Back to Journals » Neuropsychiatric Disease and Treatment » Volume 10

Disease progression model for Clinical Dementia Rating–Sum of Boxes in mild cognitive impairment and Alzheimer’s subjects from the Alzheimer’s Disease Neuroimaging Initiative

Authors Samtani MN, Raghavan N, Novak G, Nandy P, Narayan VA

Received 12 February 2014

Accepted for publication 28 February 2014

Published 24 May 2014 Volume 2014:10 Pages 929—952

DOI https://doi.org/10.2147/NDT.S62323

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Video abstract presented by Mahesh N Samtani.

Views: 718

Mahesh N Samtani, Nandini Raghavan, Gerald Novak, Partha Nandy, Vaibhav A Narayan

On behalf of the Alzheimer’s disease Neuroimaging Initiative

Janssen Research and Development, LLC, Raritan, New Jersey, USA

Background: The objective of this analysis was to develop a nonlinear disease progression model, using an expanded set of covariates that captures the longitudinal Clinical Dementia Rating Scale–Sum of Boxes (CDR–SB) scores. These were derived from the Alzheimer’s disease Neuroimaging Initiative ADNI-1 study, of 301 Alzheimer’s disease and mild cognitive impairment patients who were followed for 2–3 years.
Methods: The model describes progression rate and baseline disease score as a function of covariates. The covariates that were tested fell into five groups: a) hippocampal volume; b) serum and cerebrospinal fluid (CSF) biomarkers; c) demographics and apolipoprotein Epsilon 4 (ApoE4) allele status; d) baseline cognitive tests; and e) disease state and comedications.
Results: Covariates associated with baseline disease severity were disease state, hippocampal volume, and comedication use. Disease progression rate was influenced by baseline CSF biomarkers, Trail-Making Test part A score, delayed logical memory test score, and current level of impairment as measured by CDR–SB. The rate of disease progression was dependent on disease severity, with intermediate scores around the inflection point score of 10 exhibiting high disease progression rate. The CDR–SB disease progression rate in a typical patient, with late mild cognitive impairment and mild Alzheimer’s disease, was estimated to be approximately 0.5 and 1.4 points/year, respectively.
Conclusions: In conclusion, this model describes disease progression in terms of CDR–SB changes in patients and its dependency on novel covariates. The CSF biomarkers included in the model discriminate mild cognitive impairment subjects as progressors and nonprogressors. Therefore, the model may be utilized for optimizing study designs, through patient population enrichment and clinical trial simulations.

Keywords: NONMEM®, beta-regression, CSF Aß1–42, hippocampal volume, trial enrichment


Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other article by this author:

Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose

Samtani MN, Nuamah I, Gopal S, Remmerie B, Sliwa JK, Alphs L

Neuropsychiatric Disease and Treatment 2013, 9:721-730

Published Date: 20 May 2013

Readers of this article also read:

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010