Contributions of the Rey Auditory Verbal Learning Test (RAVLT) to Cognitive Impairment on the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) Abbey J. Hughes, PhD, Aeysha Brown, MA, Krina Patel, BS, & Meghan Beier, PhD Department of Physical Medicine & Rehabilitation, Johns Hopkins University School of Medicine Annual Meeting of the Consortium of MS Centers 1 May 31 st , 2019 Disclosures • Research Support: – CMSC (PI: Beier) – NICHD 1K23HD086154 (PI: Hughes) – NMSS R-1702-27078 (PI: Beier) • Consultant: – Can Do MS (Hughes, Beier) • The present research represents no conflicts of interest with any of our funding sources or consulting organizations 2
Brief Cognitive Assessment in MS • Cognitive impairment affects 40-70% of individuals with MS (Chiaravallotti et al., 2008) • An expert panel recently convened by the NMSS recommended (Kalb et al., 2018) – Early baseline screening and annual re-screening • BICAMS (at least SDMT) – Positive screen followed by comprehensive assessment • MACFIMS or other 5/30/2019 3 Brief Cognitive Assessment in MS • Examples of abbreviated assessment – BICAMS (Langdon et al., 2012) – Abbreviated MACFIMS (Gromisch et al., 2018) - 30 s SDMT (vs 90 s) - 1 trial BVMT-R (vs 3) - 2 trials CVLT-II (vs 5) - 1 letter COWAT (vs 3) • 1 card sort DKEFS (vs 2) • Improves efficiency, but cost effectiveness is still problematic 5/30/2019 4
RAVLT as alternative to CVLT-II • Some evidence for RAVLT as a potential alternative to the CVLT-II (Beier et al., 2019) – Both measures have 5 trials – RAVLT used in German BICAMS (Filser et al., 2018) – Have shown acceptable equivalence at greater levels of impairment for TBI (Stallings et al., 1995) 5/30/2019 5 Objective • To examine a modified version of the BICAMS – using the RAVLT (instead of CVLT-II) – in assessing cognitive impairment in MS – Examine correlations between the RAVLT and CVLT-II learning trial scores – Compare the rates of cognitive impairment observed on the RAVLT version versus the standard BICAMS – Assess the degree to which the RAVLT vs CVLT-II contribute to cognitive impairment on the standard BICAMS 6
Participants • N = 100 • Recruited from a university-affiliated MS center • Gender: 76% female • Race: 83% white • Age: mean 46.2 years (19-72) • Education: mean 15.5 years (10-22) • MS Type: 77% RRMS 7 Measures • Measures – Standard BICAMS • CVLT-II learning trials • BVMT-R learning trials • SDMT • Impairment defined as: – ≥ 1 BICAMS measure ≥ 1.5 SD below normative mean – ≥ 1 BICAMS measure ≥ 2.0 SD below normative mean – Modified version • RAVLT learning trials • BVMT-R learning trials • SDMT 8
Analyses • Pearson’s r correlation between RAVLT and CVLT-II • Cohen’s kappa (κ) comparing rates of impairment between standard BICAMS and modified version • Step-wise logistic regression – Step 1: CVLT-II or RAVLT – Step 2: SDMT and BVMT-R – Outcome: BICAMS impairment (dichotomized) – Covariates: age, gender, education 9 Results • Impaired at 1.5 SD – CVLT-II: 15% – RAVLT: 16% – BICAMS: 40% – Modified BICAMS: 41% • Impaired at 2.0 SD • RAVLT vs CVLT-II: – CVLT-II: 9% r = .61, p < .001 – RAVLT: 9% – BICAMS: 29% – Modified BICAMS: 28% 5/30/2019 10
Results • Rates of impairment (1.5 SD ) Modified BICAMS (w/ RAVLT) Unimpaired Impaired Total Unimpaired 55 4 59 Standard BICAMS Impaired 3 37 40 (w/ CVLT-II) Total 58 41 99 • κ = .85, p < .001 5/30/2019 11 Results • Rates of impairment (2.0 SD ) Modified BICAMS (w/ RAVLT) Unimpaired Impaired Total Unimpaired 68 2 71 Standard BICAMS Impaired 3 26 29 (w/ CVLT-II) Total 71 28 99 • κ = .88, p < .001 5/30/2019 12
