AD危险因素及干预因素.ppt

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1、AD危险因素及干预因素危险因素及干预因素12021/2/21AD的危险因素与干预22021/2/21运动锻炼与AD关系目的：whetheranactivityspecificexerciseprogramcouldimproveabilitytoperformbasicmobilityactivitiesinlong-termcareresidentswithAD.方式：Anactivityspecificexerciseprogramwascomparedtoawalkingprogramandtoanattentioncontrol.评估方法：assessedusingthesubscal

2、esoftheAcuteCareIndexofFunction;functionalmobilitywasmeasuredusingthe6-MinuteWalktest.32021/2/21Theprogramwasdesignedtobeimplemented5timesperweekbyanursingassistantorfamilymemberunderthesupervisionofaphysicaltherapist.thisstudysuggestthatwalkingprogramsmaynotbesufficienttoimprovemobilitylimitationsi

3、nindividualswhoaredependentintransfersandsupportthebenefitofatargeted,simpleexerciseprograminreducingmobilitylimitationsininstitutionalizedpatientswithmoderatetoseverecognitiveimpairment.-ARandomizedControlledTrialofanActivitySpecificExerciseProgramforIndividualsWithAlzheimerDiseaseinLong-termCareSe

4、ttings.JGeriatrPhysTher;34:50-56.42021/2/21regularleisureexercisemaydecreasetheriskofdevelopingdementiainlate-life-APOE4allele,cognitivedysfunction,andobstructivesleepapneainchildren.Neurology.2007;69(3):243-9.52021/2/21VascularFactors与AD高血压:Thereisfairlyrobustevidencelinkingmidlifehypertensiontothe

5、developmentofdementiainlaterlife.individualswithraisedsystolicbloodpressure(160mmHg)atmidlifehadasignificantlyhigherriskofADlaterinlife-MidlifevascularriskfactorsandAlzheimersdiseaseinlaterlife:longitudinal,populationbasedstudy.BritMedJ.2001;322:1447-51.cerebrovascularatherosclerosisandincreasedburd

6、enofsubcorticalwhitematterlesionscommonlyfoundinAD.62021/2/21卒中或TIA增加发生AD：TheriskofdevelopingAD,andnotmerelyvasculardementia,issignificantlyincreasedinindividualswithstrokeortransientischemicattacks-TheroleofcerebralischemiainAlzheimersdisease.NeurobiolAging.2000;21:321-30.Cerebralhypoxiaaccruingfro

7、msleepapneahasbeenlinkedtoAD-MidliferespiratoryfunctionandincidenceofAlzheimersdisease:A29-yearlongitudinalstudyinwomen.NeurobiolAging.2007;28(3):343-50.72021/2/21营养、饮食与AD“Mediterraneandiet:Thediethasrecentlybeenlinkedtoareducedriskoflate-lifecognitivedecline123,124,MCI,AD,andconversionfromMCItoAD-M

8、editerraneandietandmildcognitiveimpairment.ArchNeurol.;66(2):216-25.Omega-3fattyacids:largeobservationalstudiessupportthenotionthatfishconsumption,amajorsourceofomega-3fattyacids,maysubstantiallydiminishtheriskofADandotherdementias-DonepezilandvitaminEinthetreatmentofmildcognitiveimpairment.NEnglJMe

9、d.2005;352:2379-88.Thiamine(VitaminB1)：ThiaminedeficiencyhasbeenlinkedtoADinsomestudies-ThiamineandAlzheimersdisease:apilotstudy.ArchNeurol.1988;45(8):833-5.82021/2/21Coffee:Severalstudieshavefoundthatcoffeeconsumptionatmidlifeisassociatedwithadecreasedriskofdementia/ADlaterinlife-Alzheimersdiseasea

10、ndcoffee:aquantitativereview.NeurolRes.2007;29(1):91-5(5).Alcohol:consumptionofmoderatequantitiesofredwine(250-500mL/day)wasassociatedwithalowerriskofAD(RR,0.53)andall-causedementia(RR,0.56)-NutritionalfactorsandriskofincidentdementiainthePAQUIDlongitudinalcohort.JNutrHealthAging.2004;8(3):150-4.920

