You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Efficacy and Safety of Memantine in Patients With Mild to Moderate Vascular Dementia: A Randomized, Placebo-Controlled Trial (MMM 300)
Abstract 1:
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


Title 2:
The Consortium to Investigate Vascular Impairment of Cognition: methods and first findings.
Abstract 2:
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


Title 3:
Donepezil in vascular dementia
Abstract 3:
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


Title 4:
Progression of impairment in patients with vascular cognitive impairment without dementia
Abstract 4:
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


Title 5:
Efficacy and Tolerability of Donepezil in Vascular Dementia: Positive Results of a 24-Week, Multicenter, International, Randomized, Placebo-Controlled Clinical Trial
Abstract 5:
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
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