Blood-brain barrier crossing renin-angiotensin drugs and cognition in the elderly : A meta-analysis

Journal article

Ho, Jean, Moriarty, Frank, Manly, Jennifer J., Larson, Eric B., Evans, Denis A., Rajan, Kumar B., Hudak, Elizabeth M., Hassan, Lamiaa, Liu, Enwu, Sato, Nobuyuki, Hasebe, Naoyuki, Laurin, Danielle, Carmichael, Pierre-Hugues and Nation, Daniel A.. (2021). Blood-brain barrier crossing renin-angiotensin drugs and cognition in the elderly : A meta-analysis. Hypertension. 78(3), pp. 629-643. https://doi.org/10.1161/HYPERTENSIONAHA.121.17049
AuthorsHo, Jean, Moriarty, Frank, Manly, Jennifer J., Larson, Eric B., Evans, Denis A., Rajan, Kumar B., Hudak, Elizabeth M., Hassan, Lamiaa, Liu, Enwu, Sato, Nobuyuki, Hasebe, Naoyuki, Laurin, Danielle, Carmichael, Pierre-Hugues and Nation, Daniel A.
Abstract

Hypertension is an established risk factor for cognitive decline and dementia in older adults, highlighting the potential importance of antihypertensive treatments in prevention efforts. Work surrounding antihypertensive treatments has suggested possible salutary effects on cognition and neuropathology. Several studies have specifically highlighted renin-angiotensin system drugs, including AT1-receptor blockers and angiotensin-converting-enzyme inhibitors, as potentially benefiting cognition in later life. A small number of studies have further suggested renin-angiotensin system drugs that cross the blood-brain barrier may be linked to lower dementia risk compared to their nonpenetrant counterparts. The present meta-analysis sought to evaluate the potential cognitive benefits of blood-brain barrier crossing renin-angiotensin system drugs relative to their nonpenetrant counterparts. We harmonized longitudinal participant data from 14 cohorts from 6 countries (Australia, Canada, Germany, Ireland, Japan, United States), for a total of 12 849 individuals at baseline, and assessed for blood-brain barrier crossing potential within antihypertensive medications used by cognitively normal participants. We analyzed 7 cognitive domains (attention, executive function, language, verbal memory learning, recall, mental status, and processing speed) using ANCOVA (adjusted for age, sex, and education) and meta-analyses. Older adults taking blood-brain barrier-crossing renin-angiotensin drugs exhibited better memory recall over up to 3 years of follow-up, relative to those taking nonpenetrant medications, despite their relatively higher vascular risk burden. Conversely, those taking nonblood-brain barrier-penetrant medications showed better attention over the same follow-up period, although their lower vascular risk burden may partially explain this result. Findings suggest links between blood-brain barrier crossing renin-angiotensin drugs and less memory decline.

Keywordsrenin-angiotensin system; hypertension; dementia; cognition; angiotensin converting enzyme inhibitors; blood-brain barrier; angiotensin receptor blockers
Year2021
JournalHypertension
Journal citation78 (3), pp. 629-643
PublisherLippincott Williams & Wilkins
ISSN0194-911X
Digital Object Identifier (DOI)https://doi.org/10.1161/HYPERTENSIONAHA.121.17049
PubMed ID34148364
Scopus EID2-s2.0-85112783749
Research or scholarlyResearch
Page range629-643
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All rights reserved
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Controlled
Output statusPublished
Publication dates
Online21 Jun 2021
Publication process dates
Accepted28 Apr 2021
Deposited24 Nov 2021
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Harvey, Nicholas C., Kanis, John A., Liu, Enwu, Johansson, Helena, Lorentzon, Mattias and McCloskey, Eugene. (2019). Appendicular lean mass and fracture risk assessment: Implications for FRAX(R) and sarcopenia. Osteoporosis International. 30(3), pp. 537 - 539. https://doi.org/10.1007/s00198-019-04904-z
Temporal changes in access to FRAX in Thailand between 2010 and 2018
Chotiyarnwong, Pojchong, Harvey, Nicholas C., Johansson, Helena, Liu, Enwu, Lorentzon, Mattias, Kanis, John A. and McCloskey, Eugene V.. (2019). Temporal changes in access to FRAX in Thailand between 2010 and 2018. Archives of Osteoporosis. 14(1), pp. 1 - 7. https://doi.org/10.1007/s11657-019-0613-2
