Effects of donepezil on memory and cognition in multiple sclerosis Randomised multicentre trial on safety and efficacy of rivastigmine in cognitively impaired multiple sclerosis patients Actual reality: a new approach to functional assessment in persons with multiple sclerosis. Cognitive effects of modafinil in patients with multiple sclerosis: A clinical trial. Computer-Assisted Cognitive Rehabilitation of Attention Deficits for Multiple Sclerosis Prospective memory, emotional valence, and multiple sclerosis Maintenance cognitive stimulation therapy for dementia: single-blind, multicentre, pragmatic randomised controlled trial. Maintenance cognitive stimulation therapy: an economic evaluation within a randomized controlled trial. Effects of neuropsychological treatment in patients with multiple sclerosis The clinical efficacy and safety of galantamine in the treatment of Alzheimer's disease. Impact of Armodafinil on Cognition in Multiple Sclerosis: A Randomized, Double-blind Crossover Pilot Study Neuropsychological rehabilitation does not improve cognitive performance but reduces perceived cognitive deficits in patients with multiple sclerosis: a randomised, controlled, multi-centre trial The effect of functional electrical stimulation on the physiological cost of gait in people with multiple sclerosis Memantine induces reversible neurologic impairment in patients with MS Lisdexamfetamine dimesylate improves processing speed and memory in cognitively impaired MS patients: a phase II study Three-Month Test-Retest Reliability of Center of Pressure Motion During Standing Balance in Individuals with Multiple Sclerosis. The effects of rivastigmine on processing speed and brain activation in patients with multiple sclerosis and subjective cognitive fatigue The effects of amantadine and pemoline on cognitive functioning in multiple sclerosis. Depression, cognitive impairment and social stress in multiple sclerosis. Activation patterns in multiple sclerosis on the Computerized Tests of Information Processing The efficacy of galantamine in the treatment of Alzheimer's disease: comparison of patients previously treated with acetylcholinesterase inhibitors to patients with no prior exposure. Disability as an outcome in MS clinical trials Short-Term Cognitive Training Improves Mental Efficiency and Mood in Patients with Multiple Sclerosis A pilot study examining functional brain activity 6 months after memory retraining in MS: the MEMREHAB trial Prospective memory and the efficacy of a memory strategy in multiple sclerosis. Non‐cognitive benefits of galantamine (Reminyl®) treatment in vascular dementia Amantadine treatment of fatigue associated with multiple sclerosis.
Acetylcholinesterase inhibitors are used to treat dementia associated with Alzheimer 's disease , but their cognitive benefits may extend to additional disorders such as multiple sclerosis ( MS ) . A single-center double-blind placebo-controlled r and omized clinical trial evaluated the effectiveness of donepezil in a sample of 69 MS persons selected for initial memory difficulties . Subjects received neuropsychological assessment at baseline and after 24 weeks of treatment . The primary outcome was change in total recall on the Selective Reminding Test , a measure of verbal learning and memory . Secondary outcomes included other neuropsychological tests from the Brief Repeatable Battery , patient-reported change in memory , and physician-reported impression of cognitive change .  Donepezil improved memory performance on the SRT compared to placebo . This benefit remained significant after controlling for various covariates including Exp and ed Disability Status Scale ( EDSS ) , MS subtype , interferon beta use , treatment group beliefs , gender , baseline selected reminding test ( SRT ) score , and reading ability . Subjects on donepezil were more likely to report memory improvement ( 65.7 % ) than those on placebo ( 32.4 % ) . The clinician also reported cognitive improvement in more donepezil ( 54.3 % ) than placebo ( 29.4 % ) subjects . No serious adverse events related to study medication occurred . However , more donepezil ( 34.3 % ) than placebo ( 8.8 % ) subjects reported unusual/abnormal dreams .  Donepezil improved learning and memory in MS patients with initial cognitive difficulties in a single-center clinical trial . Replication of results in a larger multi-center investigation is warranted in order to more definitively assess the efficacy of this intervention Background : Cognitive decline has been recognised as a frequent symptom in multiple sclerosis ( MS ) .  