This article was downloaded by: [McMaster University] On: 14 February 2015, At: 00:50 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
The Clinical Neuropsychologist Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ntcn20
Cognition in MCI and Alzheimer’s Disease: Baseline Data from a Longitudinal Study of the NTB ab
c
d
John Harrison , Dorene M. Rentz , Trent McLaughlin , Timothy e
d
f
d
Niecko , Keith M. Gregg , Ronald S. Black , Jacqui Buchanan , d
g
Enchi Liu , Michael Grundman & for the ELN-AIP-901 Study Investigator Group a
Metis Cognition Ltd., Wiltshire, UK
b
Department of Medicine, Imperial College, London, UK
c
Click for updates
Department of Neurology, Brigham and Women’s Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA d
Janssen Alzheimer Immunotherapy Research and Development, LLC, South San Francisco, CA, USA, e
Niecko Health Economics, LLC, Naples, FL, USA
f
Pfizer Inc., Collegeville, PA, USA
g
Global R&D Partners Inc., San Diego, CA, USA Published online: 13 Feb 2014.
To cite this article: John Harrison, Dorene M. Rentz, Trent McLaughlin, Timothy Niecko, Keith M. Gregg, Ronald S. Black, Jacqui Buchanan, Enchi Liu, Michael Grundman & for the ELNAIP-901 Study Investigator Group (2014) Cognition in MCI and Alzheimer’s Disease: Baseline Data from a Longitudinal Study of the NTB, The Clinical Neuropsychologist, 28:2, 252-268, DOI: 10.1080/13854046.2013.875595 To link to this article: http://dx.doi.org/10.1080/13854046.2013.875595
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources
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This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
The Clinical Neuropsychologist, 2014 Vol. 28, No. 2, 252–268, http://dx.doi.org/10.1080/13854046.2013.875595
Cognition in MCI and Alzheimer’s Disease: Baseline Data from a Longitudinal Study of the NTB John Harrison1,2, Dorene M. Rentz3, Trent McLaughlin4, Timothy Niecko5, Keith M. Gregg4, Ronald S. Black6, Jacqui Buchanan4, Enchi Liu4, and Michael Grundman7 for the ELN-AIP-901 Study Investigator Group 1
Metis Cognition Ltd., Wiltshire, UK Department of Medicine, Imperial College, London, UK 3 Department of Neurology, Brigham and Women’s Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA 4 Janssen Alzheimer Immunotherapy Research and Development, LLC, South San Francisco, CA, USA, 5 Niecko Health Economics, LLC, Naples, FL, USA 6 Pfizer Inc., Collegeville, PA, USA 7 Global R&D Partners Inc., San Diego, CA, USA
Downloaded by [McMaster University] at 00:50 14 February 2015
2
Baseline data are summarized from a study examining the psychometric properties of the Neuropsychological Test Battery (NTB) and its subtests, and correlating the NTB with other cognitive and functional assessments. A multicenter, longitudinal, non-interventional study included mild to moderate Alzheimer’s disease (AD, n = 196), mild cognitive impairment (MCI, n = 70), or normal cognition participants (NC, n = 75). The NTB, other cognitive assessment tools, functional/behavioral questionnaires, and health outcome assessments were administered. At baseline composite NTB, NTB memory, and NTB executive function z-scores were significantly lower for participants with AD compared with MCI, and for participants with MCI compared with NC. The composite NTB z-score had high test–retest reliability between screening and baseline. The results of this study suggest that NTB exhibits good reliability in patients with mild to moderate AD and MCI. Keywords: Alzheimer’s disease; Cognition; MCI; Neuropsychological Test Battery; Psychometric properties.
