***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: Subcortical vascular dementia ( VaD ) is characterized by executive dysfunction and behavioral problems , reflecting deterioration of the frontal lobe . This study aim ed to determine whether rivastigmine , a dual inhibitor of acetylcholinesterase ( AChE ) and butyrylcholinesterase ( BuChE ) , has any effects on the typical symptoms of subcortical VaD. Patients receiving rivastigmine  showed a slight improvement in executive functions and in behavior . Side effects in both groups were tolerable and there were no study withdrawals . Moreover , there are no drug interactions with other therapies previously and concomitantly assumed . Improvements in domains that characterize subcortical VaD were observed , indicating that rivastigmine may have provided targeted treatment in areas of the brain that are particularly affected in this patient population BACKGROUND The majority of patients with Alzheimer 's disease ( AD ) or vascular dementia display , in addition to cognitive impairment , various degrees of behavioral disturbances . As the use of cholinesterase inhibitors for the treatment of cognitive impairment in dementia becomes widespread , many of these patients will be treated concomitantly with cholinesterase inhibitors and with anti-psychotic drugs to ameliorate behavioral disturbances . Despite the widespread use of this combination in clinical practice , the safety and tolerability of such combination therapy has not been evaluated in controlled clinical trials . This pilot study examined the effects of addition of risperidone 0.5 - 2 mg/day to patients on rivastigmine 3 - 12 mg/day , and vice versa . METHODS 65 patients suffering from AD , 10 from vascular dementia , and 15 from both were r and omized to open label rivastigmine and risperidone , alone or in combination , for 20 weeks . Adverse events caused by co-administration were assessed . RESULTS No clinical ly relevant adverse interactions were observed . CONCLUSIONS These preliminary results indicate that rivastigmine and risperidone can be safely co-administered . Confirmation of these results in large clinical trials studies is warranted Further to recent data indicating that patients with vascular dementia ( VaD ) show a cholinergic deficit , we aim ed to determine whether rivastigmine , a dual inhibitor of acetylcholinesterase ( AChE ) and butyrylcholinesterase ( BuChE ) , has any effects on the symptoms of VaD. Patients aged 65 - 80 , with a diagnosis of dementia and probable VaD , received rivastigmine 3 - 6 mg/day ( n=8 ) or cardioaspirin ( n=8 ) in an open study for 22 months . At 22 months , patients treated with rivastigmine showed significant improvements in executive function and behavioural symptoms ( both p<0.05 vs. both baseline and control group ) , which were reflected in reduced caregiver stress ( p<0.05 vs. baseline and controls ) . Baseline scores of global response , cognition , word fluency and activities of daily living were maintained in patients receiving rivastigmine , and there was no increase in benzodiazepine or neuroleptic intake . In contrast , the control group showed no improvements in any domain , and significant deterioration in global response and executive function ( both p<0.05 vs. baseline and rivastigmine group ) . Side effects in both groups were tolerable and there were no study withdrawals . Long-term rivastigmine treatment appeared to be safe and effective in this patient population . In particular , improvements in domains particularly relevant to this condition were observed . These benefits may reflect the drug 's dual inhibitory effects on the cholinergic system , and its particular activity in frontal areas of the brain . A large , double-blind study of rivastigmine in patients with VaD would be worthwhile A number of studies have suggested that cerebral changes , particularly deep white matter lesions ( WML ) visualized on magnetic resonance imaging ( MRI ) , may be involved in the genesis of late life depression . This has been confirmed in a prospect i ve study which also found a relationship between the presence of WML and poor 3-year outcome in elderly depressed subjects . Most studies find these lesions to predominate in frontal lobe and basal ganglia , supporting the hypothesis of " fronto-striatal " dysfunction in depression . To investigate whether WML are associated with mood disturbance in dementia , proton density and T2-weighted images were obtained in 80 subjects with dementia ( dementia with Lewy bodies , n = 27 ; Alzheimer 's disease , n = 28 ; vascular dementia , n = 25 ) and 26 age-matched normal controls .  