- Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112–17. 10.1016/S0140-6736(05)67889-016360788
- Kehoe PG, Miners S, Love S. Angiotensins in Alzheimer’s disease – friend or foe? Trends Neurosci 2009;32:619–28. 10.1016/j.tins.2009.07.00619796831
- Piau A, Nourhashémi F, Hein C, Caillaud C, Vellas B. Progress in the development of new drugs in Alzheimer’s disease. J Nutr Health Aging 2011;15:45–57. 10.1007/s12603-011-0012-x21267520
- Cummings J. Lessons learned from Alzheimer disease: clinical trials with negative outcomes. Clin Transl Sci 2018;11:147–52. 10.1111/cts.1249128767185
- Cummings J, Ritter A, Zhong K. Clinical trials for disease-modifying therapies in Alzheimer’s disease: a primer, lessons learned, and a blueprint for the future. J Alzheimers Dis 2018;64:S3–S22. 10.3233/JAD-17990129562511
- Gillette Guyonnet S, Abellan Van Kan G, Andrieu S, Aquino JP, Arbus C, Becq JP, et al. Prevention of progression to dementia in the elderly: rationale and proposal for a health-promoting memory consultation (an IANA Task Force). J Nutr Health Aging 2008;12:520–9. 10.1007/bf0298320418810298
- Kivipelto M, Helkala EL, Laakso MP, Hänninen T, Hallikainen M, Alhainen K, et al. Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ 2001;322:1447–51. 10.1136/bmj.322.7300.144711408299
- Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging 2000;21:49–55. 10.1016/S0197-4580(00)00096-810794848
- Skoog I, Gustafson D. Update on hypertension and Alzheimer’s disease. Neurol Res 2006;28:605–11. 10.1179/016164106X13050616945211
- Honig LS, Tang MX, Albert S, Costa R, Luchsinger J, Manly J, et al. Stroke and the risk of Alzheimer disease. Arch Neurol 2003;60:1707–12. 10.1001/archneur.60.12.170714676044
- Davies NM, Kehoe PG, Ben-Shlomo Y, Martin RM. Associations of anti-hypertensive treatments with Alzheimer’s disease, vascular dementia, and other dementias. J Alzheimers Dis 2011;26:699–708. 10.3233/JAD-2011-11034721709373
- Li NC, Lee A, Whitmer RA, Kivipelto M, Lawler E, Kazis LE, Wolozin B. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ 2010;340:b5465. 10.1136/bmj.b546520068258
- Barthold D, Joyce G, Wharton W, Kehoe P, Zissimopoulos J. The association of multiple anti-hypertensive medication classes with Alzheimer’s disease incidence across sex, race, and ethnicity. PLOS ONE 2018;13:e0206705. 10.1371/journal.pone.020670530383807
- Levi Marpillat N, Macquin-Mavier I, Tropeano AI, Bachoud-Levi AC, Maison P. Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis. J Hypertens 2013;31:1073–82. 10.1097/HJH.0b013e3283603f5323552124
- Hajjar I, Brown L, Mack WJ, Chui H. Impact of Angiotensin receptor blockers on Alzheimer disease neuropathology in a large brain autopsy series. Arch Neurol 2012;69:1632–8. 10.1001/archneurol.2012.101022964777
- Hajjar I, Levey A. Association between angiotensin receptor blockers and longitudinal decline in tau in mild cognitive impairment. JAMA Neurol 2015;72:1069–70. 10.1001/jamaneurol.2015.100126368351
- Wharton W, Zhao L, Steenland K, Goldstein FC, Schneider JA, Barnes LL, et al. Neurofibrillary tangles and conversion to mild cognitive impairment with certain antihypertensives. J Alzheimers Dis 2019;70:153–61. 10.3233/JAD-19001131177216
- Iturria-Medina Y, Sotero RC, Toussaint PJ, Mateos-Pérez JM, Evans AC, Alzheimer’s Disease Neuroimaging Initiative. Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Nat Commun 2016;7:11934. 10.1038/ncomms1193427327500
- Walker VM, Kehoe PG, Martin RM, Davies NM. Repurposing antihypertensive drugs for the prevention of Alzheimer’s disease: a Mendelian randomization study [published online ahead of print July 23 2019]. Int J Epidemiol 2019. 10.1093/ije/dyz155
