Object. Neuropsychological changes are thought to reflect trends in disease progression when monitoring the effectiveness of pharmacological treatment with acetylcholinesterase inhibitors (AChEI) in patients with amnesic mild cognitive impairment (a-MCI). Due to high inter-individual variability in the response to AChEI treatment, psychometric instruments usually administered by clinicians might fail to detect quantitatively subtle but clinically significant modifications in neuropsychological functioning when group analyses are conducted. Single-case approaches can increase statistical validity of longitudinal assessments. The aim of this study is to provide a proof of concept for a practical single-case statistical method to evaluate AChEI treatment effectiveness in patients with a-MCI in clinical settings. Materials. Three consecutive a-MCI patients undergoing AChEI treatment were recruited according to Petersen’s criteria (2004). Treatment effectiveness was assessed by evaluating anterograde long-term episodic memory. Ad hoc use frequency-, length in syllables- and semantic category-balanced word lists were created and used as verbal learning test material. Methods. The C statistic for single-case time series analyses [Neumann, 1941; Young, 1941] was adopted. C tests the null hypothesis that a time series/time series aggregations follows a random trend. Eight observations are sufficient for its test statistic z to approximately be normally distributed (with a critic z = 1.64 at α = .05 for a bidirectional hypothesis [Young, 1941]). Eight different 15-words lists were thus administered at 3 time points according to an A-B-A’ repeated measures design: before the beginning of treatment (A; baseline), after 8 weeks of treatment (B; intervention) and after 2 wash-out weeks from treatment suspension occurred at time B (A’; inversion). The outcome variable was the number of words immediately recalled. Patients were classified as good- or bad-responders to AChEI treatment depending upon the significance of AB and BA’ time series aggregations trends. Results. One patient was classified as a good-responder (AB and BA’ p < .01; AA’ p > .05). Two patients were classified as bad-reponders (no significant trends). Discussion. It has been provided a proof of concept that C statistic can discriminate between a-MCI patients who do and do not benefit from AChEI treatment. This method could be extended to other clinical scenarios requiring single-patient-level analyses due to high inter-individual treatment response variability. Conclusions. Single-case approaches are encouraged when evaluating effectiveness of AChEI treatment in a-MCI. The C statistic subserves this aim and is suitable for clinical settings since it requires a small number of observations.

Aiello, E., Difonzo, T., Zago, S. (2019). Good- or bad-responders? A novel single-case statistical method to evaluate pharmacological treatment effectiveness through neuropsychological changes in amnesic mild cognitive impairment. Intervento presentato a: Annual Meeting of Milan Center for Neuroscience, Milan, Italy.

Good- or bad-responders? A novel single-case statistical method to evaluate pharmacological treatment effectiveness through neuropsychological changes in amnesic mild cognitive impairment

Edoardo Nicolò Aiello
Primo
;
2019

Abstract

Object. Neuropsychological changes are thought to reflect trends in disease progression when monitoring the effectiveness of pharmacological treatment with acetylcholinesterase inhibitors (AChEI) in patients with amnesic mild cognitive impairment (a-MCI). Due to high inter-individual variability in the response to AChEI treatment, psychometric instruments usually administered by clinicians might fail to detect quantitatively subtle but clinically significant modifications in neuropsychological functioning when group analyses are conducted. Single-case approaches can increase statistical validity of longitudinal assessments. The aim of this study is to provide a proof of concept for a practical single-case statistical method to evaluate AChEI treatment effectiveness in patients with a-MCI in clinical settings. Materials. Three consecutive a-MCI patients undergoing AChEI treatment were recruited according to Petersen’s criteria (2004). Treatment effectiveness was assessed by evaluating anterograde long-term episodic memory. Ad hoc use frequency-, length in syllables- and semantic category-balanced word lists were created and used as verbal learning test material. Methods. The C statistic for single-case time series analyses [Neumann, 1941; Young, 1941] was adopted. C tests the null hypothesis that a time series/time series aggregations follows a random trend. Eight observations are sufficient for its test statistic z to approximately be normally distributed (with a critic z = 1.64 at α = .05 for a bidirectional hypothesis [Young, 1941]). Eight different 15-words lists were thus administered at 3 time points according to an A-B-A’ repeated measures design: before the beginning of treatment (A; baseline), after 8 weeks of treatment (B; intervention) and after 2 wash-out weeks from treatment suspension occurred at time B (A’; inversion). The outcome variable was the number of words immediately recalled. Patients were classified as good- or bad-responders to AChEI treatment depending upon the significance of AB and BA’ time series aggregations trends. Results. One patient was classified as a good-responder (AB and BA’ p < .01; AA’ p > .05). Two patients were classified as bad-reponders (no significant trends). Discussion. It has been provided a proof of concept that C statistic can discriminate between a-MCI patients who do and do not benefit from AChEI treatment. This method could be extended to other clinical scenarios requiring single-patient-level analyses due to high inter-individual treatment response variability. Conclusions. Single-case approaches are encouraged when evaluating effectiveness of AChEI treatment in a-MCI. The C statistic subserves this aim and is suitable for clinical settings since it requires a small number of observations.
abstract + poster
mild cognitive impairment, acetylcholinesterase inhibitors, psychometrics
English
Annual Meeting of Milan Center for Neuroscience
2019
2019
none
Aiello, E., Difonzo, T., Zago, S. (2019). Good- or bad-responders? A novel single-case statistical method to evaluate pharmacological treatment effectiveness through neuropsychological changes in amnesic mild cognitive impairment. Intervento presentato a: Annual Meeting of Milan Center for Neuroscience, Milan, Italy.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/254029
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