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Brain Imaging and Behavior

, Volume 11, Issue 2, pp 383–390 | Cite as

Cognitive resilience in clinical and preclinical Alzheimer’s disease: the Association of Amyloid and Tau Burden on cognitive performance

  • Dorene M. Rentz
  • Elizabeth C. Mormino
  • Kathryn V. Papp
  • Rebecca A. Betensky
  • Reisa A. Sperling
  • Keith A. Johnson
SI: Resilience/Reserve in AD

Abstract

We explored the cross-sectional relationships between β-amyloid (Aβ) and inferior temporal tau deposition (IFT Tau) on cognitive performance and whether cognitive reserve (CR) modifies these associations. We studied 156 participants classified into groups of clinically normal (CN = 133), mild cognitive impairment (MCI = 17) and Alzheimer disease (AD = 6) dementia. AMNART IQ served as a proxy of CR and cognitive performance was assessed using the MMSE. In separate linear regression models predicting MMSE, we examined the interactions of CR x global Aβ and CR x IFT tau across all participants and within the CN group alone. In the whole sample, the interaction between CR and IFT tau was significant (p < 0.003), such that higher CR participants with elevated IFT tau had better MMSE scores compared with low CR participants with similar levels of IFT tau. The interaction between CR and Aβ status did not reach significance (p = 0.093). In CN only, no cross-sectional interactions among CR, Aβ, and IFT tau were observed on MMSE. These findings imply that CR may be protective against early AD processes and enable some individuals to remain cognitively stable despite elevated tau and Aβ burden.

Keywords

Aging Preclinical Alzheimer’s disease Amyloid PET imaging Tau PET imaging Resilience 

Notes

Compliance with ethical standards

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

The National Institute on Aging (P01 AG036694, RO1 AG037497, RO1EB014894) and the Alzheimer’s Association IIRG-08-90,934 funded this study.

Conflict of interest

D. Rentz received research support from the NIH grants P01 AG036694, R01 MH090291, U01 AG024904, R01 AG027435, R01 AG037497 and P50 AG005134, Alzheimer Association grant IIRG-08-90,934 and Fidelity Biosciences. She has also served as a paid consultant for Eli Lilly, Lundbeck Pharmaceuticals, Janssen Alzheimer Immunotherapy, Biogen, Idec and Neurotrack. These relationships are not related to the content in the manuscript.

E. Mormino received funding from NIH grant F32AG044054 and P01 AG036694 and has served as a paid consultant for Janssen Pharmaceuticals and Biogen Idec. These relationships are not related to the content in the manuscript.

K. Papp was supported by NIA grant T32AG023480–08, the Charles King Trust, and NIH grant P01 AG036694 and has served as a paid consultant for Biogen Idec. These relationships are not related to the content in the manuscript.

R. Betensky received funding from NIH grants R01 CA075971, R03 CA165070, UL 1RR025758, P50 NS051343, P50 NS051343, P30 CA006516, P50 AG005134, P01 AG036694, R01 NS070834, R01 NS070834 and R01 AG026484.

R. Sperling has served as a paid consultant for Abbvie, Biogen, Bracket, Genentech, Lundbeck, Roche, and Sanofi. She has served as a co-investigator for Avid, Eli Lilly, and Janssen Alzheimer Immunotherapy clinical trials. She has spoken at symposia sponsored by Eli Lilly, Biogen, and Janssen. R. Sperling receives research support from Janssen Pharmaceuticals, and Eli Lilly and Co. These relationships are not related to the content in the manuscript. She also receives research support from the following grants: P01 AG036694, U01 AG032438, U01 AG024904, R01 AG037497, R01 AG034556, K24 AG035007, P50 AG005134, U19 AG010483, R01 AG027435, Fidelity Biosciences, Harvard NeuroDiscovery Center, and the Alzheimer’s Association.

K. Johnson has served as paid consultant for Bayer, Bristol-Myers Squibb, GE Healthcare, Janssen Alzheimer’s Immunotherapy, Siemens Medical Solutions, and Genzyme. He is a site coinvestigator for Lilly/Avid, Bristol-Myers Squibb, Pfizer, Janssen Immunotherapy, and Navidea. He has spoken at symposia sponsored by Janssen Alzheimer’s Immunotherapy and Pfizer. T. Benzinger has served on an advisory board for Eli Lilly and has received research funding from Avid Radiopharmaceuticals. These relationships are not related to the content in the manuscript. K. Johnson receives funding from NIH grants R01EB014894, R21 AG038994, R01 AG026484, R01 AG034556, P50 AG00513421, U19 AG10483, P01 AG036694, R13 AG042201174210, R01 AG027435, and R01 AG037497 and the Alzheimer’s Association grant ZEN-10-174,210.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Dorene M. Rentz
    • 1
    • 2
  • Elizabeth C. Mormino
    • 1
  • Kathryn V. Papp
    • 1
    • 2
  • Rebecca A. Betensky
    • 3
  • Reisa A. Sperling
    • 1
    • 2
    • 4
  • Keith A. Johnson
    • 1
    • 2
    • 4
    • 5
  1. 1.Department of Neurology, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  2. 2.Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  3. 3.Department of BiostatisticsHarvard School of Public HealthBostonUSA
  4. 4.Department of Radiology, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  5. 5.Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General HospitalHarvard Medical SchoolBostonUSA

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