***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: Objective To investigate whether angiotensin receptor blockers protect against  Alzheimer ’s disease and dementia or reduce the progression of both diseases . Design Prospect i ve cohort analysis . Setting Administrative data base of the US Veteran Affairs , 2002 - 6 . Population 819 491 predominantly male participants ( 98 % ) aged 65 or more with cardiovascular disease . Main outcome measures Time to incident Alzheimer ’s disease or dementia in three cohorts ( angiotensin receptor blockers , lisinopril , and other cardiovascular drugs , the “ cardiovascular comparator ” ) over a four year period ( fiscal years 2003 - 6 ) using Cox proportional hazard models with adjustments for age , diabetes , stroke , and cardiovascular disease . Disease progression was the time to admission to a nursing home or death among participants with pre-existing Alzheimer ’s disease or dementia . Results Hazard rates for incident dementia in the angiotensin receptor blocker group were 0.76 ( 95 % confidence interval 0.69 to 0.84 ) compared with the cardiovascular comparator and 0.81 ( 0.73 to 0.90 ) compared with the lisinopril group . Compared with the cardiovascular comparator , angiotensin receptor blockers in patients with pre-existing Alzheimer ’s disease were associated with a significantly lower risk of admission to a nursing home ( 0.51 , 0.36 to 0.72 ) and death ( 0.83 , 0.71 to 0.97 ) . Angiotensin receptor blockers exhibited a dose-response as well as additive effects in combination with angiotensin converting enzyme inhibitors . This combination compared with angiotensin converting enzyme inhibitors alone was associated with a reduced risk of incident dementia ( 0.54 , 0.51 to 0.57 ) and admission to a nursing home ( 0.33 , 0.22 to 0.49 ) . Minor differences were shown in mean systolic and diastolic blood pressures between the groups . Similar results were observed for Alzheimer ’s disease . Conclusions Angiotensin receptor blockers are associated with a significant reduction in the incidence and progression of Alzheimer ’s disease and dementia compared with angiotensin converting enzyme inhibitors or other cardiovascular drugs in a predominantly male population Mild-to-moderate AD patients were r and omized to placebo or rosiglitazone ( RSG ) 2 , 4 or 8 mg . Primary end points at Week 24 were mean change from baseline in AD Assessment Scale-Cognitive ( ADAS-Cog ) and Clinician 's Interview-Based Impression of Change Plus Caregiver Input global scores in the intention-to-treat population ( N=511 ) , and results were also stratified by apolipoprotein E ( APOE ) genotype ( n=323 ) . No statistically significant differences on primary end points were detected between placebo and any RSG dose . There was a significant interaction between APOE ɛ4 allele status and ADAS-Cog ( P=0.014 ) . Exploratory analyses demonstrated significant improvement in ADAS-Cog in APOE ɛ4-negative patients on 8 mg RSG ( P=0.024 ; not corrected for multiplicity ) . APOE ɛ4-positive patients did not show improvement and showed a decline at the lowest RSG dose ( P=0.012 ; not corrected for multiplicity ) . Exploratory analyses suggested that APOE ɛ4 non-carriers exhibited cognitive and functional improvement in response to RSG , whereas APOE ɛ4 allele carriers showed no improvement and some decline was noted . These preliminary findings require confirmation in appropriate clinical studies BACKGROUND Type-2 Diabetes Mellitus ( DM-2 ) is an important risk factor for Alzheimer disease ( AD ) and vascular dementia ( VD ) . The role of insulinic therapy on cognitive decline is controversial . OBJECTIVE To evaluate cognitive impairment in patients with AD and DM-2 treated with either oral antidiabetic drugs or combination of insulin with other diabetes medications .  METHODS 104 patients with mild-to-moderate AD and DM-2 were divided into two groups , according to antidiabetic pharmacotherapy : group A , patients treated with oral antidiabetic drugs and group B , patients treated with insulin combined with other oral antidiabetic medications .  