Cholinesterase inhibitors ( ChEIs ) are employed for the treatment of Alzheimer ’s disease , but there is some evidence that ChEIs might also be effective in MS patients with cognitive deficits , particularly deficits of memory function . Objective : The aim of this study was to evaluate efficacy on memory function and safety of the ChEI rivastigmine in MS patients with cognitive deficits as measured by the change from baseline of the total recall score of the selective reminding test ( SRT ) after 16 weeks of treatment . Methods : Efficacy and safety of rivastigmine were analysed in a 16-week , multicentre , double-blind , r and omised , placebo-controlled study , followed by an optional one-year open-label treatment phase . Effects of rivastigmine and placebo were compared by an analysis of covariance . Results : In total , 86 patients were enrolled . Patients who received rivastigmine ( n = 43 ) showed a non-significant increase in total recall score ( sum of all words immediately recalled over all six trials ) over placebo ( n = 38 ) after 16 weeks of treatment ( p = 0.2576 ) . Other outcome measures provided no evidence supporting benefits of rivastigmine . Treatment with rivastigmine was well tolerated . Conclusions : With the results of this study , the need for an effective therapy in cognitively impaired MS patients is still required . Thus , intensive and continued clinical research is required to explore therapeutic options for cognitive deficits in MS patients OBJECTIVE To examine the use of an innovative approach for assessing everyday life activities of people with multiple sclerosis ( MS ) :  Actual Reality . Actual Reality is a performance-based assessment approach that involves the use of the internet to perform real , everyday life activities . DESIGN A between-subjects design . SETTING Outpatient rehabilitation institute . PARTICIPANTS Persons ( n=21 ) with clinical ly definite MS and healthy controls ( HCs ) ( n=18 ) without any reported neurologic disabilities participated in this study . Participants were between the ages of 21 to 60 years , and the sample consisted of volunteer sample . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Participants were asked to  access the internet to purchase airline tickets for a round trip flight  and were administered the  Minimal Assessment of Cognitive Functioning in Multiple Sclerosis .  Participants also completed question naires to assess quality of life ( Functional Assessment of Multiple Sclerosis ) , functional status ( Functional Behavior Profile ) , and prior Internet experience . RESULTS The MS group displayed significantly more difficulties than the HC group in accurately and independently completing the Actual Reality task primarily because of cognitive impairment . Self-report of quality of life and functional status were not correlated with Actual Reality performance in the group of people with MS . However , the self-report measures were significantly associated with affective symptomatology . CONCLUSIONS These results provide initial evidence supporting the use of the Actual Reality approach in assessing persons with MS performing everyday life activities .  Actual Reality is a significant step forward in increasing the sensitivity , accessibility , and relevancy of functional assessment s in people with cognitive and physical disabilities PURPOSE / OBJECTIVE To assess the efficacy of modafinil for the treatment of new learning and memory deficits and fatigue in multiple sclerosis . Only 1 previous study in the literature , to our knowledge , examined the effect of modafinil on cognition specifically in persons with multiple sclerosis . RESEARCH METHOD / DESIGN Sixteen patients with a diagnosis of multiple sclerosis ( MS ) and documented new learning impairment completed the study . In a 5-week r and omized , double-blinded , crossover design , participants received either a single daily oral dose of modafinil ( 200 mg ) or placebo for 2 weeks . A 1-week washout period was included between study arms . RESULTS No effect of modafinil was noted on learning and memory performance . Participants taking 200 mg of modafinil showed improvement in 1 of the 2 working memory measures administered , the Wechsler Adult Intelligence Scale-III ( WAIS-III ) Letter-Number Sequencing task , as compared with those on placebo . Treatment with modafinil did not have a beneficial effect in reducing self-reported fatigue . No changes were noted on the Modified Fatigue Impact Scale or the Fatigue Severity Scale with the treatment of modafinil , as compared with placebo . CONCLUSIONS / IMPLICATION S Findings indicate that 200 mg of modafinil has the potential to improve working memory in persons with MS . These findings suggest that modafinil may enhance aspects of cognition in persons with MS and may be an effective adjunct to clinical rehabilitation interventions Background . Although a growing body of evidence has highlighted the role of cognitive rehabilitation ( CR ) in the management of cognitive dysfunctions in multiple sclerosis ( MS ) , there is still no evidence for a vali date d therapeutic approach . Objective . We propose a new therapeutic strategy characterized by a computer-based intensive attention training program in MS patients with predominant attention deficits . We aim to investigate the effectiveness of our rehabilitation procedure , tailored for those with impaired abilities , using functional magnetic resonance imaging ( fMRI ) . Methods . Using a double-blind r and omized controlled study , we enrolled 12 MS patients , who underwent a CR program ( experimental group ) , and 11 age-gender – matched MS patients , who underwent