Association of Leukocyte Telomere Length with Mild Cognitive Impairment and Alzheimer's Disease: Role of Folate and Homocysteine

Dement Geriatr Cogn Disord. 2019;48(1-2):56-67. doi: 10.1159/000501958. Epub 2019 Aug 22.

Abstract

Background: Leukocyte telomere length (LTL) is associated with the aging process and age-related degenerative diseases. The relation of peripheral blood LTL to mild cognitive impairment (MCI) and Alzheimer's disease (AD) and the role of folate and homocysteine (Hcy) in this relation remain unclear.

Objectives: We aimed to investigate the association between LTL and the risks of MCI/AD, and to explore whether folate and Hcy may play a role in this association.

Methods: This case-control study included 129 MCI subjects, 131 AD patients and 134 healthy controls. LTL was assessed using real-time polymerase chain reaction assay. Serum folate levels were tested by chemiluminescence enzyme immunoassay, and serum Hcy levels were measured using the enzymatic cycling method. Data were analyzed using multivariate logistic regression and multivariable linear regression with adjustment for potential confounders.

Results: The mean LTL was 1.56 ± 0.25 in controls, 1.44 ± 0.23 in MCI, and 1.28 ± 0.28 in AD patients (p< 0.01). In multivariate logistic regression, subjects in the longest LTL tertile had lower OR for MCI (OR 0.246; 95% CI 0.101-0.597) and AD (OR 0.123; 95% CI 0.044-0.345) in comparison to subjects in the shortest tertile. Shorter LTL was dose-dependently related to the ORs of MCI and AD. Further, serum folate concentration was positively associated with LTL (p < 0.01), while serum Hcy level was negatively associated with LTL (p < 0.05). In stratified analyses, LTL-MCI/AD association varied by serum folate and Hcy level.

Conclusions: Shorter LTL is associated with the risks of MCI/AD. Folate and Hcy might play an important role in this association.

Keywords: Alzheimer’s disease; Biological markers; Case-control study; Mild cognitive impairment; Telomeres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / diagnosis
  • Case-Control Studies
  • Cognitive Dysfunction* / blood
  • Cognitive Dysfunction* / diagnosis
  • Correlation of Data
  • Female
  • Folic Acid / blood*
  • Homocysteine / blood
  • Humans
  • Leukocytes / pathology*
  • Male
  • Middle Aged
  • Telomere Shortening*

Substances

  • Homocysteine
  • Folic Acid