INTRODUCTION Valid and reliable measures of cognition that track progression, including changes in the earliest stages of the disease course, are needed for clinical trials of Alzheimer’s disease (AD). A cognitive outcome measure commonly used in clinical trials, the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), has shown poor sensitivity in discerning cognitive change in patients with mild cognitive impairment (MCI) and early AD (Sevigny, Peng, Liu, Lines, 2010; Winblad et al., 2008). In contrast, the Neuropsychological Test Battery (NTB) was developed to track clinical progression in AD clinical trials and was shown to be a potentially useful assessment in patients with mild to moderate AD (Harrison et al., 2007). It evaluates cognitive Address correspondence to: John Harrison, BSc(Hons), PhD, CSci, CPsychol, Metis Cognition Ltd, Park House, Kilmington Common, Warminster, Wiltshire, BA12 6QY, UK. E-mail: [email protected] (Received 26 July 2013; accepted 10 December 2013)
© 2014 Taylor & Francis
Downloaded by [McMaster University] at 00:50 14 February 2015
BASELINE NTB STUDY DATA
253
domains that are known to be affected in patients with AD, some of which are inadequately assessed with the ADAS-Cog (e.g., visual memory, delayed recall, and executive function) (Harrison et al., 2007). It is a composite of nine widely used neuropsychological tests that assess immediate and delayed recall of verbal and visual information, attention, verbal fluency, and executive function (Harrison et al., 2007). These individual measures have previously been shown to be reliable, valid for use in AD, and sensitive to cognitive decline (Gilman et al., 2005). A comparison of the NTB and ADAS-Cog in clinical trials in patients with AD showed the NTB to be more sensitive than the ADAS-Cog in patients with mild AD (Black et al., 2009). The purpose of this study was to gather both cross-sectional and longitudinal data and to use the baseline cross-sectional data to explore the psychometric properties of the NTB versus other neuropsychological measures across a range of cognitive performance from normal cognition (NC) to MCI and AD. This paper summarizes baseline data from the study, including cross-sectional psychometric properties of the NTB: test–retest reliability and correlation with other cognitive and functional/behavioral assessments. METHOD Study design ELN-AIP-901 was a multicenter, longitudinal, non-interventional, observational study conducted at 39 sites, 22 in the United States and 17 in Europe, during 2006–2009. No study medication was dispensed. Site-specific, local, independent ethics committees approved the protocol and related informed consent forms before implementation of the study and also approved subsequent protocol amendments and related documents. The study was conducted in accordance with the International Conference on Harmonization Tripartite Guidelines on Good Clinical Practice and in compliance with the Declaration of Helsinki 1964 as modified in October 2000. This trial was registered with the EU Clinical Trials Register (Eudra CT Number 2006-A00393-48). Under the original protocol the study duration was 78 weeks. By protocol amendment the duration was extended to 156 weeks. Subsequently the study extension was stopped once all participants had the opportunity to complete week 104, because of low enrollment in the extension and high dropout rate by the next visit, and because data collected out to week 104 was considered to be sufficient to characterize the NTB in the three participant populations. Participants The study included male and female participants in three clinical groups: mild to moderate AD (n = 