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 Koh 1, , Seong Hye Choi 2, , Jee Hyang Jeong 3, , Jae-Won Jang 4, , Kyung Won Park 5, , Eun-Joo Kim 6, , Hee Jin Kim 7, , Jin Yong Hong 8, , Soo Jin Yoon 9, , Bora Yoon 10, , Ju-Hee Kang 11, , Jong-Min Lee 12, , Hyun-Hee Park 1, , Jungsoon Ha 1, 13, , Young Ju Suh 14, , Suyeon Kang 15, ,

  • 1 Department of Neurology, Hanyang University College of Medicine, Guri 11923, Korea
  • 2 Department of Neurology, Inha University School of Medicine, Incheon 22332, Korea
  • 3 Department of Neurology, Ewha Womans University School of Medicine, Seoul 07985, Korea
  • 4 Department of Neurology, Kangwon National University School of Medicine, Chuncheon 24289, Korea
  • 5 Department of Neurology, Dong-A Medical Center, Dong-A University College of Medicine, Busan 49201, Korea
  • 6 Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan 49241, Korea
  • 7 Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
  • 8 Department of Neurology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
  • 9 Department of Neurology, Eulji University Hospital, Eulji University School of Medicine, Daejeon 35233, Korea
  • 10 Department of Neurology, Konyang University College of Medicine, Daejeon 35365, Korea
  • 11 Department of Pharmacology, Inha University School of Medicine, Incheon 22212, Korea
  • 12 Department of Biomedical Engineering, Hanyang University, Seoul 04763, Korea
  • 13 GemVax and Kael Co., Ltd, Seongnam 13461, Korea
  • 14 Department of Biomedical Sciences, Inha University School of Medicine, Incheon 22332, Korea
  • 15 Department of Statistics, Inha University, Incheon 22212, Korea

received: October 29, 2019 ; accepted: February 25, 2020 ; published: March 3, 2020 ;

https://doi.org/10.18632/aging.102893
How to Cite

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+.

Abbreviations

ADD: Alzheimer’s disease dementia; APOE: Apolipoprotein E; Aβ: Amyloid β; BDS-ADL: Blessed Dementia Scale- Activities of Daily Living; BMI: Body mass index; CDR-SB: Clinical Dementia Rating-Sum of Boxes; CERAD: Consortium to Establish a Registry for AD; CSF: cerebrospinal fluid; CU: cognitively unimpaired; DM: Diabetes mellitus; DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders-4th Edition; FA: Flip Angle; FMM: flutemetamol; GDS: Geriatric Depression Scale; KBASE-V: Validation cohort of the Korean Brain Aging Study for the Early Diagnosis and Prediction of AD; LM: Logical Memory; MCI: mild cognitive impairment; MMSE: Mini-Mental State Examination; MNA: Mini Nutritional Assessment; MRI: magnetic resonance imaging; NIA-AA: National Institute on Aging-Alzheimer’s Association; PA: Physical activity; PET: positron emission tomography; PiB: Pittsburgh compound-B; p-tau: tau phosphorylated at Thr181; SUVR: standard uptake value ratio; TE: echo time; TI: inversion time; TL: telomere length; TR: repetition time; t-tau: total tau.