Validating a New Serum Anticholinergic Activity Assay in Cognitively Healthy Older Adults

Abstract

Introduction We developed a new serum anticholinergic activity (SAA) assay that measures anticholinergic activity specifically at muscarinic M1 receptors and eliminates many of the drawbacks of the existing SAA assay. We aimed to study the relationship between changes in working memory and executive function with changes in SAA using the new assay in cognitively healthy older adults. Methods Cognitively healthy participants aged 50 years or above, received a single dose of 0.4 mg of intravenous scopolamine. Cognition and SAA were measured before, and 30 minutes after receiving scopolamine. Cognition was measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB) (See Figure 1 for details). Results Ten participants were recruited, and nine (mean age = 69.8 years, SD = 9.5, range 59-86 years) completed the study and were analyzed. The one participant who did not complete the study experienced severe nausea after the scopolamine dose and was withdrawn. Following scopolamine, participants experienced increase in SAA (SAA pre = 0.90 ± 0.97 vs. SAA post = 12.0 ± 3.70; t-test (df = 8) = - 9.6, p < 0.001). In addition, there was a decline in working memory (t-test(df=8) = - 2.350, p=0.047). Finally, there was an association between change in SAA and change in working memory (Spearman's rho = 0.68, p = 0.042), and executive function (Spearman's rho = 0.72, p = 0.027). Conclusions In our sample of cognitively healthy older adults, the new SAA assay was able to detect the scopolamine induced increase in anticholinergic load which correlated significantly with the observed decline in working memory and executive function. This research was funded by Internal Chart: https://apps.aagponline.org/abstracts/uploads/2022/xeztdk55pd2t91n.pdf We developed a new serum anticholinergic activity (SAA) assay that measures anticholinergic activity specifically at muscarinic M1 receptors and eliminates many of the drawbacks of the existing SAA assay. We aimed to study the relationship between changes in working memory and executive function with changes in SAA using the new assay in cognitively healthy older adults. Cognitively healthy participants aged 50 years or above, received a single dose of 0.4 mg of intravenous scopolamine. Cognition and SAA were measured before, and 30 minutes after receiving scopolamine. Cognition was measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB) (See Figure 1 for details). Ten participants were recruited, and nine (mean age = 69.8 years, SD = 9.5, range 59-86 years) completed the study and were analyzed. The one participant who did not complete the study experienced severe nausea after the scopolamine dose and was withdrawn. Following scopolamine, participants experienced increase in SAA (SAA pre = 0.90 ± 0.97 vs. SAA post = 12.0 ± 3.70; t-test (df = 8) = - 9.6, p < 0.001). In addition, there was a decline in working memory (t-test(df=8) = - 2.350, p=0.047). Finally, there was an association between change in SAA and change in working memory (Spearman's rho = 0.68, p = 0.042), and executive function (Spearman's rho = 0.72, p = 0.027). In our sample of cognitively healthy older adults, the new SAA assay was able to detect the scopolamine induced increase in anticholinergic load which correlated significantly with the observed decline in working memory and executive function.