White Matter Integrity Determined With Diffusion Tensor Imaging in Older Adults Without Dementia: Influence of Amyloid Load and Neurodegeneration
Open accessAbstract
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 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. 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.
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The current results are consistent with previous studies reporting that decreased fibre tract integrity in posterior parietal and medial temporal white matter is associated with imminent conversion from asymptomatic cognitive status to mild cognitive impairment within 2 years or with abnormal CSF amyloid and neuroinjury markers.
“The current results are consistent with previous studies on presumed preclinical Alzheimer’s disease, reporting decreased fibre tract integrity within the posterior parietal white matter and medial temporal white matter to be associated with imminent conversion from asymptomatic cognitive status to mild cognitive impairment within 2 years (Zhuang et al., 2012) or with the presence of both abnormal”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Kantarci et al., 2014
The Results (Voxel-based Analysis; page unavailable) report decreased white-matter integrity in temporal regions and the precuneus among participants positive for both amyloid and neurodegeneration biomarkers. But the Methods (Classification of subjects into biomarker groups; page unavailable) specify PET and MRI biomarkers, not CSF markers. The two-year conversion claim is attached to Zhuang et al., not this source. (LLM, conf=0.88)
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References 45 · Cited by 88
Research works printed but not linked: 1
- [35]Benarroch E Basic Neurosciences with Clinical Applications Philadelphia, PA Elsevier 2006
- Authors
- Kantarci, K., Schwarz, C. G., Reid, R. I., Przybelski, S. A., Lesnick, T. G., Zuk, S. M., Senjem, M. L., Gunter, J. L., Lowe, V., Machulda, M. M., Knopman, D. S., Petersen, R. C., & Jack, C. R.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Kantarci, Kejal
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2014-12-01
- Volume
- 71
- Issue
- 12
- Pages
- 1547
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC4810441
- OpenAlex
- W2038307247
- Cited by
- 88
- References
- 45
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 11 · 2019: 7 · 2018: 9 · 2017: 7 · 2016: 5 · 2015: 4 · 2014: 2
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904, R01AG11378, R01AG029550, P50AG044170, R01AG043392, U01AG06786, R01AG040042, U01AG006786, R01AG011378, R01AG032306, R01AG037551, R01AG041851, P50AG016574)
- National Heart, Lung, and Blood Institute (U01HL096917)
- National Institute of Neurological Disorders and Stroke (R21NS066147)
- National Center for Research Resources (C06RR018898)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- white matter integrity, Alzheimer's disease, amyloid-beta, mild cognitive impairment, fractional anisotropy, fornix, hippocampal atrophy, amyloid PET, Pittsburgh compound B, diffusion tensor imaging, cognitive performance, older adults
- MeSH terms
- Aged, Aged, 80 and over, Female, Humans, Longitudinal Studies, Male, Biomarkers, Amyloid beta-Peptides, Anisotropy, Neurodegenerative Diseases, Positron-Emission Tomography, Diffusion Tensor Imaging, Cognitive Dysfunction, White Matter, Gray Matter
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