Patterns of medication prescription by dementia diagnosis in Australian nursing home residents: A cross-sectional study
Liu, Enwu, Dyer, Suzanne M., Whitehead, Craig, O'Donnell, Lisa Kouladjian, Gnanamanickam, Emmanuel S., Harrison, Stephanie L., Milte, Rachel and Crotty, Maria. (2019). Patterns of medication prescription by dementia diagnosis in Australian nursing home residents: A cross-sectional study. Journal of Pharmacy Practice and Research. 49(1), pp. 33 - 40. https://doi.org/10.1002/jppr.1457
Alternative staffing structures in a clustered domestic model of residential aged care in Australia
Harrison, Stephanie L., Dyer, Suzanne M., Milte, Rachel, Liu, Enwu, Gnanamanickam, Emmanuel S. and Crotty, Maria. (2019). Alternative staffing structures in a clustered domestic model of residential aged care in Australia. Australasian Journal on Ageing. 38(Suppl 2), pp. 68 - 74. https://doi.org/10.1111/ajag.12674
Should we provide outreach rehabilitation to very old people living in Nursing Care Facilities after a hip fracture? A randomised controlled trial
Crotty, Maria, Killington, Maggie, Liu, Enwu, Cameron, Ian D., Kurrle, Susan, Kaambwa, Billingsley, Davies, Owen, Miller, Michelle D., Chehade, Mellick and Ratcliffe, Julie. (2019). Should we provide outreach rehabilitation to very old people living in Nursing Care Facilities after a hip fracture? A randomised controlled trial. Age and Ageing. 48(3), pp. 373 - 380. https://doi.org/10.1093/ageing/afz005
Clustered domestic residential aged care in Australia: fewer hospitalisations and better quality of life
Dyer, Suzanne M., Liu, Enwu, Gnanamanickam, Emmanuel S., Milte, Rachel, Easton, Tiffany, Harrison, Stephanie L., Bradley, Clare E., Ratcliffe, Julie and Crotty, Maria. (2018). Clustered domestic residential aged care in Australia: fewer hospitalisations and better quality of life. Medical Journal of Australia. 208(10), pp. 433 - 438. https://doi.org/10.5694/mja17.00861
Associations between the drug burden index, potentially inappropriate medications and quality of life in residential aged care
Harrison, Stephanie L., Kouladjian O'Donnell, Lisa, Bradley, Clare E., Milte, Rachel, Dyer, Suzanne M., Gnanamanickam, Emmanuel S., Liu, Enwu, Hilmer, Sarah N. and Crotty, Maria. (2018). Associations between the drug burden index, potentially inappropriate medications and quality of life in residential aged care. Drugs and Aging. 35(1), pp. 83-91. https://doi.org/10.1007/s40266-017-0513-3
Direct health and residential care costs of people living with dementia in Australian residential aged care
Gnanamanickam, Emmanuel S., Dyer, Suzanne M., Milte, Rachel, Harrison, Stephanie L., Liu, Enwu, Easton, Tiffany, Bradley, Clare, Bilton, Rebecca, Shulver, Wendy, Ratcliffe, Julie, Whitehead, Craig and Crotty, Maria. (2018). Direct health and residential care costs of people living with dementia in Australian residential aged care. International Journal of Geriatric Psychiatry. 33(7), pp. 859 - 866. https://doi.org/10.1002/gps.4842
Psychotropic medications in older people in residential care facilities and associations with quality of life: a cross-sectional study
Harrison, Stephanie L., Bradley, Clare E., Milte, Rachel, Liu, Enwu, O'Donnell, Lisa K., Hilmer, Sarah N. and Crotty, Maria. (2018). Psychotropic medications in older people in residential care facilities and associations with quality of life: a cross-sectional study. BMC Geriatrics. 18(60), pp. 1 - 8. https://doi.org/10.1186/s12877-018-0752-0
Costs of potentially inappropriate medication use in residential aged care facilities
Harrison, S. L., O'Donnell, L. K., Milte, R., Dyer, S. M., Gnanamanickam, E. S., Bradley, C., Liu, Enwu, Hilmer, S. N. and Crotty, M.. (2018). Costs of potentially inappropriate medication use in residential aged care facilities. BMC Geriatrics. 18(9), pp. 1 - 10. https://doi.org/10.1186/s12877-018-0704-8
Diagnosis of dementia in residential aged care settings in Australia: An opportunity for improvements in quality of care?
