Cognitive effects of cilostazol in Alzheimer's dementia patients with peripheral arterial occlusive disease: A case-control study

Abstract

Aim: Alzheimer's dementia (AD) is a slowly progressing neurodegenerative disease, characterized by beta-amyloid deposition and neurofibrillary tangles. Peripheral atherosclerosis may deteriorate these processes via endothelial cell dysfunction and microvascular impairment. Cilostazol - a phosphodiesterase 3 inhibitor - is a standard treatment for peripheral arterial occlusive disease and a potential treatment for preserving cognitive function in AD patients. We aimed to determine whether cilostazol is beneficial in AD patients with peripheral arterial occlusive disease by evaluating Cognitive Abilities Screening Instrument (CASI) domains.

Methods: We conducted a retrospective case-control study of 62 AD patients in Taiwan. Thirty-one patients had peripheral arterial occlusive disease and were receiving cilostazol plus acetylcholinesterase inhibitors (AchEIs) or N-methyl d-aspartate antagonists, whereas 31 others were receiving AchEIs. Therapeutic responses were measured using neuropsychological assessments. The CASI was administered at baseline and 12 months later; different domains were analyzed between the groups using univariate and multivariate analyses.

Results: Age, sex, education duration, ApoE ε4 gene status, and initial Mini-Mental State Examination scores were not different between the two groups. Except for fluency, no CASI domains showed a statistical difference between the groups. A significant difference was observed in category fluency (P = 0.010). In the logistic regression analysis, after adjusting for covariate effects, category fluency still showed a significant difference between the groups (P = 0.013).

Conclusions: In AD patients with peripheral arterial occlusive disease who have received Food and Drug Administration-approved pharmacotherapy, cilostazol, as an antiplatelet, may help to preserve general cognitive function, with significant preservation in category fluency. Geriatr Gerontol Int 2023; 23: 194-199.

Keywords: acetylcholinesterase inhibitors; cilostazol; cognitive ability screening instrument; peripheral arterial disease; peripheral arterial occlusive disease.