- Kehoe PG. The coming of age of the angiotensin hypothesis in Alzheimer’s disease: progress toward disease prevention and treatment? J Alzheimers Dis 2018;62:1443–66. 10.3233/JAD-17111929562545
- Hanon O, Latour F, Seux ML, Lenoir H, Forette F, Rigaud AS, REAL.FR Group. Evolution of blood pressure in patients with Alzheimer’s disease: a one year survey of a French Cohort (REAL.FR). J Nutr Health Aging 2005;9:106–11. 10.1016/S0035-3787(05)85355-X15791354
- Hong KS, Kang DW, Bae HJ, Kim YK, Han MK, Park JM, et al. Effect of cilnidipine vs losartan on cerebral blood flow in hypertensive patients with a history of ischemic stroke: a randomized controlled trial. Acta Neurol Scand 2010;121:51–7. 10.1111/j.1600-0404.2009.01299.x19925528
- Zhao Z, Tuor UI, Barber P. Chronic treatment with losartan and cerebral ischemic tolerance. J Exp Stroke Transl Med 2009;2:32–40. 10.6030/1939-067X-2.2.32
- Carmichael O, Schwarz C, Drucker D, Fletcher E, Harvey D, Beckett L, et al. Longitudinal changes in white matter disease and cognition in the first year of the Alzheimer disease neuroimaging initiative. Arch Neurol 2010;67:1370–8. 10.1001/archneurol.2010.28421060014
- Niwa K, Younkin L, Ebeling C, Turner SK, Westaway D, Younkin S, et al. Abeta 1-40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation. Proc Natl Acad Sci US 2000;97:9735–40. 10.1073/pnas.97.17.9735
- Buée L, Hof PR, Bouras C, Delacourte A, Perl DP, Morrison JH, Fillit HM. Pathological alterations of the cerebral microvasculature in Alzheimer’s disease and related dementing disorders. Acta Neuropathol 1994;87:469–80. 10.1007/bf002941738059599
- Kalaria RN. Linking cerebrovascular defense mechanisms in brain ageing and Alzheimer’s disease. Neurobiol Aging 2009;30:1512–14. 10.1016/j.neurobiolaging.2007.10.02018187235
- Miners JS, Baig S, Palmer J, Palmer LE, Kehoe PG, Love S. Abeta-degrading enzymes in Alzheimer’s disease. Brain Pathol 2008;18:240–52. 10.1111/j.1750-3639.2008.00132.x18363935
- Lambert JC, Dallongeville J, Ellis KA, Schraen-Maschke S, Lui J, Laws S, et al. Association of plasma Aβ peptides with blood pressure in the elderly. PLOS ONE 2011;6:e18536. 10.1371/journal.pone.001853621525986
- van Oijen M, Hofman A, Soares HD, Koudstaal PJ, Breteler MM. Plasma Abeta(1–40) and Abeta(1–42) and the risk of dementia: a prospective case–cohort study. Lancet Neurol 2006;5:655–60. 10.1016/S1474-4422(06)70501-416857570
- Miners JS, Ashby E, Van Helmond Z, Chalmers KA, Palmer LE, Love S, Kehoe PG. Angiotensin-converting enzyme (ACE) levels and activity in Alzheimer’s disease, and relationship of perivascular ACE-1 to cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 2008;34:181–93. 10.1111/j.1365-2990.2007.00885.x17973905
- Miners JS, Baig S, Tayler H, Kehoe PG, Love S. Neprilysin and insulin-degrading enzyme levels are increased in Alzheimer disease in relation to disease severity. J Neuropathol Exp Neurol 2009;68:902–14. 10.1097/NEN.0b013e3181afe47519606063
- Akatsu H, Ogawa N, Kanesaka T, Hori A, Yamamoto T, Matsukawa N, Michikawa M. Higher activity of peripheral blood angiotensin-converting enzyme is associated with later-onset of Alzheimer’s disease. J Neurol Sci 2011;300:67–73. 10.1016/j.jns.2010.09.03021040931
- Lehmann DJ, Cortina-Borja M, Warden DR, Smith AD, Sleegers K, Prince JA, et al. Large meta-analysis establishes the ACE insertion–deletion polymorphism as a marker of Alzheimer’s disease. Am J Epidemiol 2005;162:305–17. 10.1093/aje/kwi20216033878
- Kehoe PG, Wong S, Al Mulhim N, Palmer LE, Miners JS. Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology. Alzheimers Res Ther 2016;8:50. 10.1186/s13195-016-0217-727884212
