Tag Archives: dementia

In the News: FDA Approves 2nd Oral GLP-1, Another Vaccine Reduces Risk of Dementia, and Costs of Vaccine-Preventable Diseases

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Friday’s blog post (Position Paper: Expediting Drug Approval for Pediatric IBD) has been updated to reflect the recent approval of Stelara (ustekinumab) for the treatment of pediatric patients 2 years and older with moderately to severely active Crohn’s disease. Here’s a link: Johnson & Johnson (JNJ) Gains FDA Approval for Pediatric Crohn’s Disease Treatment. Thanks to Matthew Kowalik, MD, the Director (Acting) of Division of Gastroenterology for FDA/CDER/OND/OII, for bringing this to my attention.

Congratulatons to Rachel Rosen who is the pediatric gastroenterology recipient of  this year’s AGA Institute Council Section Research Mentor Award.

B Lovelace Jr, NBC News, 4/1/26: FDA approves weight loss pill from Eli Lilly

“The daily pill, called Foundayo [orforglipron], follows the approval of Novo Nordisk’s Wegovy pill in recent months. The lowest dose is expected to cost $149 a month for people paying out of pocket…Foundayo will be offered in six doses, with patients typically starting on the lowest dose and working their way up to reduce side effects. It can be taken at any time of day without meal restrictions — unlike the Wegovy pill, which must be taken on an empty stomach each morning…Phase 3 clinical trial data found that Foundayo helped people lose 12.4% of their weight, on average, at its highest dose after 72 weeks — similar to the Wegovy pill but less than injectable versions of Wegovy and Zepbound.”

The FDA has asked Lilly for more safety data. NBC News 4/14/26: FDA asks Lilly for more safety data on weight loss pill Foundayo

Related blog posts:

Also, there was a recent article in Nature (Genetic predictors of GLP1 receptor agonist weight loss and side effects) showing that a genetic variant can predict whether GLP-1 response is more robust. Explainer: Why obesity drugs work better for some people: these genes hold clues

AS Bukhbinder et al. Neurology 2026; 106 (8) e214782. Open Access! Risk of Alzheimer Dementia After High-Dose vs Standard-Dose Influenza Vaccination

This was a retrospective study comparing the high dose influenza vaccine (H-IIV) compared to the standard dose (S-IIV) in 65+ patients. The H-IIV group included 120,775 unique participants (185,183 person-trials; mean age 74.4 years, SD 5.5; 57.3% female), and the S-IIV group included 44,022 participants (53,918 person-trials; mean age 73.0, SD 6.1; 56.4% female).

Key findings:

  • H-IIV was associated with significantly lower AD risk during months 1–25 postvaccination (minimum NNT = 185.2 at 25 months), with a stronger effect among women.

Also, infectious disease outbreaks are expensive. M Baker, American Action Forum 4/3/26. Vaccines Protect More Than Health – They Protect Economic Capacity

“Routine childhood immunizations in the United States from 1994 through 2023 are estimated to have prevented roughly 508 million illnesses, 32 million hospitalizations, and more than 1 million deaths. Those gains translated into approximately $540 billion in direct medical cost savings and nearly $2.7 trillion in total societal savings. Put simply, every $1 spent on childhood immunizations generated about $11 in savings…Adult vaccination also produces meaningful economic gains, particularly through reduced absenteeism, less presenteeism, and better labor-market continuity. Evidence suggests that adult immunization programs can return up to 19 times their initial investment.”

“In South Carolina, a 2025–2026 outbreak with 993 cases generated an estimated $35.5 million in costs, compared with $66,193 to vaccinate the same number of children through VFC. Those costs are only growing – the outbreak in South Carolina has not yet abated.”

Shingles Vaccine Linked to Lower Dementia Risk

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L Carroll. NBC News, 4/2/25: Shingles vaccine may protect against dementia, new study suggests

An excerpt:

It’s been shown that reactivation of the chickenpox virus can lead to the accumulation of aberrant proteins associated with Alzheimer’s…

The new research, published Wednesday in Nature, analyzed data from more than 280,000 older adults in Wales and found that people who received the original shingles live virus vaccine were 20% less likely to develop dementia of any type than those who were not vaccinated...

The new study was possible because of an unusual public health policy in Wales that provided a “natural experiment” to explore the potential impact of the vaccine on dementia risk. With the rollout of the vaccine on Sept. 1, 2013, in Wales, shots were offered to people who were 79 on that date but not given to people who had turned 80. That allowed the German and Stanford University researchers to compare two groups of people with similar health characteristics who differed only by one week in age...

