Blood–brain barrier permeable β-blockers linked to lower risk of Alzheimer’s disease in hypertension

Research output: Contribution to journalJournal articlepeer-review

Standard

Blood–brain barrier permeable β-blockers linked to lower risk of Alzheimer’s disease in hypertension. / Beaman, Emily; Bonde, Anders Nissen; Larsen, Sara Marie Ulv; Ozenne, Brice Maxime Hugues; Lohela, Terhi Johanna; Nedergaard, Maiken; Gislason, Gunnar Hilmar; Knudsen, Gitte Moos; Holst, Sebastian Camillo.

In: Brain, Vol. 146, No. 3, 2023, p. 1141–1151.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Beaman, E, Bonde, AN, Larsen, SMU, Ozenne, BMH, Lohela, TJ, Nedergaard, M, Gislason, GH, Knudsen, GM & Holst, SC 2023, 'Blood–brain barrier permeable β-blockers linked to lower risk of Alzheimer’s disease in hypertension', Brain, vol. 146, no. 3, pp. 1141–1151. https://doi.org/10.1093/brain/awac076

APA

Beaman, E., Bonde, A. N., Larsen, S. M. U., Ozenne, B. M. H., Lohela, T. J., Nedergaard, M., Gislason, G. H., Knudsen, G. M., & Holst, S. C. (2023). Blood–brain barrier permeable β-blockers linked to lower risk of Alzheimer’s disease in hypertension. Brain, 146(3), 1141–1151. https://doi.org/10.1093/brain/awac076

Vancouver

Beaman E, Bonde AN, Larsen SMU, Ozenne BMH, Lohela TJ, Nedergaard M et al. Blood–brain barrier permeable β-blockers linked to lower risk of Alzheimer’s disease in hypertension. Brain. 2023;146(3):1141–1151. https://doi.org/10.1093/brain/awac076

Author

Beaman, Emily ; Bonde, Anders Nissen ; Larsen, Sara Marie Ulv ; Ozenne, Brice Maxime Hugues ; Lohela, Terhi Johanna ; Nedergaard, Maiken ; Gislason, Gunnar Hilmar ; Knudsen, Gitte Moos ; Holst, Sebastian Camillo. / Blood–brain barrier permeable β-blockers linked to lower risk of Alzheimer’s disease in hypertension. In: Brain. 2023 ; Vol. 146, No. 3. pp. 1141–1151.

Bibtex

@article{78d555e30f454e5da49d2cc983cb1fad,
title = "Blood–brain barrier permeable β-blockers linked to lower risk of Alzheimer{\textquoteright}s disease in hypertension",
abstract = "Alzheimer{\textquoteright}s disease is a neurodegenerative disorder where pathological accumulation of amyloid-β and tau begin years before symptom onset. Emerging evidence suggests that β-blockers (β-adrenergic antagonists) increase brain clearance of these metabolites by enhancing cerebrospinal fluid flow. Our objective was to determine whether β-blockers treatments that easily cross the blood-brain barrier reduce the risk of Alzheimer{\textquoteright}s disease compared to less permeable β-blockers.Data from the Danish national registers were used to identify a retrospective cohort of individuals with hypertension, and those treated with β-blockers were included in the analysis. Persons with indications for β-blocker use other than hypertension (e.g., heart failure) were only retained in a sensitivity analysis. β-blockers were divided into three permeability groups: low, moderate, and high. We used multivariable cause-specific Cox regression to model the effect of β-blocker blood-brain barrier permeability on time to dementia outcomes, adjusting for baseline comorbidities, demographics, and socioeconomic variables. Death was modeled as a competing risk. The 10-year standardized absolute risk was estimated as the averaged person-specific risks per treatment.In a cohort of 69,081 (median age = 64.4 years, 64.8% female) people treated with βBs for hypertension, highly BBB-permeable βBs were associated with reduced risk of Alzheimer{\textquoteright}s disease versus low permeability βBs (−0.45%, p < 0.036). This effect was specific to Alzheimer{\textquoteright}s diagnoses and did not extend to dementia in general. Propensity score analysis matching high and low BBB-permeable patients also detected a decreased Alzheimer{\textquoteright}s risk (−0.92%, p < 0.001) in the high permeability group compared to the low, as did a 1-year landmark analysis (−0.57%, p < 0.029) in which events within the first year of follow-up were ignored as likely unrelated to treatment.Our results suggest that amongst people taking β-blockers for hypertension, treatment with highly blood-brain barrier permeable β-blockers reduces the risk of Alzheimer{\textquoteright}s disease compared to low permeability drugs. Our findings support the hypothesis that highly permeable β-blockers protect against Alzheimer{\textquoteright}s disease by promoting waste brain metabolite clearance.",
keywords = "Faculty of Health and Medical Sciences, Alzheimer's disease and dementia, β-adrenergic signaling, Hypertension, Adrenergic alpha-2 Receptor Antagonists, Blood brain barrier",
author = "Emily Beaman and Bonde, {Anders Nissen} and Larsen, {Sara Marie Ulv} and Ozenne, {Brice Maxime Hugues} and Lohela, {Terhi Johanna} and Maiken Nedergaard and Gislason, {Gunnar Hilmar} and Knudsen, {Gitte Moos} and Holst, {Sebastian Camillo}",
year = "2023",
doi = "10.1093/brain/awac076",
language = "English",
volume = "146",
pages = "1141–1151",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "3",

