1、谁能“吹”散我们的“脑雾”达能中国开放科研中心王旖 博士新冠感染的神经病变与脑功能改变目录HEALTHY AGING营养与脑血管功能消费者对脑健康的需求改善睡眠营养素与脑功能抗炎抗氧化营养素与脑功能新冠期间中国人群关注健康焦点HEALTH CONCERN SINCE COVID-19 CHINAHEALTHY AGING2022年11月，世界卫生组织在更新版的新冠肺炎个人康复指南里，引入了一个新的新冠后遗症名词“脑雾”。在新冠患者康复过程中，可能会出现思维能力(称为“认知”)的各种困难，包括记忆力、注意力、信息处理、计划和组织方面的问题，被称为“脑雾”。什么是脑雾WHAT IS BRAIN F

2、OGHEALTHY AGINGCShort term(4Short term(4-12 weeks after COVID12 weeks after COVID-19 diagnosis)19 diagnosis)Long term(12 weeks after COVIDLong term(12 weeks after COVID-19 diagnosis)19 diagnosis)Fatigue(51%,95%CI 39-64%,low certainty)General pain or discomfort(40%,95%CI 24-58%,low certainty)Shortnes

3、s of breath(38%,95%CI:27-51%,very low certainty)Sleep disturbances(26%,95%CI 24-29%,low certainty)Anxiety(29%,95%CI:16-48%,very low certainty)Cough(28%,95%CI:22-35%,low certainty)Fatigue(47%,95%CI 27-68%,very low certainty)General pain or discomfort(27%,95%CI 25-29%,low certainty)Sleep disturbances(

4、26%,95%CI 24-29%,low certainty)Shortness of breath(22%,95%CI 12-35%,very low certainty)Anxiety or depression(22%,95%CI 19-25%,low certainty)Depression or post-traumatic stress disorder(22%,95%CI 12-32%,very low certainty)Hair loss(22%,95%CI 20-24%,low certainty)https:/covid19-sciencetable.ca/science

5、brief/understanding-the-post-covid-19-condition-long-covid-and-the-expected-burden-for-ontario/?154,068 人COVID-19队列VS 5,638,795 对照组，5,859,621历史对照新冠感染后与脑相关症状RISKS AND 12-MONTH BURDENS OF INCIDENT POST ACUTE COVID-19 NEUROLOGIC OUTCOMESLong-term neurologic outcomes of COVID-19.Nat Med 28,24062415(2022

6、).HEALTHY AGINGC肺功能心脑：炎性反应血管神经：（睡眠、认知）肝功能新冠感染对健康的影响新冠感染对健康的影响IMPACT OF COVID-19 AND POST-COVID CONDITION ON VARIOUS ORGAN SYSTEMShttps:/doi.org/10.47326/ocsat.2021.02.44.1.0HEALTHY AGINGC荟萃分析：新冠的辅助改善方案荟萃分析：新冠的辅助改善方案OVERVIEW OF SOME PROPOSED PHARMACOLOGICAL AGENTS WITH POTENTIAL BENEFICIAL EFFECTS IN

7、 COVID-19 PATIENTHEALTHY AGINGPharmacology&Therapeutics 219(2021)107703新冠感染对脑神经的作用机制新冠感染对脑神经的作用机制POTENTIAL MECHANISMS OF COVID-19 IN NEURAL SYSTEMHEALTHY AGINGCHEALTHY AGING新冠感染对心脑血管健康的作用机制新冠感染对心脑血管健康的作用机制POTENTIAL MECHANISMS OF SARS-COV-2-INDUCED CARDIOVASCULAR COMPLICATIONSWHO WHO 关于脑健康康复指导关于脑健康康复

8、指导HEALTHY AGINGCN N-3 3 脂肪酸对心血管和炎性反应的影响脂肪酸对心血管和炎性反应的影响POTENTIAL CARDIOPROTECTIVE AND ANTI-INFLAMMATION MECHANISMS OF N-3 PUFAS IN THE SETTING OF COVID-19Darwesh AM,Bassiouni W,Sosnowski DK,SeubertJM.Pharmacol Ther.2021 Mar;219:107703.HEALTHY AGINGn-3 supplements have been found to be 12 to 21%effect

9、ive in reducing the risk of Covid-19.Increasing severity of the disease and the need for mechanical ventilation and hospitalization due to polyunsaturated fatty acid deficiencyn-3 fatty acid deficiency increased mortality in patients with Covid-19.Elevated levels of fatty acids in patients lungs and

