【高血压英文课件】Clinical-Trials-of-Anti-Hypertensive

Clinical Trials of Anti-Hypertensive Medication for MCI and dementiaIngmar Skoog,M.D.,Ph.D.Institute of Neuroscience and PhysiologyUnit of Neuropsychiatric EpidemiologySahlgrenska Academy at Gteborg UniversityGteborg,SwedenDISCLOSURESl lConsultant:AstraZeneca for the SCOPE triall lSpeakers Bureau:Esai,JansenCilag,AstraZeneca,Shire,Pfizer,NovartisBackgroundl lPrevalence of hypertension increases with agel lMore than 50%of elderly populations have hypertension with current criteria(140/90)l lAn emerging problem in the developing worldEnd-organ damagel lThe arterial treel lHeartl lKidneyl lBrainl lEyesSystolicSystolicBloodBloodPressurePressure140Cardiovascular RiskHYPERTENSION IN RELATION TO COGNITIONHypertensionStroke White Matter LesionsCognitive impairmentA Brjesson Hanson 2001A Brjesson Hanson 2001Hypertension and the brainl lCerebral autoregulationl lBlood brain barrier dysfunctionl lDecreased cerebral blood floowl lStroke(hemorrhagic,ischemic)l lWhite matter lesionsl lDementia and Alzheimers diseaseRISK OF DEMENTIA IN RELATION TO STROKE70+GteborgAgeAgeStroke Stroke patientspatientsAge-matchedAge-matched controlscontrols%OROR95%-CI95%-CI70-8070-8018183 36.76.7(2.6-17.6)(2.6-17.6)80+80+343410104.84.8(2.8-8.3)(2.8-8.3)AllAll28287 74.74.7(3.0-7.4)(3.0-7.4)Lindn,Skoog et al Lindn,Skoog et al NeuroepidemiologyNeuroepidemiology 2004 2004Cognitive impairment in non-demented stroke patients70+GteborgStrokeStrokeControlsControlsCognitiveCognitive DisturbanceDisturbance%ORORMemoryMemory 6 6 2 2 2.6*2.6*LanguageLanguage1616 1 113.8*13.8*PraxisPraxis36362121 2.1*2.1*GnosiaGnosia2020 5 5 4.8*4.8*AbstractionAbstraction1717 9 9 2.0*2.0*AnyAny61613131 3.5*3.5*Lindn,Skoog et al Lindn,Skoog et al NeuroepidemiologyNeuroepidemiology 2004 2004SILENT INFARCTSl lThe frequency of silent infarcts on MRI increases with age(VermeerVermeer et al,Stroke 2003)et al,Stroke 2003)l lIncreases the incidence of dementia(HR 2.3(95-%CI 1.1-4.7)during 3.6 years follow-upl lRelated to worse performance on psychometric testing at baselinel lIncreases risk of clinical stroke on follow-up (VermeerVermeer et al.N Engl J Med 2003)et al.N Engl J Med 2003)RISK OF DEMENTIA IN RELATION TO RISK OF DEMENTIA IN RELATION TO INFARCTS ON CT AND HISTORY OF STROKEINFARCTS ON CT AND HISTORY OF STROKEAT AGE 85AT AGE 85H-70 STUDY,GTEBORG,SWEDENH-70 STUDY,GTEBORG,SWEDENORORNo No infarctsinfarcts/No history/No history1.01.0InfarctsInfarcts/No history/No history (”(”silentsilent infarctsinfarcts”)”)2.5*2.5*No No infarctsinfarcts/HistoryHistory 4.4*4.4*InfarctsInfarcts+HistoryHistory5.2*5.2*LiebetrauLiebetrau&Skoog.Stroke 2004&Skoog.Stroke 2004Hypertension and the brainl lCerebral autoregulationl lBlood brain barrier dysfunctionl lDecreased cerebral blood floowl lStroke(hemorrhagic,ischemic)l lWhite matter lesionsl lDementia and Alzheimers diseaseWHITE MATTER LESIONS IN RELATION TO DEMENTIA IN 85-YEAR-OLDS%No dementia34Alzheimers disease64*Vascular dementia70*Other dementias80*Skoog et al J Geriatr Psychiatry Neurol 1994Cognitive function in non-demented 85-year-olds in relation to white matter lesionsNo No WMLsWMLsWMLsWMLs(N)(N)MeanMean(N)(N)meanmeanVerbal Verbal abilityability(76)(76)1919(36)(36)1717VisuospatialVisuospatial abilityability(81)(81)1313(42)(42)9*9*PerceptualPerceptual speed