- Benicky J, Sanchez-Lemus E, Honda M, Pang T, Orecna M, Wang J, et al. Angiotensin II AT(1) receptor blockade ameliorates brain inflammation. Neuropsychopharmacology 2011;36:857–70. 10.1038/npp.2010.22521150913
- Zhou J, Ando H, Macova M, Dou J, Saavedra JM. Angiotensin II AT1 receptor blockade abolishes brain microvascular inflammation and heat shock protein responses in hypertensive rats. J Cereb Blood Flow Metab 2005;25:878–86. 10.1038/sj.jcbfm.960008215729290
- Barnes JM, Barnes NM, Costall B, Horovitz ZP, Ironside JW, Naylor RJ, Williams TJ. Angiotensin II inhibits acetylcholine release from human temporal cortex: implications for cognition. Brain Res 1990;507:341–3. 10.1016/0006-8993(90)90294-L2337775
- Barnes JM, Barnes NM, Costall B, Horovitz ZP, Ironside JW, Naylor RJ, Williams TJ. Angiotensin II inhibits cortical cholinergic function: implications for cognition. J Cardiovasc Pharmacol 1990;16:234–8. 10.1097/00005344-199008000-000091697379
- Rogawski MA, Wenk GL. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer’s disease. CNS Drug Rev 2003;9:275–308. 10.1111/j.1527-3458.2003.tb00254.x14530799
- Tian M, Zhu D, Xie W, Shi J. Central angiotensin II-induced Alzheimer-like tau phosphorylation in normal rat brains. FEBS Lett 2012;586:3737–45. 10.1016/j.febslet.2012.09.00422982863
- Zhu D, Shi J, Zhang Y, Wang B, Liu W, Chen Z, Tong Q. Central angiotensin II stimulation promotes β amyloid production in Sprague Dawley rats. PLOS ONE 2011;6:e16037. 10.1371/journal.pone.001603721297982
- Kehoe PG, Hibbs E, Palmer LE, Miners JS. Angiotensin-III is increased in Alzheimer’s disease in association with amyloid-β and tau pathology. J Alzheimers Dis 2017;58:203–14. 10.3233/JAD-16126528387670
- Culman J, von Heyer C, Piepenburg B, Rascher W, Unger T. Effects of systemic treatment with irbesartan and losartan on central responses to angiotensin II in conscious, normotensive rats. Eur J Pharmacol 1999;367:255–65. 10.1016/S0014-2999(98)00983-210079000
- DeKosky ST, Shih WJ, Schmitt FA, Coupal J, Kirkpatrick C. Assessing utility of single photon emission computed tomography (SPECT) scan in Alzheimer disease: correlation with cognitive severity. Alzheimer Dis Assoc Disord 1990;4:14–23. 10.1097/00002093-199040100-000022317335
- Imran MB, Kawashima R, Awata S, Sato K, Kinomura S, Ono S, et al. Tc-99m HMPAO SPECT in the evaluation of Alzheimer’s disease: correlation between neuropsychiatric evaluation and CBF images. J Neurol Neurosurg Psychiatry 1999;66:228–32. 10.1136/jnnp.66.2.22810071106
- Shiraishi H, Chang CC, Kanno H, Yamamoto I. The relationship between cerebral blood flow and cognitive function in patients with brain insult of various etiology. J Clin Neurosci 2004;11:138–41. 10.1016/j.jocn.2003.02.01314732371
- Danielyan L, Klein R, Hanson LR, Buadze M, Schwab M, Gleiter CH, Frey WH. Protective effects of intranasal losartan in the APP/PS1 transgenic mouse model of Alzheimer disease. Rejuvenation Res 2010;13:195–201. 10.1089/rej.2009.094420370487
- Fogari R, Mugellini A, Zoppi A, Derosa G, Pasotti C, Fogari E, Preti P. Influence of losartan and atenolol on memory function in very elderly hypertensive patients. J Hum Hypertens 2003;17:781–5. 10.1038/sj.jhh.100161314578918
- Tedesco MA, Ratti G, Mennella S, Manzo G, Grieco M, Rainone AC, et al. Comparison of losartan and hydrochlorothiazide on cognitive function and quality of life in hypertensive patients. Am J Hypertens 1999;12:1130–4. 10.1016/S0895-7061(99)00156-910604491
- Tedesco MA, Ratti G, Di Salvo G, Natale F. Does the angiotensin II receptor antagonist losartan improve cognitive function? Drugs Aging 2002;19:723–32. 10.2165/00002512-200219100-0000112390049
- McGuinness B, Todd S, Passmore AP, Bullock R. Systematic review: blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. J Neurol Neurosurg Psychiatry 2008;79:4–5. 10.1136/jnnp.2007.11850518079296
- Anderson C, Teo K, Gao P, Arima H, Dans A, Unger T, et al. Renin–angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies. Lancet Neurol 2011;10:43–53. 10.1016/S1474-4422(10)70250-720980201
- Staessen JA, Thijs L, Richart T, Odili AN, Birkenhäger WH. Placebo-controlled trials of blood pressure-lowering therapies for primary prevention of dementia. Hypertension 2011;57:e6–7. 10.1161/HYPERTENSIONAHA.110.16514221189407
- van Middelaar T, van Vught LA, van Gool WA, Simons EMF, van den Born BH, Moll van Charante EP, Richard E. Blood pressure-lowering interventions to prevent dementia: a systematic review and meta-analysis. J Hypertens 2018;36:1780–7. 10.1097/HJH.000000000000182929927845
- Peters R, Yasar S, Anderson CS, Andrews S, Antikainen R, Arima H, et al. Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis. Neurology 2020;94:e267–e281. 10.1212/WNL.000000000000873231827004
- Ding J, Davis-Plourde KL, Sedaghat S, Tully PJ, Wang W, Phillips C, et al. Antihypertensive medications and risk for incident dementia and Alzheimer’s disease: a meta-analysis of individual participant data from prospective cohort studies. Lancet Neurol 2020;19:61–70. 10.1016/S1474-4422(19)30393-X
- Kehoe PG, Passmore PA. The renin-angiotensin system and antihypertensive drugs in Alzheimer’s disease: current standing of the angiotensin hypothesis? J Alzheimers Dis 2012;30(Suppl. 2):S251–68. 10.3233/JAD-2012-111376
- Kehoe PG. Angiotensins and Alzheimer’s disease: a bench to bedside overview. Alzheimers Res Ther 2009;1:3. 10.1186/alzrt319674436
- Kehoe PG, Blair PS, Howden B, Thomas DL, Malone IB, Horwood J, et al. The Rationale and Design of the Reducing Pathology in Alzheimer’s Disease through Angiotensin TaRgeting (RADAR) trial. J Alzheimers Dis 2018;61:803–14. 10.3233/JAD-17010129226862
- Webster L, Groskreutz D, Grinbergs-Saull A, Howard R, O’Brien JT, Mountain G, et al. Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations. Health Technol Assess 2017;21(26). 10.3310/hta21260
- Webster L, Groskreutz D, Grinbergs-Saull A, Howard R, O’Brien JT, Mountain G, et al. Core outcome measures for interventions to prevent or slow the progress of dementia for people living with mild to moderate dementia: systematic review and consensus recommendations. PLOS ONE 2017;12:e0179521. 10.1371/journal.pone.017952128662127
- Hajjar I, Hart M, Milberg W, Novak V, Lipsitz L. The rationale and design of the antihypertensives and vascular, endothelial, and cognitive function (AVEC) trial in elderly hypertensives with early cognitive impairment: role of the renin angiotensin system inhibition. BMC Geriatr 2009;9:48. 10.1186/1471-2318-9-4819922631
- Hajjar I, Hart M, Chen YL, Mack W, Novak V, C Chui H, Lipsitz L. Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: results of a pilot randomized clinical trial. J Am Geriatr Soc 2013;61:194–201. 10.1111/jgs.1210023350899
- Williamson JD, Pajewski NM, Auchus AP, Bryan RN, Chelune G, Cheung AK, et al. Effect of Intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA 2019;321:553–61. 10.1001/jama.2018.2144230688979
- Williamson JD, Supiano MA, Applegate WB, Berlowitz DR, Campbell RC, Chertow GM, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥ 75 years: a randomized clinical trial. JAMA 2016;315:2673–82. 10.1001/jama.2016.705027195814
- Barnes JM, Barnes NM, Costall B, Horovitz ZP, Naylor RJ. Angiotensin II inhibits the release of [3H]acetylcholine from rat entorhinal cortex in vitro. Brain Res 1989;491:136–43. 10.1016/0006-8993(89)90095-42765877