11、21/2/21VitaminsCandE:LowbloodlevelsoffolicacidandincreasedplasmahomocysteinehavebeenpositedasriskfactorsforthedevelopmentofADanddementia.Theacceleratedrateofbrainatrophyinelderlywithmildcognitiveimpairmentcanbeslowedbytreatmentwithhomocysteine-loweringBvitamins.-Homocysteine-loweringbyBvitaminsslows

12、therateofacceleratedbrainatrophyinmildcognitiveimpairment:arandomizedcontrolledtrial.PLoSOne.Sep8;5(9):e12244.102021/2/21Workplace/environmentalexposures环境/工作场所暴露HeavyMetals:ExposuretoheavymetalshasbeenassociatedwithcognitivedeficitsandAD.retainedcumulativedoseofironresultingfrompreviousenvironmenta

13、lexposurewasassociatedwithlowertestscoresinsevencognitivedomains.SomestudieshavelinkedaluminumexposureindrinkingwatertoincreasedriskofAD104,thoughthistopicremainscontroversial.-AluminiumasariskfactorinAlzheimersdisease,withemphasisondrinkingwater.BrainResBull.2001;55(2):187-96.Pesticides/herbicides:

14、exposuretofumigantsordefoliantssignificantlyincreasedtheincidenceofAD-RiskfactorsforAlzheimersdisease:apopulation-based,longitudinalstudyinManitoba,Canada.IntJEpidemiol.2001;30:590-7.112021/2/21药物与ADNonsteroidalanti-inflammatorydrugs(NSAIDs):thereiscurrentlyinsufficientevidencetorecommendprescribing

15、NSAIDsforthespecificintentionofreducingtheriskofdementiaorAD-Primarypreventionofdementia.AlzheimersDementia.2007;3(4):348-54.122021/2/21社会因素与ADSocialStimulation:loneliness,definedasthefeelingofbeingdisconnectedfromothers,mayincreaseriskoflate-lifedementiaandratesofcognitivedeclineintheelderly-Loneli

16、nessandriskofAlzheimerdisease.ArchGenPsychiatry.2007;64(2):234-40.AD与婚姻状态关系：withnever-marriedindividualsshoulderinggreaterrisk患AD-MaritalstatusandriskofAlzheimersdisease:aFrenchpopulation-basedcohortstudy.Neurology.1999;53(9):1953-8.132021/2/21精神因素与ADNeuroticism,a.k.a.distressproneness,ameasureofani

17、ndividualstendencytoexperiencenegativeemotionssuchasanxietyandanger,hasbeenlinkedtoexcessiveADriskandacceleratedcognitivedecline-PronenesstopsychologicaldistressisassociatedwithriskofAlzheimersdisease.Neurology.2003;61:1479-85.conscientiousness,atendencytowardself-disciplineandgoaldirection,maydimin

18、ishtheriskofAD,MCIandcognitivedecline-ConscientiousnessandtheincidenceofAlzheimerdiseaseandmildcognitiveimpairment.ArchGenPsychiatry.2007;64(10):1204-12.higherlevelsofspiritualityandprivatereligiouspracticeswereassociatedwithslowerdiseaseprogressioninpatientswithprobableAlzheimerdementia-Cognitivede

19、clineinAlzheimerdisease:Impactofspirituality,religiosity,andQOL.Neurology.2007;68:1509-14.142021/2/21Stress:ProlongedpsychologicalstresshasbeenassociatedwithmemorylossandhippocampalatrophyandmaypredisposetoAD.Chronicstressengendershypercortisolemiaandaugmentedcirculatingandsalivarycortisollevelshave

20、beenreportedinsporadicAD.(ii)Depression:Severalstudieshaveshownanassociationbetweenahistoryofdepressionandsubsequentdementia,particularlyAD.152021/2/21Cognitiveengagement认知锻炼与ADParticipationincognitiveexercisesandleisureintellectualactivitieshasbeenassociatedwithareducedriskofdevelopingAD.Cognitivel