10、 a cytokine storm are the main reasons for mortality in Covid-19 patients.荟萃分析：荟萃分析：N N-3 3 脂肪酸与新冠脂肪酸与新冠POLYUNSATURATED FATTY ACIDS ON THE SEVERITY AND MORTALITY OF COVID PATIENTS:A SYSTEMATIC REVIEWLife Sciences 299(2022)120489他汀类在辅助治疗中的应用他汀类在辅助治疗中的应用STATINS IN COVID-19 THERAPYHEALTHY AGINGCLife(Ba

11、sel).2021 Jun 16;11(6):565.维生素C与肺炎、感染和新冠感染VITAMIN C DEFICIENCY IN PNEUMONIA,SEPSIS AND COVID-19Study TypeCohortVitamin C(mol/L)(%Deficient,%Hypovitaminosis C)PneumoniaCase controlHealthy volunteers(n=50)56 2a(0%b,8%c)Community-acquired pneumonia(n=50)23 3(22%,62%)Case controlHealthy volunteers(n=20)

12、66 3Pneumonia cases(n=11)31 9Intervention(placebo group)Pneumonia/bronchitis(n=29):Week 024 5(40%)bWeek 219 3(37%)Week 424 6(25%)Intervention(control group)Pneumonia cases(n=70):Day 041Day 5102324Day 15203235Day 3039SepsisIntervention(baseline)Sepsis with ARDS(n=83):Day 022(1137)dDay 223(937)Day 426

13、(941)Day 729(1239)ObservationalSeptic shock patients(n=24)15 2(38%b,88%c)Intervention(baseline)Severe sepsis patients(n=24)18 2Severe COVID-19ObservationalCritically ill COVID-19(n=21)22 4(45%b,70%c)eSurvivors(n=11)29 7(40%,50%)Non-survivors(n=10)15 2(50%,90%)ObservationalCOVID-associated ARDS(n=18)

14、17 with 9 mol/L1 with 14 mol/LNutrients.2020 Dec 7;12(12):3760.HEALTHY AGINGPatientsPatientsInterventionInterventionDose(Duration)Dose(Duration)Patient OutcomesPatient OutcomesPneumoniaPneumoniaPneumonia/bronchitis(n=57):Oral vitamin C(28 day):respiratory symptom score in most severely illPlacebo(n=

15、29)0 g/day17%mortality in placebo groupTreatment(n=28)0.2 g/day4%mortality in treatment groupPneumonia(n=140):Oral vitamin C(10 day):hospital length of stay:Control(n=70)0 g/day24 days in control groupLow dose(n=39)0.250.8 g/day19 days in low dose groupHigh dose(n=31)0.51.6 g/day15 days in high dose

16、 groupSepsisSepsisSepsis and ARDS(n=167):IV vitamin C(4 day):X systemic organ failure scoreX C-reactive protein,thrombomodulinX ventilator-free days28 day mortalityICU-free dayshospital-free daysPlacebo(n=83)0 mg/kg bw/dayTreatment(n=84)200 mg/kg/daySeptic shock(n=100):IV vitamin C(until ICU dischar

17、ge)vasopressor durationICU length of stayX length of mechanical ventilationX renal replacement therapyX ICU mortalityPlacebo(n=50)0 g/dayTreatment(n=50)6 g/daySeptic shock(n=28):IV vitamin C(3 day):norepinephrine dose and duration28 day mortalityX ICU length of stayPlacebo(n=14)0 mg/kg bw/dayTreatme

18、nt(n=14)100 mg/kg bw/daySevere sepsis(n=24)IV vitamin C(4 day):systemic organ failure scoreC-reactive protein,procalcitonin,thrombomodulinPlacebo(n=8)0 mg/kg bw/dayLow dose(n=8)50 mg/kg bw/dayHigh dose(n=8)200 mg/kg bw/daySevere COVIDSevere COVID-1919Critical COVID-19(n=54)IV vitamin C(7 day):X vent

19、ilation-free daysPaO2/FiO2Interleukin-628 day mortality in patients with SOFA scores 345 项目应用VC的临床研究45 CLINICALTRIALS.GOV INVESTIGATING VITAMIN C WITH OR WITHOUT OTHER TREATMENTS FOR COVID-19.HEALTHY AGINGThe 28-day mortality from randomization(day 1)to day 28 in a trial of high-dose intravenous vit

