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1、AD的危险因素与干预,运动锻炼与AD关系,目的：whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with AD.方式：An activity specific exercise program was compared to a walking program and to an attention control.评估方法：assessed using the subscale
2、s of the Acute Care Index of Function;functional mobility was measured using the 6-Minute Walk test.,The program was designed to be implemented 5 times per week by a nursing assistant or family member under the supervision of a physical therapist.this study suggest that walking programs may not be s
3、ufficient to improve mobility limitations in individuals who are dependent in transfers and support the benefit of a targeted,simple exercise program in reducing mobility limitations in institutionalized patients with moderate to severe cognitive impairment.-A Randomized Controlled Trial of an Activ
4、ity Specific Exercise Program for Individuals With Alzheimer Disease in Long-term Care Settings.J Geriatr Phys Ther 2011;34:50-56.,regular leisure exercise may decrease the risk of developing dementia in late-life-APOE 4 allele,cognitive dysfunction,and obstructive sleepapnea in children.Neurology.2
5、007;69(3):243-9.,Vascular Factors与AD,高血压:There is fairly robust evidence linking midlife hypertension to the development of dementia in later life.individuals with raised systolic blood pressure(160 mm Hg)at midlife had a significantly higher risk of AD later in life-Midlife vascular risk factors an
6、d Alzheimers disease in later life:longitudinal,population based study.Brit Med J.2001;322:1447-51.cerebrovascular atherosclerosis and increased burden ofsubcortical white matter lesions commonly found in AD.,卒中或TIA增加发生AD：The risk of developing AD,and not merely vascular dementia,is significantly in
7、creased in individuals with stroke or transient ischemic attacks-The role of cerebral ischemia in Alzheimers disease.Neurobiol Aging.2000;21:321-30.Cerebral hypoxia accruing from sleep apnea has been linked toAD-Midlife respiratory function and incidence of Alzheimers disease:A29-year longitudinal s
8、tudy in women.Neurobiol Aging.2007;28(3):343-50.,营养、饮食与AD,“Mediterranean”diet:The diet has recently been linked to a reduced risk oflate-life cognitive decline123,124,MCI,AD,and conversion from MCI to AD-Mediterranean diet and mild cognitive impairment.Arch Neurol.2009;66(2):216-25.Omega-3 fatty aci
9、ds:large observational studies support the notion that fish consumption,a major source of omega-3 fatty acids,may substantially diminish the risk of AD and other dementias-Donepezil and vitamin E in the treatment of mild cognitive impairment.N Engl J Med.2005;352:2379-88.Thiamine(Vitamin B1)：Thiamin
10、e deficiency has been linked to AD in some studies-Thiamine and Alzheimers disease:a pilot study.Arch Neurol.1988;45(8):833-5.,Coffee:Several studies have found that coffee consumption at midlife is associated with a decreased risk of dementia/AD later in life-Alzheimers disease and coffee:a quantit
11、ative review.Neurol Res.2007;29(1):91-5(5).Alcohol:consumption of moderate quantities of red wine(250-500 mL/day)was associated with a lower risk of AD(RR,0.53)and all-cause dementia(RR,0.56)-Nutritional factors and risk of incident dementia in the PAQUID longitudinal cohort.J Nutr Health Aging.2004
12、;8(3):150-4.,Vitamins C and E:Low blood levels of folic acid and increased plasma homocysteine have been posited as risk factors for the development of AD and dementia.The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowerin
13、g B vitamins.-Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment:a randomized controlled trial.PLoS One.2010 Sep 8;5(9):e12244.,Workplace/environmental exposures环境/工作场所暴露,Heavy Metals:Exposure to heavy metals has been associated with cognitiv
14、e deficits and AD.retained cumulative dose of iron resulting from previous environmental exposure was associated with lower test scores in seven cognitive domains.Some studies have linked aluminum exposure in drinking water to increased risk of AD104,though this topic remains controversial.-Aluminiu
15、m as a risk factor in Alzheimers disease,with emphasis on drinking water.Brain Res Bull.2001;55(2):187-96.Pesticides/herbicides:exposure to fumigants or defoliants significantly increased the incidence of AD-Risk factors for Alzheimers disease:a population-based,longitudinal study in Manitoba,Canada
16、.Int J Epidemiol.2001;30:590-7.,药物与AD,Nonsteroidal anti-inflammatory drugs(NSAIDs):there is currently insufficient evidence to recommend prescribing NSAIDs for the specific intention of reducing the risk of dementia or AD-Primary prevention of dementia.Alzheimers Dementia.2007;3(4):348-54.,社会因素与AD,S
17、ocial Stimulation:loneliness,defined as the feeling of being disconnected from others,may increase risk of late-life dementia and rates of cognitive decline in the elderly-Loneliness and risk of Alzheimer disease.Arch Gen Psychiatry.2007;64(2):234-40.AD 与婚姻状态关系：with never-married individuals shoulde