196), MCI (n = 70), or NC (n = 75) (Table 1). Eligible participants were 50 to 85 years of age (inclusive), had a Rosen Modified Hachinski Ischemic score ≤ 4, and had a study partner with whom the participant spent ≥ 10 hours per week and who could accompany the participant to the clinic for all study visits. Participants were receiving stable doses of medications for permitted medical conditions for ≥ 30 days before screening; if the participant was taking cholinesterase inhibitors and/or memantine, the dose(s) had to have been stable for ≥ 60 days before screening and for
Participant demographics and baseline characteristics Mean age (SD§), y Male, n (%) First-degree relatives with AD, n (%) Cholinesterase inhibitors or memantine use at baseline, n (%) Mean global NTB score at screening, actual value (SD) Mean global NTB score at baseline, actual value (SD) Mean baseline z-score (SD)e Composite NTB¶ Memory composite Executive function composite Mean baseline score (SD) MMSE# ADAS-Cog** 11 ADAS-Cog 12 ROCF†† BNT‡‡ CDR-SB§§ ADCS-CGIC¶¶ ADCS-ADLg ## MCI-ADLg *** DAD††† FAQ‡‡‡ NPI§§§ ECogg ¶¶¶ 72.9 (7.7) 36 (51.4) 25 (35.7)d 13 (18.6) –0.229 (0.6047) –0.002 (0.6320) –0.98 (0.73) –1.19 (0.93) –0.56 (0.70) 27.0 (2.5) 9.2 (4.3) 15.5 (5.9) 13.1 (8.0) 12.9 (2.2) 1.4 (0.8) 2.4 (0.5) 73.0 (0.0)i 44.5 (2.1)i 97.7 (4.9) 3.3 (3.7) 2.4 (3.5) 1.7 (0.5)i
–0.128 (0.5851) –0.002 (0.6437) –2.30 (0.69) –2.79 (0.85) –1.32 (0.76) 21.7 (3.6) 19.3 (7.1) 28.1 (7.9) 5.8b (7.7) 10.2 (3.4) 5.3f (2.4) 3.5f (0.7) 54.7 (18.8)h 32.1 (15.5)k 77.3f (18.0) 14.7 (7.3) 7.9f (10.6) 2.8 (0.8)h
‡
28.8 (1.3) 5.2 (3.2) 9.0 (5.5) 19.7 (7.8) 14.2 (1.3) 0.0 (0.2) 1.0 (0.1) 77.9 (0.3)j 53.4 (1.0)j 99.8 (0.8) 0.3 (0.8) 0.6l (2.2) 1.1 (0.1)j
0 (0.67) 0 (0.77) 0 (0.71)
–0.307 (0.7063) 0.000 (0.6655)
70.8 (10.0) 33 (44.0) 23 (30.7) 0
NC (n = 75)
Cohort MCI (n = 70)
†
75.2 (6.5) 89 (45.4) 65 (33.2)c 171 (87.2)
AD (n = 196)
*
24.4 (4.3) 14.1 (8.5) 21.3 (10.8) 10.4 (9.7) 11.6 (3.3) 3.3 (3.0) 2.7 (1.2) 68.7 (16.0) 46.0 (13.1) 86.5 (17.5) 9.2 (8.7) 5.2 (8.9) 1.8 (1.0)
–1.52 (1.18) –1.85 (1.44) –0.87 (0.92)
73.8 (7.9) 158 (46.3) 113 (33.1) 184 (54.0)
Total (n = 341)
TABLE 1. Participant and study partner demographics and baseline characteristics
Downloaded by [McMaster University] at 00:50 14 February 2015
The Clinical Neuropsychologist Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ntcn20
Cognition in MCI and Alzheimer’s Disease: Baseline Data from a Longitudinal Study of the NTB ab
c
d
John Harrison , Dorene M. Rentz , Trent McLaughlin , Timothy e
d
f
d
Niecko , Keith M. Gregg , Ronald S. Black , Jacqui Buchanan , d
g
Enchi Liu , Michael Grundman & for the ELN-AIP-901 Study Investigator Group a
Metis Cognition Ltd., Wiltshire, UK
b
Department of Medicine, Imperial College, London, UK
c
Click for updates
Department of Neurology, Brigham and Women’s Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA d
Janssen Alzheimer Immunotherapy Research and Development, LLC, South San Francisco, CA, USA, e
Niecko Health Economics, LLC, Naples, FL, USA
f
Pfizer Inc., Collegeville, PA, USA
g
Global R&D Partners Inc., San Diego, CA, USA Published online: 13 Feb 2014.
To cite this article: John Harrison, Dorene M. Rentz, Trent McLaughlin, Timothy Niecko, Keith M. Gregg, Ronald S. Black, Jacqui Buchanan, Enchi Liu, Michael Grundman & for the ELNAIP-901 Study Investigator Group (2014) Cognition in MCI and Alzheimer’s Disease: Baseline Data from a Longitudinal Study of the NTB, The Clinical Neuropsychologist, 28:2, 252-268, DOI: 10.1080/13854046.2013.875595 To link to this article: http://dx.doi.org/10.1080/13854046.2013.875595
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content.