Periventricular lesions ( PVL ) , white matter lesions ( WML ) , and basal ganglia hyperintensities ( BG ) were visually rated blind to diagnosis using a semiquantitative scale . Frontal WML were associated with higher depression scores in patients with dementia , implying a common pathophysiology of depression irrespective of diagnosis . Further study of the neurobiological basis of WML is needed . This can best be achieved by serial clinical assessment combined with in vivo and in vitro MRI and neuropathological examination BACKGROUND Vascular risk factors play a role in the development of dementia , including Alzheimer disease ( AD ) . However , little is known about the effect of body mass index and clustering of vascular risk factors on the development of dementia . OBJECTIVE To investigate the relation between  midlife body mass index and clustering of vascular risk factors and subsequent dementia and AD . DESIGN AND SETTING Participants of the Cardiovascular Risk Factors , Aging , and Dementia ( CAIDE ) study were derived from r and om , population -based sample s previously studied in a survey carried out in 1972 , 1977 , 1982 , or 1987 . After an average follow-up of 21 years , 1449 individuals ( 73 % ) aged 65 to 79 years participated in the reexamination in 1998 . MAIN OUTCOME MEASURES Dementia and AD . RESULTS Obesity at midlife ( body mass index>30 kg/m2 ) was associated with the risk of dementia and AD even after adjusting for sociodemographic variables ( odds ratio [ OR ] , 2.4 [ 95 % confidence interval ( CI ) , 1.2 - 5.1 ] ) . The association was somewhat modified by further adjusting for midlife blood pressure , total cholesterol level , and smoking ( OR , 2.1 [ 95 % CI , 1.0 - 4.6 ] ) and also for apolipoprotein E genotype and history of vascular disorders ( OR , 1.9 [ 95 % CI , 0.8 - 4.6 ] ) . Midlife obesity , high total cholesterol level , and high systolic blood pressure were all significant risk factors for dementia with ORs of around 2 for each factor , and they increased the risk additively ( OR , 6.2 for the combination ) . CONCLUSIONS Obesity at midlife is associated with an increased risk of dementia and AD later in life . Clustering of vascular risk factors increases the risk in an additive manner . The role of weight reduction for the prevention of dementia needs to be further investigated We evaluated the efficacy and safety of the central ly acting cholinesterase inhibitor , rivastigmine tartrate , for patients with mild to moderately severe Alzheimer 's disease ( AD ) with or without concurrent vascular risk factors ( VRF ) . Patients ( 45 - 90 years of age ) were r and omized to placebo ( n = 235 ) , low-dose rivastigmine ( 1 - 4 mg/day , n = 233 ) , or high-dose rivastigmine ( 6 - 12 mg/day , n = 231 ) for 26 weeks . Efficacy measures included the Alzheimer 's Disease Assessment Scale-Cognitive subscale ( ADAS-Cog ) , the Clinician 's Interview Based Impression of Change ( CIBIC-Plus ) , the Progressive Deterioration Scale ( PDS ) , the Global Deterioration Scale ( GDS ) , and the Mini-Mental State Examination ( MMSE ) . For efficacy and safety analysis , patients were categorized by baseline Modified Hachinski Ischemic Score ( MHIS ) for the determination of VRF ( MHIS > 0 : presence of VRF ; MHIS = 0 : absence of VRF ) . As early as 12 weeks , the mean change from the baseline ADAS-Cog score was significantly different for those patients treated with high-dose rivastigmine compared with placebo controls in both MHIS categories . However , the treatment difference between high-dose rivastigmine and placebo at each time-point was larger for patients with MHIS > 0 . The proportion of responders was significantly greater in the high-dose rivastigmine group for each level of improvement . No differences were noted between treatment groups regarding safety evaluations . Rivastigmine is effective in both categories of patients , and those with VRF experience greater clinical benefit ( cognition , activities of daily living , and disease severity ) Narasimhalu K , Effendy S , Sim CH , Lee JM , Chen I , Hia SB , Xue HL , Corrales MP , Chang HM , Wong MC , Chen CP , Tan EK . A r and omized controlled trial of rivastigmine in patients with cognitive impairment no dementia because of cerebrovascular disease . Acta Neurol Sc and : 2010 : 121 : 217–224 . © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard This article reports the development and psychometric