Proton Pump Inhibitors and Risk of Mild Cognitive Impairment and Dementia.
OBJECTIVES
To examine the risk associated with the use of proton pump inhibitors (PPIs) of conversion to mild cognitive impairment (MCI), dementia, and specifically Alzheimer's disease (AD).


DESIGN
Observational, longitudinal study.


SETTING
Tertiary academic Alzheimer's Disease Centers funded by the National Institute on Aging.


PARTICIPANTS
Research volunteers aged 50 and older with two to six annual visits; 884 were taking PPIs at every visit, 1,925 took PPIs intermittently, and 7,677 never reported taking PPIs. All had baseline normal cognition or MCI.


MEASUREMENTS
Multivariable Cox regression analyses evaluated the association between PPI use and annual conversion of baseline normal cognition to MCI or dementia or annual conversion of baseline MCI to dementia, controlling for demographic characteristics, vascular comorbidities, mood, and use of anticholinergics and histamine-2 receptor antagonists.


RESULTS
Continuous (always vs never) PPI use was associated with lower risk of decline in cognitive function (hazard ratio (HR) = 0.78, 95% confidence interval (CI) =0.66-0.93, P = .005) and lower risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.69-0.98, P = .03). Intermittent use was also associated with lower risk of decline in cognitive function (HR = 0.84, 95% CI = 0.76-0.93, P = .001) and risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.74-0.91, P = .001). This lower risk was found for persons with normal cognition or MCI.


CONCLUSION
Proton pump inhibitors were not associated with greater risk of dementia or of AD, in contrast to recent reports. Study limitations include reliance on self-reported PPI use and lack of dispensing data. Prospective studies are needed to confirm these results to guide empirically based clinical treatment recommendations.
['Goldstein|Felicia C|FC|', 'Steenland|Kyle|K|', 'Zhao|Liping|L|', 'Wharton|Whitney|W|', 'Levey|Allan I|AI|', 'Hajjar|Ihab|I|']
D000368:Aged D000544:Alzheimer Disease D003071:Cognition D003072:Cognition Disorders D018450:Disease Progression D005260:Female D006801:Humans D008137:Longitudinal Studies D008297:Male D009483:Neuropsychological Tests D011446:Prospective Studies D054328:Proton Pump Inhibitors D012307:Risk Factors
proton pump inhibitors mild cognitive impairment Alzheimer's disease cognitive functioning