21、ystimulatingleisureactivitiesincludereading,playingamusicalinstrument,doingcrosswordpuzzles,writingforpleasure,etc-Leisureactivitiesandtheriskofdementiaintheelderly.NEnglJMed.2003;348(25):2508-16.-InfluenceofleisureactivityontheincidenceofAlzheimersdisease.Neurology.2001;57(12):2236-42.participating

22、inmentallystimulatingleisureactivitieswasassociatedwithanoverallriskreductionof50%fordementia(OR0.50,95%CI,0.420.61).162021/2/21leisureactivities休闲活动与痴呆Amongleisureactivities,reading,playingboardgames,playingmusicalinstruments,anddancingwereassociatedwithareducedriskofdementia.-VergheseJ1,LiptonRB,K

23、atzMJ,HallCB,Leisureactivitiesandtheriskofdementiaintheelderly.NEnglJMed.2003Jun19;348(25):2508-16.172021/2/21身体锻炼与ADPreviousworkhassuggestedthatPAmayreduceriskofdevelopingAD.PAdoesnotseemtobeassociatedwithrapidityofcognitivechange,butitseemstorelatetoprolongationofsurvivalofpatientswithAD.182021/2/

24、21192021/2/21Education与ADYearsofformaleducationexertafairlystrongandreproducibleimpactonADincidence-InfluenceofeducationandoccupationontheincidenceofAlzheimersdisease.JAmMedAssoc.1994;271(13):1004-10.educationyearsareoftensignificantlylowerintheADgroupsthancognitively-normalindividuals。202021/2/21Th

25、edelineationofriskfactorsforthedevelopmentofADoffershopefortheadventofeffectivepreventionorinterventionsthatmightretardtheonsetofsymptoms.Althoughsomeriskfactorsareheritableandlargelybeyondourcontrol,othersaredeterminedbylifestyleorenvironmentandarepotentiallymodifiable.-212021/2/21营养因素与AD营养是AD的保护性因

26、素NutritionseemstobeoneofthefactorsthatmayplayaprotectiveroleinAlzheimerdisease.Severalstudieshaveshowntheexistenceofacorrelationbetweencognitiveskillsandtheserumconcentrationsoffolate,vitaminB-12,vitaminB-6,and,morerecently,homocysteine.nutritionalfactorshavetobestudiednotalonebutwiththeotherfactors

27、relatedtoAlzheimerdisease:genetics,estrogen,antiinflammatorydruguse,andsocioeconomicvariables.Alzheimerdisease:protectivefactors.AmJClinNutr.2000V71N2:643S-649S222021/2/21吸烟与ADIfsmokingisariskfactorforAlzheimerdisease(AD)butasmokerdiesofanothercausebeforedevelopingormanifestingAD,smoking-relatedmort

28、alitymaymasktherelationshipbetweensmokingandAD.Further,age-specificmortalityratesarehigherinsmokersbecausetheydieearlierthannonsmokers.ifwefailtotakeintoaccountthecompetingriskofdeathwhenweestimatetheeffectofsmokingonAD,webiastheresultsandareinfactonlycomparingtheincidenceofADinnonsmokerswiththatint

29、hehealthiestsmokers.-Smoking,death,andAlzheimerdisease:acaseofcompetingrisks.:300-6232021/2/21吸烟增加痴呆和AD风险：Prospectivepopulation-basedcohortstudyin6,868participants,Afterameanfollow-uptimeof7.1years,currentsmokingatbaselinewasassociatedwithanincreasedriskofdementia(HR1.47)andAD(HR1.56).Currentsmoking

30、increasestheriskofdementiaADandvasculardementia(VaD)RelationbetweensmokingandriskofdementiaandAlzheimerdisease:theRotterdamStudy.:998-1005242021/2/21脑白质病变与ADIncreasedwhitematterhyperintensitiesWMHsareassociatedwithaging,decreasedglucosemetabolism,anddeclineinexecutivefunctionbutdonotaffectAD-specifi

