Alzheimer's disease (AD) is neurodegenerative disorder that is associated with memory and cognitive decline in the older adults. Scopolamine is commonly used as a behavioral model in studying cognitive disorders including AD. Many studies have also concurrently examined the neurochemical mechanisms underlying the behavioral modifications by scopolamine treatment. Nonetheless, the scopolamine model has not become a standard tool in the early assessment of drugs. Furthermore, the use of scopolamine as a pharmacological model to study AD remains debatable. This report reviews the scopolamine-induced cellular and molecular changes and discusses how these changes relate to AD pathogenesis.
The consumption of medications with anticholinergic activity has been suggested to result in the adverse effects of mental confusion, visual disturbance, and muscle weakness, which may lead to falls. Existing published evidence linking anticholinergic drugs with falls, however, remains weak. This study was conducted to evaluate the relationship between anticholinergic cognitive burden (ACB) and the long-term risk of hospitalization with falls and fractures in a large population study. The dataset comprised information from 25,639 men and women (aged 40-79 years) recruited from 1993 to 1997 from Norfolk, United Kingdom into the European Prospective Investigation into Cancer (EPIC)-Norfolk study. The time to first hospital admission with a fall with or without fracture was obtained from the National Health Service hospital information system. Cox-proportional hazards analyses were conducted to adjust for confounders and competing risks. The fall hospitalization rate was 5.8% over a median follow-up of ~ 19.4 years. The unadjusted incidence rate ratio for the use of any drugs with anticholinergic properties was 1.79 (95% CI 1.66-1.93). The hazard ratios (95% CI) for ACB scores of 1, 2-3, and ≥ 4 compared with ACB = 0 for fall hospitalization were 1.20 (1.09-1.33), 1.42 (1.25-1.60), and 1.39 (1.21-1.60) after adjustment for age, gender, medical conditions, physical activity, and blood pressure. Medications with anticholinergic activity are associated with an increased risk of subsequent hospitalization with a fall over a 19-year follow-up period. The biological mechanisms underlying the long-term risk of hospitalization with a fall or fracture following baseline ACB exposure remains unclear and requires further evaluation.
Anticholinergic burden (ACB) from medications impairs cognition in schizophrenia. Cognition is a predictor of functional capacity; however, little is known about ACB effect on functional capacity in this population. This study assesses the relationship between ACB and functional capacity across the life span in individuals with schizophrenia after controlling for ACB effect on cognition. A cross-sectional analysis was performed with data collected from 6 academic tertiary health centers. Two hundred and twenty-three community-dwelling participants with schizophrenia or schizoaffective disorder were included in this study. Main variables were ACB, antipsychotic olanzapine equivalents, functional capacity, cognition, and negative symptoms. Simultaneous linear regression analyses were performed to assess the association between ACB, functional capacity, and cognition and then between ACB and cognition. A mediation analysis was then performed to examine whether cognition mediated ACB effect on functional capacity if there was an association between ACB and cognition. Mean age of participants was 49.0 years (SD = 13.1, range 19-79), and 63.7% of participants had severe ACB, ie, a total score of 3 or above. Regression analyses revealed that ACB, age, education, and cognition independently predicted functional capacity and that ACB predicted cognition among those aged 55 years and older. Mediation analysis showed that cognition did partially mediate the effect of ACB on functional capacity in this older cohort. In conclusion, people with schizophrenia are exposed to severe ACB that can have a direct negative impact on functional capacity after controlling for its impact on cognition. Reducing ACB could improve functional capacity and potentially real-world function in schizophrenia.
This study examined the use of potentially inappropriate medicines that may affect cognition (PIMcog) in people with dementia and its associated factors. Medical records of all outpatients with dementia attending a tertiary hospital in Vietnam between January 1, 2015, and December 31, 2016, were examined. Medicine use was assessed against a list of PIMcog. Variables associated with having a PIMcog were assessed using a multiple logistic regression. Of the 128 patients, 41% used a PIMcog, 39.1% used cholinesterase inhibitors (CEIs) concomitantly with anticholinergics, and 18% used antipsychotics. The number of hospital visits (adjusted odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.02-1.16) and number of treating specialists (adjusted OR: 0.61; 95% CI: 0.45-0.83) were associated with PIMcog use. This study highlights a high-level use of medicines that can further impair cognition or reduce the effectiveness of CEIs in people with dementia. Efforts to improve quality use of medicines for this population are warranted.