Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis

Sumowski et al. [1] showed that greater intellectual enrichment lessened the negative effect of brain atrophy on cognitive performance in Multiple Sclerosis (MS). MS patients with high intellectual enrichment performed similarly in memory tasks regardless of brain atrophy values on MRI while brain atrophy was associated with lower performances in patients with low intellectual enrichment.

We previously showed that educational background protects cognitive efficiency in patients with newly diagnosed patients with relapsing-remitting MS (RRMS). [2] Low-educated (LE) RRMS patients, but not high-educated (HE) patients, had lower performances than matched healthy controls on most neuropsychological tests including the memory test used by Sumowski et al. However, cognitive scores between LE and HE controls showed no difference. LE and HE RRMS patients did not differ regarding age, gender, disability, or MRI measures, so the effect of education on cognition was not attributable to a different distribution by chance.

Sumowski et al. only observed a correlation between brain atrophy and cognitive performance in patients with low intellectual enrichment. In our study, almost none of the MRI measures correlated with cognitive scores in LE patients, which suggests that a limited amount of tissue damage could be sufficient to induce cognitive disturbances in these patients. In addition, lower compensatory capacities in these patients could not counteract the cognitive deficits related to brain involvement. By contrast, cognitive performances of HE patients were negatively correlated with MRI measures indicating that education-dependent cognitive compensation—as we showed for cognitive compensation in RRMS [3]—could be limited by tissue damage accumulation and disease progression.

Both studies demonstrated two different intellectual enrichment variables and the protective effect of a strong intellectual background on brain damage. However, we obtained different results according to MRI correlations, which could be explained by differences in the two MS populations including: disease course (we studied only early RRMS); number of years of education (16.1±2.3 years [1] vs 13±2.9 years) [2]); or the disease duration (10.5±7 years [1] vs 2±2.19 years [2]).

Further studies are needed to understand the compensatory effect of intellectual background on cognitive efficiency preservation in MS patients. The ceiling effect due to the progression of the disease should also be elucidated.

References

1. Sumowski JF, Wylie GR, Chiaravalloti N, et al. Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis. Neurology 2010;74:1942-1945.

2. Bonnet M, Deloire M, Salort E, Dousset V, Petry KG, Brochet B. Evidence of cognitive compensation associated with educational level in early relapsing-remitting multiple sclerosis. J Neurol Sci 2006;251:23-28.

3. Bonnet M, Allard M, Dilharreguy B, Deloire M, Petry KG, Brochet B. Cognitive compensation failure in multiple slcerosis. Neurology, 2010 in press.

Disclosures: Dr. Bonnet has received speaker honoraria from Bayer Schering Pharma. Dr. Brochet serves on scientific advisory boards for Bayer Schering Pharma, Novartis, and Merck Serono; received funding for travel or speaker honoraria from Bayer Schering Pharma, Merck Serono, Biogen Idec, Novartis, and Teva Pharmaceutical Industries Ltd./Sanofi-Aventis; serves as LEN editor for SEP et Neurosciences; and has received institutional research support from Biogen Idec, Novartis, Roche, Sanofi-Aventis, Bayer Schering Pharma, Teva Pharmaceutical Industries Ltd., Peptimmune, Eli Lilly and Company, and AB Science.

We reported negative correlations between brain atrophy and cognition in MS patients with lower reserve, but not patients with higher reserve. [1,4] In contrast, Bonnet et al. found only one correlation between MRI measures and cognition in patients with lower reserve, but several correlations among patients with higher reserve. [2]

The cognitive reserve hypothesis states that patients with higher reserve can withstand more severe neurologic disease before suffering cognitive decline. [5] The negative impact of neuropathology on cognition is weaker among higher reserve patients, as we have shown in MS [1,4] and others have shown in aging and Alzheimer disease. [6-7] In this context, Bonnet et al.’s [2] findings conflict with the cognitive reserve literature, and therefore prompted this review of their study.

Bonnet et al. defined low reserve as educational attainment as less than 12 years. However, the LE MS group had much lower verbal intelligence than the LE control group. Considering that verbal intellectual decline is very rare in MS, [8] the MS group probably had lower intelligence before disease onset. The observed cognitive differences between the LE MS and control groups likely represent premorbid differences rather than disease-induced cognitive decline—especially given the short disease duration of the MS group.

Because lower cognition among MS patients was likely developmental rather than disease-induced, a correlation between MRI measures and cognition cannot be expected. Among HE MS patients, Bonnet et al. reported correlations between MRI parameters and performance on eight cognitive tasks. However, MS patients only differed from controls on one task, suggesting that most of the correlations were due to an uncontrolled non-disease variable, such as age—which likely correlates with both cognition and MRI measures. If so, correlations should also be evident among controls but these analyses were not performed. Finally, differential statistical power is another explanation for fewer correlations among LE patients (N = 19) relative to HE patients (N = 24), especially given the high risk of Type I error (5 MRI parameters * 15 cognitive scores = 75 correlations performed for each group, with an uncorrected alpha of .05).

The cognitive reserve literature supports the notion that neuropathology is more likely related to cognition among patients with lesser reserve, [1,4-7] and the exception posed by Bonnet and colleagues [2] appears confounded.

References

4. Sumowski JF, Chiaravalloti N, Wylie GR, DeLuca J. Cognitive reserve moderates the negative effect of brain atrophy on cognitive efficiency in multiple sclerosis. J Int Neuropsychol Soc 2009;15:606-612.

5. Stern Y. Cognitive reserve. Neuropsychologia 2009; 47:2015-2028.

6. Bennett DA, Wilson RS, Schneider JA, et al. Education modifies the relation of AD pathology to level of cognitive function in older persons. Neurology 2003;60:1909-1915.

7. Rentz DM, Locascio JL, Becker JA, et al. Cognition, reserve, and amyloid deposition in normal aging. Ann Neurol 2010; 67: 353-364.

8 Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol 2008;7:1139-1151.