properties of the Alzheimer 's Disease Cooperative Study - Clinical Global Impression of Change ( ADCS-CGIC ) . At present , a number of unvali date d CGIC scales are used in clinical trials , with various methods for making ratings . The ADCS-CGIC was design ed on the basis of a survey of  ADCS clinicians  and by adapting existing instruments . It includes an organized but unstructured format , with which a clinician can address clinical ly relevant change . The instrument 's reliability and validity were assessed in a prospect i ve trial of Alzheimer 's disease ( AD ) and healthy subjects over a 12-month period . It showed good short-term reliability at 1 and 2 months , with 90 and 94 % of AD subjects , respectively , rated as having changed not at all or only minimally . The ADCS-CGIC 's  face validity was demonstrated by untreated . AD subjects rated as having worsened over time at both 6 months ( 56 % rated as having worsened ) and 12 months ( 81 % rated as having worsened ) , whereas only 2 % of control subjects showed minimal worsening . As a measure of predictive validity , ADCS-CGIC ratings at 12 months were significantly associated with change on four severity scales . As with other measures , change ratings were sensitive to dementia severity . Moderately impaired subjects showed greater worsening than other subjects . ADCS-CGIC ratings of greater worsening were made after the informant interview , regardless of whether informants or subjects were interviewed first . The ADCS-CGIC is a valid and reliable instrument for use in clinical trials We developed a set of informant-based items describing performance of activities of daily living ( ADL ) by patients with Alzheimer 's disease ( AD ) to identify which ADL are useful for assessment of patients in clinical trials .  Evaluation of ADL is an important outcome measure in AD clinical trials . For clinical trial measurement , ADL should have broad applicability , good test-retest reliability , scaling to cover a range of performance , and sensitive to detect change in disease progression . A total of 45 ADL items developed from literature review and clinical experience were administered to informants of 242 AD patients and 64 elderly controls as part of the multicenter Alzheimer 's Disease Cooperative Study Instrument protocol . Half of the subjects were re-evaluated at 1 and 2 months and all at 6 and 12 months . Controls performed virtually all ADL items optimally at baseline and at 12 months . Among subjects with AD , 27 of the 45 ADL were widely applicable , i.e. , performed at baseline or premorbidly by > 90 % of subjects ; showed good test-retest reliability between baseline and 1 and 2 months ; correlated with MMSE scores of AD patients cross-sectionally ; and showed a decline in performance from baseline to 12 months in at least 20 % of AD patients . ADL could be identified that capture change in functional ability in patients across the entire range of the MMSE . The remaining 18 ADL included several that may be useful for trials that target specific population s , e.g. , women with AD . Because change on specific items depends on baseline MMSE , ADL evaluation should include items relevant to the severity of dementia of patients enrolled in a clinical trial Recent data indicate that patients with vascular dementia ( VaD ) show a cholinergic deficit . Having obtained good results in a previous study comparing rivastigmine , an inhibitor of acetylcholinesterase ( AChE ) and butyrylcholine-sterase ( BuChE ) , vs. aspirin , we aim ed to compare the efficacy and tolerability of rivastigmine vs. aspirin plus nimodipine .  Patients with a diagnosis of dementia and probable VaD received rivastigmine 3 - 6 mg/day ( n = 32 ) or aspirin plus nimodipine ( n = 32 ) in an open study for 16 months . Patients treated with rivastigmine showed superior benefits , compared with those receiving aspirin plus nimodipine , in attention , executive function , instrumental activities of daily living , and behavioural and psychotic disturbances . Side-effects in both groups were tolerable and there were no study withdrawals . The benefits observed with rivastigmine may reflect its inhibitory effects on AChE and BuChE , and the drug 
    Output:
    
Primary and secondary outcome measures showed no statistically significant difference when considering neurocognitive abilities , function , neuropsychiatric symptoms and global performance .
Rivastigmine is capable of inducing side effects that lead to withdrawal in a significant proportion of patients