DISCUSSION
The current study investigated the association between six PPI agents
and the risk of dementia, compared different time interval of PPIs
treatment and dementia events. The
results indicated no association between dementia events and PPI agents,
including dexlansoprazole, lansoprazole, pantoprazole, omeprazole,
esomeprazole and rabeprazole. To the best of our knowledge, this was the
first study concerned the association between PPIs use and dementia risk
based on FAERS database.
With the widespread use of PPI agents, PPIs-associated adverse events
had caught health professionals’ attention, as well as the public and
the media. In FAERS database, nearly three quarter of the PPIs AE cases
were reported by non-health professionals. To reduce the influence of
non-health professionals, we only included cases reported by health
professionals. However, the number of dementia cases treated by PPIs
were increasing by years in FAERS, the risk of stimulated reporting
could not be complete ruled out.
Based on the β-amyloid enhancement [8], vitamin B12 deficiency
phenomena [9] and the widespread PPIs use, the risk of dementia and
PPIs use had become a hot topic. Professor Akter first revealed five
different PPI agents had varying degrees of influence on different
cognitive domains associated with dementia based on the Cambridge
Neuropsychological Test Automated Battery (CANTAB) software test
[10]. Professor Haenisch conducted the first epidemiological
investigation, indicated PPIs might have an impact on dementia risk
based on the German Study on Aging, Cognition and Dementia in Primary
Care Patients (AgeCoDe) [11]. Then, professor Gomm conducted the
first prospective cohort study, revealed regular PPIs treatment had a
significantly increased risk of dementia using data derived from the
largest German statutory health insurer, Allgemeine Ortskrankenkassen
(AOK) [12], which had been hotly commented.
However, conflicting results had been gradually published. Professor
Lochhead conducted a nationwide prospective cohort study and divided PPI
users into four groups based on duration of PPIs treatment, revealed a
modest association between duration of PPIs use and cognitive function,
however, Lochhead stated that the results could not support PPIs use
increases dementia risk [33]. Professor Taipale finished a
nationwide nested case–control study which set a lag window of
different duration, found PPIs use was not associated with risk of
Alzheimer’s disease with a 3-year lag window [34]. Professor Gray
reported a prospective cohort study and found no association between
PPIs exposure and dementia risk after a mean follow-up of 7.5 years
[20]. Professor Cooksey conducted a large population-based study
based on electronic health-data from the Secure Anonymised Information
Linkage (SAIL) Databank from 1999 to 2015, could not confirm an
association between PPIs use and an increased risk of dementia [17].
The current study based the FAERS big data, indicated no significant
signal between PPIs use and the risk of dementia. Even compared in
different time duration, no significant difference of dementia events
was found between short- and long- time interval groups.
Our study revealed no association between dementia risk and PPIs
treatment based on the FAERS real world big data, however, certain
limitations existed. FAERS is a spontaneous reporting system, voluntary
and opened to health professional as well as the public, so
under-reporting, over-reporting or missing data was inevitable [35].
The time event comparison only included limited cases with time data
reported. Although non-health professionals’ reports excluded, the risk
of stimulated reporting could not be eliminated.
In summary, the current study revealed no association between six PPI
agents and the risk of dementia based on the FAERS data. Our findings
suggested that dementia events might not be considered as a factor in
discontinuing PPIs treatment.
Conflicts of Interest
The authors have no conflicts.
Funding information
National Key Research and Development Program of China (Number:
2020YFC2008302).
Sichuan Science and Technology Program (Number: 2020JDR0143).
Data availability
statement
All original data could be downloaded freely in FAERS website.
https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html
Authors Contributions
Bin Wu and Ting Xu designed the research.
Bin Wu, Fang-yuan Tian, Qiao-zhi Hu, Feng-bo Wu, Yu-wen Li and Ting Xu
wrote the article.
Bin Wu and Fang-yuan Tian collected the data.
Bin Wu and Qiao-zhi Hu performed data analysis.
Bin Wu, Feng-bo Wu, Yu-wen Li and Ting Xu contributed to data
interpretation and intellectual content.