Large healthcare databases are increasingly being used for population-based studies of drug efficacy [1]. The Marshfield Clinic Personalized Medicine Research Project (PMRP) in central Wisconsin currently represents one of the largest population-based DNA Biobanks in the world (www.mfldclin.edu/pmrp) [2]. The PMRP database was constructed specifically for use in the areas of genetic epidemiology and pharmacogenetics [3]. With more than 19,000 participants, it would be inefficient and cost-prohibitive to manually reconstruct complete medication exposure histories within the PMRP. Validated electronic text searching algorithms will be required. Natural language processing (NLP) has shown promise in terms of reconstructing accurate medication use histories in the PMRP database [4]. The current study extends this work in the context of characterizing efficacy for a single drug class, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).Methods. This study received prior approval from the Marshfield Clinic Institutional Review Board. The study was conducted in accordance with the basic Principles of the Declaration of Helsinki. The design represents a retrospective observational study utilizing a test sample of 100 participants from the Marshfield Clinic PMRP database. At present, the PMRP database contains coded electronic medical records for more than 19,000 participants. The large majority receive their health care through Marshfield Clinic, a horizontally integrated, multi-specialty group practice located in central Wisconsin. This community exhibits very low inand out-migration rates. For patients residing in ZIP codes associated with Marshfield Clinic, the electronic medical record captures 95% of all outpatient encounters and 93% of all inpatient encounters. Because Marshfield Clinic has maintained this highly integrated medical record for over a decade, all clinical data moved into the PMRP database from medical records is amenable to electronic abstraction (i.e. programmable review through the use of text-mining algorithms).For the current study, a test set of older study persons was selected because they typically have a higher frequency of clinical conditions associated with lipid lowering therapy [5]. A sample cohort of older people was identified within the PMRP database through an initial data interrogation strategy that used age and diagnostic codes. In order to avoid a potential provider-bias against the use of statin-based lipid lowering therapy in patients with advanced cognitive impairment, PMRP participants with a prior diagnosis of dementia were not included in the current study. The initial electronic search strategy yielded 336 unique PMRP participants aged 80 years and older with no underlying diagnosis of dementia. From this pre-selected group of PMRP participants, a sample of 100 unique persons was selected for further study.Manual abstraction. Documents for these 100 older participants were reviewed by a licensed practicing physician (C. B.-S.). Records were not abstract...

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Alzheimer's disease (AD) is a complex neurological disorder that results in cognitive decline. The incidence rates of AD have been increasing, particularly among individuals 60 years of age or older. In June 2021, the US FDA approved aducanumab, the first humanized monoclonal antibody, as a potential therapeutic option for AD. Clinical trials have shown this drug to effectively target the accumulation of Aβ (beta-amyloid) plaques in the brain, and its effectiveness is dependent on the dosage and duration of treatment. Additionally, aducanumab has been associated with improvements in cognitive function. Biogen, the pharmaceutical company responsible for developing and marketing aducanumab, has positioned it as a potential breakthrough for treating cerebral damage in AD. However, the drug has raised concerns due to its high cost, limitations, and potential side effects. AD is a progressive neurological condition that affects memory, cognitive function, and behaviour. It significantly impacts the quality of life of patients and caregivers and strains healthcare systems. Ongoing research focuses on developing disease-modifying therapies that can halt or slow down AD progression. The pathogenesis of AD involves various molecular cascades and signaling pathways. However, the formation of extracellular amyloid plaques is considered a critical mechanism driving the development and progression of the disease. Aducanumab, as a monoclonal antibody, has shown promising results in inhibiting amyloid plaque formation, which is the primary pathological feature of AD. This review explores the signaling pathways and molecular mechanisms through which aducanumab effectively prevents disease pathogenesis in AD.