Development of Novel Measures for Alzheimer's Disease Prevention Trials (NoMAD)

Overview

Journal Contemp Clin Trials

Publisher Elsevier

Date 2021 May 2

PMID 33933666

Citations 4

Authors

Sophie A Bell

Hannah R Cohen

Seonjoo Lee

Hyun Kim

Adam Ciarleglio

Howard Andrews

Andres M Rivera

Kay Igwe

Adam M Brickman

D P Devanand

Philip D Harvey

Lon S Schneider

Terry E Goldberg

Affiliations

Soon will be listed here.

Abstract

Introduction: Assessment of cognition and everyday function is essential in clinical trials for Alzheimer's disease (AD). Two novel measures of cognition (No Practice Effects (NPE) cognitive battery and Miami Computerized Functional Assessment Scale (CFAS)) were designed to have robust psychometric properties and reduced practice and ceiling effects. This study aims to evaluate if the NPE and CFAS demonstrate stronger psychometric properties and reduced practice effects compared with established measures, including the Preclinical Alzheimer Cognitive Composite (PACC), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Functional Activities Questionnaire (FAQ).

Methods: This parallel group, four-site study will randomize 320 cognitively intact adults aged 60 to 85 years to novel or well-established measures of cognition and function. All participants will receive assessments at baseline (week 0), 3-months, and 12-months, as well as a brain MRI scan and Apolipoprotein E genetic test at study entry. Analyses will determine psychometric properties of the NPE and CFAS, compare the sensitivity of measures to AD risk markers, and identify cognitive domains within the NPE.

Discussion: Practice effects have been a major limitation of Alzheimer's disease clinical trials that typically assess cognitive changes over serial assessments. Detection of functional impairment in cognitively normal individuals with biomarkers for Alzheimer's disease requires instruments sensitive to very subtle functional changes. This study is intended to support the validation of two new composite measures, the NPE battery and the CFAS, which may advance clinical testing of interventions for individuals across the spectrum of early stage Alzheimer's disease.

Trial Registration: NCT03900273.

Citing Articles

Novel measures of cognition and function for the AD spectrum in the Novel Measures for Alzheimer's Disease Prevention Trials (NoMAD) project: Psychometric properties, convergent validation, and contrasts with established measures.

Kim H, Lee S, Levine A, Huber B, Andrews H, Kerner N Alzheimers Dement. 2024; 20(8):5089-5101.

PMID: 38963127 PMC: 11350053. DOI: 10.1002/alz.13757.

Original research: longitudinal evaluation of cognitively demanding daily function using performance-based functional assessment highlights heterogeneous trajectories in cognitive and functional abilities in people with Parkinson's disease.

Carlisle T, Fought A, Olson K, Lopez-Esquibel N, Simpson A, Medina L Front Neurosci. 2023; 17:1200347.

PMID: 37434765 PMC: 10330725. DOI: 10.3389/fnins.2023.1200347.

Rationale for the selection of dual primary endpoints in prevention studies of cognitively unimpaired individuals at genetic risk for developing symptoms of Alzheimer's disease.

Caputo A, Racine A, Paule I, Tariot P, Langbaum J, Coello N Alzheimers Res Ther. 2023; 15(1):45.

PMID: 36879340 PMC: 9987044. DOI: 10.1186/s13195-023-01183-z.

The Current Landscape of Prevention Trials in Dementia.

Lee J, Howard R, Schneider L Neurotherapeutics. 2022; 19(1):228-247.

PMID: 35587314 PMC: 9130372. DOI: 10.1007/s13311-022-01236-5.

References

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View

Rosser A, Hodges J . Initial letter and semantic category fluency in Alzheimer's disease, Huntington's disease, and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 1994; 57(11):1389-94. PMC: 1073192. DOI: 10.1136/jnnp.57.11.1389. View

Donohue M, Sperling R, Salmon D, Rentz D, Raman R, Thomas R . The preclinical Alzheimer cognitive composite: measuring amyloid-related decline. JAMA Neurol. 2014; 71(8):961-70. PMC: 4439182. DOI: 10.1001/jamaneurol.2014.803. View

Weuve J, Proust-Lima C, Power M, Gross A, Hofer S, Thiebaut R . Guidelines for reporting methodological challenges and evaluating potential bias in dementia research. Alzheimers Dement. 2015; 11(9):1098-109. PMC: 4655106. DOI: 10.1016/j.jalz.2015.06.1885. View

