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

Chih-Chuan Pan; Che-Sheng Chu; Chien-Liang Chen; Yao-Chung Chuang; Nai-Ching Chen

doi:10.3390/ijerph18168576

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

Int J Environ Res Public Health. 2021 Aug 13;18(16):8576. doi: 10.3390/ijerph18168576.

Authors

Chih-Chuan Pan¹, Che-Sheng Chu^{1

2

3

4}, Chien-Liang Chen^{5

6}, Yao-Chung Chuang^{7

8}, Nai-Ching Chen⁷

Affiliations

¹ Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
² Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
³ Non-Invasive Neuromodulation Consortium for Mental Disorders, Society of Psychophysiology, Taipei 114, Taiwan.
⁴ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁵ Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
⁶ Department of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
⁷ Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
⁸ Department of Neurology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

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.

Keywords: Alzheimer’s disease; acetylcholinesterase inhibitors; moderators; predictor; rapid cognitive decline.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / drug therapy
Alzheimer Disease* / epidemiology
Cholinesterase Inhibitors / therapeutic use
Cognitive Dysfunction* / epidemiology
Disease Progression
Female
Follow-Up Studies
Humans
Male
Mental Status and Dementia Tests

Substances

Cholinesterase Inhibitors