title: White matter integrity determined with diffusion tensor imaging in older adults without dementia: influence of amyloid load and neurodegeneration.
abstract: OBJECTIVE
  Pathophysiologic mechanisms leading to loss of white matter integrity and the temporal positioning of biomarkers of white matter integrity relative to the biomarkers of gray matter neurodegeneration and amyloid load in the course of Alzheimer disease (AD) are poorly understood.
  
  
  OBJECTIVE
  To investigate the effects of AD-related gray matter neurodegeneration and high β-amyloid on white matter microstructure in older adults without dementia.
  
  
  METHODS
  A population-based, longitudinal cohort study was conducted. Participants included in the Mayo Clinic Study of Aging (N = 701) who underwent magnetic resonance imaging, diffusion tensor imaging (DTI), and positron emission tomography studies with diagnoses of cognitively normal ([CN] n = 570) or mild cognitive impairment ([MCI] n = 131) were included. Both groups were divided into biomarker-negative, amyloid-positive-only, neurodegeneration-positive-only, and amyloid plus neurodegeneration-positive groups based on their amyloid load shown on carbon 11-labeled Pittsburgh Compound B positron emission tomography, AD hypometabolic pattern shown on fludeoxyglucose F 18 positron emission tomography, and/or hippocampal atrophy shown on magnetic resonance imaging.
  
  
  METHODS
  Fractional anisotropy (FA) determined using DTI.
  
  
  RESULTS
  No FA alterations were observed in biomarker-negative MCI and amyloid-positive-only CN and MCI groups compared with biomarker-negative CN participants on voxel-based analysis (P < .05; familywise error corrected). Conversely, the neurodegeneration-positive-only and amyloid plus neurodegeneration-positive CN and MCI groups consistently had decreased FA in the fornix, which correlated with cognitive performance (ρ = 0.38; P < .001). Patients with MCI had more extensive white matter involvement than did those with CN, and the greatest FA decreases were observed in the amyloid plus neurodegeneration-positive MCI group (P < .05; familywise error corrected).
  
  
  CONCLUSIONS
  A high amyloid load does not influence diffusion tensor imaging-based measures of white matter integrity in the absence of coexistent gray matter neurodegeneration in older adults without dementia.
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Schwarz
authors.affiliation: Department of Information Technology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Reid
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Przybelski
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lesnick
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Zuk
authors.affiliation: Department of Information Technology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: Department of Information Technology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Val
authors.initials: V
authors.lastname: Lowe
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Machulda
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016880:Anisotropy; D015415:Biomarkers; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D066128:Gray Matter / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D049268:Positron-Emission Tomography; D066127:White Matter / Q000378:metabolism / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers