Relationships Between a New Cultured Cell-Based Serum Anticholinergic Activity Assay and Anticholinergic Burden Scales or Cognitive Performance in Older Adults.

Objectives: Anticholinergic burden has been associated with deleterious effects on cognition particularly in those with an underlying brain disorder. We developed a new assay based on cultured cells to measure serum anticholinergic activity (cSAA). We report on its relationships with established anticholinergic burden rating scales and cognitive assessments in older patients with mild cognitive impairment (MCI) or major depressive disorder (MDD) in remission or both.
Design: The study was cross sectional in nature.
Setting: This was a five-centre study conducted in Toronto, Canada.
Participants: Serum samples were collected and cSAA levels were measured in 311 participants aged 60 years or older (154 with MCI, 57 with MDD, and 100 with MCI + MDD).
Measurements: The cSAA assay uses radio-ligand binding to cultured cells stably expressing the muscarinic M1 receptors, with an added procedure to remove potential confounds associated with serum proteins. Lists of medications were used to calculate Anticholinergic Burden and Anticholinergic Drug Scale total scores. Participants also completed a comprehensive cognitive battery.
Results: Higher cSAA levels were associated with higher anticholinergic burden and anticholinergic drug scale scores, and also with lower performance on executive function tests, after adjusting for age, gender, education, and diagnosis.
Conclusions: These results support the use of the cSAA assay as a laboratory measure of anticholinergic burden.
Competing Interests: CONFLICTS OF INTEREST AND SOURCES OF FUNDING W.W., and N.H. have nothing to disclose. T.K.R. has received research support from Brain Canada, Brain and Behavior Research Foundation, BrightFocus Foundation, Canada Foundation for Innovation, Canada Research Chair, Canadian Institutes of Health Research, Centre for Aging and Brain Health Innovation, National Institutes of Health, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, and the Weston Brain Institute. T.K.R. also received in-kind equipment support for an investigator-initiated study from Magstim, and in-kind research accounts from Scientific Brain Training Pro. R.R., B.G.P. and J.N.N. have a patent No.62/466,651 US provisional patent for a cell-based assay and kits for assessing serum anticholinergic activity, status pending. S.K. reports grants from BrightFocus Foundation, grants from Center for Aging and Brain Health Innovation, grants from Brain Canada, grants from University of Toronto, grants from Brain and Behavior Foundation, grants from National Institute of Aging, grants from Canadian Institute of Health research, non-financial support from Soterix Medical, outside the submitted work. N. A. and S.C. report grants from Health Canada and the Chagnon Family, grants from Canada Brain Research Fund, grants from CAMH Foundation during the conduct of the study. L.M. reports non-financial support from Brainsway Ltd, outside the submitted work. K.L. reports grants from Abbvie, personal fees from Abide, personal fees from BioXcel, personal fees from Cerevel, personal fees from ICG Pharma, personal fees from Kondor Pharma, other from Highmark Interactive, personal fees from Otsuka, personal fees from Exciva, outside the submitted work. C.E.F. reports grants from Vielight Inc, grants from Hoffman LaRoche, outside the submitted work. B.H.M. holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He reports grants from Brain Canada, grants from Canadian Institutes of Health Research, grants from Centre for Addiction and Mental Health (CAMH) Foundation, grants from Patient-Centred Outcomes Research Institute, grants from US National Institutes of Health, non-financial support from Eli Lilly, non-financial support from Pfizer, non-financial support from Capital Solutions Design LLC, from HAPPYneuron, c, outside the submitted work. A.J.F. reports grants from Brain Canada, during the conduct of the study; grants from National Institutes of Health, grants from Patient-Centered Outcomes Research Institute, grants from Canadian Institutes of Health Research, grants from Brain Canada, grants from Alzheimer's Association, grants from AGE-WELL, outside the submitted work. B.G.P. reports research support from the Peter & Shelagh Godsoe Endowed Chair in Late-Life Mental Health, CAMH Foundation and Discovery Fund, National Institute of Aging, Brain Canada, the Canadian Institutes of Health Research, the Alzheimer's Drug Discovery Foundation, the Ontario Brain Institute, the Centre for Aging and Brain Health Innovation, the Bright Focus Foundation, the Alzheimer's Society of Canada, the W. Garfield Weston Foundation, the Weston Brain Institute, the Canadian Consortium on Neurodegeneration in Aging and Genome Canada. Honoraria from the American Geriatrics Society. This work has been made possible by Brain Canada through the Canada Brain Research Fund, with the financial support of Health Canada and the Chagnon Family; and by CAMH Foundation. The sponsor had no role in the design of the study, collection or analysis of the data, or in writing the manuscript.
(Copyright © 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)