White matter integrity determined with diffusion tensor imaging in older adults without dementia: Influence of amyloid load and neurodegeneration

Kejal Kantarci, Christopher G. Schwarz, Robert I. Reid, Scott A. Przybelski, Timothy G. Lesnick, Samantha M. Zuk, Matthew L. Senjem, Jeffrey L. Gunter, Val Lowe, Mary M. Machulda, David S. Knopman, Ronald C. Petersen, Clifford R. Jack

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: A population-based, longitudinal cohort studywas 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.

Original languageEnglish (US)
Pages (from-to)1547-1554
Number of pages8
JournalJAMA neurology
Issue number12
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Clinical Neurology


Dive into the research topics of 'White matter integrity determined with diffusion tensor imaging in older adults without dementia: Influence of amyloid load and neurodegeneration'. Together they form a unique fingerprint.

Cite this