***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 Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events .  Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure . METHODS In the Cardiovascular Health Study , 5888 adults 65 years and older were recruited from 4 US centers . At baseline in 1989 - 1990 , participants underwent an extensive examination , and all subsequent cardiovascular events were ascertained and classified . RESULTS At baseline , 1961 men and 2941 women were at risk for an incident myocardial infa rct ion or stroke . During follow-up that averaged 6.7 years , 572 subjects had a coronary event , 385 had a stroke , and 896 died . After adjustment for potential confounders , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and pulse pressure were directly associated with the risk of incident myocardial infa rct ion and stroke . Only SBP was associated with total mortality . Importantly , SBP was a better predictor of cardiovascular events than DBP or pulse pressure . In the adjusted model for myocardial infa rct ion , a 1-SD change in SBP , DBP , and pulse pressure was associated with hazard ratios ( 95 % confidence intervals ) of 1.24 ( 1.15 - 1.35 ) , 1.13 ( 1.04 - 1.22 ) , and 1.21 ( 1.12 - 1.31 ) , respectively ; and adding pulse pressure or DBP to the model did not improve the fit . For stroke , the hazard ratios ( 95 % confidence intervals ) were 1.34 ( 1.21 - 1.47 ) with SBP , 1.29 ( 1.17 - 1.42 ) with DBP , and 1.21 ( 1.10 - 1.34 ) with pulse pressure . The association between blood pressure level and cardiovascular disease risk was generally linear ; specifically , there was no evidence of a J-shaped relationship . In those with treated hypertension , the hazard ratios for the association of SBP with the risks for myocardial infa rct ion and stroke were less pronounced than in those without treated hypertension . CONCLUSION In this population -based study of older adults , although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events , SBP was the best single predictor of cardiovascular events Midlife hypertension is associated with later development of cognitive impairment , vascular dementia ( VsD ) , and possibly Alzheimer 's disease ( AD ) . Neuropathic cerebrovascular lesions and brain atrophy have been associated with elevated blood pressure ( BP ) , however , to our knowledge there have been no prospect i ve investigations of an association of blood pressure levels measured in midlife with the microscopic lesions of AD . We investigated the relationship of  BP level in midlife to development of neurofibrillary tangles ( NFT ) , neuritic plaques ( NP ) , and low brain weight at autopsy among Japanese-American men who were members of the Honolulu Heart Program/Honolulu-Asia aging Study ( HHP/HAAS ) cohort . The HHP/HAAS is a population -based , longitudinal study of cognitive function and dementia with 36 years of follow-up . Neocortical and hippocampal NFT and NP were counted per mm(2 ) , and fixed brain weight was measured for 243 decedents . Elevated systolic BP , ( > or = 160 mm Hg ) in midlife was associated with low brain weight and greater numbers of NP in both neocortex and hippocampus . Diastolic BP elevation , ( > or = 95 mm Hg ) was associated with greater numbers of NFT in hippocampus . Results indicate that in addition to the accepted association of high BP with neuropathic cerebrovascular lesions , there is a direct relationship with brain atrophy , NP and NFT We consider the problem of separating the direct effects of an exposure from effects relayed through an intermediate variable ( indirect effects ) . We show that adjustment for the intermediate variable , which is the most common method of estimating direct effects , can be biased . We also show that , even in a r and omized crossover trial of exposure , direct and indirect effects can not be separated without special assumptions ; in other words , direct and indirect effects are not separately identifiable when only exposure is r and omized . If the exposure and intermediate never interact to cause disease and if intermediate effects can be controlled , that is , blocked by a suitable intervention , then a trial r and omizing both exposure and the intervention can separate direct from indirect effects . Nonetheless , the estimation must be carried out using the G-computation algorithm . Conventional adjustment methods remain biased . When exposure and the intermediate interact to cause disease , direct and indirect effects will not be separable even in a trial in which both the exposure and the intervention blocking intermediate effects are r and omly assigned . Nonetheless , in such a trial , one can still estimate the fraction of exposure-induced disease that could be prevented by control of the intermediate . Even in the absence of an intervention blocking the intermediate effect , the fraction of exposure-induced disease that could