***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND The order and magnitude of pathologic processes in Alzheimer 's disease are not well understood , partly because the disease develops over many years . Autosomal dominant Alzheimer 's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease . METHODS In this prospect i ve , longitudinal study , we analyzed data from 128 participants who underwent baseline clinical and cognitive assessment s , brain imaging , and cerebrospinal fluid ( CSF ) and blood tests .  We used the participant 's age at baseline assessment and the parent 's age at the onset of symptoms of Alzheimer 's disease to calculate the estimated years from expected symptom onset ( age of the participant minus parent 's age at symptom onset ) . We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes . RESULTS Concentrations of amyloid-beta (Aβ)(42 ) in the CSF appeared to decline 25 years before expected symptom onset . Aβ deposition , as measured by positron-emission tomography with the use of Pittsburgh compound B , was detected 15 years before expected symptom onset . Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset . Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset . Global cognitive impairment , as measured by the Mini-Mental State Examination and the Clinical Dementia Rating scale , was detected 5 years before expected symptom onset , and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset . CONCLUSIONS We found that autosomal dominant Alzheimer 's disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer 's disease , brain amyloid deposition , and brain metabolism as well as progressive cognitive impairment . Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer 's disease . ( Funded by the National Institute on Aging and others ; DIAN Clinical Trials.gov number , NCT00869817 . ) Background Studies examining whether genetic risk information about common , complex diseases can motivate individuals to improve health behaviors and advance planning have shown mixed results . Examining the influence of different study recruitment strategies may help reconcile inconsistencies . Methods Secondary analyses were conducted on data from the REVEAL study , a series of r and omized clinical trials examining the impact of genetic susceptibility testing for Alzheimer ’s disease ( AD ) . We tested whether  self-referred participants ( SRPs ) were more likely than  actively recruited participants ( ARPs ) to report health behavior and advance planning changes after AD risk and APOE genotype disclosure . Results Of 795 participants with known recruitment status , 546 ( 69 % ) were self-referred and 249 ( 31 % ) had been actively recruited . SRPs were younger , less likely to identify as African American , had higher household incomes , and were more attentive to AD than ARPs ( all P < 0.01 ) . They also dropped out of the study before genetic risk disclosure less frequently ( 26 % versus 41 % , P < 0.001 ) . Cohorts did not differ in their likelihood of reporting a change to at least one health behavior 6 weeks and 12 months after genetic risk disclosure , nor in intentions to change at least one behavior in the future . However , interaction effects were observed where ε4-positive SRPs were more likely than ε4-negative SRPs to report changes specifically to mental activities ( 38 % vs 19 % , p < 0.001 ) and diets ( 21 % vs 12 % , p = 0.016 ) six weeks post-disclosure , whereas differences between ε4-positive and ε4-negative ARPs were not evident for mental activities ( 15 % vs 21 % , p = 0.413 ) or diets ( 8 % versus 16 % , P = 0.190 ) . Similarly , ε4-positive participants were more likely than ε4-negative participants to report intentions to change long-term care insurance among SRPs ( 20 % vs 5 % , p < 0.001 ) , but not ARPs ( 5 % versus 9 % , P = 0.365 ) . Conclusions Individuals who proactively seek AD genetic risk assessment are more likely to undergo testing and use results to inform behavior changes than those who respond to genetic testing offers . These results demonstrate how the behavioral impact of genetic risk information may vary according to the models by which services are provided , and suggest that how participants are recruited into translational genomics research can influence findings .Trial registration Clinical Trials.gov NCT00089882 and BACKGROUND The apolipoprotein E ( APOE ) genotype provides information on the risk of Alzheimer 's disease , but the genotyping of patients and their family members has been discouraged . We examined the effect of genotype disclosure in a prospect i ve , r and omized , controlled trial . METHODS We r and omly assigned 162 asymptomatic adults who had a parent with Alzheimer 's disease to receive the results of their own APOE genotyping ( disclosure group ) or not to receive such results ( nondisclosure group ) . We measured symptoms of anxiety , depression , and test-related distress 6 weeks , 6 months , and 1 year after disclosure or nondisclosure . RESULTS There were no significant differences between the two groups in changes in time-averaged measures of anxiety ( 4.5 in the disclosure group and 4.4 in the nondisclosure group , P=0.84 ) , depression ( 8.8 and 8.7 , respectively ; P=0.98 ) , or test-related distress ( 6.9 and 7.5 , respectively ; P=0.61 ) . Secondary comparisons between the nondisclosure group and a disclosure subgroup of subjects carrying the APOE epsilon4 allele ( which is associated with increased risk ) also revealed no significant differences . However , the epsilon4-negative subgroup had a significantly lower level of test-related distress than did the epsilon4-positive subgroup ( P=0.01 ) . Subjects with clinical ly meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the epsilon4-positive and epsilon4-negative subgroups . Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures ( P<0.001 for both comparisons ) . CONCLUSIONS The disclosure of APOE genotyping results to adult children of patients with Alzheimer 's disease did not result in significant short-term psychological risks . Test-related distress was reduced among those who learned that they were APOE epsilon4-negative . Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure . ( Clinical Trials.gov number , NCT00571025 . Purpose : The REVEAL study is a r and omized , controlled study of the psychological and behavioral impact of APOE disclosure in a risk assessment protocol provided to first degree relatives of patients with Alzheimer ’s disease . The protocol presents risk information as cumulative incidence curves . This article describes how these curves were estimated . Methods : Curves were calculated using Bayes ’ rule to compute the posterior survival curves incorporating APOE information . Results : A combination of survival data from the MIRAGE study and gender- and age-specific APOE odds ratios were used to create risk curves for males and females within each of the 6 APOE genotypes . Conclusion : Utilizing comparative genotype relative risk information and survival data from family studies , estimates of gender- , age- , and genotype-specific risk can be generated for use in a risk assessment research study that features genotype disclosure Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more This study explored the extent to which recipients of genetic susceptibility testing for Alzheimer 's disease ( AD )  communicated their results to others . It also examined demographic characteristics , along with beliefs about AD , associated with such communication . Participants ( N = 271 ) in a r and omized clinical trial involving genetic testing for Apolipoprotein E ( APOE ) gene variants among first-degree relatives of AD patients reported their communication behaviors 6 weeks after the results disclosure . Information on beliefs about AD and genetic testing was collected at baseline . Eighty-two percent of participants receiving APOE genotype information shared their results with someone . Specifically , 64 % shared with family members , 51 % with spouse or significant others , 35 % with friends , and 12 % with health care professionals . Greater AD treatment optimism was associated with communicating results to family ( OR = 1.43 ) , spouse ( OR = 1.62 ) , friends ( OR = 1.81 ) , and health care professionals ( OR = 2.20 ) . Lower perceived risk ( OR = 0.98 ) and higher perceived importance of genetics in the development of AD ( OR = 1.93 ) were associated with results communication in general . Lower perceived drawbacks of AD genetic testing  was associated with results communication to friends ( OR = 0.65 ) . Beliefs about AD risks and causes , genetic testing , and development of treatments partly may determine the interpersonal communication patterns of genetic susceptibility test results & NA ; Advances in genetic research have provided a basis for susceptibility testing for Alzheimer disease ( AD ) . Prior surveys have examined attitudes toward genetic testing for AD in hypothetical scenarios , but it is unclear what reasons would motivate people to seek testing in real‐life situations . This study presents data from the first r and omized trial to evaluate genetic susceptibility testing for asymptomatic adult children of people with AD . We examined ( 1 ) reasons endorsed as motivations for seeking testing , ( 2 ) demographic characteristics associated with these reasons , and ( 3 ) how these reasons related to the eventual decision to pursue testing . Eligible participants were 206 adult children of people with AD ( mean age 53 years ; 72 % female ; 93 % white ) , 77.7 % of whom ( n = 160 ) went on to seek testing . Participants endorsed numerous reasons for seeking susceptibility testing ( mean 7.2 ) , encompassing a range of motivations . The most commonly endorsed reasons were as follows : ( 1 ) to contribute to research ( 93.9 % ) , ( 2 ) to arrange personal affairs ( 87.4 % ) , and ( 3 ) the hope that effective treatment will be developed ( 86.8 % ) . Women strongly endorsed more reasons for seeking testing than men ( p < 0.05 ) . The best predictor of actual pursuit of testing was strong endorsement of the need to prepare family members for AD ( odds ratio = 3.3 , p < 0.01 ) . Findings suggest that genetic susceptibility testing is of interest to individuals at risk for AD for a variety of reasons , even in the relative absence of available treatments Introduction Research is underway to develop an early medical test for Alzheimer 's disease ( AD ) . Methods To evaluate potential dem and for such a test , we conducted a cross-sectional telephone survey of 2,678 r and omly selected adults across the United States and four European countries . Results Most surveyed adults ( 67 % ) reported that they are " somewhat " or " very likely " to get an early medical test if one becomes available in the future . Interest was higher among those worried about developing AD , those with an immediate blood relative with AD , and those who have served as caregivers for AD patients . Older respondents and those living in Spain and Pol and also exhibited greater interest in testing . Knowing AD is a fatal condition did not influence dem and for testing , except among those with an immediate blood relative with the disease . Conclusions Potential dem and for early medical testing for AD could be high . A predictive test could not only advance medical research , it could transform political and legal l and scapes by creating a large constituency of asymptomatic , diagnosed adults CONTEXT Oxidative processes have been suggested as elements in the development of Alzheimer disease ( AD ) , but whether dietary intake of vitamin E and other antioxidant nutrients prevents its development is unknown . OBJECTIVE To examine whether intake of antioxidant nutrients , vitamin E , vitamin C , and beta carotene is associated with incident AD . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve study , conducted from 1993 to 2000 , of individuals selected in a stratified r and om sample of community-dwelling residents . The 815 residents 65 years and older were free of AD at baseline and were followed up for a mean of 3.9 years . They completed food frequency question naires an average of 1.7 years after baseline . MAIN OUTCOME MEASURE Incident AD diagnosed in clinical evaluations with st and ardized criteria . RESULTS Increasing vitamin E intake from foods was associated with decreased risk of developing AD after adjustment for age , education , sex , race , APOE epsilon 4 , and length of follow-up . Relative risks ( 95 % confidence intervals [ CIs ] ) from lowest to highest quintiles of intake were 1.00 , 0.71 ( 0.24 - 2.07 ) , 0.62 ( 0.26 - 1.45 ) , 0.71 ( 0.27 - 1.88 ) , and 0.30 ( 0.10 - 0.92 ) ( P for trend = .05 ) . The protective association of vitamin E was observed only among persons who were AP 
    Output:
    
In this group , disclosure of an increased risk was not associated with anxiety , depression or changes in perceived risk in relation to family history .
Disclosure of an increased risk did lead to an increase in specific test-related distress levels , health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning .
Conclusion In cognitively healthy research participants with a first-degree relative with AD , disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels , but does increase test-related distress and results in behavior changes concerning insurance and health .