Longitudinal Normative Standards for Cognitive Tests and Composites Using Harmonized Data from Two Wisconsin AD-risk-enriched Cohorts

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2024 Mar 28

PMID 38539269

Authors

Erin M Jonaitis

Bruce P Hermann

Kimberly D Mueller

Lindsay R Clark

Lianlian Du

Tobey J Betthauser

Karly Cody

Carey E Gleason

Bradley T Christian

Sanjay Asthana

Richard J Chappell

Nathaniel A Chin

Sterling C Johnson

Rebecca E Langhough

Affiliations

Soon will be listed here.

Abstract

Introduction: Published norms are typically cross-sectional and often are not sensitive to preclinical cognitive changes due to dementia. We developed and validated demographically adjusted cross-sectional and longitudinal normative standards using harmonized outcomes from two Alzheimer's disease (AD) risk-enriched cohorts.

Methods: Data from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center were combined. Quantile regression was used to develop unconditional (cross-sectional) and conditional (longitudinal) normative standards for 18 outcomes using data from cognitively unimpaired participants (N = 1390; mean follow-up = 9.25 years). Validity analyses (N = 2456) examined relationships between percentile scores (centiles), consensus-based cognitive statuses, and AD biomarker levels.

Results: Unconditional and conditional centiles were lower in those with consensus-based impairment or biomarker positivity. Similarly, quantitative biomarker levels were higher in those whose centiles suggested decline.

Discussion: This study presents normative standards for cognitive measures sensitive to pre-clinical changes. Future directions will investigate potential clinical applications of longitudinal normative standards.

Highlights: Quantile regression was used to construct longitudinal norms for cognitive tests. Poorer percentile scores were related to concurrent diagnosis and Alzheimer's disease biomarkers. A ShinyApp was built to display test scores and norms and flag low performance.

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Longitudinal normative standards for cognitive tests and composites using harmonized data from two Wisconsin AD-risk-enriched cohorts.

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References

Donohue M, Sun C, Raman R, Insel P, Aisen P . Cross-validation of optimized composites for preclinical Alzheimer's disease. Alzheimers Dement (N Y). 2017; 3(1):123-129. PMC: 5527287. DOI: 10.1016/j.trci.2016.12.001. View

Maidman A, Wang L, Zhou X, Sherwood B . Quantile partially linear additive model for data with dropouts and an application to modeling cognitive decline. Stat Med. 2023; 42(16):2729-2745. DOI: 10.1002/sim.9745. View

Hughes C, Berg L, Danziger W, COBEN L, Martin R . A new clinical scale for the staging of dementia. Br J Psychiatry. 1982; 140:566-72. DOI: 10.1192/bjp.140.6.566. View

Jak A, Bondi M, Delano-Wood L, Wierenga C, Corey-Bloom J, Salmon D . Quantification of five neuropsychological approaches to defining mild cognitive impairment. Am J Geriatr Psychiatry. 2009; 17(5):368-75. PMC: 2743175. DOI: 10.1097/JGP.0b013e31819431d5. View

Berman S, Koscik R, Clark L, Mueller K, Bluder L, Galvin J . Use of the Quick Dementia Rating System (QDRS) as an Initial Screening Measure in a Longitudinal Cohort at Risk for Alzheimer's Disease. J Alzheimers Dis Rep. 2017; 1(1):9-13. PMC: 5557032. DOI: 10.3233/ADR-170004. View

Cheung Y, Xu Y, Feng L, Feng L, Nyunt M, Chong M . Unconditional and Conditional Standards Using Cognitive Function Curves for the Modified Mini-Mental State Exam: Cross-Sectional and Longitudinal Analyses in Older Chinese Adults in Singapore. Am J Geriatr Psychiatry. 2014; 23(9):915-24. DOI: 10.1016/j.jagp.2014.08.008. View

Gross A, Hassenstab J, Johnson S, Clark L, Resnick S, Kitner-Triolo M . A classification algorithm for predicting progression from normal cognition to mild cognitive impairment across five cohorts: The preclinical AD consortium. Alzheimers Dement (Amst). 2017; 8:147-155. PMC: 5476965. DOI: 10.1016/j.dadm.2017.05.003. View