be prevented by control of the intermediate can be estimated with the G-computation algorithm if data are obtained on additional confounding variables . ( Epidemiology 1992;3:143–155 BACKGROUND Alzheimer disease ( AD ) is considered a leading cause of death , but few studies have examined the contribution of AD to mortality based on follow-up of representative US cohorts . OBJECTIVE To examine mortality rates , duration of survival , causes of death , and the contribution of AD  to the risk of mortality in an aging community-based cohort , controlling for other predictors . DESIGN Fifteen-year prospect i ve epidemiological study . Mortality rates per 1000 person-years and the population -attributable risk of mortality were determined . Cox proportional hazards models were used to estimate relative risk of mortality due to AD , adjusting for relevant covariates . Death certificates were abstract ed for listed causes of death . SETTING A largely blue-collar rural community in southwestern Pennsylvania . PARTICIPANTS A community-based cohort of 1670 adults 65 years and older at study enrollment . MAIN OUTCOME MEASURE Mortality . RESULTS In the overall cohort , AD was a significant predictor of mortality , with a hazard ratio of 1.4 after adjusting for covariates . The population -attributable risk of mortality from AD was 4.9 % based on the same model . Examining the sexes separately , AD increased mortality risk only among women . Death certificates of AD subjects were more likely to list dementia/AD , other brain disorders , pneumonia , and dehydration , and less likely to include cancer . CONCLUSIONS Alzheimer disease was responsible for 4.9 % of the deaths in this elderly cohort . Alzheimer disease increased the risk of mortality 40 % in the cohort as a whole and separately in women but not in men . The mean ( SD ) duration of survival with AD was 5.9 ( 3.7 ) years , and longer with earlier age at onset The reproducibility of ambulatory , home , and clinic blood pressures  was compared in 13 untreated mildly hypertensive and 14 normotensive subjects . Each subject had two sets of daily ambulatory recordings , home self-measured readings ( over 6 days ) , and clinic measurements taken 2 weeks apart . Comparisons over the 2 weeks within and among the methods of measurements were made using a repeated- measures analysis of variance . The results showed that there was no consistent average change in the ambulatory or home pressures and no change in clinic diastolic pressures , but the clinic systolic pressure of the hypertensive subjects dropped 6 mm Hg ( p less than 0.05 ) , while that of the normotensive subjects showed no significant change . Test-retest correlations of each of the three methods were similar in magnitude , indicating a similar level of reliability . Test-retest correlations of the ambulatory st and ard deviations , however , were low , indicating a low reliability of this measure of daily pressure variability . These results suggest that the reproducibility of ambulatory pressures may be as good or better than that of home or clinic measurements . They also suggest that the average ambulatory pressure may be preferable as the measurement in clinical trials , since it may be less influenced by measurement anxiety , particularly in hypertensive subjects A prospect i ve analysis of risk factors for Alzheimer 's disease was a major objective of the Canadian Study of Health and Aging , a nationwide , population -based study . Of 6,434 eligible subjects aged 65 years or older in 1991 , 4,615 were alive in 1996 and participated in the follow-up study . All participants were cognitively normal in 1991 when they completed a risk factor question naire . Their cognitive status was reassessed 5 years later by using a similar two-phase procedure , including a screening interview , followed by a clinical examination when indicated . The analysis included 194 Alzheimer 's disease cases and 3,894 cognitively normal controls . Increasing age , fewer years of education , and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer 's disease . Use of nonsteroidal anti-inflammatory drugs  ,  wine consumption , coffee consumption  , and  regular physical activity  were associated with a reduced risk of Alzheimer 's disease . No statistically significant association was found for family history of dementia , sex , history of depression , estrogen replacement therapy , head trauma , antiperspirant or antacid use , smoking , high blood pressure , heart disease , or stroke . The protective associations warrant further study . In particular , regular physical activity could be an important component of a preventive strategy against Alzheimer 's disease and many other conditions BACKGROUND It is uncertain whether high blood pressure increases the risk of developing Alzheimer disease ( AD ) . OBJECTIVE To examine the association between incident AD and  blood pressure  