R H B Benedict

University at Buffalo, The State University of New York, Buffalo, New York, United States

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Publications (95)

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    Full-text Poster · Mar 2016
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    [Show abstract] [Hide abstract] ABSTRACT: Objective: To investigate the reliability and validity of a Brazilian-Portuguese adaptation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Method: A Brazilian sample of 58 multiple sclerosis (MS) patients and 58 healthy controls (HC) were administered the Brazilian-Portuguese BICAMS test battery, comprising the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test Second Edition (CVLT2), and the Brief Visuospatial Memory Test Revised (BVMTR). Mean differences between groups on BICAMS tests were assessed using analysis of covariance (ANCOVA), controlling for age, gender, education, anxiety, and depression. Test-retest data were obtained from 49 of the MS patients, two weeks after the initial assessment. Results: The MS patient group scored significantly lower on all BICAMS tests (CVLT2 F1,110 = 28.99, p < .001; BVMTR F1,110 = 7.77, p < .01; SDMT F1,110 = 21.09, p < .001). Mixed-factor ANCOVAs tested differences in learning curves across trials for CVLT2 and BVMTR. HCs had significantly steeper learning curves on both CVLT2 (F1,111 = 10.82, p < .01) and BVMTR (F1,110 = 7.816, p < .01). These findings support diagnostic validity of the Brazilian-Portuguese adaptation. Test-retest reliability was satisfactory for SDMT, CVLT2, and BVMTR (.86, .84, and .77, respectively). Conclusion: The results suggest that this Brazilian version of the BICAMS will be a valid and reliable measure once complete normative data become available.
    Full-text Article · Oct 2015 · The Clinical Neuropsychologist
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    Seth E Frndak · Lauren N Irwin · Victoria M Kordovski · [...] · Ralph H B Benedict
    [Show abstract] [Hide abstract] ABSTRACT: Determine if a recently validated online survey of negative work events can predict future job loss among multiple sclerosis (MS) patients. Evaluated were 284 employed individuals (63 healthy controls, 221 MS patients), every three months, using an online vocational monitoring tool. Job loss rates in MS patients were compared with the healthy controls. Survey responses from MS patients suffering job loss (n=23) were then compared to those maintaining employment. Analyses focused on the frequency of negative work events. While 23 (10%) of MS patients lost their job after baseline, there was no job loss among the healthy controls. Compared to stably employed patients, those suffering job loss had been diagnosed with MS later in life, were more likely to report a progressive disease course, and had greater physical disability as measured by the Patient Derived Disease Steps (PDDS). Declining patients were also more likely to report negative work events within three months of job loss (e.g., verbal criticism for errors or removal of responsibilities). Stepwise logistic regression predicting MS job loss retained the PDDS, age at diagnosis, years working for employer and reporting a negative work event. The results show that physical disability and patient reported risk factors for job loss can be monitored using an online survey tool. The tool can trigger clinical assessments to help prevent unemployment and assist patients in procuring disability benefits. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text Article · Jul 2015 · Journal of the neurological sciences
  • Declan T Chard · Ralph H B Benedict
    [Show abstract] [Hide abstract] ABSTRACT: Cognitive deficits occur in 40%-70% of people with multiple sclerosis (MS); they occur early in the clinical course of the disease, and may substantially reduce day-to-day functioning, affecting employment, instrumental activities of daily living, and adherence to medications.(1) There are currently no treatments proven to slow cognitive decline in MS, and as such it is unsurprising that cognition is not usually assessed as part of a routine clinical review. However, given the substantial difficulties that cognitive dysfunction causes people with MS, it represents a highly clinically relevant target of further research and major unmet need. Increasingly, neuropsychological testing is considered in the development of new neurologic disability metrics for clinical trials(2) and as measures of MS disease activity.(3</SUP)
    Article · Jan 2015 · Neurology
  • Article · Dec 2014 · Neurology: Clinical Practice (Print)
  • [Show abstract] [Hide abstract] ABSTRACT: The Symbol Digit Modalities Test (SDMT) has been proposed to replace the Paced Auditory Serial Addition Test-3 (PASAT-3) in the Multiple Sclerosis Functional Composite because it has the same validity but easy and shorter administration. However, among the two tests, the one that is most affected by culture is still unknown. The purpose of this study was to compare the performance of Argentinian and North American populations on the SDMT and PASAT-3. The SDMT and PASAT-3 were administered to 137 healthy volunteers from Buffalo, NY, and 137 healthy participants from Buenos Aires, Argentina. Participants were matched by gender, age (±2), and education (±1). Significant differences were found on the SDMT but not on the PASAT-3. Significant and low correlations were found between the tests and years of education. The SDMT is more affected by culture than is the PASAT-3. Possible interpretations of this result are presented.