Cognitive functions were assessed by the Mini Mental State Examination ( MMSE ) and the Clinician 's Global Impression ( CGI ) , with a follow-up of 12 months . RESULTS At the end of the study , the MMSE scores showed a significant worsening in 56.5 % patients of group A and in 23.2 % patients of group B , compared to baseline MMSE scores ( P=.001 ) . Also CGI-C scores showed a significant worsening for all domains after 12 months in group A vs group B ( P=.001 ) . The two groups were matched for body mass index , serum lipids , triglycerides , Apo epsilon4 allele and smoke habit . Conversely , ischemic heart disease and hypertension were significantly higher in group B ( P=.002 ) . After adjustment for this risk variables , our results remained significant ( P=.001 ) . CONCLUSIONS Our study suggests that insulinic therapy could be effective in slowing cognitive decline in patients with AD To test the effects of the PPAR-γ agonist pioglitazone on cognition , regional cerebral blood flow ( rCBF ) , and plasma levels of Aβ40 and Aβ42 , we conducted a 6-month , r and omized , open-controlled trial in patients with mild Alzheimer disease ( AD ) accompanied with type II diabetes mellitus . We r and omly assigned 42 patients to either the group treated with 15 - 30 mg pioglitazone daily ( n=21 , pioglitazone group ) or not ( n=21 , control group ) . The pioglitazone group improved cognition and rCBF in the parietal lobe , while the control group showed no such improvement . The plasma Aβ40/Aβ42 ratio increased in the control group , but showed no significant change in the pioglitazone group . Both groups showed good control of diabetes during the study . In addition , pioglitazone treatment result ed in a decrease in fasting plasma insulin levels , indicating enhanced insulin sensitivity . The results of this pilot study demonstrated that pioglitazone  exhibited cognitive and functional improvements , and stabilization of the disease in diabetic patients with AD . Pioglitazone may offer a novel strategy for the treatment of AD Background : There is growing evidence that vascular risk factors ( VRF ) contribute to cognitive decline . Whether their treatment can slow down the progression of Alzheimer disease ( AD ) remains unsettled . The aim of this observational study was to evaluate whether the treatment of VRF is associated with a slower cognitive decline in patients who have AD without cerebrovascular disease ( CVD ) . Methods : We recruited 301 consecutive patients who had AD without CVD ( mean age 71.7 years ; 69.4 % women ; first Mini-Mental State Examination [ MMSE ] mean score 21.6 ; mean follow-up 2.3 years ) , who had attended a memory clinic between 1997 and 2003 . VRF sought were high blood pressure , dyslipidemia , diabetes mellitus , tobacco smoking , and atherosclerotic disease . Only 21 patients ( 7.0 % ) had no VRF . Others were classified as having no VRF treated ( n = 72 ; 25.7 % ) , some VRF treated ( n = 119 ; 42.5 % ) , or all VRF treated ( n = 89 ; 31.8 % ) . We compared MMSE progression over time among these 3 groups using a mixed r and om effects regression model . Results : Baseline MMSE scores were similar in the 3 groups . With adjustment for confounding factors , MMSE progression over time differed significantly between groups ( p = 0.002 ) . Patients with all their VRF treated declined less than those with none of their VRF treated . Those with some VRF treated tended to have an intermediate decline . Conclusions : In patients who have Alzheimer disease without CVD , treatment of vascular risk factors ( VRF ) is associated with a slower decline in Mini-Mental State Examination score . R and omized controlled trials are needed to confirm this association , but our data suggest that dementia should not prevent treatment of VRF Background : Data from epidemiological studies and animal models imply that disturbances in cholesterol metabolism are linked to Alzheimer ’s disease susceptibility . Lipid lowering agents ( LLAs ) may have implication s for the prevention of Alzheimer ’s disease . Objective : To investigate whether LLAs are associated with a slower cognitive decline in Alzheimer ’s disease . Methods : An observational study in 342 Alzheimer patients followed in a memory clinic for 34.8 months ( mean age 73.5 years , mini-mental state examination score ( MMSE ) 21.3 at entry ) ; 129 were dyslipaemic treated with LLAs ( 47 % with statins ) , 105 were untreated dyslipaemic , and 108 were normolipaemic . The rate of cognitive decline was calculated as the difference