speed(78)(78)1414(38)(38)12*12*Skoog et al.Skoog et al.ActaActa NeurolNeurol ScandScand 1996 1996Hypertension and the brainl lCerebral autoregulationl lBlood brain barrier dysfunctionl lDecreased cerebral blood floowl lStroke(hemorrhagic,ischemic)l lWhite matter lesionsl lAlzheimers diseaseLONGITUDINAL STUDIES ON BLOOD PRESSURE AND ALZHEIMERS DISEASEPrevious high blood pressurePrevious high blood pressure 5-15 years5-15 yearsAlzheimers disease in late lifeAlzheimers disease in late lifeThe H70-study in GothenburgThe H70-study in Gothenburg Skoog et al.Lancet 1996 The Honolulu-Asia Aging StudyThe Honolulu-Asia Aging Study Launer et al.Neurobiol Aging 2000 The Rotterdam StudyThe Rotterdam Study Ruitenberg et al.Dissertation 2000Kaiser Permanente,USA Whitmer et al.Neurology 2005 Kuopio,FinlandKuopio,FinlandKivipelto et al.BMJ 2001Kungsholmen Kungsholmen StudyStudy QiuQiu et al et al ArchArch NeurolNeurol 2003 2003ChineseChinese StudyStudy Wu et al Life Science 2003 Wu et al Life Science 2003Relation to AD pathologyHONOLULU-ASIA AGING STUDYHigh midlife systolic blood pressure Neuritic plaque in old agePetrovitch et al.Neurobiology of Aging 2000Possible pathogenetic mechanismsl lIschemia increases production of beta-amyloidl lBlood-brain barrier dysfunctionl lRenin-angiotensin systemA 15-year follow-up of blood pressure and dementiaSkoog et al.Skoog et al.LancetLancet 1996 1996BLOOD PRESSURE INALZHEIMERS DISEASEl lIncreased before onsetl lLower just before or after onsetHypertension and risk of MCIHRHR(95%-CI)(95%-CI)All MCIAll MCI1.401.40 (1.06-1.77)(1.06-1.77)AmnesticAmnestic MCI MCI1.101.10 (0.79-1.63)(0.79-1.63)Non-amnesticNon-amnestic MCI MCI1.701.70 (1.13-2.42)(1.13-2.42)Reitz et al.Arch Neurol.2007;64:1734-40 Blood pressure and cognitive functionl lMidlife:High blood pressure related to lower cognitive functionl lOld age:Low blood pressure related to lower cognitive functionTreatment of hypertension and MCI/dementia/Alzheimer diseaseANTIHYPERTENSIVE DRUGSl lAngiotensin Converting Enzyme Inhibitors or Angiotensin II type 1(AT1)receptor blockerl lBeta-blockers l lCalcium-channel blockersl lDiureticsTreatment targets in relation to dementia/MCIDementiaDementiaADLADLSocial Social abiliyabiliyMild Mild CognitiveCognitive ImpairmentImpairmentNormalNormalObservational studiesBLOOD PRESSURE AND DEMENTIA IS IT DANGEROUS TO TREAT HYPERTENSION IN THE ELDERLY?A 15-year follow-up of blood pressure and Alzheimers diseaseSkoog et al.Skoog et al.LancetLancet 1996 1996BLOOD PRESSURE IN RELATION TO DEMENTIA IN 85-YEAR-OLDSBlood pressure mmHg mmHg mmHgSystolic 162 148*151*Diastolic 79 78 76*No Alzheimers VascularDementia disease dementiaSkoog et al.Hypertension 1998LOW BLOOD PRESSURE AND ALZHEIMERS DISEASEl lA risk A risk factorfactor for for AlzheimersAlzheimers diseasedisease?lA consequence of Alzheimers diseaseBlood pressure decreases during the course of Alzheimers diseaseLower blood pressure is related to brain atrophy and number of neurons in certain areas of the brainHONOLULU-ASIA AGING STUDYHigh midlife blood pressure in men not treated for hypertension Alzheimers disease in old ageVascular dementia in old ageLauner et al.Neurobiology of Aging 2000Prospective Population Study of Women in GothenburgHigh midlife blood pressure in women not treated for hypertension Dementia in old ageSkoog et al 2008ANTIHYPERTENSIVE DRUGS AND RISK OF DEMENTIAIndianapolis(Indianapolis(prevalenceprevalence)ORORDementiaDementia 0.670.67AlzheimersAlzheimers DiseaseDisease 0.590.59(Richards et al.J Am(Richards et al.J Am GeriatrGeriatr SocSoc 2000;48:1035-41 2000;48:1035-41Kungsholmen(Kungsholmen(incidenceincidence)RR(95%-CIRR(95%-CI)DementiaDementia 0.7(0.6-1.0)0.7(0.6-1.0)(Guo et al.