title: Searching for the neural basis of reserve against memory decline: intellectual enrichment linked to larger hippocampal volume in multiple sclerosis.
abstract: OBJECTIVE
  Active engagement in intellectually enriching activities (e.g. reading, hobbies) builds 'reserve' against memory decline in elders and persons with multiple sclerosis (MS), but the neural basis for this protective influence of enrichment is unknown. Herein the neuroanatomical basis of reserve against memory decline in MS patients is investigated.
  
  
  METHODS
  Relapse-onset MS patients (N = 187) underwent 3.0 T magnetic resonance imaging of the brain to quantify T2 lesion volume (T2LV) and normalized volumes of total brain, total white, total grey (using SIENAX) and thalamus, caudate, putamen, pallidum, amygdala and hippocampus (using FIRST). Patients completed a survey quantifying their engagement in early life intellectual enrichment (i.e. reading, hobbies). Verbal and visuospatial episodic memory was assessed with neuropsychological tasks in a representative subsample (N = 97).
  
  
  RESULTS
  Controlling for demographics and T2LV, intellectual enrichment was specifically linked to larger normalized hippocampal volume (r(p) = 0.213, P = 0.004), with no link to other brain volumes/structures. Moreover, greater intellectual enrichment moderated/attenuated the negative relationship between normalized total brain volume (i.e. overall cerebral atrophy) and normalized hippocampal volume (i.e. hippocampal atrophy; P = 0.001) whereby patients who engaged in more early life intellectual enrichment better maintained hippocampal volume in the face of worse overall cerebral atrophy. Finally, the link between greater intellectual enrichment and better memory was partially mediated through larger hippocampal volume.
  
  
  CONCLUSIONS
  These findings support larger hippocampal volume as one key component of the neuroanatomical basis of reserve against memory decline in MS. These findings are consistent with previous literature on experience-dependent neuroplasticity within the hippocampus.
authors: Neuropsychology and Neuroscience, Kessler Foundation, West Orange, NJ, USA.|Rutgers, New Jersey Medical School, Newark, NJ, USA.
authors: J F
authors: JF
authors: Sumowski
authors: Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors: M A
authors: MA
authors: Rocca
authors: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors: V M
authors: VM
authors: Leavitt
authors: Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors: G
authors: G
authors: Riccitelli
authors: Neuropsychology and Neuroscience, Kessler Foundation, West Orange, NJ, USA.|Rutgers, New Jersey Medical School, Newark, NJ, USA.
authors: J
authors: J
authors: Sandry
authors: Neuropsychology and Neuroscience, Kessler Foundation, West Orange, NJ, USA.|Rutgers, New Jersey Medical School, Newark, NJ, USA.
authors: J
authors: J
authors: DeLuca
authors: Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors: G
authors: G
authors: Comi
authors: Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors: M
authors: M
authors: Filippi
mesh_terms: D000328:Adult; D058245:Cognitive Reserve / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D061212:Memory, Episodic; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000503:physiopathology*
keywords: cognitive disorders; cognitive reserve; hippocampus; memory; multiple sclerosis
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