- Miners JS, van Helmond Z, Raiker M, Love S, Kehoe PG. ACE variants and association with brain Aβ levels in Alzheimer’s disease. Am J Transl Res 2010;3:73–80.21139807
- Miners S, Ashby E, Baig S, Harrison R, Tayler H, Speedy E, et al. Angiotensin-converting enzyme levels and activity in Alzheimer’s disease: differences in brain and CSF ACE and association with ACE1 genotypes. Am J Transl Res 2009;1:163–77.19956428
- Medvedev AE, Radko SP, Yurinskaya MM, Vinokurov MG, Buneeva OA, Kopylov AT, et al. Neurotoxic effects of Aβ6-42 peptides mimicking putative products formed by the angiotensin converting enzyme. J Alzheimers Dis 2018;66:263–70. 10.3233/JAD-18050030282362
- Mogi M, Li JM, Tsukuda K, Iwanami J, Min LJ, Sakata A, et al. Telmisartan prevented cognitive decline partly due to PPAR-gamma activation. Biochem Biophys Res Commun 2008;375:446–9. 10.1016/j.bbrc.2008.08.03218715543
- Wang J, Ho L, Chen L, Zhao Z, Zhao W, Qian X, et al. Valsartan lowers brain beta-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease. J Clin Invest 2007;117:3393–402. 10.1172/JCI3154717965777
- Zou K, Yamaguchi H, Akatsu H, Sakamoto T, Ko M, Mizoguchi K, et al. Angiotensin-converting enzyme converts amyloid beta-protein 1–42 (Abeta(1–42)) to Abeta(1–40), and its inhibition enhances brain Abeta deposition. J Neurosci 2007;27:8628–35. 10.1523/JNEUROSCI.1549-07.200717687040
- Fogari R, Zoppi A. Effect of antihypertensive agents on quality of life in the elderly. Drugs Aging 2004;21:377–93. 10.2165/00002512-200421060-0000315084140
- Fox NC, Ridgway GR, Schott JM. Algorithms, atrophy and Alzheimer’s disease: cautionary tales for clinical trials. Neuroimage 2011;57:15–18. 10.1016/j.neuroimage.2011.01.07721296168
- Hua X, Gutman B, Boyle CP, Rajagopalan P, Leow AD, Yanovsky I, et al. Accurate measurement of brain changes in longitudinal MRI scans using tensor-based morphometry. Neuroimage 2011;57:5–14. 10.1016/j.neuroimage.2011.01.07921320612
- Thompson WK, Holland D, Alzheimer’s Disease Neuroimaging Initiative. Bias in tensor based morphometry Stat-ROI measures may result in unrealistic power estimates. Neuroimage 2011;57:1–4. 10.1016/j.neuroimage.2010.11.09221349340
- Clement C, Selman LE, Kehoe PG, Howden B, Lane JA, Horwood J. Challenges to and facilitators of recruitment to an Alzheimer’s disease clinical trial: a qualitative interview study. J Alzheimers Dis 2019;69:1067–75. 10.3233/JAD-19014631156168
- Kehoe PG, Turner N, Howden B, Jarutyte L, Clegg SL, Malone IB, et al. Safety and efficacy of losartan for the reduction of brain atrophy in clinically diagnosed Alzheimer’s disease (the RADAR trial): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol 2021;20:895–906. 10.1016/S1474-4422(21)00263-534687634
- McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939–44. 10.1212/wnl.34.7.9396610841
- Rosen WG, Terry RD, Fuld PA, Katzman R, Peck A. Pathological verification of ischemic score in differentiation of dementias. Ann Neurol 1980;7:486–8. 10.1002/ana.4100705167396427
- Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol 2006;3:77–101. 10.1191/1478088706qp063oa
- Sandelowski M. Sample size in qualitative research. Res Nurs Health 1995;18:179–83. 10.1002/nur.47701802117899572
- Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, et al. Atrophy of medial temporal lobes on MRI in ‘probable’ Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry 1992;55:967–72. 10.1136/jnnp.55.10.9671431963
- Frisoni GB, Fox NC, Jack CR, Scheltens P, Thompson PM. The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol 2010;6:67–77. 10.1038/nrneurol.2009.21520139996
