Effect of intellectual enrichment on AD biomarker trajectories
Longitudinal imaging study
Citation Manager Formats
Make Comment
See Comments

Abstract
Objective: To investigate the effect of age, sex, APOE4 genotype, and lifestyle enrichment (education/occupation, midlife cognitive activity, and midlife physical activity) on Alzheimer disease (AD) biomarker trajectories using longitudinal imaging data (brain β-amyloid load via Pittsburgh compound B PET and neurodegeneration via 18fluorodeoxyglucose (FDG) PET and structural MRI) in an elderly population without dementia.
Methods: In the population-based longitudinal Mayo Clinic Study of Aging, we studied 393 participants without dementia (340 clinically normal, 53 mild cognitive impairment; 70 years and older) who had cognitive and physical activity measures and at least 2 visits with imaging biomarkers. We dichotomized participants into high (≥14 years) and low (<14 years) education levels using the median. For the entire cohort and the 2 education strata, we built linear mixed models to investigate the effect of the predictors on each of the biomarker outcomes.
Results: Age was associated with amyloid and neurodegeneration trajectories; APOE4 status appears to influence only the amyloid and FDG trajectories but not hippocampal volume trajectory. In the high-education stratum, high midlife cognitive activity was associated with lower amyloid deposition in APOE4 carriers. APOE4 status was associated with lower FDG uptake in the entire cohort and in participants with lower education but not the high-education cohort.
Conclusions: There were minimal effects of lifestyle enrichment on AD biomarker trajectories (specifically rates). Lifetime intellectual enrichment (high education, high midlife cognitive activity) is associated with lower amyloid in APOE4 carriers. High education is protective from the APOE4 effect on FDG metabolism. Differing education levels may explain the conflicting results seen in the literature.
GLOSSARY
- AD=
- Alzheimer disease;
- FDG=
- 18fluorodeoxyglucose;
- MCI=
- mild cognitive impairment;
- MCSA=
- Mayo Clinic Study of Aging;
- MET=
- metabolic equivalent;
- MPRAGE=
- magnetization-prepared rapid gradient echo;
- PCA=
- principal components analysis;
- PiB=
- Pittsburgh compound B;
- ROI=
- region of interest;
- TIV=
- total intracranial volume
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by the authors.
Supplemental data at Neurology.org
- Received June 23, 2015.
- Accepted in final form November 25, 2015.
- © 2016 American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
More Online
Hastening the Diagnosis of Amyotrophic Lateral Sclerosis
Dr. Brian Callaghan and Dr. Kellen Quigg
► Watch
Topics Discussed
Alert Me
Recommended articles
-
Article
Cognitive activity relates to cognitive performance but not to Alzheimer disease biomarkersChristopher M. Gidicsin, Jacqueline E. Maye, Joseph J. Locascio et al.Neurology, June 10, 2015 -
Articles
APOE modifies the association between Aβ load and cognition in cognitively normal older adultsK. Kantarci, V. Lowe, S.A. Przybelski et al.Neurology, December 21, 2011 -
Article
Weighting and standardization of frequencies to determine prevalence of AD imaging biomarkersRosebud O. Roberts, David S. Knopman, Jeremy A. Syrjanen et al.Neurology, October 13, 2017 -
Article
Association of education with Aβ burden in preclinical familial and sporadic Alzheimer diseaseJulie Gonneaud, Christophe Bedetti, Alexa Pichet Binette et al.Neurology, August 05, 2020