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.

Drug-induced parkinsonism

Drug-induced parkinsonism (DIP) is the most common drug-induced movement disorder and is most commonly associated with antipsychotic drugs, monoamine reuptake inhibitors, and calcium channel blockers. DIP manifests as a typical movement disorder, which makes it practically indistinguishable from idiopathic Parkinson's disease (PD) and requires differential diagnosis. DIP symptoms develop fairly quickly (hours to weeks) after the antipsychotic is started or after the dose is increased. Therefore, DIP is predominantly a clinical diagnosis that must be kept in mind when a patient develops typical symptoms during treatment onset or increasing the dose of drugs that most often lead to such an adverse reaction (ADR). DIP evaluation includes using the Naranjo algorithm, which helps assess a causal relationship between drug intake and the development of parkinsonism symptoms. The primary DIP treatment is the reduction of the dose of the inducer drug, or its cancellation, or replacement with another drug. In patients with schizophrenia and antipsychotic-induced DIP, dose reduction, replacement with another medication, or prescription of a drug with anticholinergic activity may be possible. The awareness of the doctor and the patient about the possibility of developing this ADR is crucial in the prevention of DIP. Therefore, choosing a drug with the lowest risk of developing DIP is necessary for pharmacotherapy.

Anticholinergic Exposure in Elderly Complex Chronic Patients: A Cross-Sectional Study

Background: Elderly patients with multiple chronic conditions are closely linked to polymedication, a condition that is also highly associated with the presence of adverse effects, such as those observed by anticholinergic activity. Anticholinergic burden is defined in a very variable way and is described inconsistently using different scores and providing different interpretations of the risk of suffering from anticholinergic adverse effects Objective: the objective is to analyse the anticholinergic risk exposure in elderly complex chronic patients. Methods: A observational multicentre study was performed for a cohort of complex chronic patients over 65 years who received treatment with at least one drug with anticholinergic activity. Anticholinergic exposure was assessed using ten scales included in the Anticholinergic Burden Calculator. Results: 473 patients were recruited, being 67.7% with excessive polypharmacy. 80 was the total number of anticholinergic drugs with any scale, with a median of 2 drugs with anticholinergic activity per patient (IQR=2). Three scales evaluated more than 70% of the patients (Chew:79.1%; Drug Burden Index (DBI):77.8%; Anticholinergic Cognitive Burden (ACB):75.9%). The percentage of different drugs with anticholinergic properties evaluated ranged from 13.8% (Anticholinergic Burden Classification (ABC)) to 57.5% (DBI) and anticholinergic drugs prescriptions oscillated from 14% (Anticholinergic Risk Scale (ARS)) to 53.3%(DBI). 71.1% of patients were at risk (moderate and high risk) according to DBI vs. 9.7% by ARS at the opposite side. Important differences of anticholinergic risk in patients with excessive polypharmacy were in ACB, ABC and DBI scales. Conclusions: This study has highlighted clear differences between the scales used. DBI seems to be the scale that identifies a higher number of elderly chronic complex patients at risk of developing anticholinergic adverse effects.

The impact of long-term exposure to anticholinergics among people with intellectual disabilities: a scoping review protocol

Background: Older adults with intellectual disability often take multiple medicines with anticholinergic activity and sedative properties to manage multi-morbidity; the use of medication with anticholinergic activity has been found to be associated with various cognitive and physical impairments. However, there are limited studies that have examined the long-term impact of anticholinergic use among older adults. Therefore, this protocol is designed to conduct a scoping review to examine the available data on the long-term impact of anticholinergic use in older adults with intellectual disability. Aim and objectives: The aim of this scoping review is to a) map and b) examine the existing research literature to answer the research question: What is the impact on cognitive and physical outcomes of long-term exposure to medications with anticholinergic activity among older adults with intellectual disabilities? Methods and analysis: This scoping review will follow the methodology framework of Arksey and O’Malley and its developed version by Levac. The framework consists of a six-stage process to be conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) reporting guidelines. The search strategy will include the following electronic data bases: Pubmed, Cochrane library, EMBASE, Medline, Science Direct, CINAHL Complete and PsycINFO. The search will include terms related to ‘Anticholinergic burden’, ‘Intellectual disability’, ‘Adverse drug reaction’ and ‘long-term impact’ with Boolean operator ‘and’. The scoping review will include studies with at least 3 months exposure to anticholinergics. The collected data will be mapped as a tabular presentation of the various physical and cognitive adverse effects associated with long-term use of anticholinergics in this group of population.

CUMULATIVE CHOLINOLYTIC EFFECT IN CLINICAL PRACTICE (LITERATURE REVIEW)

Anticholinergic agents are widely used in clinical practice. However, they can cause various cumulative side effects (dry mouth, drowsiness, confusion, residual urine accumulation, etc.). The purpose of the study is to perform an analytical review of the literature dedicated to causes, complications and rehabilitation of patients with cumulative anticholinergic effect. The analytical review of the literature highlights the risks and benefits of using anticholinergic drugs. Anticholinergic agents make up to one third of all medicines for the aged people. Recent data have proved the relationship between the long-term use of anticholinergics and dementia. New results relating to the cholinergic system in the regulation of cerebral vascularisation and in neuritis indicate that anticholinergics may contribute to the absolute risk and progression of neurodegenerative diseases. It has been proven that more than 600 drugs taken by aged patients carry the so-called "anticholinergic load". The number of drugs with anticholinergic properties is constantly increasing, they include: antidepressants, antihistamines, antiparkinsonian, antipsychotic, antispasmodic, mydriatic drugs, drugs for the treatment of overactive bladder and many others. Conclusions. The number of drugs that have anticholinergic activity and can cause complications associated with anticholinergic load is increasing. To assess the anticholinergic action of drugs, several methods have been proposed, taking into account the amount of dose and the intensity of anticholinergic activity of drugs. The research of the general medical community about the anticholinergic load problem and high alertness when prescribing drugs with anticholinergic properties can prevent the cumulative anticholinergic effect development and severe complications, and, thus, save the life and health of patients.

ANTICHOLINERGIC BURDEN IN DEMENTIA

Background: The anticholinergic burden is associated with a greater risk of functional/ cognitive decline and morbidity/mortality. Objectives: Our aim was to quantify the anticholinergic burden in the first visit in our dementia tertiary outpatient clinic. Methods: We performed a retrospective analysis of all first visit medical records of patients referred from primary health care to the outpatient dementia clinic of a tertiary hospital in Porto Alegre with a final diagnosis of dementia or Mild Cognitive Impairment (MCI) between 2014-2019. We evaluated all medications in use and we calculated a final score using Brazilian Anticholinergic Activity Drug (BAAD) score. This scale classified drugs according to its central anticholinergic activity from 1 to 3, with higher values indicating greater activity. The final score is the sum of the score for each drug. We divided the sample in two groups (score=0 and ⩾ 1) and performed a logist regression using age, sex, dementia diagnosis and MMSE as covariates. Results: We identified 199 final diagnoses of dementia (mostly Alzheimer’s Disease (AD) [45.2%]) and 39 of MCI. Most patients with dementia (76.4%) and MCI (74.3%) had at least a BAAD score = 1. Median (IQI) BAAD score was higher in VD, 4 (1.0-6.5). In the regression analysis, BAAD score was associated with MMSE, controlling for covariates. Conclusions: In our sample, the anticholinergic burden was high and correlated with dementia severity.