APOE 4/4 here. I have esophageal dysmotility, once-a-month dysphagia (difficulty swallowing), and GERD (heartburn). Been on PPIs for three years. Tapered off in December, 2018 because of dementia risk. GERD is returning now - lung pain and congestion, irritated sinuses, ears, eyes. I know from past experience that this will turn into pneumonias and sinus infections. Those are inflammations also bad in themselves and bad for APOE4s.
I’m facing a choice between lifetime PPI use or elective surgery with risks. I knew about the JAMA study showing a link between PPI and dementia - bad news for APOE4s. So I looked up everything about the association and post it below. The evidence is mixed, I’d say leaning against an association. The mechanism of an association could be reduced nutrient uptake, but I get plenty of good nutrients, vitamins, minerals. If the mechanism is mitochondrial, I’m taking ALC, A Lipoic Acid, CoQ10, magnesium glycinate, benfotiamine, self-injected methyl B-12, some of that for many years.
Similar evidence casts doubt on H2s as well, and they intolerably bother me subjectively (depression, slow thinking) when PPIs don’t.
My university-hospital gastro dept is pushing me to have surgery on my lower esophageal sphincter. Clear up a hiatal hernia and tighten up the LES. I’m a bit worried because this dept will schedule urgent requests for followups on failures of past treatment 2 or 3 months into the future. Also, the surgeon’s nurse says that the surgery is for achalasia; but I quite definitely know that is not the diagnosis (that was an initial diagnosis overturned by further interpretations requested by the first investigator of a senior physician). I got an informal second opinion from another gastro who warned a) that a tightened LES with a weak esophagus could result in daily dysphagia (cure worse than disease) and b) these surgeries can accidentally damage the crucial vagus nerve resulting in disability and in one local case death as the result of elective surgery. All advice welcome. Initial surgery consult is on Jan 31.
Major studies run two for an association, and four against an association. Here are, I think, ALL the refereed studies on the association of PPIs (one on H2s) and dementia. Also, I reference two review articles on possible mechanism of an association (which I can follow superficially, but I lack biomedical training so don’t understand in any depth).
ASSOCIATION PPIS AND DEMENTIA
https://www.ncbi.nlm.nih.gov/pubmed/26882076
JAMA Neurol. 2016 Apr;73(4):410-6. doi: 10.1001/jamaneurol.2015.4791.
Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis.
CONCLUSIONS AND RELEVANCE: 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.
https://www.ncbi.nlm.nih.gov/pubmed/28199356
PLoS One. 2017 Feb 15;12(2):e0171006. doi: 10.1371/journal.pone.0171006. eCollection 2017.
Risk of dementia from proton pump inhibitor use in Asian population: A nationwide cohort study in Taiwan.
Conclusions: An increased risk for dementia was identified among the Asian PPI users. Cumulative PPI use was significantly associated with dementia.
WEAK ASSOCIATION
https://www.ncbi.nlm.nih.gov/pubmed/27903560
WEAK ASSOCIATION OF H2S AND DEMENTIA
https://www.ncbi.nlm.nih.gov/pubmed/17661965
NO ASSOCIATION PPIS AND DEMENTIA
Transcript of podcast discussion by two research teams
https://www.geripal.org/2018/02/ppi-and-dementia.html
https://jamanetwork.com/journals/jamane ... le/2487379
Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis
JAMA Neurol. 2016;73(4):410-416. doi:10.1001/jamaneurol.2015.4791
Conclusions and Relevance 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.
https://www.alzforum.org/news/research- ... entia-risk
“A similar analysis associated both intermittent and regular PPI use with a lower hazard ratio, 0.82, of being diagnosed with AD. Goldstein and colleagues also analyzed data from people with normal cognition during their first visit separately from those who already had MCI, to see if either group might be more vulnerable to PPIs. They found no increased risk for cognitive decline in either group. Lastly, the authors focused on people 75 and older to more closely mirror the populations tracked in previous studies. Once again, they detected no PPI-associated increase in dementia risk.”
https://www.ncbi.nlm.nih.gov/pubmed/28728964
Gastroenterology. 2017 Oct;153(4):971-979.e4. doi: 10.1053/j.gastro.2017.06.061. Epub 2017 Jul 18.
Association Between Proton Pump Inhibitor Use and Cognitive Function in Women.
“Because of shared clinical indications, we examined associations for H2 receptor antagonists (H2RAs) as a secondary aim….Among individuals who did not use PPIs regularly, duration of H2RA use was associated with poorer cognitive scores”
CONCLUSIONS: In an analysis of data from the Nurses' Health Study II, we did not observe a convincing association between PPI use and cognitive function. Our data do not support the suggestion that PPI use increases dementia risk. Because our primary hypothesis related to PPI use, our findings for H2RAs should be interpreted with caution.
https://www.ncbi.nlm.nih.gov/pubmed/28695906
No Association Between Proton Pump Inhibitor Use and Risk of Alzheimer's Disease.
Am J Gastroenterol. 2017 Dec;112(12):1802-1808. doi: 10.1038/ajg.2017.196. Epub 2017 Jul 11.
No Association Between Proton Pump Inhibitor Use and Risk of Alzheimer's Disease.
CONCLUSIONS: In conclusion, we found no clinically meaningful association between PPI use and risk of AD. The results for longer duration of cumulative use or use with higher doses did not indicate dose-response relationship.
WEAKER NO ASSOCIATION
https://www.ncbi.nlm.nih.gov/pubmed/27903560
https://www.ncbi.nlm.nih.gov/pubmed/26744954
OVERVIEW AND LACK OF CONSENSUS
https://www.alzforum.org/news/research- ... entia-risk
“Besides Goldstein and Haenisch’s work, previous studies have suggested positive, negative, or neutral associations between PPIs and cognitive decline (Nevado-Hurtado et al., 2016; Tai et al., 2017; Booker et al., 2016; Boustani et al., 2007). Last April, a consensus panel of nine international experts in gastroesophageal reflux deemed the results too inconclusive to change their safety recommendations for use of over-the-counter PPIs (Johnson et al., 2017).”
Actually, Johnson 2017 is silent on the issue:
https://www.ncbi.nlm.nih.gov/pubmed/28233274
MECHANISMS OF ACTION
https://www.ncbi.nlm.nih.gov/pubmed/29376492
Curr Med Chem. 2018;25(18):2166-2174. doi: 10.2174/0929867325666180129101049.
Is the Use of Proton-pump Inhibitors a Risk Factor for Alzheimer's Disease? Molecular Mechanisms and Clinical Implications.
https://www.hindawi.com/journals/np/2018/5257285/
Neural Plasticity
Volume 2018, Article ID 5257285, 9 pages
https://doi.org/10.1155/2018/5257285
Review Article
Proton Pump Inhibitors and Dementia: Physiopathological Mechanisms and Clinical Consequences