title: Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease.
abstract: OBJECTIVE
  To test whether higher global functional connectivity of the left frontal cortex (LFC) in Alzheimer disease (AD) is associated with more years of education (a proxy of cognitive reserve [CR]) and mitigates the association between AD-related fluorodeoxyglucose (FDG)-PET hypometabolism and episodic memory.
  
  
  METHODS
  Forty-four amyloid-PET-positive patients with amnestic mild cognitive impairment (MCI-Aβ+) and 24 amyloid-PET-negative healthy controls (HC) were included. Voxel-based linear regression analyses were used to test the association between years of education and FDG-PET in MCI-Aβ+, controlled for episodic memory performance. Global LFC (gLFC) connectivity was computed through seed-based resting-state fMRI correlations between the LFC (seed) and each voxel in the gray matter. In linear regression analyses, education as a predictor of gLFC connectivity and the interaction of gLFC connectivity × FDG-PET hypometabolism on episodic memory were tested.
  
  
  RESULTS
  FDG-PET metabolism in the precuneus was reduced in MCI-Aβ+ compared to HC (p= 0.028), with stronger reductions observed in MCI-Aβ+ with more years of education (p= 0.006). In MCI-Aβ+, higher gLFC connectivity was associated with more years of education (p= 0.021). At higher levels of gLFC connectivity, the association between precuneus FDG-PET hypometabolism and lower memory performance was attenuated (p= 0.027).
  
  
  CONCLUSIONS
  Higher gLFC connectivity is a functional substrate of CR that helps to maintain episodic memory relatively well in the face of emerging FDG-PET hypometabolism in early-stage AD.
authors.affiliation: From the Institute for Stroke and Dementia Research (N.F., M. Duering, M. Dichgans, M.E.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; University of California at San Francisco (M.W.); Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans); and German Center for Neurodegenerative Diseases (M. Dichgans), Munich, Germany.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Franzmeier
authors.affiliation: From the Institute for Stroke and Dementia Research (N.F., M. Duering, M. Dichgans, M.E.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; University of California at San Francisco (M.W.); Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans); and German Center for Neurodegenerative Diseases (M. Dichgans), Munich, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Duering
authors.affiliation: From the Institute for Stroke and Dementia Research (N.F., M. Duering, M. Dichgans, M.E.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; University of California at San Francisco (M.W.); Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans); and German Center for Neurodegenerative Diseases (M. Dichgans), Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiner
authors.affiliation: From the Institute for Stroke and Dementia Research (N.F., M. Duering, M. Dichgans, M.E.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; University of California at San Francisco (M.W.); Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans); and German Center for Neurodegenerative Diseases (M. Dichgans), Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.affiliation: From the Institute for Stroke and Dementia Research (N.F., M. Duering, M. Dichgans, M.E.), Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany; University of California at San Francisco (M.W.); Munich Cluster for Systems Neurology (SyNergy) (M. Dichgans); and German Center for Neurodegenerative Diseases (M. Dichgans), Munich, Germany. Michael.Weiner@ucsf.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Ewers
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000209:etiology*; D058245:Cognitive Reserve / Q000502:physiology*; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000209:etiology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000473:pathology; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000473:pathology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D049268:Positron-Emission Tomography; D062706:Prodromal Symptoms
chemical_list: D019788:Fluorodeoxyglucose F18; D010100:Oxygen