a placebo intervention ( control group ) . fMRI was recorded during the execution of a cognitive task broadly used for assessing attention abilities in MS patients ( paced visual serial addition test ) . Results . Significant effects were detected both at a phenotypic and at an intermediate phenotypic level . After CR , the experimental group , in comparison with the control group , showed a specific enhanced performance in attention abilities as assessed by the Stroop task with an effect size of 0.88 , which was associated with increased activity in the posterior cerebellar lobule and in the superior parietal lobule . Conclusions . Our study demonstrates that intensive CR tailored for those with impaired abilities affects neural plasticity and improves some aspects of cognitive deficits in MS patients . The reported neurophysiological and behavioral effects corroborate the benefits of our therapeutic approach , which might have a reliable application in the clinical management of cognitive deficits in MS Cognitive impairments in multiple sclerosis ( MS ) extend to tasks dem and ing prospect i ve memory ( PM ) : remembering to perform an intended act during ongoing activity . This study investigated whether emotional content influenced the effects of MS on PM , following evidence that emotional valence can influence other aspects of memory . Thirty participants with MS were compared to 30 controls on a PM task , Virtual Week , in which emotion was manipulated . People with MS showed a consistent deficit in PM performance across manipulations of task and valence . Results indicated that emotionally positive tasks improved the PM performance of MS participants , with implication s for rehabilitation BACKGROUND There is good evidence for the benefits of short-term cognitive stimulation therapy for dementia but little is known about possible long-term effects . AIMS To evaluate the effectiveness of maintenance cognitive stimulation therapy ( CST ) for people with dementia in a single-blind , pragmatic r and omised controlled trial including a sub study with participants taking acetylcholinesterase inhibitors ( AChEIs ) . METHOD The participants were 236 people with dementia from 9 care homes and 9 community services . Prior to r and omisation all participants received the 7-week , 14-session CST programme . The intervention group received the weekly maintenance CST group programme for 24 weeks . The control group received usual care . Primary outcomes were cognition and quality of life ( clinical trial registration : IS RCT N26286067 ) . RESULTS For the intervention group at the 6-month primary end-point there were significant benefits for self-rated quality of life ( Quality of Life in Alzheimer 's Disease ( QoL-AD ) P = 0.03 ) . At 3 months there were improvements for proxy-rated quality of life ( QoL-AD P = 0.01 , Dementia Quality of Life scale ( DEMQOL ) P = 0.03 ) and activities of daily living ( P = 0.04 ) . The intervention subgroup taking AChEIs showed cognitive benefits ( on the Mini-Mental State Examination ) at 3 ( P = 0.03 ) and 6 months ( P = 0.03 ) . CONCLUSIONS Continuing CST improves quality of life ; and improves cognition for those taking AChEIs BACKGROUND Cognitive Stimulation Therapy ( CST ) is effective and cost-effective for people with mild-to-moderate dementia when delivered biweekly over 7 weeks . AIMS To examine whether longer-term ( maintenance ) CST is cost-effective when added to usual care . METHODS Cost-effectiveness analysis within multicenter , single-blind , pragmatic r and omized controlled trial ; subgroup analysis for people taking acetylcholinesterase inhibitors ( ACHEIs ) . A total of 236 participants with mild-to-moderate dementia received CST for 7 weeks . They were r and omized to either weekly maintenance CST added to usual care or usual care alone for 24 weeks . RESULTS Although outcome gains were modest over 6 months , maintenance CST appeared cost-effective when looking at self-rated quality of life as primary outcome , and cognition ( MMSE ) and proxy-rated quality -adjusted life years as secondary outcomes . CST in combination with ACHEIs  offered cost-effectiveness gains when outcome was measured as cognition . CONCLUSIONS Continuation of CST is likely to be cost-effective for people with mild-to-moderate dementia The chronic and progressive nature of multiple sclerosis ( MS ) often excludes patients from neuropsychological treatment . At the Multiple Sclerosis Rehabilitation Hospital , Haslev , 40 patients with mild to moderate cognitive and behavioral impairment associated with MS were r and omized to either specific cognitive treatment ( 20 pts ) by direct training , compensatory strategies and neuropsychotherapy , or to non‐specific , deliberately diffuse mental stimulation ( 20 pts ) . Treatment was for a mean of 46 days . The effects of treatment were evaluated by neuropsychological tests before treatment , immediately after treatment ( short‐term effects ) and 6 months later ( long‐term effects ) . After short‐term treatment , effects on cognitive measures were not convincing , but on the Beck Depression Inventory ( BDI ) the specific cognitive treatment group reported significantly less depression . After 6 months only this group showed an effect , since the visuo‐spatial memory was improved . However , the depression ratings ( BDI ) were almost maintained from the short‐term level . Interestingly , the non‐specific treatment group rated themselves as significantly more depressed . Conclusively , it is worth while to offer specific neuropsychological treatment to MS patients with cognitive and behavioral dysfunction Alzheimer 's disease is a progressive , neurodegenerative condition characterized by deficits in cognition , inability to perform activities of daily living , and alterations in behavior . Galantamine hydrobromide is the newest acetylcholinesterase inhibitor ( AChEI ) approved in the United States for the treatment of mild-to-moderate AD . The safety and efficacy of galantamine has been demonstrated in multiple r and omized , Phase III trials of > 2,600 patients with mild-to-moderate AD . Studies have found that galantamine  improved or maintained performance in all domains of AD ( cognition , function , behavior , and caregiver burden ) in the short term and slowed the decline in performance or maintained baseline performance through 12 months . The dual mechanism of action may make galantamine a reasonable treatment option for both newly diagnosed patients and patients who have not benefitted from or have poorly tolerated current therapy Objective : Examine the efficacy of armodafinil in improving cognition in patients with multiple sclerosis ( MS ) . Background : Many patients with MS experience cognitive difficulties .  Armodafinil has shown promise as a cognitive enhancer in other patient population s. No studies have examined whether armodafinil improves cognition in patients with MS . Methods : We conducted a double-blind , placebo-controlled , crossover study testing the efficacy of armodafinil in reducing cognitive problems in patients with MS . We r and omized 17 patients to receive a dose of  lactose placebo  about 2 hours before they underwent a neuropsychological testing session . After a week-long washout period , we gave them a single 250-mg dose of armodafinil about 2 hours before testing them a second time . We r and omized another 16 patients to receive the active drug first , then the placebo .  We excluded 3 of the participants before analyzing the data . Results : After correcting for multiple comparisons of the 8 neuropsychological dependent measures , we found that the patients had significantly improved delayed memory on a list-learning task after they took armodafinil ( P=0.0005 ) , but no improvement on measures of executive function , visual memory , processing speed , or self-reported fatigue . Conclusions : Results provide preliminary evidence that armodafinil may improve delayed verbal recall in patients with MS . A larger trial showing enhanced memory among patients taking long-term armodafinil  could serve as a foundation for its possible clinical use as a memory enhancer in patients with MS Background : There is preliminary evidence on the positive effects of neuropsychological rehabilitation on cognition in multiple sclerosis ( MS ) , but the generalisability of the findings is limited by method ological problems . Objective : The aim of the present study was to determine the effects of strategy -oriented neuropsychological rehabilitation on MS . Methods : A total of 102 relapsing – remitting MS patients with subjective and objective attentional deficits were r and omised into an intervention and a control group .  Neuropsychological assessment  s were performed at baseline , at three months immediately after the intervention , and at six months . Patients in the intervention group received neuropsychological rehabilitation once a week in 60-minute sessions for 13 consecutive weeks . The control group received no intervention . Results : Neuropsychological rehabilitation including computer-based attention and working memory retraining , psychoeducation , strategy learning and psychological support did not improve cognitive performance but had a positive effect on perceived cognitive deficits . The intervention group perceived significantly fewer deficits than the control group both immediately after the intervention and at six months . The personal rehabilitation goals were also well achieved . Conclusions : Strategy -oriented neuropsychological rehabilitation did not improve cognitive performance but reduced perceived cognitive deficits in MS Objective Functional electrical stimulation ( FES ) is used clinical ly in the management of drop foot in people suffering from neurological conditions . The aim of the study was to investigate the effects of FES , in terms of speed and physiological cost of gait , in people with multiple sclerosis ( pwMS ) . Methods Twelve pwMS and 12 healthy matched controls walked at their own preferred walking speed ( PWS ) for 5 min around a 10 m elliptical course . Subjects with MS completed the protocol with and without using their FES . In addition , control subjects completed the protocol twice