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Front. Aging Neurosci. | doi: 10.3389/fnagi.2018.00070

Early-life cognitive activity is related to reduced neurodegeneration in Alzheimer disease signature regions in late life.

 Kang Ko1, 2,  Min soo Byun3,  Dahyun Yi3,  Jun Ho Lee1, 4, Chan Hyung Kim2, 5 and  Dong Young Lee1, 3, 4*
  • 1Department of Neuropsychiatry, Seoul National University, South Korea
  • 2Department of Psychiatry, College of Medicine, Yonsei university, South Korea
  • 3Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, South Korea
  • 4Department of Psychiatry, Seoul National University College of Medicine, South Korea
  • 5Institute of Behavioral Science in Medicine, College of Medicine, Yonsei university, South Korea

Background: Although increased cognitive activity (CA), both current and past, is known to be associated with a decreased occurrence of Alzheimer’s disease (AD) dementia in older adults, the exact neural mechanisms underlying the association between CA during different stages of life and human dementia remain unclear. Therefore, we investigated whether CA during different life stages is associated with cerebral amyloid-beta (Aß) pathology and AD-related neurodegeneration in non-demented older adults.

Methods: Cross-sectional analyses of data collected between April 2014 and March 2016 from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort. In total, 321 community-dwelling, non-demented older adults were involved in this study. Cerebral Aß deposition and Aß positivity were measured using 11C-Pittsburgh compound B (PiB)-positron emission tomography (PET). AD-signature region cerebral glucose metabolism (AD-CMglu) and AD-related neurodegeneration (AD-ND) positivity were measured using 18F-fluorodeoxyglucose (FDG)-PET. In addition, CA in early, mid, and late life was systematically evaluated using a structured questionnaire.

Results: Of the 321 participants, 254 were cognitively normal (CN) and 67 had mild cognitive impairment. The mean age of participants was 69.6 years old [standard deviation (SD) = 8.0]. Higher early-life CA was associated with significantly increased AD-CMglu (B = 0.035, SE = 0.013, P = .009) and a decreasing AD-ND trend (OR = 0.65, 95% CI 0.43–0.98, P = .04) but was not associated with Aß deposition or positivity. We observed no association between midlife CA and any AD-related brain changes. Late-life CA showed an association with both global Aß deposition and AD-CMglu, although it was not statistically significant. Sensitivity analyses controlling for current depression or conducted only for CN individuals revealed similar results.

Conclusions: Our results suggest that CA in early life may be protective against late-life AD-related neurodegeneration, independently of cerebral Aß pathology.

Keywords: Cognitive activity, early life, midlife, late life, Alzheimer’s disease, neurodegeneration, glucose metabolism, amyloid beta deposition, the KBASE study

Keywords: cognitive activity, early life, midlife, late life, Alzheimer’s disease, neurodegeneration, amyloid beta deposition, the KBASE study, glucose metabolism

Received: 16 Oct 2017; Accepted: 01 Mar 2018.

Edited by:

Ai-Ling Lin, University of Kentucky, United States

Reviewed by:

Jorge Valero, Achucarro Basque Center for Neuroscience, Spain
Fanny Elahi, University of California, San Francisco, United States  

Copyright: © 2018 Ko, Byun, Yi, Lee, Kim and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Dong Young Lee, Seoul National University, Department of Neuropsychiatry, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea,