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Research Paper|Volume 12, Issue 5|pp 4407—4423

Telomere shortening reflecting physical aging is associated with cognitive decline and dementia conversion in mild cognitive impairment due to Alzheimer’s disease

Seong-Ho Koh1, Seong Hye Choi2, Jee Hyang Jeong3, Jae-Won Jang4, Kyung Won Park5, Eun-Joo Kim6, Hee Jin Kim7, Jin Yong Hong8, Soo Jin Yoon9, Bora Yoon10, Ju-Hee Kang11, Jong-Min Lee12, Hyun-Hee Park1, Jungsoon Ha1,13, Young Ju Suh14, Suyeon Kang15
  • 1Department of Neurology, Hanyang University College of Medicine, Guri 11923, Korea
  • 2Department of Neurology, Inha University School of Medicine, Incheon 22332, Korea
  • 3Department of Neurology, Ewha Womans University School of Medicine, Seoul 07985, Korea
  • 4Department of Neurology, Kangwon National University School of Medicine, Chuncheon 24289, Korea
  • 5Department of Neurology, Dong-A Medical Center, Dong-A University College of Medicine, Busan 49201, Korea
  • 6Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan 49241, Korea
  • 7Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
  • 8Department of Neurology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
  • 9Department of Neurology, Eulji University Hospital, Eulji University School of Medicine, Daejeon 35233, Korea
  • 10Department of Neurology, Konyang University College of Medicine, Daejeon 35365, Korea
  • 11Department of Pharmacology, Inha University School of Medicine, Incheon 22212, Korea
  • 12Department of Biomedical Engineering, Hanyang University, Seoul 04763, Korea
  • 13GemVax and Kael Co., Ltd, Seongnam 13461, Korea
  • 14Department of Biomedical Sciences, Inha University School of Medicine, Incheon 22332, Korea
  • 15Department of Statistics, Inha University, Incheon 22212, Korea
Received: October 29, 2019Accepted: February 25, 2020Published: March 3, 2020
https://doi.org/10.18632/aging.102893

Copyright © 2020 Koh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We investigated whether telomere length (TL) reflecting physical rather than chronological aging is associated with disease progression in the different cognitive stages of Alzheimer’s disease (AD). Study participants included 89 subjects with amyloid pathology (A+), determined through amyloid PET or cerebrospinal fluid analysis, including 26 cognitively unimpaired (CU A+) individuals, 28 subjects with mild cognitive impairment (MCI A+), and 35 subjects with AD dementia (ADD A+). As controls, 104 CU A- individuals were selected. The participants were evaluated annually over two years from baseline. Compared to the highest TL quartile group of MCI A+ participants, the lowest TL quartile group yielded 2-year differences of -9.438 (95% confidence interval [CI] = -14.567 ~ -4.309), -26.708 (-41.576 ~ -11.839), 3.198 (1.323 ~ 5.056), and 2.549 (0.527 ~ 4.571) on the Mini-Mental State Examination, Consortium to Establish a Registry for AD, Clinical Dementia Rating-Sum of Boxes, and Blessed Dementia Scale-Activities of Daily Living, respectively. With this group, the lowest TL quartile group had a significantly greater probability of progressing to ADD than the highest TL quartile group (hazard ratio = 13.16, 95% CI = 1.11 ~ 156.61). Telomere shortening may be associated with rapid cognitive decline and conversion to dementia in MCI A+.