Brain Imaging and Behavior

, Volume 11, Issue 2, pp 357–367 | Cite as

Cognitive reserve and cortical thickness in preclinical Alzheimer’s disease

  • Corinne Pettigrew
  • Anja Soldan
  • Yuxin Zhu
  • Mei-Cheng Wang
  • Timothy Brown
  • Michael Miller
  • Marilyn Albert
  • the BIOCARD Research Team
SI: Resilience/Reserve in AD


This study examined whether cognitive reserve (CR) alters the relationship between magnetic resonance imaging (MRI) measures of cortical thickness and risk of progression from normal cognition to the onset of clinical symptoms associated with mild cognitive impairment (MCI). The analyses included 232 participants from the BIOCARD study. Participants were cognitively normal and largely middle aged (M age = 56.5) at their baseline MRI scan. After an average of 11.8 years of longitudinal follow-up, 48 have developed clinical symptoms of MCI or dementia (M time from baseline to clinical symptom onset = 7.0 years). Mean thickness was measured over eight ‘AD vulnerable’ cortical regions, and cognitive reserve was indexed by a composite score consisting of years of education, reading, and vocabulary measures. Using Cox regression models, CR and cortical thickness were each independently associated with risk of clinical symptom onset within 7 years of baseline, suggesting that the neuronal injury occurring proximal to symptom onset has a direct association with clinical outcomes, regardless of CR. In contrast, there was a significant interaction between CR and mean cortical thickness for risk of progression more than 7 years from baseline, suggesting that individuals with high CR are better able to compensate for cortical thinning that is beginning to occur at the very earliest phase of AD.


Cognitive reserve Cortical thickness Preclinical AD Magnetic resonance imaging Alzheimer’s disease 



This study was supported in part by grants from the National Institutes of Health (U19-AG033655, P50-AG005146, and T32-AG027668). The BIOCARD Study consists of 7 Cores with the following members: (1) the Administrative Core (Marilyn Albert, Barbara Rodzon); (2) the Clinical Core (Ola Selnes, Marilyn Albert, Anja Soldan, Rebecca Gottesman, Ned Sacktor, Guy McKhann, Scott Turner, Leonie Farrington, Maura Grega, Gay Rudow, Daniel D’Agostino, Scott Rudow); (3) the Imaging Core (Michael Miller, Susumu Mori, Tilak Ratnanather, Timothy Brown, Hayan Chi, Anthony Kolasny, Kenichi Oishi, Thomas Reigel, Laurent Younes); (4) the Biospecimen Core (Abhay Moghekar, Richard O’Brien, Abby Spangler); (5) the Informatics Core (Roberta Scherer, David Shade, Ann Ervin, Jennifer Jones, Matt Toepfner, Lauren Parlett, April Patterson, Aisha Mohammed); (6) the Biostatistics Core (Mei-Cheng Wang, Qing Cai, Yuxin Zhu); and (7) the Neuropathology Core (Juan Troncoso, Barbara Crain, Olga Pletnikova, Gay Rudow, and Karen Fisher). The authors are grateful to the members of the BIOCARD Scientific Advisory Board who provide continued oversight and guidance regarding the conduct of the study including: Drs. John Cernansky, David Holtzman, David Knopman, Walter Kukull, and John McArdle, and Drs. Neil Buckholtz, John Hsiao, Laurie Ryan, and Jovier Evans, who provide oversight on behalf of the National Institute on Aging and the National Institute of Mental Health (NIMH), respectively. The authors thank the members of the BIOCARD Resource Allocation Committee who provide ongoing guidance regarding the use of the biospecimens collected as part of the study, including: Drs. Constantine Lyketsos, Carlos Pardo, Gerard Schellenberg, Leslie Shaw, Madhav Thambisetty, and John Trojanowski.

The authors acknowledge the contributions of the Geriatric Psychiatry Branch of the intramural program of NIMH who initiated the study (Principle investigator: Dr. Trey Sunderland). The authors are particularly indebted to Dr. Karen Putnam, who has provided ongoing documentation of the Geriatric Psychiatry Branch study procedures and the data files received from NIMH.

Compliance with ethical standards

Author disclosures

C. Pettigrew, A. Soldan, X. Zhu, M. C. Wang, and T. Brown declare no conflicts of interest. Dr. Miller owns a significant equity share in “Anatomy Works”. This arrangement is being managed by the Johns Hopkins University in accordance with its conflict of interest policies. Dr. Albert is an advisor to Eli Lilly.

Ethical approval

All procedures performed in studies 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. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11682_2016_9581_MOESM1_ESM.docx (198 kb)
ESM 1 (DOCX 198 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Corinne Pettigrew
    • 1
  • Anja Soldan
    • 1
  • Yuxin Zhu
    • 2
  • Mei-Cheng Wang
    • 2
  • Timothy Brown
    • 3
  • Michael Miller
    • 3
    • 4
    • 5
  • Marilyn Albert
    • 1
  • the BIOCARD Research Team
  1. 1.Department of NeurologySchool of Medicine, Johns Hopkins UniversityBaltimoreUSA
  2. 2.Department of Biostatistics, Bloomberg School of Public HealthJohns Hopkins UniversityBaltimoreUSA
  3. 3.Center for Imaging ScienceJohns Hopkins UniversityBaltimoreUSA
  4. 4.Institute for Computational MedicineJohns Hopkins UniversityBaltimoreUSA
  5. 5.Department of Biomedical EngineeringWhiting School of Engineering, Johns Hopkins UniversityBaltimoreUSA

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