Identifying Sensitive Measures of Cognitive Decline at Different Clinical Stages of Alzheimer’s Disease
Year: 2020
Type: article
Abstract: OBJECTIVE: Alzheimer's disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging - Alzheimer's Association (NIA-AA) research framework. METHOD: Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models. RESULTS: 1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (β = -.58, p < .001). Word List Delayed Recall (β = -.22, p < .05) and Trail Making Test (β = 6.2, p < .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1-year decline until Stage 3 (β = -1.13, p < .001) and 4 (β = -2.23, p < .001). CONCLUSIONS: We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.
Authors: Roos J. Jutten, Sietske A.M. Sikkes, Rebecca E. Amariglio, Rachel F. Buckley, Michael J. Properzi, Gad A. Marshall, Dorene M. Rentz, Keith A. Johnson, Charlotte E. Teunissen, Bart N.M. Van Berckel, Wiesje M. Van der Flier, Philip Scheltens, Reisa A. Sperling, Kathryn V. Papp, for the Alzheimer Disease Neuroimaging Initiative
Institutions: Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam UMC Location Vrije Universiteit Amsterdam, Harvard University, Massachusetts General Hospital, Brigham and Women's Hospital, The University of Melbourne, Florey Institute of Neuroscience and Mental Health
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,980
Funders: U.S. Department of Defense, Alzheimer's Association, Eli Lilly and Company, Biogen, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Vanderbilt University Medical Center, Eisai, Stichting Dioraphte, Alzheimer Nederland, H. Lundbeck A/S, IXICO, Amsterdam Neuroscience, GIESKES-STRIJBIS FONDS, National Institutes of Health, Genentech, National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering
Awards: G104586243, Michigan Alzheimer's Disease Core Center, G1298807586, UC Davis Alzheimer's Disease Core Center, Indiana Alzheimer Disease Center, G1554142629, G1593117279, G1650819308, G1711016037, Wake Forest Alzheimer's Disease Core Center, G1880935189, G2105457377, G2189010064, G2340207221, University of Kentucky Alzheimer's Disease Core Center, G2423387114, G2471646051, G2522063444, Neurobiology of Alzheimer's Disease and Aging, G2835601961, G29951154, Alzheimer's Disease Research Center, G3130427885, G3146424788, G3216574877, National Alzheimer's Coordinating Center, Alzheimer's Disease Research Center, G3710456697, G3870774570, G4119534169, Mentoring Imaging Research in Early AD, Alzheimer's Disease Core Center, G43180419, Cleveland Alzheimer's Disease Research Center, The Alzheimer's Disease Research Center at the University of California, Irvine, G4475667458, G4501223628, Stanford Alzheimer's Disease Research Center, G4800177743, G4860885537, Oregon Alzheimer's Disease Center, G5021443450, Rush Alzheimer's Disease Core Center, G5207404921, G5324093878, EFFECTS OF TRAUMATIC BRAIN INJURY (TBI) AND POST TRAUMATIC STRESS DISORDER (PTSD) ON ALZHEIMER'S DISEASE (AD) IN VETERANS USING IMAGING AND BIOMARKERS IN THE AD NEUROIMAGING INITIATIVE (ADNI)", G5389965057, G5654639750, Alzheimer's Disease Neuroimaging Initiative, G5740349702, G5850682332, Alzheimer's Disease Core Center, Alzheimer's Disease Research Center - Overall, G6210868510, G6371410416, G6412110892, G6447063303, University of Kansas Alzheimer's Disease Core Centers, G6719828067, G6899163935, Alzheimer's Disease Research Center, Alzheimer Disease Research Center, Yale Alzheimer Disease Research Center, Arizona Alzheimer's Disease Core Center, Johns Hopkins Alzheimer's Disease Research Center, G7298697282, Boston University Alzheimer's Disease Center, Alzheimer's Disease Research Center, G764699806, G781725486, Alzheimer's Disease Core Center, Emory Alzheimer's Disease Center, University of Florida - Mt. Sinai Medical Center AD Research Center, G8228018387, Optimizing semantic memory measures to detect tau- and amyloid- related cognitive change, G8895907669, G8957659042, G9000039018, G9000074849, G9000122335, UCSD Shiley-Marcos Alzheimer's Disease Research Center P30, Alzheimer's Disease Research Center, Impact of Amyloid and Tau on the Aging Brain: The Harvard Aging Brain Study, New Approaches to Dementia Heterogeneity, Wisconsin Alzheimer's Disease Research Center, National Alzheimer's Coordinating Center, Massachusetts Alzheimer's Disease Research Center (MADRC), New Approaches to Dementia Heterogeneity, G920654007
OpenAlex ID: W3092358139