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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 subsca
2、les 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
3、be sufficient 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
4、Activity 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 sleep apnea in children. Ne
5、urology. 2007;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 r
6、isk factors and Alzheimers disease in later life: longitudinal, population based study. Brit Med J. 2001;322:1447-51. cerebrovascular atherosclerosis and increased burden of subcortical 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 dement
7、ia, is significantly increased 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 diseas
8、e:A29-year longitudinal study 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 of late-life cognitive decline123,124, MCI, AD, and conversion from MCI to AD-Mediterranean diet and mild cognitive impairment. Arch Neurol.
9、2009;66(2):216-25. Omega-3 fatty acids: 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
10、;352:2379-88. Thiamine (Vitamin B1)： Thiamine 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 late
11、r in life-Alzheimers disease and coffee: a quantitative 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 dement
12、ia in the PAQUID longitudinal cohort. J Nutr Health Aging. 2004;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 cognitiv
13、e impairment can be slowed by treatment with homocysteine-lowering 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,H
14、eavy Metals: Exposure to heavy metals has been associated with cognitive 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
15、increased risk of AD104, though this topic remains controversial.-Aluminium 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
16、for Alzheimers disease: a population-based, longitudinal study in Manitoba, Canada. 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 dementi
17、a or AD-Primary prevention of dementia. Alzheimers Dementia. 2007;3(4):348-54.,社会因素与AD,Social 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 dise
18、ase. Arch Gen Psychiatry. 2007;64(2):234-40. AD 与婚姻状态关系： with never-married individuals shouldering 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 in
19、dividuals tendency to experience negative emotions such as anxiety and anger, has been linked to excessive 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
20、-discipline and goaldirection, may diminish the risk of AD, MCI and cognitive decline-Conscientiousness and the incidence of Alzheimer disease and mild cognitive impairment. Arch Gen Psychiatry. 2007;64(10):1204-12. higher levels of spirituality and private religious practices were associated with s
21、lower disease progression in patients with probable Alzheimer dementia-Cognitive decline in Alzheimer disease: Impact 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 predispo
22、se to AD. Chronic stress engenders hypercortisolemia and augmented circulating and salivary cortisol levels have been reported 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
23、与AD,Participation in cognitive exercises and leisure intellectual activities has been associated with a reduced risk of developing AD. Cognitively stimulating leisure activities include reading, playing a musical instrument,doing crossword puzzles, writing for pleasure, etc-Leisure activities and th
24、e risk of dementia in the elderly. N Engl J Med.2003;348(25):2508-16.-Influence of leisure activity on the incidence of Alzheimers 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.
25、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 dancing 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
26、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 associated 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 e
27、xert a fairly strong and reproducible impact on AD incidence-Influence of education and occupation on the incidence of Alzheimers disease. J Am Med Assoc. 1994;271(13):1004-10. education years are often significantly lower in the AD groups than cognitively-normal individuals。,The delineation of risk
28、 factors for the development of AD offers hope for the advent of effective prevention or interventions that might retard the onset of symptoms. Although some risk factors are heritable and largely beyond our control, others are determined by lifestyle or environment and are potentially modifiable. -
29、,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 of a correlation between cognitive skills and the serum concentrations of folate, vitamin B-12, vitamin B-6, and, more recently, homocysteine.
30、nutritional factors have to be studied not alone but with the other factors related to Alzheimer disease: genetics, estrogen, antiinflammatory drug use, and socioeconomic variables. Alzheimer disease: protective factors. Am J Clin Nutr.2000V71N2 :643S-649S,吸烟与AD,If smoking is a risk factor for Alzhe
31、imer 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, age- specific mortality rates are higher in smokers because they die earlier than nonsmokers. if we fail to take into account
32、 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 healthiest smokers. -Smoking, death, and Alzheimer disease: a case of competing risks. Alzheimer Dis Assoc Disord.2012V26N4
33、 :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 risk of dementia (HR 1.47) and AD (HR 1.56). Current smoking increases the risk of dementia（AD and vascular dem
34、entia (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 Rotterdam Study. Neurology.2007V69N10 :998-1005,脑白质病变与AD,Increased white matter hyperintensities （WMHs） are ass
35、ociated 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 additive although not necessarily independent of the amyloid pathway. -,The present study sought
36、 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 Epidemiologic Studies Depression Scale assessed depressive symptoms among the AD caregivers at ba
37、seline 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 persistently absent depression (N = 90, 49.5%). Depressive symptom trajectories and associ
38、ated 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 stages of life, and some may interact with other genetic factors. Evidence co
39、nsistently 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 that a higher risk of AD is associated with high aluminium intake thr
40、ough 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 alcohol consumption, physical exercise, perimenopausal hormone r
41、eplacement 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. Neurologia.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-s
42、ugar 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 sporadic Alzheimers disease pathogenesis. Accumulating
43、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, type 2 diabetes and Alzheimers disease. Curr Opin
44、 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 consistently shown that T2D is a risk factor fo
45、r 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 quality of life and improve longevity. -
46、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 for the involvement of insulin resis
47、tance in sporadic Alzheimers disease pathogenesis.,Studies of cerebral structure demonstrated a pronounced cortical, subcortical, and hippocampal atrophy in T2D patients. Accumulating evidence also shows that T2D is a risk factor for dementia, particularly vascular dementia and Alzheimers disease.-H
48、igh-sugar diets, type 2 diabetes and Alzheimers Disease. 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 Alzheimers disease brai
49、ns, increasing Alzheimers disease Braak stage was associated with progressively reduced expression levels of insulin, insulin growth factor (IGF) 1 and 2 and respective receptors, Alzheimers disease patients show increased fasting plasma insulin levels, decreased cerebrospinal fluid (CSF) insulin levels, and/or decreased CSF/plasma insulin ratio, apart from increased amyloid b levels, which suggest a decrease in insulin clearance that may provoke an elevation of plasma amyloid b levels, disruption of