Downloaded by [McMaster University] at 00:50 14 February 2015
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
The Clinical Neuropsychologist, 2014 Vol. 28, No. 2, 252–268, http://dx.doi.org/10.1080/13854046.2013.875595
Cognition in MCI and Alzheimer’s Disease: Baseline Data from a Longitudinal Study of the NTB John Harrison1,2, Dorene M. Rentz3, Trent McLaughlin4, Timothy Niecko5, Keith M. Gregg4, Ronald S. Black6, Jacqui Buchanan4, Enchi Liu4, and Michael Grundman7 for the ELN-AIP-901 Study Investigator Group 1
Metis Cognition Ltd., Wiltshire, UK Department of Medicine, Imperial College, London, UK 3 Department of Neurology, Brigham and Women’s Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA 4 Janssen Alzheimer Immunotherapy Research and Development, LLC, South San Francisco, CA, USA, 5 Niecko Health Economics, LLC, Naples, FL, USA 6 Pfizer Inc., Collegeville, PA, USA 7 Global R&D Partners Inc., San Diego, CA, USA
Downloaded by [McMaster University] at 00:50 14 February 2015
2
Baseline data are summarized from a study examining the psychometric properties of the Neuropsychological Test Battery (NTB) and its subtests, and correlating the NTB with other cognitive and functional assessments. A multicenter, longitudinal, non-interventional study included mild to moderate Alzheimer’s disease (AD, n = 196), mild cognitive impairment (MCI, n = 70), or normal cognition participants (NC, n = 75). The NTB, other cognitive assessment tools, functional/behavioral questionnaires, and health outcome assessments were administered. At baseline composite NTB, NTB memory, and NTB executive function z-scores were significantly lower for participants with AD compared with MCI, and for participants with MCI compared with NC. The composite NTB z-score had high test–retest reliability between screening and baseline. The results of this study suggest that NTB exhibits good reliability in patients with mild to moderate AD and MCI. Keywords: Alzheimer’s disease; Cognition; MCI; Neuropsychological Test Battery; Psychometric properties.
INTRODUCTION Valid and reliable measures of cognition that track progression, including changes in the earliest stages of the disease course, are needed for clinical trials of Alzheimer’s disease (AD). A cognitive outcome measure commonly used in clinical trials, the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), has shown poor sensitivity in discerning cognitive change in patients with mild cognitive impairment (MCI) and early AD (Sevigny, Peng, Liu, Lines, 2010; Winblad et al., 2008). In contrast, the Neuropsychological Test Battery (NTB) was developed to track clinical progression in AD clinical trials and was shown to be a potentially useful assessment in patients with mild to moderate AD (Harrison et al., 2007). It evaluates cognitive Address correspondence to: John Harrison, BSc(Hons), PhD, CSci, CPsychol, Metis Cognition Ltd, Park House, Kilmington Common, Warminster, Wiltshire, BA12 6QY, UK. E-mail: [email protected] (Received 26 July 2013; accepted 10 December 2013)
© 2014 Taylor & Francis
Downloaded by [McMaster University] at 00:50 14 February 2015
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253
domains that are known to be affected in patients with AD, some of which are inadequately assessed with the ADAS-Cog (e.g., visual memory, delayed recall, and executive function) (Harrison et al., 2007). It is a composite of nine widely used neuropsychological tests that assess immediate and delayed recall of verbal and visual information, attention, verbal fluency, and executive function (Harrison et al., 2007). These individual measures have previously been shown to be reliable, valid for use in AD, and sensitive to cognitive decline (Gilman et al., 2005). A comparison of the NTB and ADAS-Cog in clinical trials in patients with AD showed the NTB to be more sensitive than the ADAS-Cog in patients with mild AD (Black et al., 2009). The purpose of this study was to gather both cross-sectional and longitudinal data and to use