Bolstering the case for the shingles vaccine protecting against dementia were the findings from a study published in Nature Medicine in 2024 that analyzed medical records from more than 100,000 patients. That analysis suggested the newer shingles vaccine was associated with even better protection against dementia.

Actual study:Eyting, M., Xie, M., Michalik, F. et al. . Nature (2025). https://doi.org/10.1038/s41586-025-08800-x Open Access! A natural experiment on the effect of herpes zoster vaccination on dementia

My take: Avoiding shingles is a great reason to get the vaccine. Lowering the risk of Alzheimer’s may convince more to take the shot.

For those wanting a deeper dive on this topic: Eric Topol, The Shingles Vaccine and Reduction of Dementia

Related blog posts:

Flu Shots & Other Vaccines Linked to Lower Rates of Dementia

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10/26/23 Washington Post: Flu shots may protect against the risk of Alzheimer’s, related dementias

An excerpt:

A number of studies have found that people receiving vaccinations for flu and several other infectious diseases appear less likely than the unvaccinated to develop dementia, although scientists aren’t sure why…

In the flu study, the researchers took participants from a national patient database, two groups of 935,887 each, one group vaccinated, the other not. To avoid the potential influence of various factors that could affect the results, the scientists ensured that each group shared many of the same characteristics… found that an annual flu vaccination for three consecutive years reduced the dementia risk 20 percent over the next four to eight years, while six shots doubled it to a 40-percent reduction…

“All this requires further studies, but vaccination, along with good diet, exercise, intellectual and emotional stimulation are key factors for healthy aging,” Hotez said.

The article notes reductions in dementia with Shingles vaccine, Tdap or Td, and pneumococcal vaccines.

These cliffs of the calanques (near Cassis, France) are about 260 meters in elevation

Study: PPIs Did Not Cause Dementia in Older Adults

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Thanks to Ben Gold for encouraging me to review this article:

RS Mehta et al. Gastroenterol 2023; ; 165: 564-572. Open Access! Association of Proton Pump Inhibitor Use With Incident Dementia and Cognitive Decline in Older Adults: A Prospective Cohort Study

The authors used data from ASPirin in Reducing Events in the Elderly (ASPREE), a randomized prospective trial of aspirin in the United States and Australia, including 18,934 community-based adults ≥65 years of all races/ethnicities (enrollment 2010-2014). Final cognitive testing was done in 2017. Key Findings:

  • Baseline PPI use vs nonuse was not associated with incident dementia (multivariable hazard ratio, 0.88, cognitive impairment without dementia (multivariable hazard ratio, 1.00), or with changes in overall cognitive test scores over time.
  • Also, no associations were observed between H2RA use and all cognitive endpoints.

My take: ” These data provide reassurance about the safety of long-term use of PPIs among older adults.” PPIs are unlikely to have negative effects on cognition.

Related blog posts:

More Good News for PPIs: NO Increased Risk of Dementia

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From ACG SmartBrief (thanks to Ben Gold for this):

A study published in The American Journal of Gastroenterology found no link between the use of proton-pump inhibitors and increased dementia risk. The study, led by Muhammad Ali Khan, MD, examined 11 studies with a combined 642,949 participants, and researchers said “PPI use among patients who have a valid indication for it, should not be curtailed because of concerns about dementia risk.”

The American Journal of Gastroenterology: January 2, 2020 – Volume Publish Ahead of Print – Issue – p doi: 10.14309/ajg.0000000000000500

Abstract

INTRODUCTION:

Long-term use of proton pump inhibitors (PPIs) has been associated with a wide variety of potentially serious adverse effects including a possible increased risk of dementia. Studies evaluating this association have reached divergent conclusions. We aimed to evaluate this proposed association further and to assess the quality of the evidence in its support.

METHODS:

We searched MEDLINE, EMBASE, ISI Web of Science, and Cochrane databases for studies examining a link between PPI use and dementia, up to February 2019. Studies reporting summary results as hazard ratio (HR) or odds ratio (OR) were pooled using the DerSimonian and Laird random-effects model for meta-analyses. Methodological quality of individual observational studies was assessed using the Newcastle-Ottawa scale and the overall quality of evidence rated as per the GRADE approach.

