Longitudinal change of biomarkers in cognitive decline

Raymond Y. Lo, Alan E. Hubbard, Leslie M. Shaw, John Q. Trojanowski, Ronald Carl Petersen, Paul S. Aisen, Michael W. Weiner, William J. Jagust

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Objective: To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Design: Cohort study. Setting: The 59 study sites for the Alzheimer's Disease Neuroimaging Initiative. Participants: A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Main Outcome Measures: Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Results: Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Conclusion: Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent.

Original languageEnglish (US)
Pages (from-to)1257-1266
Number of pages10
JournalArchives of Neurology
Volume68
Issue number10
DOIs
StatePublished - Oct 2011

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Alzheimer Disease
Biomarkers
Cerebrospinal Fluid
Cognition
Atrophy
Cognitive Dysfunction
Alzheimer's Disease
Amyloid
Neuroimaging
Positron-Emission Tomography
Cohort Studies
Magnetic Resonance Imaging
Outcome Assessment (Health Care)
Mild Cognitive Impairment
Pathology
Glucose

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Lo, R. Y., Hubbard, A. E., Shaw, L. M., Trojanowski, J. Q., Petersen, R. C., Aisen, P. S., ... Jagust, W. J. (2011). Longitudinal change of biomarkers in cognitive decline. Archives of Neurology, 68(10), 1257-1266. https://doi.org/10.1001/archneurol.2011.123

Longitudinal change of biomarkers in cognitive decline. / Lo, Raymond Y.; Hubbard, Alan E.; Shaw, Leslie M.; Trojanowski, John Q.; Petersen, Ronald Carl; Aisen, Paul S.; Weiner, Michael W.; Jagust, William J.

In: Archives of Neurology, Vol. 68, No. 10, 10.2011, p. 1257-1266.

Research output: Contribution to journalArticle

Lo, RY, Hubbard, AE, Shaw, LM, Trojanowski, JQ, Petersen, RC, Aisen, PS, Weiner, MW & Jagust, WJ 2011, 'Longitudinal change of biomarkers in cognitive decline', Archives of Neurology, vol. 68, no. 10, pp. 1257-1266. https://doi.org/10.1001/archneurol.2011.123
Lo RY, Hubbard AE, Shaw LM, Trojanowski JQ, Petersen RC, Aisen PS et al. Longitudinal change of biomarkers in cognitive decline. Archives of Neurology. 2011 Oct;68(10):1257-1266. https://doi.org/10.1001/archneurol.2011.123
Lo, Raymond Y. ; Hubbard, Alan E. ; Shaw, Leslie M. ; Trojanowski, John Q. ; Petersen, Ronald Carl ; Aisen, Paul S. ; Weiner, Michael W. ; Jagust, William J. / Longitudinal change of biomarkers in cognitive decline. In: Archives of Neurology. 2011 ; Vol. 68, No. 10. pp. 1257-1266.
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