Title | Cognitive Variability Predicts Incident Alzheimer's Disease and Mild Cognitive Impairment Comparable to a Cerebrospinal Fluid Biomarker. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Gleason, CE, Norton, D, Anderson, ED, Wahoske, M, Washington, DT, Umucu, E, Koscik, RL, N Dowling, M, Johnson, SC, Carlsson, CM, Asthana, S |
Corporate Authors | Alzheimer’s Disease Neuroimaging Initiative |
Journal | J Alzheimers Dis |
Volume | 61 |
Issue | 1 |
Pagination | 79-89 |
Date Published | 2018 |
ISSN | 1875-8908 |
Keywords | Aged, Aged, 80 and over, Algorithms, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Cognitive Dysfunction, Cross-Sectional Studies, Female, Humans, Incidence, Logistic Models, Male, Middle Aged, Neuropsychological Tests, Peptide Fragments, Statistics, Nonparametric, tau Proteins |
Abstract | BACKGROUND: Alzheimer's disease (AD) biomarkers are emerging as critically important for disease detection and monitoring. Most biomarkers are obtained through invasive, resource-intense procedures. A cognitive marker, intra-individual cognitive variability (IICV) may provide an alternative or adjunct marker of disease risk for individuals unable or disinclined to undergo lumbar puncture. OBJECTIVE: To contrast risk of incident AD and mild cognitive impairment (MCI) associated with IICV to risk associated with well-established biomarkers: cerebrospinal fluid (CSF) phosphorylated tau protein (p-tau181) and amyloid-β 42 (Aβ42) peptide. METHODS: Dispersion in cognitive performance, IICV, was estimated with a published algorithm, and included Trail Making Test A and B, Rey Auditory Verbal Learning Test (RAVLT), and the American National Adult Reading Test (ANART). CSF biomarkers were expressed as a ratio: p-tau181/Aβ42, wherein high values signified pathognomonic profiles. Logistic regression models included longitudinal data from 349 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who completed lumbar puncture. All subjects were cognitively healthy (n = 105) or diagnosed with MCI (n = 244) at baseline. We examined odds of conversion associated with baseline elevations in IICV and/or ratio of CSF p-tau181/Aβ42. RESULTS: When included in models alone or in combination with CSF p-tau181/Aβ42, one standard IICV unit higher was associated with an estimated odds ratio for incident AD or MCI of 2.81 (95% CI: 1.83-4.33) in the most inclusive sample, and an odds ratio of 3.41 (95% CI: 2.03-5.73) when restricted to participants with MCI. Iterative analyses suggested that IICV independently improved model fit even when individual index components were included in comparative models. CONCLUSIONS: These analyses provide preliminary support for IICV as a marker of incident AD and MCI. This easily-disseminated, non-invasive marker compared favorably to well-established CSF biomarkers. |
DOI | 10.3233/JAD-170498 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 29125485 |
PubMed Central ID | PMC5714663 |
Grant List | P50 AG033514 / AG / NIA NIH HHS / United States R01 AG027161 / AG / NIA NIH HHS / United States R01 AG054059 / AG / NIA NIH HHS / United States RF1 AG057547 / AG / NIA NIH HHS / United States |