31、cpathologicprogression,suggestingthatthevascularcontributiontodementiaisprobablyadditivealthoughnotnecessarilyindependentoftheamyloidpathway.-252021/2/21ThepresentstudysoughttodetermineifsubgroupsofbereavedADcaregiversfollowdistinctivedepressivesymptomtrajectoriesandthecharacteristicsassociatedwithm

32、embershipindepressivesymptomsubgroups.TheCenterforEpidemiologicStudiesDepressionScaleassesseddepressivesymptomsamongtheADcaregiversatbaselineandthreefollow-upvisits.Threepostlossdepressivesymptomtrajectoriesemerged:persistentlysyndromaldepression(N=30,16.5%);syndromal-becoming-thresholdleveldepressi

33、on(N=62,34.0%);andpersistentlyabsentdepression(N=90,49.5%).DepressivesymptomtrajectoriesandassociatedrisksamongbereavedAlzheimerdiseasecaregivers.AmJGeriatrPsychiatry.V16N2:145-55262021/2/21环境因素与ADSeveralenvironmentalfactorscontributesignificantlytoriskofPDandAD.Somemayalreadybeactiveintheearlystage

34、soflife,andsomemayinteractwithothergeneticfactors.EvidenceconsistentlysuggeststhatahigherriskofADisassociatedwithpesticides,hypertensionandhighcholesterollevelsinmiddleage,hyperhomocysteinaemia,smoking,traumaticbraininjuryanddepression.272021/2/21WeakevidencealsosuggeststhatahigherriskofADisassociat

35、edwithhigh aluminium intake through drinking water,excessive exposure to electromagnetic fields from electrical grids,DM and hyperinsulinaemia,obesity in middle age,excessive alcohol consumption and chronic anaemia.alowerriskofADisassociatedwithmoderate alcohol consumption,physical exercise,perimeno

36、pausal hormone replacement therapy and good cognitive reserve.WeakevidencesuggeststhatlowerriskofADisassociatedwiththeMediterraneandiet,coffeeandhabitualNSAIDconsumptionParkinsondiseaseandAlzheimerdisease:environmentalriskfactors.282021/2/21饮食与AD高糖饮食影响认知，促进神经退行性疾病发生如ADhigh-sugardietscanleadtocogniti

37、veimpairmentpredisposingtoneurodegenerativedisorderssuchasAlzheimersdisease.metabolicderangementsinducedbyhigh-fructose/sucrosedietsandpresentsevidencefortheinvolvementofinsulinresistanceinsporadicAlzheimersdiseasepathogenesis.AccumulatingevidencehasalsodemonstratedaconnectionbetweenT2DandAlzheimers

38、disease.TheriskfordevelopingT2DandAlzheimersdiseaseincreasesexponentiallywithageandhavingT2DincreasestheriskofdevelopingAlzheimersdisease.-High-sugardiets,type2diabetesandAlzheimersdisease.CurrOpinClinNutrMetabCare.V16N4:440-5292021/2/21饮食改变显著减少2型DM和AD风险TheincidenceofT2Dincreaseddramaticallyoverthel

39、astdecadesmainlyduetoWesternlifestylefactorssuchaslackofexerciseandhighcaloriediets.Toaggravatethisscenario,ithasbeenconsistentlyshownthatT2DisariskfactorforAlzheimersdiseaseandbothdisorderssharesimilardemographicprofiles,riskfactors,andclinicalandbiochemicalfeatures(e.g.insulinresistance).dietarych

40、angescansignificantlyreducetheriskofT2DandAlzheimersdiseaseandtherebyincreasethequalityoflifeandimprovelongevity.-High-sugardiets,type2diabetesandAlzheimersdisease.CurrOpinClinNutrMetabCare.V16N4:440-5302021/2/21INSULINRESISTANCE:ALINKBETWEENTYPE2DIABETESANDALZHEIMERSDISEASEmetabolicderangementsindu