(Guo et al.ArchArch NeurolNeurol 1999;56:991-996 1999;56:991-996Rotterdam(Rotterdam(incidenceincidence)RR(95%-CI RR(95%-CI)DementiaDementia 0.76(0.52-1.12)0.76(0.52-1.12)VascularVascular dementiadementia 0.30(0.11-0.99)0.30(0.11-0.99)(IntInt VeldVeld et al.et al.NeurobiolNeurobiol AgingAging,2001;,2001;22:407-41222:407-412 CasheCashe County County StudyStudy(incidenceincidence)RR(95%-CI RR(95%-CI)AlzheimersAlzheimers diseasedisease 0.64(0.64(0.41-0.98)0.41-0.98)(Khachaturian(Khachaturian et al.et al.Arch Arch NeurolNeurol 2006;63:686-92)2006;63:686-92)Honolulu Asia Studyl lFor each additional year of antihypertensive treatment there was a reduction in the risk of incident dementia(hazard ratio HR=0.94,95%CI,0.89 to 0.99)l lSame result for incident Alzheimers disease l lThus,the longer time on treatment,the lower risk of dementiaPeila et al.Stroke 2006RISK FACTORS DEMENTIA(SBU)Strong/moderate evidencel lAge*l lApoE e4l lFamily aggregationl lMidlife blood pressurel lDiabetes mellitusl lAntihypertensive drugs(protective)*l lLow educationl lLeisure activity(protective)Fratiglioni et alPREVIOUS DATA ARE BASED ON OBSERVATIONAL STUDIESRANDOMISED CONTROLLED TRIALS MORE RELIABLE THAN OBSERVATIONAL STUDIESWHAT HAVE WE LEARNED FROM RANDOMISED CONTROLLED PREVENTION TRIALS?LARGE HYPERTENSION TRIALSl lSystolicSystolic Hypertension in the Hypertension in the ElderlyElderly Program(Program(SHEPSHEP)(N=4736):(N=4736):ChlorthalidonChlorthalidon (D)(D)l lMedical Research Medical Research CouncilsCouncils(MRCMRC)TreatmentTreatment Trial of Trial of hypertension(N=4396):hypertension(N=4396):AtenololAtenolol (B),(B),HydrochlorthiazideHydrochlorthiazide (D)(D)l lThe The SystolicSystolic Hypertension in Europe Hypertension in Europe StudyStudy(Syst-EurSyst-Eur)(N=2418):(N=2418):NitrendipineNitrendipine (C)(C)l lThe The StudyStudy on on CognitionCognition and and PrognosisPrognosis in the in the ElderlyElderly (SCOPESCOPE)(N=4937):)(N=4937):CandersatanCandersatan (A)(A)l lPerindoprilPerindopril ProtectionProtection againstagainst RecurrentRecurrent Stroke Stroke StudyStudy (PROGRESSPROGRESS)(N=6105):)(N=6105):PerindoprilPerindopril (A)(A)l lThe Hypertension in the Very Elderly TrialThe Hypertension in the Very Elderly Trial (HYVETHYVET)(N=3336):(N=3336):IndapamideIndapamide (D)(D)+perindoprilperindopril (A)(A)LARGE HYPERTENSION TRIALSl lSystolicSystolic Hypertension in the Hypertension in the ElderlyElderly Program(SHEP)Program(SHEP)(N=4736):(N=4736):ChlorthalidonChlorthalidonl lMedical Research Medical Research CouncilsCouncils(MRC)(MRC)TreatmentTreatment Trial of Trial of hypertension(N=4396):hypertension(N=4396):AtenololAtenolol,HydrochlorthiazideHydrochlorthiazidel lThe The SystolicSystolic Hypertension in Europe Hypertension in Europe StudyStudy(Syst-EurSyst-Eur)(N=2418):(N=2418):NitrendipineNitrendipinel lThe The StudyStudy on on CognitionCognition and and PrognosisPrognosis in the in the ElderlyElderly (SCOPE)(N=4937):(SCOPE)(N=4937):CandersatanCandersatanl lPerindoprilPerindopril ProtectionProtection againstagainst RecurrentRecurrent Stroke Stroke StudyStudy (PROGRESS)(N=6105):(PROGRESS)(N=6105):PerindoprilPerindoprill lThe Hypertension in the Very Elderly TrialThe Hypertension in the Very Elderly Trial (HYVET)(HYVET)(N=3336):(N=3336):IndapamideIndapamide+perindoprilperindopril (N Engl J Med 2008,(N Engl J Med 2008,LancetLancet NeurolNeurol 2008)2008)SAMPLESl lSHEPSHEP 160-219/90160-219/90l lMRCMRC 160-209/115160-209/115l lSyst-EurSyst-Eur 160-219/95160-219/95 No No dementiademential lPROGRESSPROGRESS Prior stroke or TIAPrior stroke or TIA MeanMean ageage 64 64l lSCOPESCOPE 160-179/90-99160-179/90-99 MMSE 24-30MMSE 24-30 No No dementiadementia HYVETHYVET SBP SBP aboveabove 160 160 Age Age aboveabove 80 80COGNITIVE END-POINTSl lDementia(SHEP,Syst-Eur,SCOPE,PROGRESS,HYVET)l lSignificant Cognitive Decline(PROGRESS,SCOPE)COGNITIVE END-POINTSl lMean change in cognitive function Syst-Eur,Progress,SCOPE Mini Mental State Examination(MMSE)MRC:Paired associate learning,Trail Making Test MAIN RESULTSCardiovascular end pointsl lAntihypertensive treatment reduced risk of most cardiovascular end points incl strokel lAlso in HYVET,which only included persons above age 80(N Engl J Med 2008)MAIN RESULTSDEMENTIAl lDecreased incidence of dementia(Syst-Eur)l lNo difference(SHEP,SCOPE,Progress,HYVET)l lNo hypertension trial show increased risk for dementia or cognitive declineMAIN RESULTSMEAN COGNITIVE CHANGEl lNo difference:MRC,SHEP,SCOPE,Syst-Eur,l lLess decline in active treatment group:PROGRESSWHY SO NEGATIVE RESULTS?Methodological issuesl lAgeAgel lHealthyHealthy volunteervolunteer effecteffectl lSelectiveSelective attrition/attrition/missingmissing data datal lTime of Time of follow-upfollow-upl lTime in relation to Time in relation to dementiademential lDiagnosis and Diagnosis and detectiondetection of of dementiademential lTestingTesting CeilingCeiling effecteffect LearningLearning effecteffect SensitivitySensitivity to to changechangel lSubgroupsSubgroups?Risk?Risk groupsgroups?l lTypeType of of drugdrugl lEffectEffect otherother thanthan bloodblood pressurepressureSAMPLESl lSHEPSHEP AboveAbove ageage 60 60 l lMRCMRC Age 65-74Age 65-74l lSyst-EurSyst-Eur AboveAbove ageage 60(60(meanmean 70)70)No No dementiadementia HYVETHYVET Age Age aboveabove 80 80l lPROGRESSPROGRESS Prior stroke or TIAPrior stroke or TIA MeanMean ageage 64 64l lSCOPESCOPE Age 70-89(Age 70-89(meanmean 76)76)MMSE 24-30MMSE 24-30 No No dementiadementiaMethodological issuesl lAgeAgel lHealthyHealthy volunteervolunteer effecteffectl lSelectiveSelective attrition/attrition/missingmissing data datal lTime of Time of follow-upfollow-upl lTime in relation to Time in relation to dementiademential lDiagnosis and Diagnosis and detectiondetection of of dementiademential lTestingTesting CeilingCeiling effecteffect LearningLearning effecteffect SensitivitySensitivity to to changechangel lSubgroupsSubgroups?Risk?Risk groupsgroups?l lTypeType of of drugdrugl lEffectEffect otherother thanthan bloodblood pressurepressureMean test score at baselinel lSYST-EUR:28.5(max 30)in MMSEl lSCOPE:28.5 in MMSEMethodological issuesl lAgeAgel lHealthyHealthy volunteervolunteer effecteffectl lSelectiveSelective attrition/attrition/missingmissing data datal lTime of Time of