients with Mild-to-Moderate Alzheimer's Disease

Background: Stabilizing/reducing decline in the ability to perform activities of daily living (ADLs) is important in management of Alzheimer's disease (AD). Methods: Post hoc analysis of OPtimizing Transdermal Exelon In Mild-to-moderate Alzheimer's disease (OPTIMA), a double-blind trial comparing 13.3 and 9.5 mg/24 h rivastigmine patch in patients with AD demonstrating functional and cognitive decline with 9.5 mg/24 h patch. Efficacy on Alzheimer's disease Cooperative Study-instrumental ADL (ADCS-IADL) items, higher level function (HLF), and autonomy factors was assessed. Results: The ADCS-IADL, HLF, and autonomy factors favored 13.3 mg/24 h patch at all time points, reaching significance from weeks 16 to 48, 24 to 48, and 32 to 48, respectively. Higher dose patch demonstrated significantly greater efficacy on 10 of 17 ADCS-IADL items at 1 or more time points ( P < .05 vs 9.5 mg/24 h patch). More adverse events were observed with higher dose patch; study discontinuations were similar between the doses. Conclusions: Greater efficacy of 13.3 versus 9.5 mg/24 h patch on ADL, including autonomy and HLF factors, supports this additional dosing option to prolong patients' independence

Alzheimer's Disease Assessment Scale-Cognitive subscale variants in mild cognitive impairment and mild Alzheimer's disease: change over time and the effect of enrichment strategies

Background Development of new treatments for Alzheimer’s disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline. The 11-item version of the Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-Cog) was originally developed to measure cognition in patients with mild to moderate AD. Attempts to improve its properties for early AD by removing items prone to ceiling and/or by adding cognitive measures known to be impaired early have yielded a number of ADAS-Cog variants. Using Alzheimer’s Disease Neuroimaging Initiative data, we compared the performance of the 3-, 5-, 11- and 13-item ADAS-Cog variants in subjects with early AD. Given the interest in enrichment strategies, we also examined this aspect with a focus on cerebrospinal fluid (CSF) markers. Methods Subjects with mild cognitive impairment (MCI) and mild AD with available ADAS-Cog 13 and CSF data were analysed. The decline over time was defined by change from baseline. Direct cross-comparison of the ADAS-Cog variants was performed using the signal-to-noise ratio (SNR), with higher values reflecting increased sensitivity to detect change over time. Results The decline over time on any of the ADAS-Cog variants was minimal in subjects with MCI. Approximately half of subjects with MCI fulfilled enrichment criteria for positive AD pathology. The impact of enrichment was detectable but subtle in MCI. The annual decline in mild AD was more pronounced but still modest. More than 90 % of subjects with mild AD had positive AD pathology. SNRs were low in MCI but greater in mild AD. The numerically largest SNRs were seen for the ADAS-Cog 5 in MCI and for both the 5- and 13-item ADAS-Cog variants in mild AD, although associated confidence intervals were large. Conclusions The possible value of ADAS-Cog expansion or reduction is less than compelling, particularly in MCI. In mild AD, adding items known to be impaired at early stages seems to provide more benefit than removing items on which subjects score close to ceiling

der Universität Dortmund

I would like to thank Johannes Hüsing, University of Essen, for first drawing my attention to the analysis of AMD data, and Dr. Bernhard Jurklies and Malte Weismann, Eye Hospital of the University of Essen, for providing the AMD data sets analyzed. Helpful comments on the general structure of the manuscript were given by Dres. Roland Fried and Claudia Becker, University of Dortmund. Dr. Indranil Chakrabarti and Maritza Meléndez, M.Sc., M.Sc. patiently checked my use of the English language and took care of the readability of the result. Thanks also to Professor Dr. E.E. Sutter for kindly giving the permission to include Figure 2.2 into the manuscript. Matthias Schneider took a lot of effort to convert it into a printable format. In also want to thank Professor Dr. Wolfgang Urfer for encouraging me to tackle spatiotemporal statistics in the first place, and Professor Dr. Siegfried Schach for fruitful discussions on the topic while preparing the thesis. My special thanks, however, go to Professor Dr. Ursula Gather, who gave me the opportunity to join her research group, and who guided me through the last stages of my work. This doctorate thesis was written while the author was a member of the collaborative researc

Additional file 3: of Alzheimer’s Disease Assessment Scale–Cognitive subscale variants in mild cognitive impairment and mild Alzheimer’s disease: change over time and the effect of enrichment strategies

MMSE score up to 24 months for subjects with MCI and mild AD. Supplementary table providing details of MMSE score up to 24 months for subjects with MCI and mild AD. (DOCX 14 kb

Alzheimer's Disease Assessment Scale-Cognitive subscale variants in mild cognitive impairment and mild Alzheimer's disease: change over time and the effect of enrichment strategies.

BackgroundDevelopment of new treatments for Alzheimer's disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline. The 11-item version of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) was originally developed to measure cognition in patients with mild to moderate AD. Attempts to improve its properties for early AD by removing items prone to ceiling and/or by adding cognitive measures known to be impaired early have yielded a number of ADAS-Cog variants. Using Alzheimer's Disease Neuroimaging Initiative data, we compared the performance of the 3-, 5-, 11- and 13-item ADAS-Cog variants in subjects with early AD. Given the interest in enrichment strategies, we also examined this aspect with a focus on cerebrospinal fluid (CSF) markers.MethodsSubjects with mild cognitive impairment (MCI) and mild AD with available ADAS-Cog 13 and CSF data were analysed. The decline over time was defined by change from baseline. Direct cross-comparison of the ADAS-Cog variants was performed using the signal-to-noise ratio (SNR), with higher values reflecting increased sensitivity to detect change over time.ResultsThe decline over time on any of the ADAS-Cog variants was minimal in subjects with MCI. Approximately half of subjects with MCI fulfilled enrichment criteria for positive AD pathology. The impact of enrichment was detectable but subtle in MCI. The annual decline in mild AD was more pronounced but still modest. More than 90&nbsp;% of subjects with mild AD had positive AD pathology. SNRs were low in MCI but greater in mild AD. The numerically largest SNRs were seen for the ADAS-Cog 5 in MCI and for both the 5- and 13-item ADAS-Cog variants in mild AD, although associated confidence intervals were large.ConclusionsThe possible value of ADAS-Cog expansion or reduction is less than compelling, particularly in MCI. In mild AD, adding items known to be impaired at early stages seems to provide more benefit than removing items on which subjects score close to ceiling