Dyer, Suzanne M., Gnanamanickam, Emmanuel S., Liu, Enwu, Whitehead, Craig and Crotty, Maria. (2018). Diagnosis of dementia in residential aged care settings in Australia: An opportunity for improvements in quality of care? Australasian Journal on Ageing. 37(4), pp. e155 - e158. https://doi.org/10.1111/ajag.12580
Clustered domestic model of residential care is associated with better consumer rated quality of care
Gnanamanickam, Emmanuel S., Dyer, Suzanne M., Milte, Rachel, Liu, Enwu, Ratcliffe, Julie and Crotty, Maria. (2018). Clustered domestic model of residential care is associated with better consumer rated quality of care. International Journal for Quality in Health Care. https://doi.org/10.1093/intqhc/mzy181
An empirical comparison of the EQ-5D-5L, DEMQOL-U and DEMQOL-Proxy-U in a post-hospitalisation population of frail older people living in residential aged care
Ratcliffe, Julie, Flint, Thomas, Easton, Tiffany, Killington, Maggie, Cameron, Ian, Davies, Owen, Whitehead, Craig, Kurrle, Susan, Miller, Michelle D., Liu, Enwu and Crotty, Maria. (2017). An empirical comparison of the EQ-5D-5L, DEMQOL-U and DEMQOL-Proxy-U in a post-hospitalisation population of frail older people living in residential aged care. Applied Health Economics and Health Policy. 15(3), pp. 399 - 412. https://doi.org/10.1007/s40258-016-0293-7
Association of cardiovascular system medications with cognitive function and dementia in older adults living in nursing homes in Australia
Liu, Enwu, Dyer, Suzanne M., O'Donnell, Lisa Kouladjian, Milte, Rachel, Bradley, Clare E., Harrison, Stephanie L., Gnanamanickam, Emmanuel S., Whitehead, Craig and Crotty, Maria. (2017). Association of cardiovascular system medications with cognitive function and dementia in older adults living in nursing homes in Australia. Journal of Geriatric Cardiology. 14(6), pp. 407 - 415. https://doi.org/10.11909/j.issn.1671-5411.2017.06.009
Early supported discharge by caregiver-mediated exercise and e-Health support after stroke - A proof-of-concept trial
Van Den Berg, Maayken, Crotty, Maria, Liu, Enwu, Killington, Maggie, Kwakkel, Gert and van Wegen, Erwin. (2016). Early supported discharge by caregiver-mediated exercise and e-Health support after stroke - A proof-of-concept trial. Stroke. 47(7), pp. 1885 - 1892. https://doi.org/10.1161/STROKEAHA.116.013431
Hemiplegic shoulder pain reduces quality of life after acute stroke - A prospective population-based study
Adey-Wakeling, Zoe, Liu, Enwu, Crotty, Maria, Leyden, James, Kleinig, Timothy, Anderson, Craig and Newbury, Jonathon. (2016). Hemiplegic shoulder pain reduces quality of life after acute stroke - A prospective population-based study. American Journal of Physical Medicine and Rehabilitation. 95(10), pp. 758 - 763. https://doi.org/10.1097/PHM.0000000000000496
New South Wales Child Development Study (NSW-CDS): An Australian multiagency, multigenerational, longitudinal record linkage study
Carr, Vaughan J., Harris, Felicity, Raudino, Alessandra, Luo, Luming, Kariuki, Maina, Liu, Enwu, Tzoumakis, Stacy, Smith, Maxwell, Holbrook, Allyson, Bore, Miles, Brinkman, Sally, Lenroot, Rhoshel, Dix, Katherine, Dean, Kimberlie, Laurens, Kristin R. and Green, Melissa J.. (2016). New South Wales Child Development Study (NSW-CDS): An Australian multiagency, multigenerational, longitudinal record linkage study. BMJ Open. 6(2), pp. 1 - 9. https://doi.org/10.1136/bmjopen-2015-009023
Hospital admission for infection during early childhood influences developmental vulnerabilities at age 5 years
Kariuki, Maina, Raudino, Alessandra, Green, Melissa, Laurens, Kristin, Dean, Kimberlie, Brinkman, Sally, Lenroot, Rhoshel, Liu, Enwu, Harris, Felicity, Luo, Luming and Carr, Vaughn J.. (2016). Hospital admission for infection during early childhood influences developmental vulnerabilities at age 5 years. Journal of Paediatrics and Child Health. 52(9), pp. 882 - 888. https://doi.org/10.1111/jpc.13239
Hospital admission for infection during early childhood influences developmental vulnerabilities at age 5 years
