Alzheimer’s disease is a progressive neurodegenerative disorder with demonstrable pathology include amyloid beta  plaques accumulation, neurofibrillary tau tangles, oxidative stress, mitochondrial dysfunction and neuroinflammation leading to synaptic impairment. Among these Quinone dihydroxypteridine Reductase, an oxidative stress regulating enzyme is upregulated in AD with roles in electron transport, oxidative stress and neurotransmitter synthesis and induction of induced nitric acid synthase . In this context, using structure-based drug designing, we found the FDA approved NSAID dexketoprofen trometamol blocks QDPR activity. Dexketoprofen trometamol demonstrated stable interactions with critical residues in the AChE receptor, forming multiple hydrogen bonds that enhance its binding potential. The binding free energy calculations supported dexketoprofen trometamol’s high affinity for AChE, surpassing that of established AD drugs like donepezil. Moreover, previous studies on transgenic mice models of AD showed that dexketoprofen trometamol administration showed improved cognition. One of the major limitations in Alzheimer’s treatment today is that no currently approved drug addresses the multiple pathogenic pathways of the disease simultaneously. Therefore, future treatment strategies have to be multi targeted therapies. Dexketoprofen trometamol is a candidate drug, because it targets three critical mechanisms implicated in AD progression Oxidative stress, Neuroinflammation, and Cholinergic dysfunction (through acetylcholinesterase inhibition). Dexketoprofen trometamol’s established safety makes it more conducive for performing this clinical trial. This makes it a highly promising candidate for multi-targeted therapy in Alzheimer’s, potentially offering disease-modifying benefits rather than just symptomatic relief.

Hypothesis Administering 75 mg of dexketoprofen trometamol daily for 9 months will result in significant improvement in cognitive function, as measured by validated neuropsychological assessments, in patients AD compared to a standard care alone.