title: Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages.
abstract: OBJECTIVE
  Consistent with the cognitive reserve hypothesis, higher education and occupation attainments may help persons with neurodegenerative dementias to better withstand neuropathology before developing cognitive impairment. We tested here the cognitive reserve hypothesis in patients with frontotemporal dementia (FTD), with or without pathogenetic granulin mutations (GRN+ and GRN-), and in presymptomatic GRN mutation carriers (aGRN+).
  
  
  METHODS
  Education and occupation attainments were assessed and combined to define Reserve Index (RI) in 32 FTD patients, i.e. 12 GRN+ and 20 GRN-, and in 17 aGRN+. Changes in functional connectivity were estimated by resting state fMRI, focusing on the salience network (SN), executive network (EN) and bilateral frontoparietal networks (FPNs). Cognitive status was measured by FTD-modified Clinical Dementia Rating Scale.
  
  
  RESULTS
  In FTD patients higher level of premorbid cognitive reserve was associated with reduced connectivity within the SN and the EN. EN was more involved in FTD patients without GRN mutations, while SN was more affected in GRN pathology. In aGRN+, cognitive reserve was associated with reduced SN.
  
  
  CONCLUSIONS
  This study suggests that cognitive reserve modulates functional connectivity in patients with FTD, even in monogenic disease. In GRN inherited FTD, cognitive reserve mechanisms operate even in presymptomatic to clinical stages.
authors.affiliation: Centre for Neurodegenerative Disorders, University of Brescia, Brescia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Premi
authors.forename: Stefano
authors.initials: S
authors.lastname: Gazzina
authors.forename: Marco
authors.initials: M
authors.lastname: Bozzali
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.forename: Antonella
authors.initials: A
authors.lastname: Alberici
authors.forename: Mara
authors.initials: M
authors.lastname: Cercignani
authors.forename: Angelo
authors.initials: A
authors.lastname: Bianchetti
authors.forename: Roberto
authors.initials: R
authors.lastname: Gasparotti
authors.forename: Marinella
authors.initials: M
authors.lastname: Turla
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D003072:Cognition Disorders / Q000378:metabolism; D058245:Cognitive Reserve; D005260:Female; D057180:Frontotemporal Dementia / Q000378:metabolism* / Q000503:physiopathology*; D006579:Heterozygote; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D000077153:Progranulins; D012720:Severity of Illness Index
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
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