measured up to 13 years before diagnosis . DESIGN Longitudinal cohort study conducted from 1982 to 1988 , with blood pressure measured every 3 years in home interviews , and in 1973 for a portion ( 60 % ) of the sample . SETTING Community of East Boston , Mass. PARTICIPANTS Six hundred thirty-four subjects 65 years or older and without AD were selected as a stratified r and om sample of participants of the East Boston Established Population s for Epidemiologic Studies of the Elderly . MAIN OUTCOME MEASURE Alzheimer disease was diagnosed by a neurologist using a structured clinical evaluation . RESULTS High blood pressure was not associated with an increased risk of AD in logistic regression models adjusted for age , sex , and level of education . There was no association with systolic pressure measured 13 years before diagnosis ( odds ratio = 1.03/10 mm Hg ; 95 % confidence interval , 0.80 - 1.32 ) and an inverse association with systolic pressure measured 4 years before diagnosis ( odds ratio = 0.82/10 mm Hg ; 95 % confidence interval , 0.72 - 0.95 ) . Associations for diastolic pressure were in the same direction as those for systolic pressure except with wider confidence intervals . The odds ratios were not material ly different with further adjustment for cardiovascular risk factors and diseases . CONCLUSION In this large community study , high blood pressure was not associated with an increased risk of AD Cerebral small-vessel disease is common in older people and may contribute to the development of dementia . The objective of the present study was to evaluate the relationship between measures of cerebral small-vessel disease on MRI and the rate of decline in specific cognitive domains in participants from the prospect i ve , population -based Rotterdam Scan Study . Participants were 60 - 90 years of age and free from dementia at baseline in 1995 - 1996 .  White matter lesions ( WML ) , cerebral infa rcts and generalized brain atrophy were assessed on the baseline MRI . We performed  neuropsychological testing at baseline and repeatedly in 1999 - 2000 and in 2001 - 2003 . We used r and om-effects models for repeated measures to examine the association between quantitative MRI measures and rate of decline in measures of global cognitive function , information processing speed , executive function and memory . There were a total of 2266 assessment s for the 832 participants in the study , with an average time from the initial to last assessment of 5.2 years . Increasing severity of periventricular WML and generalized brain atrophy and the presence of brain infa rcts on MRI were associated with a steeper decline in cognitive function . These structural brain changes were specifically associated with decline in information processing speed and executive function . The associations between MRI measures of cerebral small-vessel disease and cognitive decline did not change after additional adjustment for vascular risk factors or depressed mood . After exclusion of participants with an incident stroke , some of the associations of periventricular WML , brain infa rcts and generalized brain atrophy with measures of information processing speed and executive function were no longer significant . This may indicate that stroke plays an intermediate role in the relationship between cerebral small-vessel disease and cognitive decline . Our results suggest that in older people cerebral small-vessel disease may contribute to cognitive decline by affecting information processing speed and executive function OBJECTIVES To assess variation in the association between blood pressure ( BP ) and risk for dementia across a spectrum of older ages and to examine BP changes before dementia onset . DESIGN Prospect i ve cohort study . SETTING A large health maintenance organization in Seattle , Washington . PARTICIPANTS A cohort of 2,356 members of a large health maintenance organization aged 65 and older who were initially without dementia . MEASUREMENTS 
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We were unable to compute summary estimates for the association between categories of systolic or diastolic BP and Alzheimer disease ; however , there did not appear to be a consistent pattern across studies .
After stratifying on age at BP assessment , we found a suggestion of an inverse association between late-life hypertension and Alzheimer disease and a suggestion of an adverse association between midlife diastolic hypertension and Alzheimer disease .
Based on existing epidemiologic research , we can not determine whether there is a causal association between BP and Alzheimer disease .
Selection bias and reverse causation may account for the suggested inverse association between late-life hypertension on Alzheimer disease , but , given the expected direction of these biases , they are less likely to account for the suggestion that midlife hypertension increases risk .