Radiological, Chemical, and Pharmacological Cholinergic System Parameters and Neurocognitive Disorders in Older Presurgical Adults

J Gerontol A Biol Sci Med Sci. 2021 May 22;76(6):1029-1036. doi: 10.1093/gerona/glaa182.

Abstract

Background: A pre-existing neurocognitive disorder (NCD) is a relevant factor for the outcome of surgical patients. To improve understanding of these conditions, we investigated the association between parameters of the cholinergic system and NCD.

Method: This investigation is part of the BioCog project (www.biocog.eu), which is a prospective multicenter observational study including patients aged 65 years and older scheduled for elective surgery. Patients with a Mini-Mental State Examination (MMSE) score ≤23 points were excluded. Neurocognitive disorder was assessed according to the fifth Diagnostic and Statistical Manual of Mental Disorders criteria. The basal forebrain cholinergic system volume (BFCSV) was assessed with magnetic resonance imaging, the peripheral cholinesterase (ChE) activities with point-of-care measurements, and anticholinergic load by analyzing the long-term medication with anticholinergic scales (Anticholinergic Drug Scale [ADS], Anticholinergic Risk Scale [ARS], Anticholinergic Cognitive Burden Scale [ACBS]). The associations of BFCSV, ChE activities, and anticholinergic scales with NCD were studied with logistic regression analysis, adjusting for confounding factors.

Results: A total of 797 participants (mean age 72 years, 42% females) were included. One hundred and eleven patients (13.9%) fulfilled criteria for mild NCD and 82 patients (10.3%) for major NCD criteria. We found that AcetylChE activity was associated with major NCD (odds ratio [95% confidence interval]: [U/gHB] 1.061 [1.010, 1.115]), as well as ADS score ([points] 1.353 [1.063, 1.723]) or ARS score, respectively ([points] 1.623 [1.100, 2.397]) with major NCD. However, we found no association between BFCSV or ButyrylChE activity with mild or major NCD.

Conclusions: AcetylChE activity and anticholinergic load were associated with major NCD. Future research should focus on the association of the cholinergic system and the development of postoperative delirium and postoperative NCD.

Keywords: Anticholinergic medication; Cholinesterase; Cognition; Magnetic resonance imaging.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Aged
  • Basal Forebrain / diagnostic imaging
  • Basal Forebrain / drug effects
  • Basal Forebrain / metabolism
  • Cholinergic Antagonists / adverse effects
  • Cholinergic Antagonists / therapeutic use*
  • Cholinergic Neurons / drug effects
  • Cholinergic Neurons / pathology
  • Cholinergic Neurons / physiology*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neurocognitive Disorders / chemically induced
  • Neurocognitive Disorders / etiology
  • Neurocognitive Disorders / pathology
  • Neurocognitive Disorders / physiopathology*
  • Neuroimaging
  • Preoperative Period*
  • Prospective Studies

Substances

  • Cholinergic Antagonists
  • Acetylcholinesterase