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May 20, 2014; 82 (20) Article

Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS

James F. Sumowski, Maria A. Rocca, Victoria M. Leavitt, Jelena Dackovic, Sarlota Mesaros, Jelena Drulovic, John DeLuca, Massimo Filippi
First published April 18, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000433
James F. Sumowski
From Neuropsychology and Neuroscience (J.F.S., J. DeLuca), Kessler Foundation Research Center, West Orange; Rutgers (J.F.S., J. DeLuca), New Jersey Medical School, Newark, NJ; Neuroimaging Research Unit (M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Manhattan Memory Center (V.M.L.), New York, NY; and Clinic of Neurology (J. Dackovic, S.M., J. Drulovic), Faculty of Medicine, University of Belgrade, Serbia.
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Maria A. Rocca
From Neuropsychology and Neuroscience (J.F.S., J. DeLuca), Kessler Foundation Research Center, West Orange; Rutgers (J.F.S., J. DeLuca), New Jersey Medical School, Newark, NJ; Neuroimaging Research Unit (M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Manhattan Memory Center (V.M.L.), New York, NY; and Clinic of Neurology (J. Dackovic, S.M., J. Drulovic), Faculty of Medicine, University of Belgrade, Serbia.
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Victoria M. Leavitt
From Neuropsychology and Neuroscience (J.F.S., J. DeLuca), Kessler Foundation Research Center, West Orange; Rutgers (J.F.S., J. DeLuca), New Jersey Medical School, Newark, NJ; Neuroimaging Research Unit (M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Manhattan Memory Center (V.M.L.), New York, NY; and Clinic of Neurology (J. Dackovic, S.M., J. Drulovic), Faculty of Medicine, University of Belgrade, Serbia.
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Jelena Dackovic
From Neuropsychology and Neuroscience (J.F.S., J. DeLuca), Kessler Foundation Research Center, West Orange; Rutgers (J.F.S., J. DeLuca), New Jersey Medical School, Newark, NJ; Neuroimaging Research Unit (M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Manhattan Memory Center (V.M.L.), New York, NY; and Clinic of Neurology (J. Dackovic, S.M., J. Drulovic), Faculty of Medicine, University of Belgrade, Serbia.
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Sarlota Mesaros
From Neuropsychology and Neuroscience (J.F.S., J. DeLuca), Kessler Foundation Research Center, West Orange; Rutgers (J.F.S., J. DeLuca), New Jersey Medical School, Newark, NJ; Neuroimaging Research Unit (M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Manhattan Memory Center (V.M.L.), New York, NY; and Clinic of Neurology (J. Dackovic, S.M., J. Drulovic), Faculty of Medicine, University of Belgrade, Serbia.
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Jelena Drulovic
From Neuropsychology and Neuroscience (J.F.S., J. DeLuca), Kessler Foundation Research Center, West Orange; Rutgers (J.F.S., J. DeLuca), New Jersey Medical School, Newark, NJ; Neuroimaging Research Unit (M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Manhattan Memory Center (V.M.L.), New York, NY; and Clinic of Neurology (J. Dackovic, S.M., J. Drulovic), Faculty of Medicine, University of Belgrade, Serbia.
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John DeLuca
From Neuropsychology and Neuroscience (J.F.S., J. DeLuca), Kessler Foundation Research Center, West Orange; Rutgers (J.F.S., J. DeLuca), New Jersey Medical School, Newark, NJ; Neuroimaging Research Unit (M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Manhattan Memory Center (V.M.L.), New York, NY; and Clinic of Neurology (J. Dackovic, S.M., J. Drulovic), Faculty of Medicine, University of Belgrade, Serbia.
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Massimo Filippi
From Neuropsychology and Neuroscience (J.F.S., J. DeLuca), Kessler Foundation Research Center, West Orange; Rutgers (J.F.S., J. DeLuca), New Jersey Medical School, Newark, NJ; Neuroimaging Research Unit (M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Manhattan Memory Center (V.M.L.), New York, NY; and Clinic of Neurology (J. Dackovic, S.M., J. Drulovic), Faculty of Medicine, University of Belgrade, Serbia.
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Citation
Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS
James F. Sumowski, Maria A. Rocca, Victoria M. Leavitt, Jelena Dackovic, Sarlota Mesaros, Jelena Drulovic, John DeLuca, Massimo Filippi
Neurology May 2014, 82 (20) 1776-1783; DOI: 10.1212/WNL.0000000000000433

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Abstract

Objective: Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time.

Methods: Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression.

Results: Patients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, ηp2 = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.126) and memory (p = 0.037, ηp2 = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment.

Conclusion: We provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS.

GLOSSARY

ANCOVA=
analysis of covariance;
EDSS=
Expanded Disability Status Scale;
GMV=
gray matter volume;
ICV=
intracranial volume;
LV=
lesion volume;
MLBG=
maximal lifetime brain growth;
MS=
multiple sclerosis;
PBVC=
percentage brain volume change;
PPMS=
primary progressive multiple sclerosis;
RRMS=
relapsing-remitting multiple sclerosis;
WLG=
Word List Generation;
WMV=
white matter volume

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received October 27, 2013.
  • Accepted in final form February 17, 2014.
  • © 2014 American Academy of Neurology
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