RESULTS:

We identified and included 11 observational studies comprising 642,949 subjects; 64% were women. Most studies were short-term ranging from 5 to 10 years. There were 158,954 PPI users and 483,995 nonusers. For studies summarizing data as adjusted HR, pooled HR for all causes of dementia was 1.10 (0.88–1.37); for Alzheimer dementia only, it was 1.06 (0.72–1.55). For studies summarizing data as adjusted OR, pooled OR for all causes of dementia was 1.03 (0.84–1.25) and for Alzheimer dementia only 0.96 (0.82–1.11). Per Newcastle-Ottawa scale assessment, 10 studies were of high quality and 1 was of moderate quality. By applying GRADE methodology, quality of evidence for both outcomes was very low.

DISCUSSION:

We found no evidence to support the proposed association between PPI use and an increased risk of dementia. PPI use among patients who have a valid indication for it, should not be curtailed because of concerns about dementia risk.

Related blog posts:

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NY Times:Supplements Don’t Help Dementia

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It is tiresome how many products are marketed with baseless claims of preventing dementia.  Some pushback:

NY Times: Supplements Won’t Prevent Dementia. But These Steps Might.

An excerpt:

The Food and Drug Administration estimates that 80 percent of older adults rely on dietary supplements, many purporting to prevent or treat Alzheimer’s and other forms of dementia…

Vitamins, various antioxidants, concoctions derived from animals and plants — “we see plenty of ads on TV, but we have no evidence that any of these things are preventive,” said Dr. Steven DeKosky, a neurologist and deputy director of the McKnight Brain Institute at the University of Florida.

Dr. DeKosky led a federally supported study of Ginkgo biloba extract, for instance, following more than 3,000 people for seven years to see if it reduced dementia. It didn’t.

Some of the steps that may help according to article:

  • Increased physical activity;

  • Blood pressure management for people with hypertension, particularly in midlife;

  • And cognitive training.

PPIs NOT Linked to Cognitive Decline/Dementia & PPIs NOT Linked to Heart Attacks

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In a prospective study (M Wod et al. Clin Gastroenterol Hepatol 2018; 16: 681-89), data on middle-aged (n=2346, 46-67 yrs) and older individuals (n=2475) were collected in the Longitudinal Study of Aging Danish Twins.  This study showed that there was no difference in cognitive decline between PPI users and non-users.

The second study (SN Landi et al. Gastroenterol 2018; 154: 861-73) used a large administrative database and reviewed more than 5 million new  users of prescription PPIs and prescription H2RAs.  The authors found no significant difference in myocardial infarctions (MIs) between PPIs and H2RAs over a 12 month period.

Related blog posts:

Recent Study Did NOT Find Dementia Risk with PPIs

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When performing retrospective studies, many times a potential association can be found with medications or diet and specific problems.  When these risks/associations are low (i.e. relative risks <2), often, these findings do not hold up, particularly with prospective studies which are much more able to control for confounding variables.

For proton pump inhibitors (PPIs), many potential complications have been suggested at  low relative risk findings in poorly-controlled studies.  A recent study has contradicted previous findings suggesting that PPIs increase the risk of dementia.

Goldstein FC, et al. J Am Geriatr Soc. 2017;doi:10.1111/jgs.14956. (Thanks to Ben Gold for this reference)

A link and an excerpt from a summary of this study from Healio Gastroenterology:

Link: Study finds no link between PPIs, dementia, Alzheimer’s risk

Excerpt:

They evaluated 10,486 volunteers within the NIH-supported Alzheimer’s Disease Centers who were aged 50 years and older and had either normal cognition or mild cognitive impairment at baseline. Participants underwent neuropsychological evaluations and self-reported PPI use at two to six annual visits between 2005 and 2015.

Overall, 884 reported they were taking PPIs at every visit, 1,925 reported they took PPIs intermittently, and 7,677 never reported taking PPIs.

Those who reported continuous PPI use showed a lower risk for cognitive function decline compared with those who never reported using PPIs (HR = 0.78; 95% CI, 0.66-0.93) as well as a lower risk for developing mild cognitive impairment or Alzheimer’s disease (HR = 0.82; 95% CI, 0.69-0.98).

Those who reported using PPIs intermittently also showed a lower risk for cognitive function decline (HR = 0.84; 95% CI, 0.76–0.93) and for developing mild cognitive impairment or Alzheimer’s disease (HR = 0.82; 95% CI, 0.74–0.91).

My take: This study provides reassurance that PPIs are unlikely to result in cognitive decline. Particularly when a study suggests a low risk of an association, further studies are needed to clarify the true risks.

Related blog posts:

Lennon Wall, Prague

More advice on Proton Pump Inhibitors

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L Laine, A Nagar. Am J Gastroenterol 2016; 111: 913-15.