    Article · Nov 2014 · Applied Neuropsychology: Adult
  • C.M. Modica · R Zivadinov · M.G. Dwyer · [...] · R H B Benedict
    [Show abstract] [Hide abstract] ABSTRACT: Background and purpose: There is a well-established correlation between deep gray matter atrophy and cognitive dysfunction in MS. However, the cause of these signs of neurodegeneration is poorly understood. Iron accumulation in the deep gray matter is higher in patients with MS compared with age- and sex-matched healthy controls, and could contribute to disease progression. Our objective was to evaluate the relationship between iron and cognition in several deep gray matter structures while accounting for the influence of volume loss. Materials and methods: Eighty-five patients with MS and 27 healthy volunteers underwent 3T MR imaging and neuropsychological examination. We used SWI filtered phase to analyze the mean phase of low-phase voxels, indicative of abnormal iron accumulation. Results: Correlations between mean phase of low-phase voxels and cognitive tests were found in the caudate nucleus (r = 0.240 and 0.232), putamen (r = 0.368, 0.252, and 0.238), globus pallidus (r = 0.235), and pulvinar nucleus of thalamus (r = 0.244, 0.255, and 0.251) (P < .05). However, correlations between structure volume and cognition were more robust. Furthermore, the introduction of structure volume into hierarchical regression analyses after iron metrics significantly improved most models, and mean phase of low-phase voxels did not account for significant variance after volume. Conclusions: These findings suggest that iron accumulation plays a significant, if minor, role in MS cognitive decline.
    Article · Jun 2014 · American Journal of Neuroradiology
  • Karen Reimers · Natalie Emmert · Ralph Benedict · Kinga Szigeti
    Article · Jul 2013 · Alzheimer's and Dementia
  • D.W. Langdon · R.H.B. Benedict · E.M. Wicklein · [...] · S Fredrikson
    [Show abstract] [Hide abstract] ABSTRACT: Objective: To assess the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) in patients with clinically isolated syndrome (CIS). Methods: 130 European CIS patients and 60 relatives completed the MSNQ. Results: The mean (SD) MSNQ score for CIS patients was 15.5 (10.8) and for their informants 11.3 (9.6). Neither the CIS patient nor relative MSNQ report scores correlated with any of the cognitive test scores in the Brief Repeatable Battery of Neuropsychological Tests, but they were significantly related to psychosocial scales including depression. Conclusions: In CIS, patient and relative MSNQ scores are influenced by psychosocial variables rather than actual objective cognitive status. Formal cognitive test assessment is recommended for CIS patients.
    Article · Apr 2013 · European Neurology
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    F. Caceres · S. Vanotti · R.H.B. Benedict · Relaccem Work Group
    [Show abstract] [Hide abstract] ABSTRACT: Cognitive impairment and psychiatric symptoms impact many aspects of the lives of people with multiple sclerosis [MS]. This literature is based largely on North American and Western European samples, and little is known about these aspects of MS disability in Latin America. RELACCEM is a longitudinal, multicenter study including MS centers in Argentina, Chile, Columbia, Venezuela, Uruguay and Mexico. The goal is to determine the prevalence of cognitive impairment (two or more cognitive domains under the 5th percentile of healthy controls performance) and the full range of neuropsychiatric symptoms in these regions, and how these symptoms relate to caregiver burden and employment. Participants were 110 patients with relapsing-remitting [RR] course and less than five years of disease duration. Thirty-four healthy controls were also recruited. All participants were evaluated in one of 14 specialized centers. In additional to overall neurological disability, both cognition and neuropsychiatric symptoms distinguished patients and controls. The prevalence of cognitive impairment was 34.5% and 20.9% presented with clinically significant neuropsychiatric symptomatology. Cognitive impairment was a significant predictor of employment status. This is the first multicenter epidemiological study of MS-associated cognitive and neuropsychiatric symptoms in Latin America. Results indicate that cognitive dysfunction and psychiatric decline symptoms, fatigue, depression and caregiver burden are already apparent at an early stage of the disease. The presence of neuropsychiatric abnormalities indicates the need for appropriate interventions as early as possible to mitigate psychosocial consequences of caregiver burden. © 2013 Elsevier B.V. All rights reserved.