Results • Outcome: BICAMS impairment (1.5 SD) Step 1 B SE Wald p Exp(B) Age -0.03 0.02 1.30 .26 0.97 Gender -0.04 0.67 0.00 .95 0.96 Education -0.25 0.13 3.69 .06 0.78 CVLT-II -0.21 0.05 21.20 <.001 0.81 Step 2 Age -0.35 0.13 6.99 .01 0.71 Gender -0.09 1.44 0.00 .95 0.92 Education -0.43 0.35 1.53 .22 0.65 CVLT-II -0.34 0.12 8.02 .01 0.72 SDMT -0.47 0.18 6.94 .01 0.62 BVMT-R -0.68 0.26 6.99 .01 0.51 5/30/2019 13 Results • Outcome: BICAMS impairment (1.5 SD) Step 1 B SE Wald p Exp(B) Age 0.00 0.02 0.01 .91 1.00 Gender 0.04 0.54 0.01 .94 1.04 Education -0.21 0.10 4.54 .03 0.81 RAVLT -0.09 0.03 9.95 <.001 0.92 Step 2 Age -0.17 0.05 11.53 .00 0.84 Gender -0.08 0.92 0.01 .93 0.92 Education -0.14 0.17 0.68 .41 0.87 RAVLT -0.11 0.06 3.51 .06 0.89 SDMT -0.29 0.08 14.11 .00 0.75 BVMT-R -0.32 0.09 12.76 .00 0.73 5/30/2019 14
Results • Outcome: BICAMS impairment (2.0 SD) Step 1 B SE Wald p Exp(B) Age -0.01 0.02 0.04 .85 1.00 Gender -0.60 0.71 0.73 .39 0.55 Education -0.15 0.13 1.26 .26 0.86 CVLT-II -0.18 0.04 19.99 <.001 0.83 Step 2 Age -0.15 0.06 5.81 .02 -0.15 -2.55 1.30 3.87 .05 -2.55 Gender Education -0.04 0.23 0.03 .86 -0.04 -0.23 0.08 9.18 <.001 -0.23 CVLT-II SDMT -0.25 0.08 8.88 <.001 -0.25 -0.28 0.10 7.78 .01 -0.28 BVMT-R 5/30/2019 15 Results • Outcome: BICAMS impairment (2.0 SD) Step 1 B SE Wald p Exp(B) 0.01 0.02 0.21 .65 1.01 Age -0.43 0.60 0.51 .48 0.65 Gender -0.15 0.11 2.15 .14 0.86 Education -0.10 0.03 10.90 <.001 0.91 RAVLT Step 2 -0.10 0.04 6.43 .01 0.91 Age -1.71 1.02 2.79 .10 0.18 Gender -0.03 0.16 0.04 .85 0.97 Education -0.10 0.05 3.74 .05 0.90 RAVLT -0.20 0.06 11.92 <.001 0.82 SDMT -0.21 0.07 10.33 <.001 0.81 BVMT-R 5/30/2019 16
Conclusions • Limitations – Cross-sectional data – Highly-resourced sample • RAVLT correlates moderately with the CVLT-II • The RAVLT provides a potential alternative verbal learning measure for brief cognitive screening in MS • Although the RAVLT can accurately predict BICAMS impairment, it does not predict BICAMS impairment beyond that of the BVMT-R and SDMT 5/30/2019 17 Acknowledgements • Johns Hopkins MS Rehabilitation Research Laboratory – Co-PI: Meghan Beier, PhD – NMSS Fellow: Jagriti “Jackie” Bhattarai, PhD – Lab Manager: Trisha Chaffee, MS – Trainees: Aeysha Brown, MA; Krina Patel, BS • Johns Hopkins Precision Medicine Center of Excellence for MS • Consortium of MS Centers Pilot Grant 18
References • Chiaravalloti, N.D. and DeLuca, J., 2008. Cognitive impairment in multiple sclerosis. The Lancet Neurology , 7 (12), pp.1139-1151. • Kalb, R., Beier, M., Benedict, R.H., Charvet, L., Costello, K., Feinstein, A., Gingold, J., Goverover, Y., Halper, J., Harris, C. and Kostich, L., 2018. Recommendations for cognitive screening and management in multiple sclerosis care. Multiple Sclerosis Journal , 24 (13), pp.1665-1680. • Langdon, D.W., Amato, M.P., Boringa, J., Brochet, B., Foley, F., Fredrikson, S., Hämäläinen, P., Hartung, H.P., Krupp, L., Penner, I.K. and Reder, A.T., 2012. Recommendations for a brief international cognitive assessment for multiple sclerosis (BICAMS). Multiple Sclerosis Journal , 18 (6), pp.891-898. • Gromisch, E.S., Portnoy, J.G. and Foley, F.W., 2018. Comparison of the abbreviated minimal assessment of cognitive function in multiple sclerosis (aMACFIMS) and the brief international cognitive assessment for multiple sclerosis (BICAMS). Journal of the neurological sciences , 388 , pp.70-75. • Beier, M., Hughes, A.J., Williams, M.W. and Gromisch, E.S., 2019. Brief and cost-effective tool for assessing verbal learning in multiple sclerosis: Comparison of the Rey Auditory Verbal Learning Test (RAVLT) to the California Verbal Learning Test–II (CVLT-II). Journal of the neurological sciences . • Filser, M., Schreiber, H., Pöttgen, J., Ullrich, S., Lang, M. and Penner, I.K., 2018. The brief international cognitive assessment in multiple sclerosis (BICAMS): results from the German validation study. Journal of neurology , 265 (11), pp.2587-2593. • Stallings, G., Boake, C. and Sherer, M., 1995. Comparison of the California verbal learning test and the Rey auditory verbal learning test in head-injured patients. Journal of Clinical and Experimental Neuropsychology , 17 (5), pp.706-712. 5/30/2019 19
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