***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 Early-onset dementia is common in Down syndrome adults , who have trisomy 21 . The amyloid precursor protein gene is on chromosome 21 , and so is over-expressed in Down syndrome , leading to amyloid β ( Aβ ) over-production , a major upstream pathway leading to Alzheimer disease ( AD ) . Statins ( microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ) , have pleiotropic effects including potentially increasing brain amyloid clearance , making them plausible agents to reduce AD risk . Animal models , human observational studies , and small scale trials support this rationale , however , there are no AD primary prevention trials in Down syndrome adults . In this study we study aim to inform the design of a full-scale primary prevention trial . Methods / Design TOP-COG is a feasibility and pilot double-blind r and omized controlled trial ( RCT ) , with a nested qualitative study , conducted in the general community . About 60 Down syndrome adults , aged ≥50 will be included . The intervention is oral simvastatin 40 mg at night for 12 months , versus placebo . The primary endpoint is recruitment and retention rates . Secondary endpoints are ( 1 ) tolerability and safety ; ( 2 ) detection of the most sensitive neurocognitive instruments ; ( 3 ) perceptions of Down syndrome adults and caregivers on whether to participate , and assessment experiences ; ( 4 ) distributions of cognitive decline , adaptive behavior , general health/ quality of life , service use , caregiver strain , and sample size implication s ; ( 5 ) whether Aβ42/Aβ40 is a cognitive decline biomarker . We will describe percentages recruited from each source , the number of contacts to achieve this , plus recruitment rate by general population size . We will calculate summary statistics with 90 % confidence limits where appropriate , for each study outcome as a whole , by treatment group and in relation to baseline age , cognitive function , cholesterol and other characteristics . Changes over time will be summarized graphically . The sample size for a definitive RCT will be estimated under alternative assumptions . Discussion This study is important , as AD is a major problem for Down syndrome adults , for whom there are currently no effective preventions or treatments . It will also delineate the most suitable assessment instruments for this population . Recruitment of intellectually disabled adults is notoriously difficult , and we shall provide valuable information on this , informing future studies .Trial registration Current Controlled Trials IS RCT N Register ID : IS RCT N67338640 ( 17 November 2011 Summary Background The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome . No study , however , has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease ( CHD ) in hypertensive patients who are not conventionally deemed dyslipidaemic . Methods Of 19 342 hypertensive patients ( aged 40–79 years with at least three other cardiovascular risk factors ) r and omised to one of two antihypertensive regimens in the Anglo-Sc and inavian Cardiac Outcomes Trial , 10 305 with nonfasting total cholesterol concentrations 6.5 mmol/L or less were r and omly assigned additional atorvastatin 10 mg or placebo .  These patients formed the lipid-lowering arm of the study . We planned follow-up for an average of 5 years , the primary endpoint being non-fatal myocardial infa rct ion and fatal CHD . Data were analysed by intention to treat . Findings Treatment was stopped after a median follow-up of 3.3 years . By that time , 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group ( hazard ratio 0.64 [ 95 % CI 0.50–0.83 ] , p = 0.0005 ) . This benefit emerged in the first year of follow-up . There was no significant heterogeneity among prespecified subgroups . Fatal and non-fatal stroke ( 89 atorvastatin vs 121 placebo , 0.73 [ 0.56–0.96 ] , p = 0.024 ) , total cardiovascular events ( 389 vs 486 , 0.79 [ 0.69–0.90 ] , p = 0.0005 ) , and total coronary events ( 178 vs 247 , 0.71 [ 0.59–0.86 ] , p = 0.0005 ) were also significantly lowered . There were 185 deaths in the atorvastatin group and 212 in the placebo group ( 0.87 [ 0.71–1.06 ] , p = 0.16 ) . Atorvastatin  lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months , and by 1.1 mmol/L after 3 years of follow-up . Interpretation The reductions in major cardiovascular events with atorvastatin are large , given the short follow-up time . These findings may have implication s for future lipid-lowering guidelines BACKGROUND Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals , their efficacy and safety in elderly people is not fully established . Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with , or at high risk of developing , cardiovascular disease and stroke . METHODS We did a r and omised controlled trial in which we assigned 5804 men ( n=2804 ) and women ( n=3000 ) aged 70 - 82 years with a history of , or risk factors for , vascular disease to pravastatin ( 40 mg per day ; n=2891 ) or placebo ( n=2913 ) . Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death , non-fatal myocardial infa rct ion , and fatal or non-fatal stroke . Analysis was by intention-to-treat . FINDINGS Pravastatin lowered LDL cholesterol concentrations by 34 % and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo ( hazard ratio 0.85 , 95 % CI 0.74 - 0.97 , p=0.014 ) . Coronary heart disease death and non-fatal myocardial infa rct ion risk was also reduced ( 0.81 , 0.69 - 0.94 , p=0.006 ) . Stroke risk was unaffected ( 1.03 , 0.81 - 1.31 , p=0.8 ) , but the hazard ratio for transient ischaemic attack was 0.75 ( 0.55 - 1.00 , p=0.051 ) . New cancer diagnoses were more frequent on pravastatin than on placebo ( 1.25 , 1.04 - 1.51 , p=0.020 ) . However , incorporation of this finding in a meta- analysis of all pravastatin and all statin trials showed no overall increase in risk . Mortality from coronary disease fell by 24 % ( p=0.043 ) in the pravastatin group . Pravastatin had no significant effect on cognitive function or disability . INTERPRETATION Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals . PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people Sleep disturbances and decrements of daytime performance have been attributed to HMG-CoA reductase inhibitors . As a rule , lipophilic compounds more readily cross the blood-brain barrier and are more likely to affect central nervous system function . The authors compared the effects of lovastatin ( 40 mg ) , a lipophilic compound , to pravastatin ( 40 mg ) , a hydrophilic compound , in a 6-week , double-blind , r and omized , placebo-controlled , three-way Latin square design , cross-over study on 22 men with hypercholesterolemia . Patients had LDL cholesterol of more than 165 mg/dL and triglyceride of less than 350 mg/dL after 6 weeks of a low-fat ( < 30 % ) , low-cholesterol ( < 300 mg/day ) diet . Compared with placebo , there were no significant effects of lovastatin or pravastatin on the following subjective and polysomnographic sleep measures : changes in total sleep time , time in each sleep stage , sleep efficiency , sleep latency , REM density , REM activity , and number of arousals . Similarly , there were no effects of the two drugs on measures of cognitive performance . A significant increase in the duration of nocturnal tumescence ( NPT ) was observed after 2 weeks of treatment with both study drugs . This effect was not significant after 6 weeks of treatment . Both lovastatin and pravastatin caused significant ( P < .05 compared with placebo ) decreases in total cholesterol ( by 20.9 and 20.6 % , respectively ) , LDL cholesterol ( by 27.8 and 29.9 % ) , and triglycerides ( by 13.6 and 3.7 % ) . Subjects ' HDL increased by 2.3 % with lovastatin ( NS ) and by 3.1 % with pravastatin ( P < .05 ) . Lipoprotein(a ) increased by 20.5 % with lovastatin and by 1.1 % with pravastatin ; these changes were not significantly different from placebo . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Few strategies are available for the prevention of cognitive impairment in elderly persons . Serum lipoprotein levels may be important predictors of cognitive function , and drugs that lower cholesterol may be effective for the prevention of cognitive impairment . OBJECTIVE To determine whether serum lipoprotein levels , the 4-year change in serum lipoprotein levels , and the use of statin drugs are associated with cognition in older women without dementia . DESIGN , SETTING , AND PARTICIPANTS An observational study of 1037 postmenopausal women with coronary heart disease enrolled in the Heart and Estrogen/progestin Replacement Study ( participants at 10 of 20 centers ) . MAIN OUTCOME MEASURE The Modified Mini-Mental State Examination was administered at the end of the study after 4 years of follow-up . Women whose score was less than 84 points ( > 1.5 SDs below the mean ) were classified as having cognitive impairment . Lipoprotein levels ( total , high-density lipoprotein , and low-density lipoprotein [ LDL ] cholesterol and triglycerides ) were measured at baseline and at the end of the study ; statin use was documented at each visit . RESULTS Compared with women in the lower quartiles , women in the highest LDL cholesterol quartile at cognitive testing had worse mean plus minus SD Modified Mini-Mental State Examination scores ( 93.7 plus minus 6.0 vs 91.9 plus minus 7.6 ; P = .002 ) and an increased likelihood of cognitive impairment ( adjusted odds ratio , 1.76 ; 95 % confidence interval , 1.04 - 2.97 ) . A reduction in the LDL cholesterol level during the 4 years tended to be associated with a lower odds of impairment ( adjusted odds ratio , 0.61 ; 95 % confidence interval , 0.36 - 1.03 ) compared with women whose levels increased . Higher total and LDL cholesterol levels , corrected for lipoprotein(a ) levels , were also associated with a worse Modified Mini-Mental State Examination score and a higher likelihood of impairment , whereas high-density lipoprotein cholesterol and triglyceride levels were not associated with cognition . Compared with nonusers , statin users had higher mean plus minus SD Modified Mini-Mental State Examination scores ( 92.7 plus minus 7.1 vs 93.7 plus minus 6.1 ; P = .02 ) and a trend for a lower likelihood of cognitive impairment ( odds ratio , 0.67 ; 95 % confidence interval , 0.42 - 1.05 ) , findings that seemed to be independent of lipid levels . CONCLUSIONS High LDL and total cholesterol levels are associated with cognitive impairment , and lowering these lipoprotein levels may be a strategy for preventing impairment . The association between statin use and better cognitive function in women without dementia requires further study The aim of this prospect i ve cohort study was to evaluate the effects of lipid lowering agent ( LLA ) intake on cognitive function in 6,830 community-dwelling elderly persons .  Cognitive performance ( global cognitive functioning , visual memory , verbal fluency , psychomotor speed , and executive function ) , clinical diagnosis of dementia , and fibrate and statin use , were evaluated at baseline , and 2 , 4 , and 7 year follow-up . Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics , mental and physical health including vascular risk factors , and genetic vulnerability ( apolipoprotein E and cholesteryl ester transfer protein ) . For women but not men , fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only ( HR = 1.29 , 95 % CI = 1.09 
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In conclusion , our meta- analysis suggests that the use of statins may reduce the risk of all-type dementia , AD , and MCI , but not of incident