the baseline cross-sectional data to explore the psychometric properties of the NTB versus other neuropsychological measures across a range of cognitive performance from normal cognition (NC) to MCI and AD. This paper summarizes baseline data from the study, including cross-sectional psychometric properties of the NTB: test–retest reliability and correlation with other cognitive and functional/behavioral assessments. METHOD Study design ELN-AIP-901 was a multicenter, longitudinal, non-interventional, observational study conducted at 39 sites, 22 in the United States and 17 in Europe, during 2006–2009. No study medication was dispensed. Site-specific, local, independent ethics committees approved the protocol and related informed consent forms before implementation of the study and also approved subsequent protocol amendments and related documents. The study was conducted in accordance with the International Conference on Harmonization Tripartite Guidelines on Good Clinical Practice and in compliance with the Declaration of Helsinki 1964 as modified in October 2000. This trial was registered with the EU Clinical Trials Register (Eudra CT Number 2006-A00393-48). Under the original protocol the study duration was 78 weeks. By protocol amendment the duration was extended to 156 weeks. Subsequently the study extension was stopped once all participants had the opportunity to complete week 104, because of low enrollment in the extension and high dropout rate by the next visit, and because data collected out to week 104 was considered to be sufficient to characterize the NTB in the three participant populations. Participants The study included male and female participants in three clinical groups: mild to moderate AD (n = 196), MCI (n = 70), or NC (n = 75) (Table 1). Eligible participants were 50 to 85 years of age (inclusive), had a Rosen Modified Hachinski Ischemic score ≤ 4, and had a study partner with whom the participant spent ≥ 10 hours per week and who could accompany the participant to the clinic for all study visits. Participants were receiving stable doses of medications for permitted medical conditions for ≥ 30 days before screening; if the participant was taking cholinesterase inhibitors and/or memantine, the dose(s) had to have been stable for ≥ 60 days before screening and for
Participant demographics and baseline characteristics Mean age (SD§), y Male, n (%) First-degree relatives with AD, n (%) Cholinesterase inhibitors or memantine use at baseline, n (%) Mean global NTB score at screening, actual value (SD) Mean global NTB score at baseline, actual value (SD) Mean baseline z-score (SD)e Composite NTB¶ Memory composite Executive function composite Mean baseline score (SD) MMSE# ADAS-Cog** 11 ADAS-Cog 12 ROCF†† BNT‡‡ CDR-SB§§ ADCS-CGIC¶¶ ADCS-ADLg ## MCI-ADLg *** DAD††† FAQ‡‡‡ NPI§§§ ECogg ¶¶¶ 72.9 (7.7) 36 (51.4) 25 (35.7)d 13 (18.6) –0.229 (0.6047) –0.002 (0.6320) –0.98 (0.73) –1.19 (0.93) –0.56 (0.70) 27.0 (2.5) 9.2 (4.3) 15.5 (5.9) 13.1 (8.0) 12.9 (2.2) 1.4 (0.8) 2.4 (0.5) 73.0 (0.0)i 44.5 (2.1)i 97.7 (4.9) 3.3 (3.7) 2.4 (3.5) 1.7 (0.5)i
–0.128 (0.5851) –0.002 (0.6437) –2.30 (0.69) –2.79 (0.85) –1.32 (0.76) 21.7 (3.6) 19.3 (7.1) 28.1 (7.9) 5.8b (7.7) 10.2 (3.4) 5.3f (2.4) 3.5f (0.7) 54.7 (18.8)h 32.1 (15.5)k 77.3f (18.0) 14.7 (7.3) 7.9f (10.6) 2.8 (0.8)h
‡
28.8 (1.3) 5.2 (3.2) 9.0 (5.5) 19.7 (7.8) 14.2 (1.3) 0.0 (0.2) 1.0 (0.1) 77.9 (0.3)j 53.4 (1.0)j 99.8 (0.8) 0.3 (0.8) 0.6l (2.2) 1.1 (0.1)j
0 (0.67) 0 (0.77) 0 (0.71)
–0.307 (0.7063) 0.000 (0.6655)
70.8 (10.0) 33 (44.0) 23 (30.7) 0
NC (n = 75)
Cohort MCI (n = 70)
†
75.2 (6.5) 89 (45.4) 65 (33.2)c 171 (87.2)
AD (n = 196)
*
24.4 (4.3) 14.1 (8.5) 21.3 (10.8) 10.4 (9.7) 11.6 (3.3) 3.3 (3.0) 2.7 (1.2) 68.7 (16.0) 46.0 (13.1) 86.5 (17.5) 9.2 (8.7) 5.2 (8.9) 1.8 (1.0)
–1.52 (1.18) –1.85 (1.44) –0.87 (0.92)
73.8 (7.9) 158 (46.3) 113 (33.1) 184 (54.0)
Total (n = 341)
TABLE 1. Participant and study partner demographics and baseline characteristics
Downloaded by [McMaster University] at 00:50 14 February 2015
