Abstract

DONEPEZIL-MEDIATED NEUROPROTECTION IN MILD-TOMODERATE ALZHEIMER'S DISEASE: A PROSPECTIVE STUDY OF COGNITIVE AND BIOMARKER OUTCOMES

Yashkumar Nareshbhai Rathod, Kinjalben Rajendrakumar Patel

Abstract

Alzheimer's disease is a progressive neurodegenerative disorder marked by cognitive decline, oxidative stress, and neuroinflammation. Donepezil, an acetylcholinesterase inhibitor widely used for symptomatic management of mild-tomoderate Alzheimer's disease, may also exert neuroprotective effects via modulation of oxidative stress, inflammatory pathways, and neurotrophic factors; however, integrated clinical evaluation of these outcomes remains limited. This prospective observational study evaluated the efficacy, safety, and neuroprotective effects of donepezil (5 or 10 mg/day) in 60 patients with mild-to-moderate Alzheimer's disease over 3 months. Cognitive function was assessed using the MMSE and ADAS-Cog scales at baseline and monthly follow-ups, with clinical improvement rated using the Clinical Global Impression–Improvement (CGI-I) scale. Biochemical parameters such as malondialdehyde (MDA), superoxide dismutase (SOD), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and brain-derived neurotrophic factor (BDNF) were measured at baseline and follow-up, alongside adverse drug reactions. All 60 patients completed the study with no dropouts. MMSE scores rose from 15.67 ± .41 to 18.94± 0.34, while ADAS-Cog scores fell from 34.02 ± 0.58 to 29.41 ± 0.46 (p < 0.001). MDA, CRP, and TNF-α decreased significantly, whereas SOD and BDNF increased significantly (p < 0.001), reflecting enhanced antioxidant defense and neurotrophic support. CGI-I assessment showed marked improvement in 73.3% of patients with no deterioration, and donepezil was well tolerated, with 55% reporting no adverse reactions and the rest experiencing only mild-to-moderate events. These findings indicate donepezil significantly improves cognitive function while reducing oxidative stress and inflammation and enhancing neurotrophic activity, with a favorable safety profile and multi-mechanistic neuroprotective effect in Alzheimer's disease management.

Keywords: Alzheimer's disease; Donepezil; Neuroprotection; MMSE; Acetylcholinesterase inhibitor; Prospective observational study.