more walking at the same PWS of the pwMS to which they were matched . Results Wearing FES lead to a significant improvement in walking speed ( 0.49 ms−1 and 0.43 ms−1 with and without their FES respectively ; P < 0.001 ) and a significant reduction in the physiological cost of gait ( 0.41 mL min−1 kg−1 m−1 and 0.46 mL min−1 kg−1 m−1 with and without FES respectively ; P = 0.017 ) in pwMS . The speed of walking , oxygen uptake , and physiological cost were significantly different between pwMS and controls both at preferred and matched speeds . Although pwMS exhibit a higher physiological cost of walking  , FES offers an orthotic benefit to pwMS and should be considered as a possible treatment option Background : Cognitive dysfunction is very common in multiple sclerosis ( MS ) and it severely impairs patients ’ quality of life . Thus , we explored whether memantine might improve cognitive performance in patients with MS . Methods : We conducted a pilot trial with memantine ( 30 mg/day ) in patients with MS with cognitive impairment . The trial was design ed as a 1-year , r and omized , double-blind , crossover study comparing memantine against a placebo in 60 patients with MS and cognitive impairment . Cognitive impairment was defined as the performance 1.5 st and ard deviations below the normative data in at least two tests of two cognitive domains in the Brief Repeatable Battery – Neuropsychology . The primary endpoint was improvement of verbal memory and the secondary endpoints were safety and improvements in the other cognitive domains , disability and quality of life . The trial was registered at www . clinical trials.org : NCT00638833 . Results : Although 19 patients had been included , the trial was halted after nine patients reported a worsening of their neurologic symptoms that deteriorated their quality of life . Seven of the nine patients in the memantine arm had blurred vision , fatigue , severe headache , increased muscle weakness , walking difficulties , or unstable gait . Only two patients in the placebo group reported neurologic symptoms and in both cases they were related with changes in their disease-modifying therapy . The adverse events only occurred on reaching the maximum dose ( 30 mg/day ) . After stopping medication , the patients reverted to their baseline disability within a few days . Conclusions : Memantine at a dose of 30 mg/day may induce transient worsening of neurologic symptoms of multiple sclerosis Multiple sclerosis ( MS ) causes cognitive impairment including slowed processing speed and problems with learning and memory . Stimulants are attractive c and i date s for improving mental speed but carry risk of addiction and other adverse behavioral effects . Lisdexamfetamine dimesylate ( LDX ) is a d-amphetamine prodrug currently approved for attention deficit ( hyperactivity ) disorder with the potential to be better tolerated due to its prolonged clinical effect . This phase II placebo-controlled , double-blind study aim ed to assess the safety and efficacy of LDX in cognitively impaired MS patients . Subjects were patients with clinical ly definite MS , aged 18–56 years , and impaired on either of two primary outcomes : the Symbol Digit Modalities Test ( SDMT ) or the  Paced Auditory Serial Addition Test ( PASAT ) . Both SDMT and PASAT are measures of cognitive processing speed . Of 174 MS patients screened , 63 were r and omized to 30 mg of LDX or placebo in a 2:1 fashion ; the dose was increased as tolerated to 70 mg over 4 weeks and then maintained for another 4 weeks . Secondary outcomes were the Brief Visuospatial Memory Test Revised ( BVMTR ) , the California Verbal Learning Test 2nd edition ( CVLT2 ) , both measures of episodic memory , and the Behavioral Rating Inventory of Executive Function for adults ( BRIEF-A ) , a self-report measure of executive function . Fatigue and depression were also evaluated . There was significant improvement in the SDMT score ( + 4.6 vs. + 1.3 ) and CVLT2 score ( + 4.7 vs. −0.9 ) in the LDX group compared with the placebo group among the 49 completers . There was no change on the other outcomes . A high proportion of both LDX-treated and placebo-treated subjects reported adverse events ( 73.5 % vs. 68.4 % ) . However , there were no serious adverse events noted in the study . These preliminary data indicate that LDX has the potential to be an efficacious treatment for MS patients with cognitive impairment BACKGROUND Balance impairment and an increased rate of falls are commonly reported in individuals with multiple sclerosis ( MS ) . Force platform-generated center of pressure ( COP ) metrics have previously been recommended as an outcome measure to quantify balance deficits and distinguish between fallers and nonfallers in MS . Information is limited regarding the preservation of postural control in individuals with MS over extended time frames in the absence of an intervention . This report examines the test-retest reliability and magnitude of change of COP motion during st and ing balance over 3 months . METHODS Twenty individuals with MS and a history of falling underwent  testing  on two