follow-upfollow-upl lTime in relation to Time in relation to dementiademential lDiagnosis and Diagnosis and detectiondetection of of dementiademential lTestingTesting CeilingCeiling effecteffect LearningLearning effecteffect SensitivitySensitivity to to changechangel lSubgroupsSubgroups?Risk?Risk groupsgroups?l lTypeType of of drugdrugl lEffectEffect otherother thanthan bloodblood pressurepressureEffect of differential drop-out in SHEPl lPlacebo group had more missed assessmentsl lCaVa events predicted missed assessmentsl l20-30%of missed assessments were assumed to be cognitively impairedl lThen active treatment reduced the risk of cognitive impairmentDiBariDiBari et al.Am J et al.Am J EpidemiolEpidemiol 2001 2001Methodological issuesl lAgeAgel lHealthyHealthy volunteervolunteer effecteffectl lSelectiveSelective attrition/attrition/missingmissing data datal lTime of Time of follow-upfollow-upl lTime in relation to Time in relation to dementiademential lDiagnosis and Diagnosis and detectiondetection of of dementiademential lTestingTesting CeilingCeiling effecteffect LearningLearning effecteffect SensitivitySensitivity to to changechangel lSubgroupsSubgroups?Risk?Risk groupsgroups?l lTypeType of of drugdrugl lEffectEffect otherother thanthan bloodblood pressurepressureTime of follow-upl lSHEPSHEP 5 5 yearsyearsl lMRCMRC 4.5 4.5 yearsyears Syst-EurSyst-Eur Median 2.0 Median 2.0 yearsyearsl lPROGRESSPROGRESS MeanMean 3.9 3.9 yearsyearsl lSCOPESCOPE MeanMean 3.7 3.7 yearsyears HYVETHYVET MeanMean 2.2 2.2 yearsyearsLONGITUDINAL STUDIES ON BLOOD PRESSURE AND ALZHEIMERS DISEASEPrevious high blood pressurePrevious high blood pressure 5-15 years5-15 yearsAlzheimers disease in late lifeAlzheimers disease in late lifeThe H70-study in GothenburgThe H70-study in Gothenburg Skoog et al.Lancet 1996 The Honolulu-Asia Aging StudyThe Honolulu-Asia Aging Study Launer et al.Neurobiol Aging 2000 The Rotterdam StudyThe Rotterdam Study Ruitenberg et al.Dissertation 2000 Kuopio,FinlandKuopio,FinlandKivipelto et al.BMJ 2001Kungsholmen Kungsholmen StudyStudyQiuQiu et al et al ArchArch NeurolNeurol 2003 2003ChineseChinese StudyStudyWu et al Life Science 2003Wu et al Life Science 2003USAUSAWhittmerWhittmer et al.et al.NeurologyNeurology 2005 2005Too short follow-up to evaluate an effect on dementia Declining blood pressure before dementia onsetA 15-year follow-up of blood pressure and dementiaSkoog et al.Skoog et al.LancetLancet 1996 1996SAMPLESl lSHEPSHEP 160-219/90160-219/90l lMRCMRC 160-209/115160-209/115l lSyst-EurSyst-Eur 160-219/95160-219/160SBP 160If lowered blood pressure is a marker of preclinical dementia,those included in hypertension trials may be at low short-term risk for dementiaMethodological issuesl lHealthyHealthy volunteervolunteer effecteffectl lSelectiveSelective attrition/attrition/missingmissing data datal lTime of Time of follow-upfollow-upl lDiagnosis and Diagnosis and detectiondetection of of dementiademential lTestingTesting CeilingCeiling effecteffect LearningLearning effecteffect SensitivitySensitivity to to changechangel lSubgroupsSubgroups?Risk?Risk groupsgroups?l lTypeType of of drugdrugl lEffectEffect otherother thanthan bloodblood pressurepressureCHANGE IN MMSE SCOREl lCeiling effect in those with 29-30l lLearning effect(test every 6 months)l lLess possibility for increase in those