A case-control study of phosphodiesterase-5 inhibitor use and Alzheimer’s disease and related dementias among male and female patients aged 65 years and older supporting the need for a phase III clinical trial

Phosphodiesterase-5 inhibitors (PDE5i) have been evaluated as a novel treatment for Alzheimer's disease and related dementias (ADRD), but two recent cohort studies have offered opposing conclusions. We performed an unmatched case-control study using electronic medical records from a large healt...

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Bibliographic Details
Published in:PloS one 2023-10, Vol.18 (10), p.e0292863-e0292863
Main Authors: Henry, David S, Pellegrino, Richard G
Format: Article
Language:English
Subjects:
Alzheimer's disease
Calcium channels
Care and treatment
Clinical trials
Computer and Information Sciences
Drug therapy
Endothelin
Impotence
Medical records
Medical research
Medicine and Health Sciences
Medicine, Experimental
Patient outcomes
Pulmonary hypertension
Respiratory agents
Type 2 diabetes
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Summary:Phosphodiesterase-5 inhibitors (PDE5i) have been evaluated as a novel treatment for Alzheimer's disease and related dementias (ADRD), but two recent cohort studies have offered opposing conclusions. We performed an unmatched case-control study using electronic medical records from a large healthcare system to evaluate the association of PDE5i use and ADRD in patients [greater than or equal to]65 years old. Odds of PDE5i exposure were 64.2%, 55.7%, and 54.0% lower in patients with ADRD than controls among populations with erectile dysfunction, benign prostatic hyperplasia, and pulmonary hypertension, respectively. We observed odds ratios less than unity among males and females and with exposure to the PDE5i sildenafil (Viagra®) and tadalafil (Cialis®). We also evaluated the odds of exposure to two other common treatments for pulmonary hypertension: endothelin receptor antagonists (ERA) and calcium channel blockers (CCB). The odds of ERA exposure were 63.2% lower, but the odds of CCB exposure were 30.7% higher, in patients with ADRD than controls among the population with pulmonary hypertension. Our results reconcile the opposing conclusions from the previous observational studies and support further research into using PDE5i for prevention and treatment of ADRD.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0292863