Patient Cognitive Reserve and MS-Related Cognitive Dysfunction Chair Timothy L. Vollmer, MD Faculty John DeLuca, PhD

Study Rationale and Objective Introduction Cognitive impairment affects approximately 2/3 of patients with MS MS-related cognitive dysfunction is only partially predicted by MRI estimates of brain pathology Study objective To determine whether higher premorbid intellectual functioning, ie, cognitive reserve (efficiency and capacity of neural networks), protects patients from MS-related cognitive dysfunction Cognitive reserve is best measured on the basis of estimated verbal intelligence as determined on the Wide Range Achievement Test–Third Edition Lower cognitive reserve: Z = -1; higher cognitive reserve: Z = +1 Sumowski JF, et al. J Clin Exp Neuropsychol. 2009;31:913-926.

Components of Cognitive Function Measurement Tools Simple processing efficiency Symbol Digit Modalities Test (SDMT) – Oral Version Complex information processing efficiency Paced Auditory Serial Addition Test (PASAT) Verbal learning and memory Logical Memory subtests (LM-I and LM-II) of the Wechsler Memory Scale–Revised Verbal learning: LM-I Verbal memory: LM-II Sumowski JF, et al. J Clin Exp Neuropsychol. 2009;31:913-926.

Simple Processing Efficiency Total Cognitive Reserve Group Lower Higher Z score Z score (Percentile) Z score (Percentile) Healthy controls +0.48 + 0.89 +0.57* (72nd) +0.46* (68th) MS patients -0.58 + 1.18 -1.16† (12th) -0.26† (40th) P value <.001 * The correlation between cognitive reserve and simple processing efficiency did not reach significance in healthy controls (r = -.01, P >.50). † The correlation between cognitive reserve and simple processing efficiency did not reach significance in MS patients (r = 21, P >.10). Sumowski JF, et al. J Clin Exp Neuropsychol. 2009;31:913-926.

Complex Information Processing Efficiency Total Cognitive Reserve Group Lower Higher Z score Z score (Percentile) Z score (Percentile) Healthy controls +0.21 + 0.84 +0.06* (52nd) +0.29* (61st) MS patients -0.50 + 1.13 -1.56† (6th) -0.20† (58th) P Value .001 The correlation between cognitive reserve and complex information processing efficiency (PASAT) did not reach significance in healthy controls (r = .15, P >.10). † There was a large significant correlation between cognitive reserve and complex information processing efficiency (PASAT) in MS patients (r = .42, P = .001). Sumowski JF, et al. J Clin Exp Neuropsychol. 2009;31:913-926.

Verbal Learning Total Cognitive Reserve Group Lower Higher Z score Z score (Percentile) Z score (Percentile) Healthy controls +0.57 + 0.84 0.23* (59th) +0.60* (73rd) MS patients -0.01 + 0.81 -1.25† (11th) +0.78† (78th) P value <.001 * The correlation between cognitive reserve and verbal learning did not reach significance in healthy controls (r = .14, P >.10). † There was a large significant correlation between cognitive reserve and verbal learning in MS patients (r = .61, P <.001). Sumowski JF, et al. J Clin Exp Neuropsychol. 2009;31:913-926.

Verbal Memory Z score Z score (Percentile) Z score (Percentile) Total Cognitive Reserve Group Lower Higher Z score Z score (Percentile) Z score (Percentile) Healthy controls +0.53 + 0.83 +0.09* (54th) +0.63* (74th) MS patients -0.12 + 0.87 -1.23† (11th) +0.63† (74th) P value <.001 * The correlation between cognitive reserve and verbal memory did not reach significance in healthy controls (r = .22, P >.10). † There was a large significant correlation between cognitive reserve and verbal memory in MS patients (r = .53, P <.001). Sumowski JF, et al. J Clin Exp Neuropsychol. 2009;31:913-926.

Conclusions The detrimental effect of MS on aspects of cognitive functioning is modified by patient cognitive reserve Higher cognitive reserve protects patients from MS-related complex information processing inefficiency and verbal learning and verbal memory deficits The protective effect of higher cognitive reserve allows patients to maintain cognitive performance comparable to that of healthy controls However, higher cognitive reserve had no significant effect on MS-related deficits in simple processing efficiency These findings may help to explain the weak association between MRI markers of MS brain pathology and cognition noted in previous studies Sumowski JF, et al. J Clin Exp Neuropsychol. 2009;31:913-926.