20、amin C(HDIVC)in patients with COVID-19.维生素C与肺炎、感染和新冠感染VITAMIN C DEFICIENCY IN PNEUMONIA,SEPSIS AND COVID-19HEALTHY AGING褪黑素在新冠病毒感染中的应用POTENTIAL EFFECTS OF MELATONIN ON THE COURSE OF COVID-19COVID-19 PhaseEffect of Melatonin TreatmentRecommended DoseProphylaxisCircadian sleepwake rhythm disorder trea

21、tment0.55 mgInsomnia treatmentAdjuvant to anti-SARS-CoV-2 vaccines25 mg10.52 mg2Early infection phase/mild clinical symptomsImprovement of sleep qualityInhibition of viral invasionFree oxygen species scavengingCytokine suppression212 mg3Pulmonary phase/severe clinical symptomsImprovement of sleep qu

22、alityAnti-inflammatory effectsReduction of“cytokine-storm”Protection of lungs and tissues from oxidative injuryRisk reduction of ventilator-induced lung injury212 mg3,4Post-infection periodImprovement of sleep qualityStabilization of the disrupted circadian sleep rhythmAntioxidant propertiesReductio

23、n of post-covid pulmonary fibrosis0.55 mgInt J Mol Sci.2021 Aug;22(16):8623.HEALTHY AGING维生素D、锌、硒与感染POTENTIAL EFFECTS OF VITAMIN D、ZINC、SELENIUM ON THE COURSE OF COVID-19Adequate supply of zinc,selenium,and vitamin D is essential for resistance to other viral infections,immune function,and reduced i

24、nflammation.Initiation of adequate supplementation in high-risk areas and/or soon after the time of suspected infection with SARS-CoV-2.2020 Aug 7;12(8):2358.Nutrients.2020 Aug 7;12(8):2358.HEALTHY AGINGC脑雾 VS 认知衰退BRAIN FOG VS COGNITIVE DECLINE HEALTHY AGING20银发一代：中国人口老龄化银发一代：中国人口老龄化SILVER AGE:CHINA

25、S AGING POPULATIONPopulation and health issues in the 60+2020-2040来源：国家卫生健康委员会2022年9月20日新闻发布会上海市健康老龄化行动方案（2022-2025年）267 Million18.9%At the end of 2021400+Million30%+203515 MillionDementia10 MillionAlzheimers disease认知障碍患者快速增长21认知障碍患者中13%处于“中年”（41-60岁）老年人认知功能和脑健康COGNITIVE DECLINE WITH AGEHEALTHY AGI

26、NGCHEALTHY AGING老年人认知功能和脑健康风险因素COGNITIVE DECLINE WITH AGE MODIFIABLE FACTORS THROUGHOUT COURSE OF LIFEJin-Tai Yu et al.J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-HEALTHY AGINGC老年人抗氧化剂需求与脑健康LOW DIETARY VITAMIN E INTAKE IS ASSOCIATED WITH HIGH RISK OF INCIDENT DEMENTIA AMONG OLDER ADULT

27、S:THE SHANGHAI AGING STUDYCumulative incidence rate of dementia I Increased most dramatically after almost 4 ncreased most dramatically after almost 4 years of followyears of follow-up in vitamin E low intake up in vitamin E low intake participants Association between vitamin E intake level and risk

28、 of dementiaAssociation between vitamin E intake level and risk of dementiaHEALTHY AGINGVitamin E intake levelVitamin E intake levelPersonPerson-yearsyearsIncidence,100 Incidence,100 personperson-year,(%)year,(%)HR(95%CI)*P valueLow intake group(13.20mg/d)Low intake group(23.63mg/d)High intake group

29、(23.63mg/d)2098.80.71Yi Wang et al Front Nutr.2022 Nov 23;9:1036795.24LPC-DHA脂肪酸在血脑屏障（BBB）转运1 ZhangW,ChenR,YangT,etal.Fatty AcidTransporting Proteins:RolesinBrainDevelopment,Aging,and StrokeJ.ProstaglandinsLeukotrienes&EssentialFatty Acids,2017:S0952327817300212.2 Chouinard-WatkinsR,LacombeR,Bazinet

30、RP.Mechanisms regulating brain docosahexaenoicacid uptake:what is therecent evidence?J.CurrentOpinioninClinical Nutrition&Metabolic Care,2018:1.3Berger JH,Charron MJ,Silver D L,et al.Major Facilitator Superfamily Domain-ContainingProtein 2a(MFSD2A)Has Rolesin BodyGrowth,Motor Function,and Lipid Meta