Kariuki, Maina, Raudino, Alessandra, Green, Melissa J., Laurens, Kristin R., Dean, Kimberlie, Brinkman, Sally A., Lenroot, Rhoshel K., Liu, Enwu, Harris, Felicity, Luo, Luming and Carr, Vaughn J.. (2016). Hospital admission for infection during early childhood influences developmental vulnerabilities at age 5 years. Journal of Paediatrics and Child Health. 52(9), pp. 882 - 888. https://doi.org/10.1111/jpc.13239
New South Wales child development study (NSW-CDS): An Australian multiagency, multigenerational, longitudinal record linkage study
Carr, Vaughn J., Harris, Felicity, Raudino, Alessandra, Luo, Luming, Kariuki, Maina, Liu, Enwu, Tzoumakis, Stacy, Smith, Maxwell, Holbrook, Allyson, Bore, Miles, Brinkman, Sally, Lenroot, Rhoshel, Dix, Katherine, Dean, Kimberlie, Laurens, Kristin R. and Green, Melissa J.. (2016). New South Wales child development study (NSW-CDS): An Australian multiagency, multigenerational, longitudinal record linkage study. BMJ Open. 6(2), pp. 1 - 9. https://doi.org/10.1136/bmjopen-2015-009023
Baseline HCV antibody prevalence and risk factors among drug users in China's National Methadone Maintenance Treatment Program
Wang, Changhe, Shi, Cynthia X., Rou, Keming, Zhao, Yan, Cao, Xiaobin, Luo, Wei, Liu, Enwu and Wu, Zunyou. (2016). Baseline HCV antibody prevalence and risk factors among drug users in China's National Methadone Maintenance Treatment Program. PLoS ONE. 11(2), pp. 1 - 14. https://doi.org/10.1371/journal.pone.0147922
Who uses methadone services in China? Monitoring the world's largest methadone programme
Sullivan, Sheena G., Wu, Zunyou, Rou, Keming, Pang, Lin, Luo, Wei, Wang, Changhe, Cao, Xiaobin, Yin, Wenyuan, Liu, Enwu and Mi, Guodong. (2015). Who uses methadone services in China? Monitoring the world's largest methadone programme. Addiction. 110(Suppl. 1), pp. 29 - 39. https://doi.org/10.1111/add.12781
Continued drug use during methadone treatment in China: A retrospective analysis of 19,026 service users
Sullivan, Sheena G., Wu, Zunyou, Cao, Xiaobin, Liu, Enwu and Detels, Roger. (2014). Continued drug use during methadone treatment in China: A retrospective analysis of 19,026 service users. Journal of Substance Abuse Treatment. 47(1), pp. 86 - 92. https://doi.org/10.1016/j.jsat.2013.12.004
Referring heroin users from compulsory detoxification centers to community methadone maintenance treatment : A comparison of three models
Yan, Liping, Liu, Enwu, McGoogan, Jennifer M., Duan, Song, Wu, Li-Tzy, Comulada, Scott and Wu, Zunyou. (2013). Referring heroin users from compulsory detoxification centers to community methadone maintenance treatment : A comparison of three models. BMC Public Health. 13(1), pp. 1-8. https://doi.org/10.1186/1471-2458-13-747
HIV and syphilis prevalence among men who have sex with men : A cross-sectional survey of 61 cities in China
Wu, Zunyou, Xu, Jie, Liu, Enwu, Mao, Yurong, Xiao, Yan, Sun, Xinhua, Liu, Yufen, Jiang, Yan, McGoogan, Jennifer M., Dou, Zhi, Mi, Guodong, Wang, Ning, Sun, Jiangping, Liu, Zhongfu, Wang, Lu, Rou, Keming, Pang, Lin, Xing, Wenge, Xu, Juan, ... National MSM Survey Group. (2013). HIV and syphilis prevalence among men who have sex with men : A cross-sectional survey of 61 cities in China. Clinical Infectious Diseases. 57(2), pp. 298-309. https://doi.org/10.1093/cid/cit210
Factors associated with mortality of HIV-positive clients receiving methadone maintenance treatment in China
Liu, Enwu, Rou, Keming, McGoogan, Jennifer M., Pang, Lin, Cao, Xiaobin, Wang, Changhe, Luo, Wei, Sullivan, Sheena G., Montaner, Julio S. G., Bulterys, Marc, Detels, Roger, Wu, Zunyou and China’s National Working Group on Methadone Maintenance Treatment. (2013). Factors associated with mortality of HIV-positive clients receiving methadone maintenance treatment in China. Journal of Infectious Diseases. 3(1), pp. 442-453. https://doi.org/10.1093/infdis/jit163
Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003-11) : A national observational cohort study
Jia, Zhongwei, Mao, Yurong, Zhang, Fujie, Ruan, Yuhua, Ma, Ye, Li, Jian, Guo, Wei, Liu, Enwu, Dou, Zhihui, Zhao, Yan, Wang, Lu, Li, Qianqian, Xie, Peiyan, Tang, Houlin, Han, Jing, Jin, Xia, Xu, Juan, Xiong, Ran, Zhao, Decai, ... Shao, Yiming. (2013). Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003-11) : A national observational cohort study. The Lancet. 382(9899), pp. 1195-1203. https://doi.org/10.1016/S0140-6736(12)61898-4