***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: Growing epidemiological evidence suggests that premorbid participation in cognitive leisure activities ( CLA ) reduces the risk of dementia by increasing cognitive reserve . We investigated the differential effect of CLA , education , and socioeconomic status ( SES ) on the development of mild cognitive impairment ( MCI ) and Alzheimer 's disease ( AD ) . Participants in the prospect i ve population -based ILSE study ( * 1930 - 1932 ; 12-year follow-up ) were examined in three examination waves ( t1:1993/94 ; t2:1997/98 ; t3:2005/07 ) . In total , 381 subjects of the original cohort ( n=500 ) were re-examined at t3 . Of these subjects 29 % received the diagnosis of MCI and 7 % of AD . Subjects participated in a thorough psychogeriatric examination and neuropsychological testing . Moreover , they took part in a detailed autobiographical interview and completed question naires including socio-demographic data and current frequency of participation in CLA . Subjects who were highly cognitively active at t1 had a significantly reduced risk of developing MCI/AD at t3 ( scores adjusted for education , SES , gender , and depressive symptoms ) . Additionally , high education and high SES separately reduced the risk of MCI and AD . Our results confirm the hypothesis that a high level of CLA acts as a protective factor against the development of MCI and AD by increasing cognitive reserve . This effect is not accounted for by important potential confounders BACKGROUND Dietary n-3 polyunsaturated fatty acids improve brain functioning in animal studies , but there is limited study of whether this type of fat protects against Alzheimer disease . OBJECTIVE To examine whether fish consumption and intake of different types of n-3 fatty acids protect against Alzheimer disease . DESIGN Prospect i ve study conducted from 1993 through 2000 , of a stratified r and om sample from a geographically defined community . Participants were followed up for an average of 3.9 years for the development of Alzheimer disease . PATIENTS A total of 815 residents , aged 65 to 94 years , who were initially unaffected by Alzheimer disease and completed a dietary question naire on average 2.3 years before clinical evaluation of incident disease . MAIN OUTCOME MEASURES Incident Alzheimer disease diagnosed in a structured neurologic examination by means of st and ardized criteria . RESULTS A total of 131 sample participants developed Alzheimer disease . Participants who consumed fish once per week or more had 60 % less risk of Alzheimer disease compared with those who rarely or never ate fish ( relative risk , 0.4 ; 95 % confidence interval , 0.2 - 0.9 ) in a model adjusted for age and other risk factors . Total intake of n-3 polyunsaturated fatty acids was associated with reduced risk of Alzheimer disease , as was intake of docosahexaenoic acid ( 22:6n-3 ) . Eicosapentaenoic acid ( 20:5n-3 ) was not associated with Alzheimer disease . The associations remained unchanged with additional adjustment for intakes of other dietary fats and of vitamin E and for cardiovascular conditions . CONCLUSION Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease Aim : To eluci date the effect of midlife  smoking on the risk of  dementia and Alzheimer ’s disease ( AD )  , and the possible modification of this relation by the apolipoprotein E ( APOE ) Ε4 . Methods : Participants of the Cardiovascular Risk Factors , Aging and Dementia study were r and omly selected from population -based sample s originally studied in midlife ( 1972 , 1977 , 1982 or 1988 ) . After an average follow-up of 21 years , 1,449 persons ( 73 % ) aged 65–79 years took part in a reexamination in 1998 . Results : Smoking in midlife increased the risk of dementia ( odds ratio , OR : 4.93 ; 95 % CI : 1.51–16.11 ) and AD ( OR : 6.56 ; 95 % CI : 1.80–23.94 ) among the APOE Ε4 carriers , but not among the APOE Ε4 noncarriers . Conclusion : Midlife smoking was associated with an increased risk of dementia and AD later in life only among those individuals carrying the APOE Ε4 allele . These results suggest that the association between smoking and AD may be complex and vary according to genotype Finnish  Geriatric Intervention Study to Prevent Cognitive Impairment and Disability ( FINGER ) is a multi‐center , r and omized , controlled trial ongoing in Finl and To evaluate the predictive effects of subjective measures of physical activity ( PA ) and objective measures of physical fitness ( PF ) on dementia risk , Participants of the prospect i ve population -based ILSE- study ( * 1930 - 1932 ; 12-year follow-up ) were examined at three examination waves ( t1 : 1993/94 ; t2 : 1997/98 ; t3 : 2005/07 ) . 381 subjects of the original cohort ( n = 500 ) were re-examined at t3 . 29 % of the subjects who were cognitively healthy at baseline received the diagnosis of mild cognitive impairment ( MCI ) and 7 % of Alzheimer 's disease ( AD ) . Subjects were screened for physical and mental health using medical interviews , physical , and neuropsychological examinations . Participants completed a question naire on their current and past PA at t1 . Subjects were classified as physically active if they reported a regular sport activity for at least 2 hours per week in the past year . Muscular strength ( h and grip ) and motor coordination ( balance ) served as objective indicators of PF . Subjects who passed the balance-test at t1 had a reduced risk of developing MCI/AD at t3 ( OR = 0.35 , 95%CI 0.19 - 0.66 , p < 0.01 ) and performed significantly better on various neuropsychological measures . Muscular strength or subjective reports of PA did not predict MCI/AD development . Our results confirm the hypothesis that PF acts as a protective factor for the development of cognitive disorders . In our study , context , motor