Abstract
We investigated the preventive and risk factors of rapid cognitive decline in patients with Alzheimer’s disease (AD). Using the Chang Gung Research Database (CGRD), we enrolled patients with AD aged over 65 years between 1 January 2001 and 30 May 2019, and followed up for at least two years. Rapid cognitive decline was defined by a Mini-Mental State Examination (MMSE) score decline of ≥4 in 2 years. A longer prescription of acetylcholinesterase inhibitors (AChEIs) was defined as 22 months based on the median treatment duration of the cohorts. The Cox proportional hazards regression model adjusted for age, sex, medication, and physical comorbidities was used to examine the candidate risk and protective factors. We analyzed data from 3846 patients with AD (1503 men, 2343 women) with a mean age and percentage of females of 77.8 ± 6.2 years and 60.9%, respectively. The mean duration of patients with AD receiving AChEIs was 658.7 ± 21.9 days. In general, 310 patients with AD showed a rapid cognitive decline, accounting for 8.1%. Treatment of a consecutive AChEI prescription for >22 months in patients with AD was a protective factor against rapid cognitive decline (adjusted hazard ratio (aHR) = 0.41, 95% confidence interval (CI) = 0.33–0.52, p < 0.001). Patients with AD aged >85 years (aHR = 0.53, 95% CI = 0.36–0.79, p < 0.01) and aged 75–85 years (aHR = 0.73, 95% CI = 0.57–0.93, p < 0.05) had a significantly lower risk of rapid cognitive decline than those aged 65–75 years. Additionally, patients with mild and moderate AD (clinical dementia rating (CDR = 1, aHR = 1.61, 95% CI = 1.26–2.07, p < 0.001; CDR = 2, aHR = 2.64, 95% CI = 1.90–3.65, p < 0.001) were more likely to have rapid cognitive decline than those with early AD (CDR = 0.5). Sex, medication with different types of AChEIs, and physical comorbidities were not associated with rapid cognitive decline. These findings indicate that it is important to maintain longer consecutive AChEI prescriptions in patients with AD to prevent cognitive decline.
Highlights
Alzheimer’s disease (AD), a progressive neurodegenerative disease, is the most common form of dementia and is characterized by a gradual decline in cognition, behavioral and social skills, and daily function [1]
Electronic medical records derived from Chang Gung Memorial Hospital (CGMH) to comprise the Chang Gung Research Database (CGRD) are used to provide real-world evidence and improve clinical and policy decisions [18]
Before receiving acetylcholinesterase inhibitors (AChEIs) was 17.2 ± 5.3 and the score declined to 15.8 ± 6.3 following
Summary
Electronic medical records derived from Chang Gung Memorial Hospital (CGMH) to comprise the Chang Gung Research Database (CGRD) are used to provide real-world evidence and improve clinical and policy decisions [18]. Using the CGRD, we enrolled patients aged ≥65 years who were diagnosed with. AD patients were required to maintain the same AChEIs (donepezil, rivastigmine, and galantamine) for at least 1 year, and undergo the Mini-Mental State Examination (MMSE) and clinical dementia rating scale (CDR) examination at least twice before 2017 to allow two-year follow-up. We excluded patients with AD during the follow-up period, patients who switched AChEIs, patients for whom MMSE or CDR were unavailable, and advanced AD patients with CDR 3–5
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