Proton pump inhibitors (PPIs) are widely used for
the treatment of gastrointestinal diseases but have
also been shown to be potentially involved in
To examine the association between the use of PPIs
omeprazole, pantoprazole, lansoprazole, esomeprazole,
or rabeprazole and the risk of incident dementia in
the elderly resarchers conducted a prospective
cohort study using observational data from 2004 to
2011, derived from the largest German statutory
health insurer, Allgemeine Ortskrankenkassen (AOK).
Data on inpatient and outpatient diagnoses (coded by
the German modification of the International
Statistical Classification of Diseases and Related
Health Problems, Tenth Revision) and drug
prescriptions (categorized according to the
Anatomical Therapeutic Chemical Classification
System) were available on a quarterly basis.
Data analysis was performed from August to November
A total of 73,679 participants 75 years of age or
older and free of dementia at baseline were
analyzed. The patients receiving regular PPI
medication were 44 percent more likely to develop
dementia than those who were not receiving the
drugs, the authors reported in JAMA Neurology.
The avoidance of PPI medication may prevent the
development of dementia. This finding is supported
by recent pharmacoepidemiological analyses on
primary data and is in line with mouse models in
which the use of PPIs increased the levels of β-amyloid
in the brains of mice. Randomized, prospective
clinical trials are needed to examine this
connection in more detail.
The current study can only provide a statistical
association between PPI prescriptions and occurrence
of dementia in the elderly. It canít prove that PPIs
actually cause dementia, said senior author Britta
Haenisch of the German Center for Neurodegenerative
Diseases in Bonn, Germany.
PPIs used for the treatment of gastroesophageal reﬂux
disease and peptic ulcers work by reduction of
gastric acid production, Haenisch said. The
underlying mechanism by which PPIs might influence
cognition is yet to be determined.
Some of the drugs may cross the blood-brain barrier
and interact with brain enzymes, or they may be
associated with vitamin B12 deficiency, which may
promote neurological damage, she said.
For more information
Association of Proton Pump Inhibitors With Risk of
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