- Chan D, Janssen JC, Whitwell JL, Watt HC, Jenkins R, Frost C, et al. Change in rates of cerebral atrophy over time in early-onset Alzheimer’s disease: longitudinal MRI study. Lancet 2003;362:1121–2. 10.1016/S0140-6736(03)14469-814550701
- Jack CR Jr, Bernstein MA, Fox NC, Thompson P, Alexander G, Harvey D, et al. The Alzheimer’s Disease Neuroimaging Initiative (ADNI): MRI methods. J Magn Reson Imaging 2008;27:685–91. 10.1002/jmri.2104918302232
- Fox NC, Scahill RI, Crum WR, Rossor MN. Correlation between rates of brain atrophy and cognitive decline in AD. Neurology 1999;52:1687–9. 10.1212/wnl.52.8.168710331700
- Freeborough PA, Fox NC. The boundary shift integral: an accurate and robust measure of cerebral volume changes from registered repeat MRI. IEEE Trans Med Imaging 1997;16:623–9. 10.1109/42.6407539368118
- Freeborough PA, Fox NC, Kitney RI. Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans. Comput Methods Programs Biomed 1997;53:15–25. 10.1016/S0169-2607(97)01803-89113464
- Leung KK, Barnes J, Modat M, Ridgway GR, Bartlett JW, Fox NC, Ourselin S, Alzheimer’s Disease Neuroimaging Initiative. Brain MAPS: an automated, accurate and robust brain extraction technique using a template library. Neuroimage 2011;55:1091–108. 10.1016/j.neuroimage.2010.12.06721195780
- Leung KK, Barnes J, Ridgway GR, Bartlett JW, Clarkson MJ, Macdonald K, et al. Automated cross-sectional and longitudinal hippocampal volume measurement in mild cognitive impairment and Alzheimer’s disease. Neuroimage 2010;51:1345–59. 10.1016/j.neuroimage.2010.03.01820230901
- Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med 2014;370:322–33. 10.1056/NEJMoa130483924450891
- Jorge Cardoso M, Leung K, Modat M, Keihaninejad S, Cash D, Barnes J, et al. STEPS: Similarity and truth estimation for propagated segmentations and its application to hippocampal segmentation and brain parcelation. Med Image Anal 2013;17:671–84. 10.1016/j.media.2013.02.00623510558
- Leung KK, Clarkson MJ, Bartlett JW, Clegg S, Jack CR, Weiner MW, et al. Robust atrophy rate measurement in Alzheimer’s disease using multi-site serial MRI: tissue-specific intensity normalization and parameter selection. Neuroimage 2010;50:516–23. 10.1016/j.neuroimage.2009.12.05920034579
- Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry 1984;141:1356–64. 10.1176/ajp.141.11.13566496779
- Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308–14. 10.1212/wnl.44.12.23087991117
- Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98. 10.1016/0022-3956(75)90026-61202204
- Smith SC, Lamping DL, Banerjee S, Harwood R, Foley B, Smith P, et al. Measurement of health-related quality of life for people with dementia: development of a new instrument (DEMQOL) and an evaluation of current methodology. Health Technol Assess 2005;9(10). 10.3310/hta9100
- Bucks RS, Ashworth DL, Wilcock GK, Siegfried K. Assessment of activities of daily living in dementia: development of the Bristol Activities of Daily Living Scale. Age Ageing 1996;25:113–20. 10.1093/ageing/25.2.1138670538
- Zekry D, Duyckaerts C, Moulias R, Belmin J, Geoffre C, Herrmann F, Hauw JJ. Degenerative and vascular lesions of the brain have synergistic effects in dementia of the elderly. Acta Neuropathol 2002;103:481–7. 10.1007/s00401-001-0493-511935264
- Sudre CH, Cardoso MJ, Ourselin S, Alzheimer’s Disease Neuroimaging Initiative. Longitudinal segmentation of age-related white matter hyperintensities. Med Image Anal 2017;38:50–64. 10.1016/j.media.2017.02.00728282640
- Sudre CH, Cardoso MJ, Bouvy WH, Biessels GJ, Barnes J, Ourselin S. Bayesian model selection for pathological neuroimaging data applied to white matter lesion segmentation. IEEE Trans Med Imaging 2015;34:2079–102. 10.1109/TMI.2015.241907225850086
