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Cognitive Variability Predicts Incident Alzheimer's Disease and Mild Cognitive Impairment Comparable to a Cerebrospinal Fluid Biomarker.
J Alzheimers Dis. 2018; 61(1):79-89.JA

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.

Authors+Show Affiliations

Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Geriatric Research, Education and Clinical Center (11G), William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA.Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA. University of Wisconsin, Department of Biostatistics and Medical Informatics, Madison, WI, USA.Wright State University, School of Education and Human Services, Dayton, OH, USA.Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA.Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Geriatric Research, Education and Clinical Center (11G), William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA.Department of Rehabilitation Sciences, University of Texas at El Paso, El Paso, TX, USA.Wisconsin Alzheimer's Institute, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.George Washington University, School of Nursing, Washington, DC, USA.Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Geriatric Research, Education and Clinical Center (11G), William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA. George Washington University, School of Nursing, Washington, DC, USA.Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Geriatric Research, Education and Clinical Center (11G), William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA. George Washington University, School of Nursing, Washington, DC, USA.Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Geriatric Research, Education and Clinical Center (11G), William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA. George Washington University, School of Nursing, Washington, DC, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29125485

Citation

Gleason, Carey E., et al. "Cognitive Variability Predicts Incident Alzheimer's Disease and Mild Cognitive Impairment Comparable to a Cerebrospinal Fluid Biomarker." Journal of Alzheimer's Disease : JAD, vol. 61, no. 1, 2018, pp. 79-89.
Gleason CE, Norton D, Anderson ED, et al. Cognitive Variability Predicts Incident Alzheimer's Disease and Mild Cognitive Impairment Comparable to a Cerebrospinal Fluid Biomarker. J Alzheimers Dis. 2018;61(1):79-89.
Gleason, C. E., Norton, D., Anderson, E. D., Wahoske, M., Washington, D. T., Umucu, E., Koscik, R. L., Dowling, N. M., Johnson, S. C., Carlsson, C. M., & Asthana, S. (2018). Cognitive Variability Predicts Incident Alzheimer's Disease and Mild Cognitive Impairment Comparable to a Cerebrospinal Fluid Biomarker. Journal of Alzheimer's Disease : JAD, 61(1), 79-89. https://doi.org/10.3233/JAD-170498
Gleason CE, et al. Cognitive Variability Predicts Incident Alzheimer's Disease and Mild Cognitive Impairment Comparable to a Cerebrospinal Fluid Biomarker. J Alzheimers Dis. 2018;61(1):79-89. PubMed PMID: 29125485.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cognitive Variability Predicts Incident Alzheimer's Disease and Mild Cognitive Impairment Comparable to a Cerebrospinal Fluid Biomarker. AU - Gleason,Carey E, AU - Norton,Derek, AU - Anderson,Eric D, AU - Wahoske,Michelle, AU - Washington,Danielle T, AU - Umucu,Emre, AU - Koscik,Rebecca L, AU - Dowling,N Maritza, AU - Johnson,Sterling C, AU - Carlsson,Cynthia M, AU - Asthana,Sanjay, AU - ,, PY - 2017/11/11/pubmed PY - 2018/7/14/medline PY - 2017/11/11/entrez KW - Alzheimer’s disease KW - amyloid beta-protein KW - biological markers KW - cerebrospinal fluid KW - cognition KW - cognitive dysfunction KW - incidence studies KW - mild cognitive impairment KW - tau protein SP - 79 EP - 89 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 61 IS - 1 N2 - 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/29125485/Cognitive_Variability_Predicts_Incident_Alzheimer's_Disease_and_Mild_Cognitive_Impairment_Comparable_to_a_Cerebrospinal_Fluid_Biomarker_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-170498 DB - PRIME DP - Unbound Medicine ER -