Highly prevalent geriatric medications and their effect on [beta]-amyloid fibril formation

• Published in: BMC neurology 2024-11, Vol.24 (1)
• Main Authors: Zaman, Zakia, Islam, Radia, Koganti, Bhavya, Falki, Vaibhavkumar, Osentoski, Tammy, Graham, Stewart, Sharoar, Md. Golam
• Format: Article
• Language: English
• Subjects: Advertising executives; Aged patients; Alfacalcidol; Alzheimer's disease; Amyloid beta-protein; Analysis; Antihypertensive drugs; Calcifediol; Cell death; Clopidogrel; Complications and side effects; Drug therapy; Health aspects; Neurons; Polypharmacy; Risk factors; Statistics; Vitamin D
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-024-03930-7

Background The unprecedented increase in the older population and ever-increasing incidence of dementia are leading to a "silver tsunami" in upcoming decades. To combat multimorbidity and maintain daily activities, elderly people face a high prevalence of polypharmacy. However, how these medications affect dementia-related pathology, such as Alzheimer's [beta]-amyloid (A[beta]) fibrils formation, remains unknown. In the present study, we aimed to analyze the medication profiles of Alzheimer's disease (AD; n = 124), mild cognitive impairment (MCI; n = 114), and non-demented (ND; n = 228) patients to identify highly prevalent drugs and to determine the effects of those drugs on A[beta] fibrils formation. Methods Study subjects ([greater than or equal to] 65 years) were recruited from an academic geriatric practice that heavily focuses on memory disorders. The disease state was defined based on the score of multiple cognitive assessments. Individual medications for each subject were listed and categorized into 10 major drug classes. Statistical analysis was performed to determine the frequency of individual and collective drug classes, which are expressed as percentages of the respective cohorts. 10 µM monomeric [beta]-amyloid (A[beta]) 42 and fibrillar A[beta] (fA[beta]) were incubated for 6-48 h in the presence of 25 µM drugs. fA[beta] was prepared with a 1:10 ratio of A[beta]42 to A[beta]40. The amount of A[beta] fibrils was monitored using a thioflavin T (Th-T) assay. Neuronal cells (N2A and SHSY-5Y) were treated with 25 µM drugs, and cell death was measured using a lactose dehydrogenase (LDH) assay. Results We noticed a high prevalence (82-90%) of polypharmacy and diverse medication profiles including anti-inflammatory (65-77%), vitamin and mineral (64-72%), anti-cholesterol (33-41%), anti-hypersensitive (35-39%), proton pump inhibitor (23-34%), anti-thyroid (9-21%), anti-diabetic (5-13%), anti-constipation (9-11%), anti-coagulant (10-13%), and anti-insomnia (9-20%) drugs in the three cohorts. Our LDH assay with 18 highly prevalent drug components showed toxic effects of Norvasc, Tylenol, Colace, and Plavix on N2A cells, and of vitamin D and Novasc on SH-SY5Y cells. All these drugs except Colace significantly reduced the amount of A[beta] fibril when incubated with A[beta]42 for a short period (6 h). However, Lipitor, vitamin D, Levothyroxine, Prilosec, Flomax, and Norvasc prominently reduce the amount of fibrils when incubated with monomeric A[beta]42 f