coordination served as a better predictor than muscular strength or self-rated PA . Since subjects with cognitive disorders due to cerebral and /or systemic disorders were excluded from the analyses , our findings suggest that the effect of skill-related PF extends beyond the reduction of cardiovascular risk factors Background Plasma concentrations of C-reactive protein ( CRP ) , a marker of chronic inflammation , have been associated with cognitive impairment in old age . However , it is unknown whether CRP is causally linked to cognitive decline . Methods and Findings Within the Prospect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) trial , with 5680 participants with a mean age of 75 years , we examined associations of CRP levels and its genetic determinants with cognitive performance and decline over 3.2 years mean follow-up . Higher plasma CRP concentrations were associated with poorer baseline performance on the Stroop test ( P = 0.001 ) and Letter Digit Tests ( P<0.001 ) , but not with the immediate and delayed Picture Learning Test ( PLT ; both P>0.5 ) . In the prospect i ve analyses , higher CRP concentrations associated with increased rate of decline in the immediate PLT ( P = 0.016 ) , but not in other cognitive tests ( all p>0.11 ) . Adjustment for prevalent cardiovascular risk factors and disease did not change the baseline associations nor associations with cognitive decline during follow-up . Four haplotypes of CRP were used and , compared to the common haplotype , carrierships associated strongly with levels of CRP ( all P<0.007 ) . In comparison to strong associations of apolipoprotein E with cognitive measures , associations of CRP haplotypes with such measures were inconsistent . Conclusion Plasma CRP concentrations associate with cognitive performance in part through pathways independent of ( risk factors for ) cardiovascular disease . However , lifelong exposure to higher CRP levels does not associate with poorer cognitive performance in old age . The current data weaken the argument for a causal role of CRP in cognitive performance , but further study is warranted to draw definitive conclusions OBJECTIVES To assess the relationship between body mass index ( BMI ) and waist-hip ratio ( WHR ) and the clinical end points of cognitive impairment and probable dementia in a cohort of older women enrolled in the Women 's Health Initiative Memory Study ( WHIMS ) . DESIGN Prospect i ve , r and omized clinical trial of hormone therapies with annual cognitive assessment s and anthropometrics . SETTING Fourteen U.S. clinical sites of the WHIMS . PARTICIPANTS Seven thous and one hundred sixty-three postmenopausal women aged 65 to 80 without dementia . MEASUREMENTS Annual cognitive  assessment s , average follow-up of 4.4 years , including classification of incident cognitive impairment and probable dementia . Height , weight , waist , and hip measurements were assessed at baseline , and a waist-hip ratio ( WHR ) of 0.8 or greater was used as a marker of central adiposity . RESULTS There were statistically significant interactions between BMI and WHR and incident cognitive impairment and probable dementia with and without adjustment for a panel of cognitive risk factors . Women with a WHR of 0.80 or greater with a BMI of 20.0 to 24.9 kg/m² had a greater risk of cognitive impairment and probable dementia than more-obese women or women with a WHR less than 0.80 , although women with a WHR less than 0.80 and a BMI of 20.0 to 24.9 kg/m² had poorer scores on cognitive assessment s. CONCLUSION WHR affects the relationship between BMI and risk of cognitive impairment and probable dementia in older women . Underweight women ( BMI < 20.0 kg/m² ) with a WHR less than 0.80 had a greater risk than those with higher BMI s. In normal-weight to obese women ( 20.0 - 29.9 kg/m² , central adiposity ( WHR ≥ 0.80 ) is associated with greater risk of cognitive impairment and probable dementia than in women with higher BMI . These data suggest that central adiposity as a risk factor for cognitive impairment and probable dementia in normal-weight women BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI  cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the  Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test .  Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions Objective : A history of depression has been linked to an increased dementia risk . This risk may be particularly high in recurrent depression due to repeated brain insult . We investigated whether there is a dose-dependent relationship between the number of episodes of elevated depressive symptoms ( EDS ) and the risk for  mild cognitive impairment ( MCI ) and dementia . Methods : A total of 1,239 older adults from the Baltimore Longitudinal Study of Aging were followed for a median of 24.7 years . Diagnoses of MCI and dementia were made based on prospect i ve data . Participants completed the Center for Epidemiologic Studies Depression Scale at 1- to 2-year intervals and were considered to have an EDS if their score was ≥16 . Kaplan-Meier survival curves , log-rank test for trend for survivor functions , and Cox proportional hazards models were conducted to examine the risk of MCI and dementia by number of EDS . Results : We observed a monotonic increase in risk for all-cause dementia and Alzheimer disease as 
    Output:
    
There was good agreement between modifiable risk factors identified in the literature review and risk factors named spontaneously by experts .
After triangulation of both methods and re-weighting by experts , strongest support was found for depression , ( midlife ) hypertension , physical inactivity , diabetes , ( midlife ) obesity , hyperlipidemia , and smoking , while more research is needed for coronary heart disease , renal dysfunction , diet , and cognitive activity .