In a recent study published in Neurologyresearchers determined whether current and cumulative use of prescription proton pump inhibitors (PPIs) increases the risk of incident dementia.
study: Cumulative use of proton pump inhibitors and risk of dementia: the Atherosclerosis Risk in Communities Study. Image credit: Sonis Photography / Shutterstock.com
Background
PPIs are usually prescribed to provide short-term relief for peptic ulcers and gastroesophageal reflux disease (GERD). Over the past decade, PPI use has increased significantly, with more than half of PPI prescriptions not associated with a documented diagnosis of a gastrointestinal problem.
The widespread use of PPIs is a serious health concern, as these drugs are associated with adverse effects such as chronic kidney disease, cardiovascular disease, stroke, and dementia. However, studies documenting the association between PPI use and dementia have produced mixed results.
Although meta-analyses of cohort and case-control studies have reported no association between PPI use and dementia, these studies have focused largely on Asian or white populations, making the results not generalizable. Furthermore, the diagnosis of dementia using the International Statistical Classification of Diseases and Related Health Problems (ICD) codes is not sensitive.
About the research
In the present study, researchers examined the association between incident dementia and current use and cumulative exposure to PPIs using the Atherosclerosis Risk in Communities (ARIC) study. The ARIC study included black and white men and women between the ages of 45 and 64 from four communities in the United States.
Data collected from the fifth visit of the ARIC study reported usual PPI use. Therefore, the current study used Visit 5 as the baseline to assess PPI use and its impact on incident dementia.
Information on all prescription and over-the-counter medications was collected from all participants and inventoried to assess PPI use. Information collected through annual telephone calls was also used to determine chronic PPI use.
Current PPI use was defined based on PPI use reported at Visit 5, while cumulative PPI exposure was defined based on the number of years of PPI use reported from Visit 1 to the annual telephone call in 2011. Those who reporting no PPI use at visit 5 were considered the reference group.
Histamine2 receptor antagonists (H2RAs), which are an alternative treatment option for GERD and other gastroesophageal problems, were studied as comparators in the secondary analysis.
Dementia was assessed using neuropsychological examinations during in-person visits, screening instruments completed during two-year telephone follow-ups, death records, and hospital discharge codes. A panel of neuropsychologists and physicians confirmed suspected cases of dementia.
A number of covariates including race, age, gender, smoking behavior, body mass index (BMI), and use of aspirin, vitamin B12, and antihypertensive medications were also included in the analysis. Other measurements, such as blood pressure and fasting blood glucose levels, were also obtained to determine the occurrence of hypertension and diabetes, respectively. Calculation of hazard ratios was adjusted for comorbidities, use of other medications, and demographic covariates.
Chronic PPI use increases the risk of dementia
Positive associations between PPI use and risk of dementia have been observed; however, these associations were not significant at a median follow-up of 5.5 years. Nevertheless, analysis of cumulative PPI use and its association with incident dementia showed a 33% increased risk of dementia in later life.
Individuals who used PPIs for more than 4.4 years while in middle age had a relatively higher risk of developing dementia later in life than individuals who did not use PPIs. The association between PPI use and dementia has been explained by two potential mechanisms, including disorders of amyloid metabolism and vitamin B12 deficiency.
PPI use has been shown to decrease levels of vitamin B12, which is essential for cognition. However, adjusting for baseline vitamin B12 supplement use in current study use did not change the results.
Additionally, studies using mouse models have reported increased levels of β-amyloid in the brain following PPI use. PPIs are thought to alter the enzyme γ-secretase, which is involved in the cleavage of β-amyloid, thereby causing the accumulation of β-amyloid plaques in the brain.
Conclusions
Although a positive association was observed between cumulative PPI use and risk of incident dementia, the association was not significant for current PPI use and increased risk of dementia. Further research is needed to elucidate the mechanisms and pathways involved in the development of dementia and its association with PPI use.