between the first and last MMSE score , divided by the time between the measurements , expressed by year . Patients were divided into slow and fast decliners according to their annual rate of decline ( lower or higher than the median annual rate of decline in the total population ) . Results : Patients treated with LLAs had a slower decline on the MMSE ( 1.5 point/year , p = 0.0102 ) than patients with untreated dyslipaemia ( 2.4 points/year ) , or normolipaemic patients ( 2.6 points/year ) . Patients with a slower decline were more likely to be treated with LLAs . Logistic regression analysis , with low annual cognitive decline as the dependent variable , showed that the independent variable LLA ( treated with or not ) was positively associated with the probability of lower cognitive decline ( odds ratio = 0.45 , p = 0.002 ) . Conclusions : LLAs may slow cognitive decline in Alzheimer ’s disease and have a neuroprotective effect . This should be confirmed by placebo controlled r and omised trials in patients with Alzheimer ’s disease and no dyslipaemia PURPOSE Animal research and cross-sectional studies suggest that serum lipid concentrations may influence cognitive function , mood , and behavior , but few clinical trials have studied these effects . SUBJECTS AND METHODS In this double-blind investigation , 209 generally healthy adults with a serum low-density-lipoprotein ( LDL ) cholesterol level of 160 mg/dL or higher were r and omly assigned to 6-month treatment with lovastatin ( 20 mg ) or placebo . Assessment s of neuropsychological performance , depression , hostility , and quality of life were conducted at baseline and at the end of the treatment period . Summary effect sizes were estimated as z scores on a st and ard deviation ( SD ) scale . RESULTS Placebo-treated subjects improved between baseline and posttreatment periods on neuropsychological tests in all five performance domains , consistent with the effects of practice on test performance ( all P < 0.04 ) , whereas those treated with lovastatin improved only on tests of memory recall ( P = 0.03 ) . Comparisons of the changes in performance between placebo- and lovastatin-treated subjects revealed small , but statistically significant , differences for tests of attention ( z score = 0.18 ; 95 % confidence interval ( CI ) , 0.06 to 0.31 ; P = 0.005 ) and psychomotor speed ( z score = 0.17 ; 95 % CI , 0.05 to 0.28 ; P = 0 . 004 ) that were consistent with greater improvement in the placebo group . Psychological well-being , as measured several ways , was not affected by lovastatin . CONCLUSION Treatment of hypercholesterolemia with lovastatin did not cause psychological distress or substantially alter cognitive function . Treatment did result in small performance decrements on neuropsychological tests of attention and psychomotor speed , the clinical importance of which is uncertain Cerebrovascular disease and vascular risk factors are associated with Alzheimer 's disease , but the evidence for their association with other neurodegenerative disorders is limited . Therefore , we compared the prevalence of cerebrovascular disease , vascular pathology and vascular risk factors in a wide range of neurodegenerative diseases and correlate them with dementia severity . Presence of cerebrovascular disease , vascular pathology and vascular risk factors was studied in 5715 cases of the National Alzheimer 's Coordinating Centre data base with a single neurodegenerative disease diagnosis ( Alzheimer 's disease , frontotemporal lobar degeneration due to tau , and TAR DNA-binding protein 43 immunoreactive deposits , α-synucleinopathies , hippocampal sclerosis and prion disease ) based on a neuropathological examination with or without cerebrovascular disease , defined neuropathologically . In addition , 210 ' unremarkable brain ' cases without cognitive impairment , and 280 cases with pure cerebrovascular disease were included for comparison . Cases with cerebrovascular disease were older than those without cerebrovascular disease in all the groups except for those with hippocampal sclerosis . After controlling for age and gender as fixed effects and centre as a r and 
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Conclusions Observational data raises the possibility that treating VRF could alter the rate of decline in AD .