    Full-text Article · Jan 2013 · Multiple Sclerosis and Related Disorders
  • Fernando Caceres · Sandra Vanotti · Ralph H. Benedict
    Conference Paper · Dec 2012
  • [Show abstract] [Hide abstract] ABSTRACT: Cognitive impairment in multiple sclerosis (MS) is common, debilitating and burdensome. Key evidence from trials was reviewed to enable recommendations to be made to guide clinical practice and research. Behavioural and pharmacological interventions on cognition reported in published studies were reviewed. Most studies evaluating behavioural treatment for impairment in learning and memory, deficits of attention and executive function have demonstrated some improvement. Controlled studies in relapsing remitting MS indicate interferon (IFN) β-1b and IFN β-1a were associated with modest cognitive improvement. The effects of symptomatic therapies such as modafinil and donepezil are inconsistent. Most studies yielding positive findings have significant methodological difficulties limiting the confidence in making any broad treatment recommendations. There are no published reports of glatiramer acetate, natalizumab and fingolimod being effective in improving cognition in controlled trials. The effects of disease modifying therapies in other forms of MS and clinically isolated syndrome have not yielded positive results. Data linking behavioural therapy, symptomatic treatment or disease modifying treatment, to either reducing cognitive decline or improving impaired cognition are limited and inconsistent. The treatment and prevention of cognitive impairment needs to remain a key research focus, identifying new interventions and improving clinical trial methodology.
    Article · Nov 2012 · Journal of Neurology
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    [Show abstract] [Hide abstract] ABSTRACT: In the largest sample studied to date, we measured cognitive functioning in children and adolescents with pediatric multiple sclerosis (n = 187) as well as those with clinically isolated syndrome (n = 44). Participants were consecutively enrolled from six United States Pediatric Multiple Sclerosis Centers of Excellence. Participants had a mean of 14.8 ± 2.6 years of age and an average disease duration of 1.9 ± 2.2 years. A total of 65 (35%) children with multiple sclerosis and 8 (18%) with clinically isolated syndrome met criteria for cognitive impairment. The most frequent areas involved were fine motor coordination (54%), visuomotor integration (50%), and speeded information processing (35%). A diagnosis of multiple sclerosis (odds ratio = 3.60, confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability (odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only independent predictors of cognitive impairment. Cognitive impairment may occur early in these patients, and prompt recognition is critical for their care.
    Full-text Article · Nov 2012 · Journal of child neurology
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    Jana Blahova Dusankova · Tomas Kalincik · Eva Havrdova · Ralph H B Benedict
    [Show abstract] [Hide abstract] ABSTRACT: The available instruments for cognitive assessment in multiple sclerosis (MS) require considerable time and resources, and are not readily available in all countries. The study aimed to examine validity of the Czech translation of the Minimal Assessment of Cognitive Function in MS (MACFIMS), to validate the Brief International Cognitive Assessment for MS (BICAMS), and to compare their outcomes. We evaluated 367 MS patients and 134 healthy controls with the MACFIMS battery, which comprises the three tests of the BICAMS (Symbol Digit Modalities Test, Brief Visuospatial Memory Test-Revised, California Verbal Learning Test, second edition). The most accurate BICAMS criterion of cognitive deficit was that of at least one of the overall three tests outside the normal range (sensitivity = 94%, specificity = 86%, p = 10(-28)). Outcomes of the Czech translation of the MACFIMS were comparable to its original. The MACFIMS and the BICAMS identified cognitive deficit in 55% and 58% of the MS patients, respectively. Both batteries predicted patient self-reported vocational status. This is the first study to show that the BICAMS is highly sensitive and specific to cognitive impairment in MS as defined by the MACFIMS. This impairment is associated with vocational status. Czech versions of the studied batteries have now been validated.
    Full-text Article · Oct 2012 · The Clinical Neuropsychologist
  • Elizabeth Fisher · Ralph H B Benedict
    [Show abstract] [Hide abstract] ABSTRACT: Cognitive impairment is a known consequence of multiple sclerosis (MS), affecting roughly 50% of all patients with MS.(1) Information processing speed and memory are the most commonly affected domains, although deficits in executive function are also frequently reported.(2) That cognitive impairment affects meaningful activities such as work is well known.(3) The pathophysiologic basis for cognitive dysfunction in MS is an area of great interest because a better understanding could lead to more sensitive markers and improved therapies to slow or prevent cognitive decline. MRI offers some insight into the associations between various types of tissue damage and cognitive impairment. Early studies reported moderate correlations between cognitive performance and global measures of white matter lesion volume and atrophy,(4) and more recent studies focusing on cortical lesions and regional gray matter atrophy have demonstrated stronger associations.(5).
    Article · Sep 2012 · Neurology
  • Sarah A. Morrow · Audrey Smerbeck · Kara Patrick · [...] · Ralph H. B. Benedict
    [Show abstract] [Hide abstract] ABSTRACT: Multiple sclerosis (MS) causes cognitive impairment including slowed processing speed and problems with learning and memory. Stimulants are attractive candidates 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 aimed to assess the safety and efficacy of LDX in cognitively impaired MS patients. Subjects were patients with clinically 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 randomized 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.
