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

Zuber Khan, Sidharth Mehan, Mohd Anas Saifi, Ghanshyam Das Gupta, Acharan S Narula, Reni Kalfin
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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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质子泵抑制剂与认知健康:解读痴呆症的关联性和共病风险综述》。
痴呆症是一个国际健康问题,主要表现为认知能力下降导致日常功能受损,目前影响着全球 5500 多万人,其中大多数居住在低收入和中等收入国家。在全球范围内,痴呆症造成的经济负担在 2019 年将达到 1.3 万亿美元。非正规照护者花费大量时间照顾患者。痴呆症给女性带来了更大的护理和残疾调整生命年负担。最近的一项研究证实,除其他神经退行性疾病外,长期服用质子泵抑制剂(PPI)与痴呆症之间也存在相关性。质子泵抑制剂通常通过减少胃酸分泌来治疗消化性溃疡和胃食管反流病(GERD)。它们通过抑制分泌胃酸的 H+、K+ ATP 酶来缓解与胃酸有关的症状。在一些观察性研究中,老年人认知能力下降和痴呆症与服用 PPIs 有关。这种关系的确切机制尚不清楚。这些药物还可能改变脑细胞的 pH 值,导致淀粉样β(Aβ)肽的积累和阿尔茨海默病(AD)的发生。尽管有令人信服的证据支持 PPIs 与痴呆症有关,但研究结果仍不一致。在一些研究中,服用 PPI 与认知能力下降之间没有相关性,这就强调了进行更多研究的必要性。长期服用 PPI 可掩盖潜在的疾病,包括癌症、乳糜泻、维生素 B12 缺乏症和肾损伤,这凸显了痴呆症的风险以及进一步调查认知健康的必要性。
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