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Original Investigation
July 10, 2017

Association of Plasma Total Tau Level With Cognitive Decline and Risk of Mild Cognitive Impairment or Dementia in the Mayo Clinic Study on Aging

Author Affiliations
  • 1Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
  • 2Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 3Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
  • 4Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana
  • 5Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
  • 6Department of Radiology, Mayo Clinic, Rochester, Minnesota
JAMA Neurol. Published online July 10, 2017. doi:10.1001/jamaneurol.2017.1359
Key Points

Question  Is plasma total tau level a prognostic marker for cognitive decline and dementia, and do these potential associations differ by elevated brain amyloid β levels?

Findings  In this cohort study of 458 patients, high levels of plasma total tau were associated with a risk of mild cognitive impairment among cognitively normal participants. However, total tau levels were not associated with risk of dementia among participants with mild cognitive impairment. Elevated brain amyloid β was not a confounder or effect modifier when examining any outcome.

Meaning  Elevated plasma total tau levels may be associated with cognitive decline, and this association is independent of elevated brain amyloid β.

Abstract

Importance  The utility of plasma total tau level as a prognostic marker for cognitive decline and dementia is not well understood.

Objectives  To determine (1) the association between plasma total tau level, cognitive decline, and risk of mild cognitive impairment (MCI) and dementia; (2) whether this association differs by the presence of elevated brain amyloid β (Aβ); and (3) whether plasma total tau level is associated with cognitive decline over a short interval of 15 months.

Design, Setting, and Participants  The present analyses included 458 participants who were enrolled in a population-based cohort study between October 2008 and June 2013. All included participants had available plasma total tau levels, Aβ positron emission tomography imaging, and a complete neuropsychological examine at the same visit, as well as at least 1 follow-up visit.

Exposures  Concentration of plasma total tau.

Main Outcomes and Measures  Risk of MCI and dementia; global and domain-specific cognitive decline.

Results  Of the 458 participants, 287 (62.7%) were men; mean (SD) age was 80.6 (5.6) years. Among cognitively normal (CN) participants oversampled for elevated brain Aβ, both the middle (hazard ratio [HR], 2.43; 95% CI, 1.25-4.72) and highest (HR, 2.02; 95% CI, 1.01-4.06) tertiles of plasma total tau level, compared with the lowest, were associated with an increased risk of MCI. Among participants with MCI, higher plasma total tau levels were not significantly associated with risk of dementia (all-cause dementia or Alzheimer disease). Among all participants, higher levels of plasma total tau, examined as a continuous variable, were associated with significant (P < .05) declines in global cognition, memory, attention, and visuospatial ability over a median follow-up of 3.0 years (range, 1.1-4.9 years). In additional analyses restricting the follow-up to 15 months, plasma total tau did not predict decline among CN participants. However, among participants with MCI, higher plasma total tau levels were associated with greater decline in both visuospatial ability (regression coefficient [b] = −0.50 [0.15], P < .001) and global cognition (b = −0.27 [0.10], P = .009) at 15 months. Adjusting for elevated brain Aβ did not attenuate any association. There was no interaction between plasma total tau level and brain Aβ for prognosis with any outcome.

Conclusions and Relevance  These results suggest that elevated plasma total tau levels are associated with cognitive decline, but the results differ based on cognitive status and the duration of follow-up. The association between plasma total tau levels and cognition is independent of elevated brain Aβ.

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