18、ring greater risk（患AD）-Marital status and risk of Alzheimers disease:a French population-based cohort study.Neurology.1999;53(9):1953-8.,精神因素与AD,Neuroticism,a.k.a.distress proneness,a measure of an individuals tendency to experience negative emotions suchas anxiety and anger,has been linked to exces
19、sive AD risk and accelerated cognitive decline-Proneness to psychological distress is associated with risk ofAlzheimers disease.Neurology.2003;61:1479-85.conscientiousness,a tendency toward self-discipline and goaldirection,may diminish the risk of AD,MCI and cognitivedecline-Conscientiousness and t
20、he incidence of Alzheimer disease andmild cognitive impairment.Arch Gen Psychiatry.2007;64(10):1204-12.higher levels of spirituality and private religious practices wereassociated with slower disease progression in patients withprobable Alzheimer dementia-Cognitive decline in Alzheimer disease:Impac
21、t of spirituality,religiosity,and QOL.Neurology.2007;68:1509-14.,Stress:Prolonged psychological stress has been associated with memory loss and hippocampal atrophy and may predispose to AD.Chronic stress engenders hypercortisolemia and augmented circulating and salivary cortisol levels have been rep
22、orted in sporadic AD.(ii)Depression:Several studies have shown an association between a history of depression and subsequent dementia,particularly AD.,Cognitive engagement认知锻炼与AD,Participation in cognitive exercises and leisure intellectual activities has been associated with a reduced risk of devel
23、oping AD.Cognitively stimulating leisure activities include reading,playing a musical instrument,doing crossword puzzles,writing for pleasure,etc-Leisure activities and the risk of dementia in the elderly.N Engl J Med.2003;348(25):2508-16.-Influence of leisure activity on the incidence of Alzheimers
24、 disease.Neurology.2001;57(12):2236-42.participating in mentally stimulating leisure activities was associated with an overall risk reduction of 50%for dementia(OR 0.50,95%CI,0.420.61).,leisure activities休闲活动与痴呆,Among leisure activities,reading,playing board games,playing musical instruments,and dan
25、cing were associated with a reduced risk of dementia.-Verghese J1,Lipton RB,Katz MJ,Hall CB,Leisure activities and the risk of dementia in the elderly.N Engl J Med.2003 Jun 19;348(25):2508-16.,身体锻炼与AD,Previous work has suggested that PA may reduce risk of developing AD.PA does not seem to be associa
26、ted with rapidity of cognitive change,but it seems to relate to prolongation of survival of patients with AD.,Education与AD,Years of formal education exert a fairly strong and reproducible impact on AD incidence-Influence of education and occupation on the incidence of Alzheimers disease.J Am Med Ass
27、oc.1994;271(13):1004-10.education years are often significantly lower in the AD groups than cognitively-normal individuals。,The delineation of risk factors for the development of AD offers hope for the advent of effective prevention or interventions that might retard the onset of symptoms.Although s
28、ome risk factors are heritable and largely beyond our control,others are determined by lifestyle or environment and are potentially modifiable.-,营养因素与AD,营养是AD的保护性因素Nutrition seems to be one of the factors that may play a protective role in Alzheimer disease.Several studies have shown the existence o
29、f a correlation between cognitive skills and the serum concentrations of folate,vitamin B-12,vitamin B-6,and,more recently,homocysteine.nutritional factors have to be studied not alone but with the other factors related to Alzheimer disease:genetics,estrogen,antiinflammatory drug use,and socioeconom
30、ic variables.Alzheimer disease:protective factors.Am J Clin Nutr.2000V71N2:643S-649S,吸烟与AD,If smoking is a risk factor for Alzheimer disease(AD)but a smoker dies of another cause before developing or manifesting AD,smoking-related mortality may mask the relationship between smoking and AD.Further,ag
31、e-specific mortality rates are higher in smokers because they die earlier than nonsmokers.if we fail to take into account the competing risk of death when we estimate the effect of smoking on AD,we bias the results and are in fact only comparing the incidence of AD in nonsmokers with that in the hea
32、lthiest smokers.-Smoking,death,and Alzheimer disease:a case of competing risks.Alzheimer Dis Assoc Disord.2012V26N4:300-6,吸烟增加痴呆和AD风险：Prospective population-based cohort study in 6,868 participants,After a mean follow-up time of 7.1 years,current smoking at baseline was associated with an increased
33、risk of dementia(HR 1.47)and AD(HR 1.56).Current smoking increases the risk of dementia（AD and vascular dementia(VaD)）.This effect is more pronounced in persons without the APOEepsilon4 allele than APOEepsilon4 carriers.-Relation between smoking and risk of dementia and Alzheimer disease:the Rotterd