Sousa A, Gomar J, Goldberg T . Neural and behavioral substrates of disorientation in mild cognitive impairment and Alzheimer's disease. Alzheimers Dement (N Y). 2018; 1(1):37-45. PMC: 5975044. DOI: 10.1016/j.trci.2015.04.002. View

Czaja S, Loewenstein D, Sabbag S, Curiel R, Crocco E, Harvey P . A Novel Method for Direct Assessment of Everyday Competence Among Older Adults. J Alzheimers Dis. 2017; 57(4):1229-1238. PMC: 5610961. DOI: 10.3233/JAD-161183. View

Calamia M, Markon K, Tranel D . Scoring higher the second time around: meta-analyses of practice effects in neuropsychological assessment. Clin Neuropsychol. 2012; 26(4):543-70. DOI: 10.1080/13854046.2012.680913. View

ROSEN W, Mohs R, Davis K . A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984; 141(11):1356-64. DOI: 10.1176/ajp.141.11.1356. View

Feinkohl I, Borchers F, Burkhardt S, Krampe H, Kraft A, Speidel S . Stability of neuropsychological test performance in older adults serving as normative controls for a study on postoperative cognitive dysfunction. BMC Res Notes. 2020; 13(1):55. PMC: 7001199. DOI: 10.1186/s13104-020-4919-3. View

10.

Gold J, Carpenter C, Randolph C, Goldberg T, Weinberger D . Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia. Arch Gen Psychiatry. 1997; 54(2):159-65. DOI: 10.1001/archpsyc.1997.01830140071013. View

11.

Selya A, Rose J, Dierker L, Hedeker D, Mermelstein R . A Practical Guide to Calculating Cohen's f(2), a Measure of Local Effect Size, from PROC MIXED. Front Psychol. 2012; 3:111. PMC: 3328081. DOI: 10.3389/fpsyg.2012.00111. View

12.

Karlsen R, Karr J, Saksvik S, Lundervold A, Hjemdal O, Olsen A . Examining 3-month test-retest reliability and reliable change using the Cambridge Neuropsychological Test Automated Battery. Appl Neuropsychol Adult. 2020; 29(2):146-154. DOI: 10.1080/23279095.2020.1722126. View

13.

Mathews M, Abner E, Kryscio R, Jicha G, Cooper G, Smith C . Diagnostic accuracy and practice effects in the National Alzheimer's Coordinating Center Uniform Data Set neuropsychological battery. Alzheimers Dement. 2014; 10(6):675-83. PMC: 4169759. DOI: 10.1016/j.jalz.2013.11.007. View

14.

Goldberg T, Egan M, Gscheidle T, Coppola R, Weickert T, Kolachana B . Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch Gen Psychiatry. 2003; 60(9):889-96. DOI: 10.1001/archpsyc.60.9.889. View

15.

Belleville S, Gauthier S, Lepage E, Kergoat M, Gilbert B . Predicting decline in mild cognitive impairment: a prospective cognitive study. Neuropsychology. 2014; 28(4):643-52. DOI: 10.1037/neu0000063. View

16.

Fleming K, Goldberg T, Gold J, Weinberger D . Verbal working memory dysfunction in schizophrenia: use of a Brown-Peterson paradigm. Psychiatry Res. 1995; 56(2):155-61. DOI: 10.1016/0165-1781(95)02589-3. View

17.

Harris P, Taylor R, Thielke R, Payne J, Gonzalez N, Conde J . Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2008; 42(2):377-81. PMC: 2700030. DOI: 10.1016/j.jbi.2008.08.010. View

18.

Goldberg T, Harvey P, Wesnes K, Snyder P, Schneider L . Practice effects due to serial cognitive assessment: Implications for preclinical Alzheimer's disease randomized controlled trials. Alzheimers Dement (Amst). 2016; 1(1):103-11. PMC: 4876902. DOI: 10.1016/j.dadm.2014.11.003. View

19.

Gerstenecker A, Eakin A, Triebel K, Martin R, Swenson-Dravis D, Petersen R . Age and education corrected older adult normative data for a short form version of the Financial Capacity Instrument. Psychol Assess. 2015; 28(6):737-49. PMC: 4712121. DOI: 10.1037/pas0000159. View

20.

Pfeffer R, Kurosaki T, Harrah Jr C, Chance J, Filos S . Measurement of functional activities in older adults in the community. J Gerontol. 1982; 37(3):323-9. DOI: 10.1093/geronj/37.3.323. View