***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 and Purpose — Based on the hypothesis of glutamate-induced neurotoxicity ( excitotoxicity ) in cerebral ischemia , this study examined the efficacy and tolerability of memantine , an uncompetitive N-methyl-d-aspartate antagonist , in the treatment of mild to moderate vascular dementia . Methods — In this multicenter , 28-week trial carried out in France , 321 patients received 10 mg/d memantine or placebo twice a day ; 288 patients were valid for intent-to-treat analysis . Patients had to meet the criteria for probable vascular dementia and have a Mini-Mental State ( MMSE ) score between 12 and 20 at inclusion . The 2 primary end points were the cognitive subscale of the Alzheimers Disease Assessment Scale ( ADAS-cog ) and the global Clinician ’s Interview Based Impression of Change ( CIBIC-plus ) . Results — After 28 weeks , the mean ADAS-cog scores were significantly improved relative to placebo . In the intention-to-treat population , the memantine group mean score had gained an average of 0.4 points , whereas the placebo group mean score had declined by 1.6 points , ie , a difference of 2.0 points ( 95 % confidence interval , 0.49 to 3.60 ) . The response rate for CIBIC-plus , defined as improved or stable , was 60 % with memantine compared with 52 % with placebo ( P = 0.227 , intention to treat ) . Among the secondary efficacy parameters , which were analyzed in the per- protocol subset , MMSE was significantly improved with memantine compared with deterioration with placebo ( P = 0.003 ) . The Gottfries-Brane-Steen Scale intellectual function subscore and the Nurses ’ Observation Scale for Geriatric Patients disturbing behavior dimension also showed differences in favor of memantine ( P = 0.04 and P = 0.07 , respectively ) . Memantine was well tolerated with a frequency of adverse events comparable to placebo . Conclusions — In patients with mild to moderate vascular dementia , memantine 20 mg/d improved cognition consistently across different cognitive scales , with at least no deterioration in global functioning and behavior . It was devoid of concerning side effects BACKGROUND The Consortium to Investigate Vascular Impairment of Cognition ( CIVIC ) is a Canadian , multi-centre , clinic-based prospect i ve cohort study of patients with Vascular Cognitive Impairment ( VCI ) . We report its organization and the impact of diagnostic criteria on the study of VCI . METHODS Nine memory disability clinics enrolled patients and recorded their usual investigations and care . A case report form included all vascular dementia ( VaD ) individual criteria for each of four sets ( National Institute of Neurological Disorders and Stroke ( NINDS-AIREN ) , Alzheimer 's Disease Diagnostic Treatment Centers ( ADDTC ) , the ICD-10 Classification of Mental and Behavioural Disorders ( ICD-10 ) , and the Diagnostic and Statistical Manual of Mental Disorders ( DSM-IV ) ) of consensus-based diagnostic criteria and for the Hachinski Ischemia Score ( HIS ) . Investigators , having completed the case report form , were asked to make a clinical judgement about the cognitive diagnosis based on the best available information , including neuroimaging . RESULTS Of 1,347 patients ( mean age 72 years ; 56 % women ) , 846 ( 63 % ) were diagnosed with dementia and 324 ( 24 % ) were diagnosed with VCI . The proportion of patients diagnosed with VaD by the diagnostic criteria was : 23.9 % ( n = 322 ) by DSM-IV , 10.2 % ( n = 137 ) by HIS , 4.3 % ( n = 58 ) by ICD-10 , 3.8 % ( n = 51 ) by ADTCC , and 3.6 % ( n = 48 ) by NINDS-AIREN . Judged against a clinical diagnosis of VaD , the sensitivity/specificity of each was : DSM-IV ( 0.77/0.80 ) ; HIS ( 0.41/0.92 ) ; ICD-10 ( 0.29/0.98 ) ; ADTCC ( 0.24/0.98 ) ; NINDS-AIREN ( 0.42/0.995 ) . Compared with a clinical diagnosis of VCI , sensitivities were lower for the diagnostic criteria , reflecting the exclusion of patients who did not have dementia . CONCLUSIONS Consensus-based criteria for VaD omit patients who do not meet dementia criteria that are modeled on Alzheimer 's disease . Even for patients who do , the proportion identified with VaD varies widely . Criteria based on empirical analyses need to be developed and vali date Objective : To evaluate the efficacy and tolerability of donepezil in patients with vascular dementia ( VaD ) . Methods : Patients ( n = 616 ; mean age , 75.0 years ) with probable or possible VaD , according to National Institute of Neurological