with 29-30 MMSE 30MMSE 30MMSE 30MMSE 30CHANGE IN COGNITIVE FUNCTIONMMSE 24MMSE 24CHANGE IN MMSE SCOREl lCeiling effect in those with 29-30l lLearning effect(test every 6 months)l lLess possibility for increase in those with 29-30 Increase in test scoresl lMRC trial in hypertensionl lSyst-Eurl lSCOPECHANGE IN MMSE SCOREl lCeiling effect in those with 29-30l lLearning effect(test every 6 months)l lLess possibility for increase in those with 29-30 CHANGE IN MMSE SCORE FROM BASELINE(SCOPE)MMSE MMSE scorescore at at baselinebaselineIncreaseIncrease%DecreaseDecrease%30(N=1653)30(N=1653)0 04444 29(N=1214)29(N=1214)3636373728(N=929)28(N=929)4343343427(N=528)27(N=528)4949373726(N=354)26(N=354)4949373725(N=177)25(N=177)5454333324 (N=81)24 (N=81)36364545Methodological issuesl lHealthyHealthy volunteervolunteer effecteffectl lSelectiveSelective attrition/attrition/missingmissing data datal lTime of Time of follow-upfollow-upl lDiagnosis and Diagnosis and detectiondetection of of dementiademential lTestingTesting CeilingCeiling effecteffect LearningLearning effecteffect SensitivitySensitivity to to changechangel lSubgroupsSubgroups?Risk?Risk groupsgroups?l lTypeType of of drugdrugl lEffectEffect otherother thanthan bloodblood pressurepressureSCOPE.Newcastle substudyChange in test scoresCandesartanCandesartanPlaceboPlacebop pAttentionAttention 0.004 0.004-0.036-0.036 0.040.04 Episodic memory Episodic memory 0.14 0.14-0.22-0.22 0.040.04 Speed of cognition Speed of cognition-2.3-2.3-17.4-17.4 0.150.15 Working memory Working memory 0.0014 0.0014 0.00100.0010 0.900.90 Executive functionExecutive function -0.0031-0.0031-0.0023-0.0023 0.950.95 Saxby et al.Saxby et al.NeurologyNeurology 2008;70:1858-66 2008;70:1858-66 Treatment of hypertension in mild cognitive impairment(MCI)Treatment targets in relation to dementiaDementiaDementiaADLADLSocial Social abiliyabiliyMild Mild CognitiveCognitive ImpairmentImpairmentNormalNormalMMSE 24-28 AT BASELINE(SCOPE)l lMore previous stroke(5.2%vs 3.0%)l lMore diabetes mellitus(14%vs 10%)l lLess myocardial infarction(4.3 vs 4.7%)l lOlder(77.3 vs 75.8)Skoog et al Am J Hypertension 2005Skoog et al Am J Hypertension 2005Major Cardiovascular events in SCOPE(per 1000 person-years)MMSEMMSE24-2824-2833.633.629-3029-3024.724.7*Cardiovascular mortality,stroke,myocardial infarctionSkoog et al Am J Hypertension 2005Skoog et al Am J Hypertension 2005Non-fatal stroke(per 1000 person-years)in SCOPEMMSEMMSE24-2824-2810.610.629-3029-307.67.6*Skoog et al Am J Hypertension 2005Skoog et al Am J Hypertension 2005Dementia(cumulative incidence)in SCOPEMMSEMMSE%24-2824-284.44.429-3029-301.01.0*Skoog et al Am J Hypertension 2005Skoog et al Am J Hypertension 2005Change in MMSE Score,ITT-0.8-0.7-0.6-0.5-0.4-0.3-0.2-0.10Changein MMSEScore(adjusted)Candn=1419Contn=1399BaselineMMSE 29-30Candn=998Contn=1010BaselineMMSE 24-28p0.20p=0.04Candn=2417Contn=2409Allpatientsp=0.20Skoog et al Am J Hypertension 2005Skoog et al Am J Hypertension 2005Treatment of hypertension in dementedTreatment targets in relation to dementiaDementiaDementiaADLADLSocial Social abiliyabiliyMild Mild CognitiveCognitive ImpairmentImpairmentNormalNormalNot many studies on antihypertensive treatment in demented individualsand no RCT Prevalence of hypertension(=blood pressure above 160/90)in 85-year-olds%Non-dementedNon-demented