This reference explains how these clinicians discuss the long-term use of proton-pump inhibitors with their adult patients.  Thanks to Ben Gold for this reference.  Here are a couple pointers:

  • “The recent studies about CKD (chronic kidney disease) and dementia, similar to many prior studies assessing PPI risk, are retrospective observational studies…This results in differences between PPI users and non-users in factors that may impact study outcomes and confound results.”
  • Gastroesophageal reflux disease: The authors suggest that PPIs for GERD can be stopped >2 weeks after symptoms resolve.  For infrequent symptoms, H2RAs, lifestyle modifications and intermittent PPIs often suffice.
  • Barrett’s esophagus: “observational sutdies suggest that PPIs may decrease progression to neoplastic Barrett’s esophagus”

WHAT WE TELL PATIENTS: “Because of inherent risk of bias and low effect sizes we cannot conclude that associations of PPIs and adverse outcomes such as dementia and CKD in recent observational studies are vailid…Nevertheless, we cannot conclude that risks do not exist…we need to ensure that benefits outweigh potential risk.  If PPIs are indicated, using the lowest effective dose and, if possible, intermittent rather than daily therapy..should decrease the risk of potential side effects.”

On the same topic, Paul Moayyedi (in Gastroenterology and Endoscopy News, August 2016): “Every study has shown that sicker patients tend to be prescribed PPIs…Sick patients tend to develop other illnesses so PPIs will be associated with about any disease you can imagine in a database.”  As such, he asserts that weak associations (OR <2) are usually due to cofounding factors.  “The only benefit [these studies]..have is that it is another opportunity to discuss with the patients about stopping their PPI therapy, as there are a significant proportion…on these drugs unnecessarily.”

purple flowers

Piling on PPIs -Now Concerns about Dementia

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A recent study (see abstract below -from Mike Hart) indicates the possibility that proton pump inhibitors (PPIs) could increase the risk of dementia to a small degree.  Despite the big numbers, this study cannot adequately control for numerous factors that could influence these results.  As is often said, association does not prove causation.  Nevertheless, this study is another reminder to use PPIs when indicated and to use them for the appropriate length of therapy.

Here’s NBC News Narrative: Popular Heartburn Drugs Linked to Dementia

ONLINE FIRST

Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis

Willy Gomm, PhD1; Klaus von Holt, MD, PhD1; Friederike Thomé, MSc1; Karl Broich, MD2; Wolfgang Maier, MD1,3; Anne Fink, MSc1,4; Gabriele Doblhammer, PhD1,4,5,6; Britta Haenisch, PhD1

JAMA Neurol. Published online February 15, 2016. doi:10.1001/jamaneurol.2015.4791
 
ABSTRACT

Importance  Medications that influence the risk of dementia in the elderly can be relevant for dementia prevention. Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases but have also been shown to be potentially involved in cognitive decline.

Objective  To examine the association between the use of PPIs and the risk of incident dementia in the elderly.

Design, Setting, and Participants  We 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 2015.

Exposures  Prescription of omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole.

Main Outcomes and Measures  The main outcome was a diagnosis of incident dementia coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The association between PPI use and dementia was analyzed using time-dependent Cox regression. The model was adjusted for potential confounding factors, including age, sex, comorbidities, and polypharmacy.

Results  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 (n = 2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70 729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001).

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.

Related blog post: Proton Pump Inhibitors Webinar

Unrelated article (from Ben Gold): J Molina-Infante et al. Am J Gastroenterol 2015; 110: 1567-1575.  This study examined 75 patients (mean age 38 years) with proton-pump inhibitor responsive esophageal eosinophilia (PPI-REE).  55 (73%) had long-term sustained histologic remission with low-dose PPI therapy (20 mg once or twice daily). In addition, the article noted that 9 of 10 relapsers with distal eosinophilia were noted to have a CYP2C19 rapid metabolizer genotype and regained histologic remission with dose intensification.

Briefly noted: AI Sharara et al. Clin Gastroenterol Hepatol 2016; 14: 317-21.  Among 414 who met inclusion criteria (at least 6 months of PPI usage and at least 1 serum magnesium level), 57 (13.8%) had at least 1 low serum magnesium –44 of these patients had recognizable causes (eg. diuretics, chronic diarrhea).  Of the remainder who continued with PPI therapy, the level was normal at final measurement and only mildly low levels were noted previously.  Thus, in patients without other reasons for low magnesium, the authors found that use of a PPI does not appear to be associated with hypomagnesemia.