31、bolismJ.PLoSONE,2012,7(11):e50629.脑健康营养素的优化HEALTHY AGINGHEALTHY AGINGC鱼油和胆碱联合摄入改善认知25鱼油和胆碱的联合摄入影响炎性因子、细胞凋亡和神经元营养因子等提高小鼠学习记忆能力鱼油和胆碱的联合摄入促进大脑中DHA转运鱼油和胆碱的联合摄入改善大脑中胆碱能神经系统HEALTHY AGINGC“智敏捷”-有关脑健康的临床验证FORTASYN CONNECT DESIGNED TO SUPPORT SYNAPSE FORMATION,PRESERVE MEMORY AND COGNITIONBRAIN BRAIN-NEUROPR

32、OTECTIONNEUROPROTECTIONPreserve brain integrity,cognition and memoryPreserve brain integrity,cognition and memory Memory loss is among the biggest concerns while aging NormalNormalagingagingbrainbrainfunctionfunctionpeakspeaksin 20in 20-30s 30s andanddeclinesdeclinesthroughoutthroughoutlifelife Nutr

33、iciahas proprietary engine,FortasynFortasynconnect connect that can be leveraged in HA Earlier intervention with Earlier intervention with SouvenaidSouvenaidbrings larger brings larger benefit benefit preserve memory and prevent brain preserve memory and prevent brain shrinkageshrinkage 15 publicati

34、ons on clinical studies with FC/15 publications on clinical studies with FC/SouvenaidSouvenaid Multimodal lifestyle intervention including Souvenaidongoing Strong IP portfolio 30 patentsStrong IP portfolio 30 patents0122436-0.6-0.4-0.20.00.2Tim e after baseline(m onths)Im provem en t0122436-45-30-15

35、0Tim e after baseline(m onths)Im provem en tAbilityAbilityto to processprocessinformation information andandmemory are memory are impactedimpactedbybynormalnormalagingagingEarlierEarlierinterventioninterventionwithwithSouvenaidSouvenaidbringsbringslargerlargerbenefitbenefitMemoryBrain volumeSouvenai

36、dSouvenaidcontains contains FortasynFortasynConnect Connect-a unique a unique combination of nutrients designed to support synapse combination of nutrients designed to support synapse formationformationTHE ENGINE THE ENGINE FORTASYN CONNECTFORTASYN CONNECTPROVEN EFFICACYPROVEN EFFICACYAGING IMPACTAG

37、ING IMPACTBrain volume Brain volume andandSynapseSynapsenumbernumberdeclinedeclinewithwithageage从食物到特殊医学用途营养品FROM DIET TO MEDICAL NUTRITION PRODUCTSFROMDESIGN THINKING TOEVIDENCE BASEDHEALTHY AGINGSLEEP DISORDER16 June,2023PRESENTATION TITLE IN CALIBRI BOLD2 MAJOR CATEGORIESDYSSOMNIA-Amount-Quality-

38、Timing PARASOMNIA-Abnormal Behavior During Sleephttps:/circadiansleepdisorders.org/info.php老年人的睡眠障碍LIFESTYLE AND SLEEP HYGIENE COUNSELLINGTREATMENT OF UNDERLYING MEDIAL CONDITION(IF ANY)Somatic Psychological Other sleep disorder NON PHARMACOLOGICAL TREATMENT Cognitive behavior therapy Chronotherapie

39、s(sleep restriction,light therapy)NIH(2005)NICE(2004/2007)ESTILVILL ET AL(2003)CLIN DRUG INVEST 23(6):351-385.*PHASE III.16 June,2023老年人睡眠管理需求PHARMACOTHERAPY GABA-erg(nonBZD)hyperarousal MT-erg(MLT-PR,tasimelteon*)CRZ-type Orexinerg(almorexant*)Certain antidepressives(off label in Europe)Tsuneki,H.,

40、Sasaoka,T.,&Sakurai,T.(2016).Sleep Control,GPCRs,and Glucose Metabolism.Trends in Endocrinology&Metabolism,27,633-642.HEALTHY AGING*仅供内部使用，如需对外使用，需通过内部POSM审核ORIENTAL COMBO FOR SLEEP1GABA,spine date seed2WESTERN COMBO FOR BRAIN3Imported fish oilMulti-vitaminsOnly for internal use,if need to communicate with consumers,need to go trough internal POSM audit.感谢聆听