    Article · Sep 2012 · Journal of Neurology
  • A. M. J. Smerbeck · J Parrish · E A Yeh · [...] · R H B Benedict
    [Show abstract] [Hide abstract] ABSTRACT: The National Multiple Sclerosis Society Consensus Neuropsychological Battery for Pediatric Multiple Sclerosis (NBPMS) was designed to detect cognitive impairment in children and adolescents with multiple sclerosis. One weakness of the battery is the reliance on published manual-based normative samples varying in size and quality. These primary sources base interpretation on discrete age bands, a practice which may be particularly problematic during periods of rapid development in childhood and adolescence. A further impediment to valid NBPMS interpretation is the lack of control for demographic factors other than age. We endeavored to develop regression-based norms for the NBPMS by gathering a demographically balanced sample of 102 healthy control children and using their performance to derive normalization, controlling for multiple demographic variables (i.e., age, age(2), gender, parent education). The regression-based normative equations were applied to the performance of 51 children with MS. For many of the major test scores, the regression-based norms more readily detected impairment. As in the case of adult MS, these results indicate that regression-based norms offer interpretive benefits over their manual-based counterparts.
    Article · Aug 2012 · The Clinical Neuropsychologist
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    [Show abstract] [Hide abstract] ABSTRACT: Cognitive dysfunction is common in multiple sclerosis (MS) and validated batteries are limited in languages other than English. We aimed to translate, cross-culturally adapt, validate, and assess reliability of Minimal Assessment of Cognitive Function in MS (MACFIMS) in Persian. The MACFIMS is a well-constructed battery in the MS literature. The battery was adapted to Persian in accordance with available guidelines. A total of 158 MS patients and 90 controls underwent neuropsychological assessment. For reliability assessment the battery was re-administered in a subset of 41 patients after a short interval using alternate forms to mitigate practice effects (approximately 10 days). Patients performed significantly worse than controls in all cognitive tests, supporting discriminant validity of our adapted battery. Approximately half of patients (46.2%) showed cognitive impairment as defined by the impairment in two or more tests. The Symbol Digit Modalities Test was the most robust test by ROC analysis. All tests showed acceptable to good level of reliability. This is the first validation of gold-standard cognitive testing in Persian. The Persian MACFIMS shows nearly the same psychometrics as its English counterpart.
    Full-text Article · Jun 2012 · The Clinical Neuropsychologist
  • [Show abstract] [Hide abstract] ABSTRACT: Background and purpose: CCSVI has been reported to occur at high frequency in MS. Its significance in relation to MR imaging parameters also needs to be determined, both in patients with MS and HCs. Therefore, this study determined the associations of CCSVI and conventional MR imaging outcomes in patients with MS and in HCs. Materials and methods: T2, T1, and gadolinium lesion number, LV, and brain atrophy were assessed on 3T MR imaging in 301 subjects, of whom 162 had RRMS, 66 had secondary-progressive MS subtype, and 73 were HCs. CCSVI was assessed using extracranial and transcranial Doppler evaluation. The MR imaging measure differences were explored with 27 borderline cases for CCSVI, added to both the negative and positive CCSVI groups to assess sensitivity of the results of these cases. Results: No significant differences between subjects with and without CCSVI were found in any of the individual diagnostic subgroups or MS disease subtypes for lesion burden and atrophy measures, independently of the CCSVI classification criteria used, except for a trend for higher T2 lesion number (irrespective of how borderline cases were classified) and lower brain volume (when borderline cases were included in the positive group) in patients with RRMS with CCSVI. No CCSVI or MR imaging differences were found between 26 HCs with, or 47 without, a familial relationship. Conclusions: CCSVI is not associated with more severe lesion burden or brain atrophy in patients with MS or in HCs.
    Article · May 2012 · American Journal of Neuroradiology
  • Article · Apr 2012 · Neurology

Publication Stats

5k Citations


  • 1992-2014
    • University at Buffalo, The State University of New York
      • • Department of Neurology
      • • Department of Psychiatry
      • • Department of Medicine
      Buffalo, New York, United States
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States
  • 2012
    • Buenos Aires Institute of Neuroscience
      Buenos Aires, Buenos Aires F.D., Argentina
  • 2003-2011
    • Buffalo Neuroimaging Analysis Center
      Buffalo, New York, United States
  • 2009
    • Buffalo Medical Group
      Buffalo, New York, United States
  • 2006
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1998-2005
    • Buffalo General Medical Center
      Buffalo, New York, United States
  • 1993-1999
    • Johns Hopkins University
      • Department of Psychiatry and Behavioral Sciences
      Baltimore, Maryland, United States
  • 1995
    • Loyola University Maryland
      Baltimore, Maryland, United States