Proton Pump Inhibitors and Cognitive Health: Review on Unraveling the Dementia Connection and Co-morbid Risks.

Zuber Khan, Sidharth Mehan, Ghanshyam Das Gupta, Acharan S Narula, Reni Kalfin, Mohd Anas Saifi

Journal: Current Alzheimer research 2024;20(11):739-757

PMID: 38424433

Abstract

Dementia, an international health issue distinguished by the impairment of daily functioning due to cognitive decline, currently affects more than 55 million people worldwide, with the majority residing in low-income and middle-income countries. Globally, dementia entails significant economic burdens in 2019, amounting to a cost of 1.3 trillion US dollars. Informal caregivers devote considerable hours to providing care for those affected. Dementia imposes a greater caregiving and disability-adjusted life-year burden on women. A recent study has established a correlation between prolonged Proton Pump Inhibitor (PPI) usage and dementia, in addition to other neurodegenerative conditions. PPIs are frequently prescribed to treat peptic ulcers and GERD (gastroesophageal reflux disease) by decreasing stomach acid secretion. They alleviate acid-related symptoms through the inhibition of acid-secreting H-K ATPase. In a number of observational studies, cognitive decline and dementia in the elderly have been linked to the use of PPIs. The precise mechanism underlying this relationship is unknown. These drugs might also alter the pH of brain cells, resulting in the accumulation of amyloid-beta (Aβ) peptides and the development of Alzheimer's disease (AD). Despite the compelling evidence supporting the association of PPIs with dementia, the results of studies remain inconsistent. The absence of a correlation between PPI use and cognitive decline in some studies emphasizes the need for additional research. Chronic PPI use can conceal underlying conditions, including cancer, celiac disease, vitamin B12 deficiency, and renal injury, highlighting dementia risk and the need for further investigations on cognitive health.

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Address: Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India (Affiliated to IK Gujral Punjab Technical University), Jalandhar, Punjab, 144603, India.; Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi-110062, India.; Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, India (Affiliated to IK Gujral Punjab Technical University), Jalandhar, Punjab, 144603, India.; Narula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC27516, USA.; Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev St., Block 23, Sofia1113, Bulgaria.; Department of Healthcare, South-West University "NeofitRilski", Ivan Mihailov St. 66, Blagoevgrad2700, Bulgaria.
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