}

RIS

TY - JOUR

T1 - Blood–brain barrier permeable β-blockers linked to lower risk of Alzheimer’s disease in hypertension

AU - Beaman, Emily

AU - Bonde, Anders Nissen

AU - Larsen, Sara Marie Ulv

AU - Ozenne, Brice Maxime Hugues

AU - Lohela, Terhi Johanna

AU - Nedergaard, Maiken

AU - Gislason, Gunnar Hilmar

AU - Knudsen, Gitte Moos

AU - Holst, Sebastian Camillo

PY - 2023

Y1 - 2023

N2 - Alzheimer’s disease is a neurodegenerative disorder where pathological accumulation of amyloid-β and tau begin years before symptom onset. Emerging evidence suggests that β-blockers (β-adrenergic antagonists) increase brain clearance of these metabolites by enhancing cerebrospinal fluid flow. Our objective was to determine whether β-blockers treatments that easily cross the blood-brain barrier reduce the risk of Alzheimer’s disease compared to less permeable β-blockers.Data from the Danish national registers were used to identify a retrospective cohort of individuals with hypertension, and those treated with β-blockers were included in the analysis. Persons with indications for β-blocker use other than hypertension (e.g., heart failure) were only retained in a sensitivity analysis. β-blockers were divided into three permeability groups: low, moderate, and high. We used multivariable cause-specific Cox regression to model the effect of β-blocker blood-brain barrier permeability on time to dementia outcomes, adjusting for baseline comorbidities, demographics, and socioeconomic variables. Death was modeled as a competing risk. The 10-year standardized absolute risk was estimated as the averaged person-specific risks per treatment.In a cohort of 69,081 (median age = 64.4 years, 64.8% female) people treated with βBs for hypertension, highly BBB-permeable βBs were associated with reduced risk of Alzheimer’s disease versus low permeability βBs (−0.45%, p < 0.036). This effect was specific to Alzheimer’s diagnoses and did not extend to dementia in general. Propensity score analysis matching high and low BBB-permeable patients also detected a decreased Alzheimer’s risk (−0.92%, p < 0.001) in the high permeability group compared to the low, as did a 1-year landmark analysis (−0.57%, p < 0.029) in which events within the first year of follow-up were ignored as likely unrelated to treatment.Our results suggest that amongst people taking β-blockers for hypertension, treatment with highly blood-brain barrier permeable β-blockers reduces the risk of Alzheimer’s disease compared to low permeability drugs. Our findings support the hypothesis that highly permeable β-blockers protect against Alzheimer’s disease by promoting waste brain metabolite clearance.

AB - Alzheimer’s disease is a neurodegenerative disorder where pathological accumulation of amyloid-β and tau begin years before symptom onset. Emerging evidence suggests that β-blockers (β-adrenergic antagonists) increase brain clearance of these metabolites by enhancing cerebrospinal fluid flow. Our objective was to determine whether β-blockers treatments that easily cross the blood-brain barrier reduce the risk of Alzheimer’s disease compared to less permeable β-blockers.Data from the Danish national registers were used to identify a retrospective cohort of individuals with hypertension, and those treated with β-blockers were included in the analysis. Persons with indications for β-blocker use other than hypertension (e.g., heart failure) were only retained in a sensitivity analysis. β-blockers were divided into three permeability groups: low, moderate, and high. We used multivariable cause-specific Cox regression to model the effect of β-blocker blood-brain barrier permeability on time to dementia outcomes, adjusting for baseline comorbidities, demographics, and socioeconomic variables. Death was modeled as a competing risk. The 10-year standardized absolute risk was estimated as the averaged person-specific risks per treatment.In a cohort of 69,081 (median age = 64.4 years, 64.8% female) people treated with βBs for hypertension, highly BBB-permeable βBs were associated with reduced risk of Alzheimer’s disease versus low permeability βBs (−0.45%, p < 0.036). This effect was specific to Alzheimer’s diagnoses and did not extend to dementia in general. Propensity score analysis matching high and low BBB-permeable patients also detected a decreased Alzheimer’s risk (−0.92%, p < 0.001) in the high permeability group compared to the low, as did a 1-year landmark analysis (−0.57%, p < 0.029) in which events within the first year of follow-up were ignored as likely unrelated to treatment.Our results suggest that amongst people taking β-blockers for hypertension, treatment with highly blood-brain barrier permeable β-blockers reduces the risk of Alzheimer’s disease compared to low permeability drugs. Our findings support the hypothesis that highly permeable β-blockers protect against Alzheimer’s disease by promoting waste brain metabolite clearance.

KW - Faculty of Health and Medical Sciences

KW - Alzheimer's disease and dementia

KW - β-adrenergic signaling

KW - Hypertension

KW - Adrenergic alpha-2 Receptor Antagonists

KW - Blood brain barrier

U2 - 10.1093/brain/awac076

DO - 10.1093/brain/awac076

M3 - Journal article

C2 - 35196379

VL - 146

SP - 1141

EP - 1151

JO - Brain

JF - Brain

SN - 0006-8950

IS - 3

ER -

ID: 310430757