title: β-amyloid, hippocampal atrophy and their relation to longitudinal brain change in cognitively normal individuals.
abstract: Recent literature has examined baseline hippocampal volume and extent of brain amyloidosis to test potential synergistic effects on worsening cognition and extent of brain atrophy. Use of hippocampal volume in prior studies was based on the notion that limbic circuit degeneration is an early manifestation of the Alzheimer's Disease (AD) pathophysiology. To clarify these interactions early in the AD process, we tested the effects of amyloid and baseline normalized hippocampal volume on longitudinal brain atrophy rates in a group of cognitively normal individuals. Results showed that the combination of elevated β-amyloid and baseline hippocampal atrophy is associated with increased rates specific to the limbic circuit and splenium. Importantly, this atrophy pattern emerged from a voxelwise analysis, corroborated by regression models over region of interests in native space. The results are broadly consistent with previous studies of the effects of amyloid and baseline hippocampal atrophy in normals, while pointing to accelerated atrophy of AD-vulnerable regions detectable at the preclinical stage.
authors.affiliation: Department of Neurology, University of California at Davis, Davis, CA, USA. Electronic address: evanfletcher@gmail.com.
authors.forename: Evan
authors.initials: E
authors.lastname: Fletcher
authors.affiliation: Douglas Mental Health University Institute, McGill University, Montreal, Canada.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Villeneuve
authors.affiliation: Department of Neurology, University of California at Davis, Davis, CA, USA.
authors.forename: Pauline
authors.initials: P
authors.lastname: Maillard
authors.affiliation: Division of Biostatistics, School of Medicine, University of California at Davis, Davis, CA, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Harvey
authors.affiliation: Department of Neurology, University of California at Davis, Davis, CA, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Reed
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley CA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Jagust
authors.affiliation: Department of Neurology, University of California at Davis, Davis, CA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001284:Atrophy; D016657:Cerebral Amyloid Angiopathy / Q000000981:diagnostic imaging / Q000473:pathology*; D003071:Cognition; D015331:Cohort Studies; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012044:Regression Analysis
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer's; Atrophy; Longitudinal; Neurodegeneration; Normals; β-amyloid