RESULTS

Characteristics Analysis

After data cleaning, we retrieved a total of 11450529 cases from January 2004 to December 2019, 5414695 of which were reported by health professionals. We screened 35251 PPIs-associated adverse event cases and 326943 dementia cases reported by health professionals (Figure 1). We further identified 2104 PPI users with dementia events reported by health professionals (Table 1). No case was identified for dexrabeprazole.
Among cases reported with age, the proportion of PPI users with dementia events was larger in below-65-year group than other age groups. Female cases were reported more than male, the ratio of female proportion versus male proportion were 1.41.
Other health professional (51.47%) reported the most cases, followed by physician (35.46%) and pharmacist (13.07%). Great Britain (27.23%) reported the most cases, followed by France (16.21%) and United States (15.9%). The number of PPI users with dementia events was almost increasing year by year (Figure 2).

Signal Detection

We first conducted signal detection based on all PPIs indications, detected no significant signals between PPIs use and dementia events, ROR = 0.99, 95%CI 0.94 - 1.03, PRR = 0.99, 95%CI 0.95 - 1.03. We then conducted signal detection in individual PPI regimens, detected no significant signals in all the six PPIs as well (Table 2).
We further conducted signal detection based on cases with the indication of GERD, 303 dementia cases were gathered out of 7537 PPI users with GERD indication reported by health professionals in FAERS. However, no significant signal between each PPIs treatment and dementia events was detected, ROR = 0.65, 95%CI 0.58 - 0.73, PRR = 0.67, 95%CI 0.60 - 0.74 (Table 2).

Time Event Comparison

We estimated the time interval from PPIs use to adverse events onset, comparing dementia event between short- and long- time interval groups. 457 dementia cases were identified out of 8848 PPI users with time interval data reported by health professionals in FAERS. We divided different short- and long- time interval with 6 months, 1 year, 3years and 5 year. However, no significant difference was found between each short- and long- time interval groups (Table 3). The OR value (95%CI) of the 6 months, 1 year, 3 years and 5 years comparison were 0.85 (0.68 - 1.06), 0.92 (0.71 - 1.18), 0.81 (0.57 - 1.15) and 0.79 (0.52 - 1.22), respectively.