occasions 3 months apart in the absence of an intervention . On both occasions , participants completed two 30-second trials of three conditions : eyes open , eyes closed , and eyes open with concurrent cognitive challenge ( dual task ) . Measures of COP area , velocity , and temporal structure were calculated and included in the reliability analysis . RESULTS The COP metrics displayed fair-to-excellent reliability over 3 months without an intervention . Reliability was maintained across the three commonly used balance conditions . CONCLUSIONS These results offer insight into the reliability of COP measures over a 3-month period in MS and can inform the use of COP metrics for future study design ( eg , sample size estimates ) and balance outcome assessment during r and omized controlled trials and fall-prevention studies in individuals with MS Background : Cognitive decline and fatigue are typical in multiple sclerosis ( MS ) . However , there is no official medication for either of these symptoms . Objective : The purpose of this study was to estimate the effects of a single dose of rivastigmine on processing speed and associated brain activity in patients with MS and subjective cognitive fatigue . Methods : Fifteen patients with MS and subjective cognitive fatigue and 13 healthy controls ( HCs ) matched for age , gender and education performed a neuropsychological assessment and functional (f)MRI . A modified version of the Paced Visual Serial Addition Test ( mPVSAT ) was used as the behavioural task during fMRIs . After the first scanning session , both groups were r and omly divided into two subgroups receiving either rivastigmine or placebo . A single dose of rivastigmine or placebo was administrated double-blindly and 2.5 hours later the scanning was repeated . Results : At baseline , the patients with MS showed slower processing speed in mPVSAT compared with the HCs . They also demonstrated stronger bilateral frontal activation after sustained cognitive effort than the HCs . Performance improvement and a further activation increase in the left anterior frontal cortex and additional activation in the right cerebellum were observed in patients who received rivastigmine but not in patients on placebo , or in HCs with placebo or rivastigmine . Conclusion : These preliminary findings suggest that rivastigmine may improve cognitive processing speed by enhancing compensatory brain activation in patients with MS BACKGROUND Amantadine hydrochloride and pemoline , both frequently used to treat the fatigue of multiple sclerosis ( MS ) , may also improve attention and other cognitive functions in MS . To our knowledge , these agents have never been compared in a placebo-controlled trial of patients with MS . OBJECTIVE To evaluate the effects of amantadine and pemoline on cognitive functioning in MS . METHODS A total of 45 ambulatory patients with MS and severe fatigue were treated for 6 weeks with amantadine , pemoline , or placebo using a parallel group design . They underwent comprehensive neuropsychological testing to determine treatment effects on cognitive functioning . Primary outcome measures were tests of attention ( Digit Span , Trail Making Test , and Symbol Digit Modalities Test ) , verbal memory ( Selective Reminding Test ) , nonverbal memory ( Benton Visual Retention Test ) , and motor speed ( Finger Tapping Test ) . RESULTS Fatigue did not significantly correlate with any of the neuropsychological outcome measures at baseline or after treatment . All three treatment groups improved on tests of attention ( P < .003 ) , verbal memory ( P < .001 ) , and motor speed ( P < .002 ) . There were no significant differences between amantadine , pemoline , and placebo . CONCLUSIONS Cognitive functioning in MS is independent of fatigue . Neither amantadine nor pemoline enhances cognitive performance in MS compared with placebo Twenty-four out- patients with established multiple sclerosis ( MS ) who had been neurologically assessed underwent detailed  psychiatric , cognitive and social assessment s. Depression was associated with significant cognitive impairment and with social stress but not with degree of neurological impairment , specific neurological symptoms , disability or h and icap . It is suggested that depression in relapsing-remitting MS may arise when cognitive deficits cause problems in occupational performance and impinge on close personal relationships RATIONALE Multiple sclerosis ( MS ) patients exhibit cognitive deficits that negatively impact quality of life . The Relative Consequence Model suggests that problems with information processing speed ( IPS ) may be the basis for many of these cognitive difficulties . OBJECTIVE To investigate , with functional magnetic resonance imaging ( fMRI ) , if an IPS task ( the Computerized Test of Information Processing ( CTIP ) ) would reveal neurophysiological differences between MS patients and matched controls . METHODS Performance and neural activation were investigated in twelve cognitively impaired MS patients and 12 matched controls as each performed the CTIP .  