34、am Study.Neurology.2007V69N10:998-1005,脑白质病变与AD,Increased white matter hyperintensities（WMHs）are associated with aging,decreased glucose metabolism,and decline in executive function but do not affect AD-specific pathologic progression,suggesting that the vascular contribution to dementia is probably
35、 additive although not necessarily independent of the amyloid pathway.-,The present study sought to determine if subgroups of bereaved AD caregivers follow distinctive depressive symptom trajectories and the characteristics associated with membership in depressive symptom subgroups.The Center for Ep
36、idemiologic Studies Depression Scale assessed depressive symptoms among the AD caregivers at baseline and three follow-up visits.Three postloss depressive symptom trajectories emerged:persistently syndromal depression(N=30,16.5%);syndromal-becoming-threshold level depression(N=62,34.0%);and persiste
37、ntly absent depression(N=90,49.5%).Depressive symptom trajectories and associated risks among bereaved Alzheimer disease caregivers.Am J Geriatr Psychiatry.2008V16N2:145-55,环境因素与AD,Several environmental factors contribute significantly to risk of PD and AD.Some may already be active in the early sta
38、ges of life,and some may interact with other genetic factors.Evidence consistently suggests that a higher risk of AD is associated with pesticides,hypertension and high cholesterol levels in middle age,hyperhomocysteinaemia,smoking,traumatic brain injury and depression.,Weak evidence also suggests t
39、hat a higher risk of AD is associated with high 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.a lower risk of AD is associated with moderate a
40、lcohol consumption,physical exercise,perimenopausal hormone replacement therapy and good cognitive reserve.Weak evidence suggests that lower risk of AD is associated with the Mediterranean diet,coffee and habitual NSAID consumption Parkinson disease and Alzheimer disease:environmental risk factors.N
41、eurologia.2012VN.,饮食与AD,高糖饮食影响认知，促进神经退行性疾病发生（如AD）high-sugar diets can lead to cognitive impairment predisposing to neurodegenerative disorders such as Alzheimers disease.metabolic derangements induced by high-fructose/sucrose diets and presents evidence for the involvement of insulin resistance in s
42、poradic Alzheimers disease pathogenesis.Accumulating evidence has also demonstrated a connection between T2D and Alzheimers disease.The risk for developing T2D and Alzheimers disease increases exponentially with age and having T2D increases the risk of developing Alzheimers disease.-High-sugar diets
43、,type 2 diabetes and Alzheimers disease.Curr Opin Clin Nutr Metab Care.2013V16N4:440-5,饮食改变显著减少2型DM和AD风险The incidence of T2D increased dramatically over the last decades mainly due to Western lifestyle factors such as lack of exercise and high calorie diets.To aggravate this scenario,it has been con
44、sistently shown that T2D is a risk factor for Alzheimers disease and both disorders share similar demographic profiles,risk factors,and clinical and biochemical features(e.g.insulin resistance).dietary changes can significantly reduce the risk of T2D and Alzheimers disease and thereby increase the q
45、uality of life and improve longevity.-High-sugar diets,type 2 diabetes and Alzheimers disease.Curr Opin Clin Nutr Metab Care.2013V16N4:440-5,INSULIN RESISTANCE:A LINK BETWEEN TYPE 2 DIABETES AND ALZHEIMERS DISEASE,metabolic derangements induced by high-fructose/sucrose diets and presents evidence fo
46、r the involvement of insulin resistance in sporadic Alzheimers disease pathogenesis.,Studies of cerebral structure demonstrateda pronounced cortical,subcortical,and hippocampal atrophy in T2D patients.Accumulating evidence also shows that T2D is a risk factor for dementia,particularly vascular demen
47、tia andAlzheimers disease.-High-sugar diets,type 2 diabetes and AlzheimersDisease.Volume 16 Number 00 Month 2013,Accumulating evidence supports the involvement of impaired insulin signaling in Alzheimers disease etiopathogenesis:reduced insulin levels and insulin receptor expression were observed in
48、 Alzheimers disease brains,increasing Alzheimersdisease Braak stage was associated with progressivelyreduced expression levels of insulin,insulin growthfactor(IGF)1 and 2 and respective receptors,Alzheimersdisease patients show increased fastingplasma insulin levels,decreased cerebrospinal fluid(CSF
49、)insulin levels,and/or decreased CSF/plasmainsulin ratio,apart from increased amyloid b levels,which suggest a decrease in insulin clearance thatmay provoke an elevation of plasma amyloid blevels,disruption of brain insulin signaling by theintracerebroventricular administration of the diabetogenicdr
50、ug streptozotocin(STZ)leads to the developmentof numerous behavioral,职业暴露与AD,most of studies(nine case-control and five cohort studies)obtained quantitative estimates of exposure.Pooled estimates suggest an increased risk of AD from case-control studies(OR(pooled)2.03;95%CI 1.38-3.00)and from cohort