- Mutsaerts HJMM, Mirza SS, Petr J, Thomas DL, Cash DM, Bocchetta M, et al. Cerebral perfusion changes in presymptomatic genetic frontotemporal dementia: a GENFI study. Brain 2019;142:1108–20. 10.1093/brain/awz03930847466
- Elvsåshagen T, Mutsaerts HJ, Zak N, Norbom LB, Quraishi SH, Pedersen PØ, et al. Cerebral blood flow changes after a day of wake, sleep, and sleep deprivation. Neuroimage 2019;186:497–509. 10.1016/j.neuroimage.2018.11.03230471387
- Ibaraki M, Nakamura K, Toyoshima H, Takahashi K, Matsubara K, Umetsu A, et al. Spatial coefficient of variation in pseudo-continuous arterial spin labeling cerebral blood flow images as a hemodynamic measure for cerebrovascular steno-occlusive disease: a comparative 15O positron emission tomography study. J Cereb Blood Flow Metab 2019;39:173–81. 10.1177/0271678X1878166729869933
- Mutsaerts HJ, Petr J, Václavů L, van Dalen JW, Robertson AD, Caan MW, et al. The spatial coefficient of variation in arterial spin labeling cerebral blood flow images. J Cereb Blood Flow Metab 2017;37:3184–92. 10.1177/0271678X1668369028058975
- Schott JM, Bartlett JW, Barnes J, Leung KK, Ourselin S, Fox NC, Alzheimer’s Disease Neuroimaging Initiative investigators. Reduced sample sizes for atrophy outcomes in Alzheimer’s disease trials: baseline adjustment. Neurobiol Aging 2010;31:1452–62, 1462.e1–2. 10.1016/j.neurobiolaging.2010.04.011
- Jin J, Sklar GE, Min Sen Oh V, Chuen Li S. Factors affecting therapeutic compliance: a review from the patient’s perspective. Ther Clin Risk Manag 2008;4:269–86. 10.2147/TCRM.S145818728716
- Kanaide H, Ichiki T, Nishimura J, Hirano K. Cellular mechanism of vasoconstriction induced by angiotensin II: it remains to be determined. Circ Res 2003;93:1015–17. 10.1161/01.RES.0000105920.33926.6014645130
- Doughan AK, Harrison DG, Dikalov SI. Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ Res 2008;102:488–96. 10.1161/CIRCRESAHA.107.16280018096818
- Lawlor B, Segurado R, Kennelly S, Olde Rikkert MGM, Howard R, Pasquier F, et al. Nilvadipine in mild to moderate Alzheimer disease: a randomised controlled trial. PLOS Med 2018;15:e1002660. 10.1371/journal.pmed.100266030248105
- de Jong DLK, de Heus RAA, Rijpma A, Donders R, Olde Rikkert MGM, Günther M, et al. Effects of nilvadipine on cerebral blood flow in patients with Alzheimer disease. Hypertension 2019;74:413–20. 10.1161/HYPERTENSIONAHA.119.1289231203725
- Mehta D, Jackson R, Paul G, Shi J, Sabbagh M. Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010–2015. Expert Opin Investig Drugs 2017;26:735–9. 10.1080/13543784.2017.1323868
- Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol 2008;7:683–9. 10.1016/S1474-4422(08)70143-118614402
- Howard R, Liu KY. Questions EMERGE as Biogen claims aducanumab turnaround. Nat Rev Neurol 2020;16:63–4. 10.1038/s41582-019-0295-931784690
- Schneider L. A resurrection of aducanumab for Alzheimer’s disease. Lancet Neurol 2020;19:111–12.31978357
Losartan to slow the progression of mild-to-moderate Alzheimer’s disease through angiotensin targeting: the RADAR RCT · References
References
Attribution. Patrick G Kehoe; Nicholas Turner; Beth Howden; Lina Jarutyt; Shona L Clegg; Ian B Malone et al. (2021). Losartan to slow the progression of mild-to-moderate Alzheimer’s disease through angiotensin targeting: the RADAR RCT. NIHR Journals Library. Copyright © Queen’s Printer and Controller of HMSO 2021. This work was produced by Kehoe et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Licensed under CC BY 4.0. NCBI Bookshelf NBK575022. CC BY 4.0. Original source ↗. Text reproduced from the Bookshelf XML without changing wording; figures, images and supplements are not reproduced.