The CTIP measures reaction time ( RT ) and errors on three tasks  ( simple RT , choice RT  and  semantic search RT ) with increasing cognitive dem and s. RESULTS Participants demonstrated increased RT with increased task complexity . Patients showed longer RTs for the choice RT condition than controls but the pattern of performance across tasks did not vary between groups . Errors were not significantly different between groups . Imaging results for both the choice and the semantic search conditions revealed significant differences between groups involving a compensatory increase in activation in MS participants compared to controls in prefrontal cortex and right temporal gyri . However , there were also areas of decreased activity in MS participants when compared with controls in left temporal gyri . CONCLUSIONS Significantly different neural activation patterns between MS patients and controls were associated with IPS , as measured by the CTIP BACKGROUND Acetylcholinesterase inhibitors ( AChEIs ) can provide benefits at the cognitive , behavioral , and functional levels to patients with Alzheimer 's disease ( AD ) . With more AChEIs now available , treatment considerations may include whether the patient has had prior exposure to an AChEI . OBJECTIVE To compare the effects of galantamine in patients with AD who were previously exposed to AChEIs  with its effects in patients with AD who had no previous exposure , using a post hoc analysis . RESULTS Patients in groups treated with galantamine 16 mg/day and 24 mg/day achieved statistically significant improvements in ADAS-cog/11 scores in comparison with those who received placebo ( naive : p = 0.003 and 0.005 , respectively ; prior exposure : p < 0.001 and 0.001 , respectively ) . Similarly , a greater number of patients treated with galantamine 16 mg/day and 24 mg/day exhibited no change or improvement in their CIBIC-plus scores compared to patients who received placebo ( naive : p < 0.001 and p = 0.077 , respectively ; prior exposure : p = 0.005 and p = 0.001 , respectively ) . There were no significant differences in adverse events between naive patients and those with prior exposure to AChEIs . CONCLUSIONS Galantamine is effective and safe in patients with AD , regardless of previous exposure to AChEIs Background : Inferences about long-term effects of therapies in multiple sclerosis ( MS ) have been based on surrogate markers studied in short-term trials . Preventing progressive disability is the key therapeutic goal but there remains no vali date d definition for its measurement in a trial context . Meanwhile , MS trials continue to shorten and to depend on unvali date d surrogates . Since there have been no treatment cl aims for improving unremitting disability , worsening of disability in the placebo/control arm must occur for effectiveness on this outcome to be shown . Methods : We examined widely-used clinical surrogates of long-term disability progression in individual patients with MS within a unique data base from the placebo arms of 31 r and omized clinical trials . Results : Detection of treatment effects in secondary progressive MS trials is undermined by noise in disability measurement . Whereas existing measures can be partially vali date d in secondary progressive MS , this is not the case in relapsing-remitting MS . Here , examination of widely used definitions of treatment failure demonstrated that disability progression was no more likely than similarly defined improvement . Existing definitions of disease progression in short-term intervention trials in relapsing-remitting patients reflect r and om variation , measurement error , and remitting relapses . Conclusion : Clinical surrogates of unremitting disability used in trials of relapsing-remitting multiple sclerosis can not be vali date d. Trials have been too short or degrees of disability change too small to measure the key outcomes . These analyses highlight the difficulty in determining effectiveness of therapy in chronic diseases Objectives : The aim of this study was to evaluate a short-term non-specific home-based 6-week cognitive training for its effect on neuropsychological deficits and depression . Subjects and Methods : Cognitive and affective abilities of patients with MS were compared with healthy controls using an identical neuropsychological test battery . Re-testing was performed after 6 weeks of cognitive home-based training . Results : Patients already showed cognitive deficits at baseline . Cognitive training result ed in a significant improvement in several skills , in particular with respect to visuoconstructive and figural long-term memory . In addition , prior depressed mood and quality of life improved in MS patients during the training period and remained up to 6 months . Conclusions : Our study corroborated the early appearance of neuropsychological deficits in MS . Mental training , although unspecific , lead to improvements with respect to attention and memory functions in patients , and to some degree in control subjects , which may last for more than 6 months Cognitive impairment in individuals with multiple sclerosis ( MS ) is now well recognized . One of the most common cognitive deficits is found in memory functioning , largely due to impaired acquisition . We examined functional brain activity 6 months after memory retraining in individuals with MS . The current report presents long term follow-up results from a r and omized clinical trial on a memory rehabilitation protocol known as the modified Story Memory Technique .  