41、cedbyhigh-fructose/sucrosedietsandpresentsevidencefortheinvolvementofinsulinresistanceinsporadicAlzheimersdiseasepathogenesis.312021/2/21Studiesofcerebralstructuredemonstratedapronouncedcortical,subcortical,andhippocampalatrophyinT2Dpatients.AccumulatingevidencealsoshowsthatT2Disariskfactorfordement

42、ia,particularlyvasculardementiaandAlzheimersdisease.-High-sugardiets,type2diabetesandAlzheimersDisease.Volume16Number00Month322021/2/21AccumulatingevidencesupportstheinvolvementofimpairedinsulinsignalinginAlzheimersdiseaseetiopathogenesis:reducedinsulinlevelsandinsulinreceptorexpressionwereobservedi

43、nAlzheimersdiseasebrains,increasingAlzheimersdiseaseBraakstagewasassociatedwithprogressivelyreducedexpressionlevelsofinsulin,insulingrowthfactor(IGF)1and2andrespectivereceptors,Alzheimersdiseasepatientsshowincreasedfastingplasmainsulinlevels,decreasedcerebrospinalfluid(CSF)insulinlevels,and/ordecrea

44、sedCSF/plasmainsulinratio,apartfromincreasedamyloidblevels,whichsuggestadecreaseininsulinclearancethatmayprovokeanelevationofplasmaamyloidblevels,disruptionofbraininsulinsignalingbytheintracerebroventricularadministrationofthediabetogenicdrugstreptozotocin(STZ)leadstothedevelopmentofnumerousbehavior

45、al,332021/2/21职业暴露与ADmostofstudies(ninecase-controlandfivecohortstudies)obtainedquantitativeestimatesofexposure.PooledestimatessuggestanincreasedriskofADfromcase-controlstudies(OR(pooled)2.03;95%CI1.38-3.00)andfromcohortstudies(RR(pooled)1.62;95%CI1.16-2.27),withmoderatetohighstatisticalheterogeneit

46、yinbothcases(respectively,I(2)=58%andI(2)=54%).Cohortstudiesshowedconsistentlyincreasedrisksforexposedmen(RR(pooled)2.05;95%CI1.51-2.80,I(2)=0%).Evidenceofdose-responserelationshipwasnotpresent.Testforpublicationbiassuggestssmallstudyeffects,mostlyforcase-controlstudies.-Occupationalexposuretoextrem

47、elylowfrequencyelectricandmagneticfieldsandAlzheimerdisease:ameta-analysis.IntJEpidemiol.V37N2:329-40342021/2/21Moreinformationonrelevantdurationandtimewindowsofexposure,onbiologicalmechanismsforthispotentialassociationandoninteractionsbetweenelectromagneticfieldsexposureandestablishedriskfactorsfor

48、ADisneeded.352021/2/21抑郁症和ADSeveralepidemiologicstudieshaveexamineddepressionasariskfactorforAlzheimerdiseasewithconflictingresults.Moststudiesreliedonself-reporteddepression,buttheagreementbetweenself-reporteddepressionandclinicaldiagnosishasbeenreportedtobeweak,therebydilutingtheassociation.Apopul

49、ation-basedcohortinOdense,Denmark,of3346personsage65-84yearswasexaminedatbaselineandafter2yearsand5years.Weusedlogisticregressionmodelstoestimateoddsratios(ORs)and95%confidenceintervals(CIs).-DepressionandtheriskofAlzheimerdisease.Epidemiology.2005V16N2:233-8362021/2/21抑郁症增加发生AD的风险RESULTS:Personswit

50、hahistoryofdepressionhadanincreasedriskofAlzheimerdiseasebothatbaseline(OR=1.7;CI=1.0-2.7)andatfollowup(at2years,1.91.0-3.3andat5years,1.60.9-2.7).DepressionandtheriskofAlzheimerdisease.:233-8372021/2/21抑郁症增加认知受损和发生痴呆的风险：Depressionhasbeenlinkedtocardiovasculardiseaseandcognitiveimpairment,includingA