Individual reserve in aging and neurological disease

Roee Holtzer, Jaeun Choi, Robert W. Motl, Frederick W. Foley, Mary Ann Picone, Michael L. Lipton, Meltem Izzetoglu, Manuel Hernandez, Mark E. Wagshul

Research output: Contribution to journalArticlepeer-review


Background and objective: Cognitive and physical functions correlate and delineate aging and disease trajectories. Whereas cognitive reserve (CR) is well-established, physical reserve (PR) is poorly understood. We, therefore, developed and evaluated a novel and more comprehensive construct, individual reserve (IR), comprised of residual-derived CR and PR in older adults with and without multiple sclerosis (MS). We hypothesized that: (a) CR and PR would be positively correlated; (b) low CR, PR, and IR would be associated with worse study outcomes; (c) associations of brain atrophy with study outcomes would be stronger in lower compared to higher IR due to compensatory mechanisms conferred by the latter. Methods: Older adults with MS (n = 66, mean age = 64.48 ± 3.84 years) and controls (n = 66, mean age = 68.20 ± 6.09 years), underwent brain MRI, cognitive assessment, and motoric testing. We regressed the repeatable battery for the assessment of neuropsychological status and short physical performance battery on brain pathology and socio-demographic confounders to derive independent residual CR and PR measures, respectively. We combined CR and PR to define a 4-level IR variable. The oral symbol digit modalities test (SDMT) and timed-25-foot-walk-test (T25FW) served as outcome measures. Results: CR and PR were positively correlated. Low CR, PR and IR were associated with worse SDMT and T25FW performances. Reduced left thalamic volume, a marker of brain atrophy, was associated with poor SDMT and T25FW performances only in individuals with low IR. The presence of MS moderated associations between IR and T25FW performance. Conclusion: IR is a novel construct comprised of cognitive and physical dimensions representing collective within-person reserve capacities.

Original languageEnglish (US)
Pages (from-to)3179-3191
Number of pages13
JournalJournal of Neurology
Issue number6
StatePublished - Jun 2023


  • Cognitive reserve
  • Individual reserve
  • Magnetic resonance imaging
  • Multiple sclerosis
  • Physical reserve

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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