Factors Affecting Rapid Cognitive Decline in Patients with Alzheimer’s Disease: A Longitudinal Follow-Up Study

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.