Behavioral memory performance and brain activity of all participants were evaluated at baseline , immediately after treatment , and 6 months after treatment . Results revealed that previously observed increases in patterns of cerebral activation during learning immediately after memory training were maintained 6 months post training Prospect i ve memory ( PM ) , which is the ability to remember to carry out actions that are planned for the future , plays an important role in professional and social life as well as in activities of daily living . This study examined PM performance among adults with multiple sclerosis ( MS ) and evaluated the efficacy of a mnemonic strategy , implementation intentions . Compared to controls , adults with MS were impaired on PM , both in terms of acting when encountering the correct circumstances ( prospect i ve component ) and in terms of remembering the correct action to perform ( retrospective component ) . The prospect ive-component deficit was greater for tasks that depended on more re source -dem and ing cognitive processes and smaller on tasks that could be performed more automatically . Use of implementation intentions improved MS-group  performance on the prospect i ve component , particularly on the more re source -dem and ing tasks , consistent with the explanation that implementation intentions improved performance by allowing the use of more automatic processes to perform these PM tasks . Implication s for providing environmental support to encourage the use of mnemonic strategies are discussed Vascular dementia ( VaD ) is a condition that involves deterioration in cognitive and non‐cognitive areas . Although cognitive impairment is the defining symptom evaluated during clinical trials , changes in non‐cognitive areas such as behavior , global functioning and activities of daily living are assessed because they assist in determining quality of life and overall well‐being . Therapy has focused traditionally on preventing and controlling risk factors , as no approved treatments are currently available for these patients . Acetylcholinesterase inhibitors ( AChEIs ) , the treatment of choice in patients with Alzheimer 's disease ( AD ) , are a potential treatment option for patients with VaD. Galantamine , an AChEI with nicotinic receptor modulation , has demonstrated clinical ly relevant benefits ( cognition , global functioning , functional ability , behavior ) in patients with either AD with cerebrovascular disease ( AD with CVD ) or probable VaD in a 6‐month , r and omized , double‐blind , placebo‐controlled study Fatigue is a common symptom of multiple sclerosis ( MS ) that is without an effective treatment . A double-blind , controlled study of fatigue treatment was conducted to evaluate the efficacy of amantadine hydrochloride in treating  MS-associated fatigue .  Since fatigue can not be characterized by a single symptom or behavior , a variety of neuropsychological , behavioral , and self-report measures were used to monitor changes across different systems . According to patients ' daily diary ratings , amantadine produced small but statistically significant improvements in fatigue across four of seven dimensions ( overall energy level , concentration , problem solving , and sense of well-being ) . In addition , patients with MS who were taking amantadine  performed slightly better on the Stroop Interference Test , an attentional measure of freedom from distracting information . Although retrospective reports by patients with MS did not confirm the degree of improvement recorded on a daily basis , the study 's results suggested that amantadine may offer modest benefits in alleviating the day-to-day subjective experience of fatigue
Whilst there was only a limited pool of relatively small trials and a number of different compounds , we found that collectively , both AChEIs ( donepezil and rivastigmine ) and stimulants ( methylpheni date , modafinil , l‐amphetamine sulfate and lisdexamfetamine dimesylate ) offered no significant benefits over placebo on measures of processing speed , working memory , verbal fluency , verbal memory , visuospatial memory or executive functioning
HighlightsCognitive deficits are present in up to 70 % of people with multiple sclerosis (MS).There are no approved treatments for these difficulties .
We examined whether adjunctive pharmacotherapies can improve cognition in MS.Acetylcholinesterase inhibitors offered no significant benefits over placebo .
Stimulant‐based medications offered no significant benefits over placebo .
& NA ; We sought to examine the effectiveness of acetylcholinesterase inhibitors ( AChEIs ) and stimulant‐based medications for improving cognitive performance in patients with multiple sclerosis ( MS ) .