Inverse association between the anticholinergic burden and hippocampus volume in a population-based cohort across the entire adult age range

Many medications of different indications have a relevant anticholinergic activity. The anticholinergic burden of medication has been shown to have significant effects on the cognition and the risk for cognitive impairment and dementia particularly in older patients. So far, most of the studies used data from geriatric patients and the effect of the anticholinergic burden on brain structures is still unexplored. Our study aimed to analyze possible associations of hippocampus and cholinergic basal forebrain volumes as vulnerable brain structures for the development of dementia and the anticholinergic burden in a population-based cohort of non-demented participants spanning the adult age range from 21 to 80 years. We analyzed associations between medication-related anticholinergic burden and structural MRI volumes from participants (n = 3087, 52.2% female) of the population-based “Study of Health in Pomerania” (SHIP). Anticholinergic burden was obtained from the current medication plan using the Anticholinergic Burden Scale (ACB). All analyses were adjusted for age, sex, education, and total intracranial volume. We found statistically significant associations between the ACB and the left and right hippocampus volume but not for the basal forebrain cholinergic system. Complementary voxel-based analysis across all participants revealed FWE-corrected (p =  < 0.05) clusters in the temporo-parietal regions reaching into frontal areas, showing reduced volumes with higher ACB scores. We identified an association between anticholinergic burden of medication on hippocampal volume suggesting a potential inverse effect of such medication. This association highlights the importance of a careful prescription of medication with anticholinergic activity at any adult age.