Targeting the Beta-2-Adrenergic Receptor and the Risk of Developing Alzheimer's Disease: A Retrospective Inception
Danique R Hutten1, Jens H J Bos1, Stijn de Vos1
1Groningen Research Institute of Pharmacy, PharmacoTherapy, -Epidemiology & -Economics, University of Groningen, Groningen, The Netherlands.
Background:
Animal studies suggested that β2-Adrenergic receptors (β2AR) may be a potential target for the treatment of Alzheimer's disease (AD).
Objective:
This retrospective inception cohort study aimed to assess the association between antagonists and agonists of the β2AR and the risk of starting treatment for AD in older adults.
Methods:
A retrospective inception cohort study was conducted among older adults who initiated either non-selective βAR antagonists or selective β2AR agonists using the University Groningen IADB.nl prescription database (study period 1994-2019). For each exposed cohort, two reference cohorts (A and B) were matched on age at index date. The main outcome was defined as at least two prescriptions for cholinesterase inhibitors (rivastigmine, galantamine, and donepezil) and/or memantine. Cox proportional hazard regression models were used to estimate hazard ratios (HR).
Results:
The risk of developing AD was elevated among patients exposed to non-selective βAR antagonists (A: aHR 3.303, 95% CI 1.230-8.869, B: aHR 1.569, 95% CI 0.560-4.394) and reduced among patients exposed to selective β2AR agonists (A: aHR 0.049, 95% CI 0.003-0.795, B: aHR 0.834, 95% CI 0.075-9.273) compared to reference patients.
Conclusion:
These findings suggest that exposure to non-selective βAR antagonists is associated with an increased risk for developing AD whereas there may be a decreased risk for developing AD after exposure to selective β2AR agonists.
Insights
Non-selective beta-2 adrenergic receptor (β2AR) antagonists were linked to a higher Alzheimer's disease (AD) risk. Selective β2AR agonists may decrease AD risk in older adults.
Area of Science:
- Pharmacology
- Neuroscience
- Geriatrics
Background:
- Animal studies indicate beta-2 adrenergic receptors (β2AR) as a potential therapeutic target for Alzheimer's disease (AD).
- The role of β2AR antagonists and agonists in AD development requires further investigation in human populations.
Purpose of the Study:
- To investigate the association between β2AR antagonists/agonists and the risk of initiating AD treatment in older adults.
- To evaluate the differential impact of selective β2AR agonists versus non-selective βAR antagonists on AD risk.
Main Methods:
- Retrospective inception cohort study utilizing the University Groningen IADB.nl prescription database (1994-2019).
- Older adults initiating non-selective βAR antagonists or selective β2AR agonists were compared to matched reference cohorts.
- Alzheimer's disease diagnosis was defined by initiating treatment with cholinesterase inhibitors or memantine.
Main Results:
- Exposure to non-selective βAR antagonists was associated with an elevated risk of developing AD (adjusted hazard ratio [aHR] > 1).
- Exposure to selective β2AR agonists showed a trend towards a reduced risk of developing AD (aHR < 1).
Conclusions:
- Non-selective βAR antagonists may increase the risk of developing Alzheimer's disease.
- Selective β2AR agonists might offer a protective effect, potentially decreasing Alzheimer's disease risk.
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