Disorders and Stroke – Association Internationale pour la Recherche en l’Enseignement en Neurosciences criteria , were r and omized to receive donepezil 5 mg/day ( n = 208 ) , donepezil 10 mg/day ( after 5 mg/day for the first 28 days ) ( n = 215 ) , or placebo ( n = 193 ) for 24 weeks . Results : Seventy-six percent of the patients enrolled had probable VaD. A total of 75.3 % of the 10 mg donepezil group and 80.8 % of the 5 mg group completed the study compared with 83.4 % of the placebo group . Both donepezil-treated groups showed improvements in cognitive function on the Alzheimer ’s Disease Assessment Scale – cognitive subscale compared with placebo , with a mean endpoint treatment difference , as measured by the change from baseline score , of approximately 2 points ( donepezil 5 mg , −1.65 [ p = 0.003 ] ; 10 mg , −2.09 [ p = 0.0002 ] ) . Greater improvements on the Clinician ’s Interview-Based Impression of Change – plus version were observed with both donepezil groups than with the placebo group ( overall donepezil treatment vs placebo p = 0.008 ) ; 25 % of the placebo group showed improvement compared with 39 % ( p = 0.004 ) of the 5 mg group and 32 % ( p = 0.047 ) of the 10 mg group . Withdrawal rates due to adverse events were low ( placebo , 8.8 % ; donepezil 5 mg , 10.1 % ; 10 mg , 16.3 % ) . Conclusions : Donepezil-treated patients demonstrated significant improvements in cognition and global function  compared with placebo-treated patients , and donepezil was well tolerated Little is known about progression , short of dementia , in vascular cognitive impairment . In the Canadian Study of Health and Aging , 149 participants ( 79.3 ± 6.7 years ; 61 % women ) were found to have vascular cognitive impairment , no dementia ( CIND ) . After 5 years , 77 participants ( 52 % ) had died and 58 ( 46 % ) had developed dementia . Women were at greater risk of dementia ( OR 2.1 , 1.0 to 4.5 ) . Of 32 participants alive without dementia , cognition had deteriorated in seven and improved in four . Half of those with vascular CIND developed dementia within 5 years , suggesting a target for preventive interventions Background and Purpose — Clinical observations suggest that patients with vascular dementia ( VaD ) may benefit from treatment with cholinesterase inhibitors . This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD. Methods — Patients ( n=603 ; mean age , 73.9 years ; 55.2 % men ) with probable ( 70.5 % ) or possible ( 29.5 % ) VaD , according to criteria of the National Institute of Neurological Disorders and Stroke ( NINDS ) and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences ( AIREN ) , were r and omized to 24 weeks of treatment with donepezil 5 mg/d ( n=198 ) , donepezil 10 mg/d ( 5 mg/d for first 28 days ; n=206 ) , or placebo ( n=199 ) . Analyses were based on the intent-to-treat population . Results — At week 24 , both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer ’s Disease Assessment Scale – cognitive subscale ( mean change from baseline score effect size : donepezil 5 mg/d , −1.90 ; P = 0.001 ; donepezil 10 mg/d , −2.33 ; P < 0.001 ) . Significant improvements in patients ’ global function were seen versus placebo at week 24 ( observed cases ) , on the Clinician ’s Interview-Based Impression of Change – Plus version only for patients on donepezil 5 mg/d ( P = 0.014 ) , and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/d ( P = 0.007 ) . Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer ’s Disease Functional Assessment and Change Scale ( mean change from baseline score effect size at week 24 : donepezil 5 mg/d , −1.31 , P = 0.02 ; donepezil 10 mg/d , −1.31 , P = 0.02 ) . Donepezil was well tolerated . Withdrawal rates due to adverse events were relatively low ( placebo , 11.1 % ; donepezil 5 mg/d , 11.1 % ; donepezil 10 mg/d , 21.8 % ; P = 0.005 versus placebo ) . Conclusions — These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition 
    Output:
    
Due to insufficient evidence , rivastigmine could not yet be recommended for the treatment of vascular dementia .
Memantine appeared to be safe and well tolerated but did not demonstrate effectiveness across all cognitive outcomes and clinical global measures .
Conclusion : Acetylcholinesterase inhibitors and NMDA receptor antagonists , in general , displayed promise as treatments for patients with vascular dementia and vascular cognitive impairment .
The most effective , evidence -based treatments were donepezil and galantamine