Alden E, Lundt E, Twohy E, Christianson T, Kremers W, Machulda M . Mayo normative studies: A conditional normative model for longitudinal change on the Auditory Verbal Learning Test and preliminary validation in preclinical Alzheimer's disease. Alzheimers Dement (Amst). 2022; 14(1):e12325. PMC: 9286327. DOI: 10.1002/dad2.12325. View

McKhann G, Knopman D, Chertkow H, Hyman B, Jack Jr C, Kawas C . The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3):263-9. PMC: 3312024. DOI: 10.1016/j.jalz.2011.03.005. View

10.

Wang C, Katz M, Chang K, Qin J, Lipton R, Zwerling J . UDSNB 3.0 Neuropsychological Test Norms in Older Adults from a Diverse Community: Results from the Einstein Aging Study (EAS). J Alzheimers Dis. 2021; 83(4):1665-1678. PMC: 8805183. DOI: 10.3233/JAD-210538. View

11.

Betthauser T, Koscik R, Jonaitis E, Allison S, Cody K, Erickson C . Amyloid and tau imaging biomarkers explain cognitive decline from late middle-age. Brain. 2019; 143(1):320-335. PMC: 6935717. DOI: 10.1093/brain/awz378. View

12.

Amieva H, Le Goff M, Millet X, Orgogozo J, Peres K, Barberger-Gateau P . Prodromal Alzheimer's disease: successive emergence of the clinical symptoms. Ann Neurol. 2008; 64(5):492-8. DOI: 10.1002/ana.21509. View

13.

Johnson S, Koscik R, Jonaitis E, Clark L, Mueller K, Berman S . The Wisconsin Registry for Alzheimer's Prevention: A review of findings and current directions. Alzheimers Dement (Amst). 2018; 10:130-142. PMC: 5755749. DOI: 10.1016/j.dadm.2017.11.007. View

14.

Monsell S, Dodge H, Zhou X, Bu Y, Besser L, Mock C . Results From the NACC Uniform Data Set Neuropsychological Battery Crosswalk Study. Alzheimer Dis Assoc Disord. 2015; 30(2):134-9. PMC: 4834278. DOI: 10.1097/WAD.0000000000000111. View

15.

Langhough Koscik R, Hermann B, Allison S, Clark L, Jonaitis E, Mueller K . Validity Evidence for the Research Category, "Cognitively Unimpaired - Declining," as a Risk Marker for Mild Cognitive Impairment and Alzheimer's Disease. Front Aging Neurosci. 2021; 13:688478. PMC: 8350058. DOI: 10.3389/fnagi.2021.688478. View

16.

Storandt M, Grant E, Miller J, Morris J . Longitudinal course and neuropathologic outcomes in original vs revised MCI and in pre-MCI. Neurology. 2006; 67(3):467-73. DOI: 10.1212/01.wnl.0000228231.26111.6e. View

17.

Betthauser T, Bilgel M, Koscik R, Jedynak B, An Y, Kellett K . Multi-method investigation of factors influencing amyloid onset and impairment in three cohorts. Brain. 2022; 145(11):4065-4079. PMC: 9679170. DOI: 10.1093/brain/awac213. View

18.

Jonaitis E, Hermann B, Mueller K, Clark L, Du L, Betthauser T . Longitudinal normative standards for cognitive tests and composites using harmonized data from two Wisconsin AD-risk-enriched cohorts. Alzheimers Dement. 2024; 20(5):3305-3321. PMC: 11095443. DOI: 10.1002/alz.13774. View

19.

Karr J, Graham R, Hofer S, Muniz-Terrera G . When does cognitive decline begin? A systematic review of change point studies on accelerated decline in cognitive and neurological outcomes preceding mild cognitive impairment, dementia, and death. Psychol Aging. 2018; 33(2):195-218. PMC: 5906105. DOI: 10.1037/pag0000236. View

20.

Albert M, DeKosky S, Dickson D, Dubois B, Feldman H, Fox N . The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3):270-9. PMC: 3312027. DOI: 10.1016/j.jalz.2011.03.008. View