Longitudinal, region-specific course of diffusion tensor imaging measures in mild cognitive impairment and Alzheimer’s disease

Nowrangi, Milap A.; Lyketsos, Constantine G.; Leoutsakos, Jeannie‐Marie S.; Oishi, Kenichi; Albert, Marilyn; Mori, Susumu; Mielke, Michelle M.

doi:10.1016/j.jalz.2012.05.2186

Cited by 121Dementia and Cognitive Impairment ResearchAdvanced Neuroimaging Techniques and ApplicationsAlzheimer's disease research and treatments

Longitudinal, region-specific course of diffusion tensor imaging measures in mild cognitive impairment and Alzheimer’s disease

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Nowrangi, Milap A., Lyketsos, Constantine G., Leoutsakos, Jeannie‐Marie S., Oishi, Kenichi, Albert, Marilyn, Mori, Susumu, Mielke, Michelle M.·2013·Alzheimer's & Dementia

DOI 10.1016/j.jalz.2012.05.2186PMC PMC3639296

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Abstract

BACKGROUND: Diffusion tensor imaging (DTI) is a promising method for identifying significant cross-sectional differences of white-matter tracts in normal controls (NC) and those with mild cognitive impairment (MCI) or Alzheimer's disease (AD). There have not been many studies establishing its longitudinal utility. METHODS: Seventy-five participants (25 NC, 25 amnestic MCI, and 25 AD) had 3-Tesla MRI scans and clinical evaluations at baseline and 3, 6, and 12 months. Fractional anisotropy (FA) and mean diffusivity (MD) were analyzed at each time-point and longitudinally in eight a priori-selected areas taken from four regions of interest (ROIs). RESULTS: Cross-sectionally, MD values were higher, and FA values lower in the fornix and splenium of the AD group compared with either MCI or NC (P < .01). Within-group change was more evident in MD than in FA over 12 months: MD increased in the inferior, anterior cingulum, and fornix in both the MCI and AD groups (P < .01). CONCLUSIONS: There were stable, cross-sectional, region-specific differences between the NC and AD groups in both FA and MD at each time-point over 12 months. Longitudinally, MD was a better indicator of change than FA. Significant increases of fornix MD in the MCI group suggest this is an early indicator of progression.

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For all analyses, mean diffusivity was used as the primary DTI measure in autosomal-dominant Alzheimer's disease because previous studies found mean diffusivity to be the most sensitive DTI marker to detect fibre tract alterations.
“For all analyses, we used mean diffusivity as our primary DTI measure in autosomal-dominant Alzheimer’s disease, since previous studies found mean diffusivity to be the most sensitive DTI marker to detect fibre tract alterations (Clerx et al., 2012; Nowrangi et al., 2013).”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Nowrangi et al., 2013
The Discussion (page not provided) says MD may be more sensitive to change over 12 months than FA, supporting the rationale for choosing MD. But the study examined normal controls, MCI, and AD—not autosomal-dominant AD—and its tentative longitudinal finding does not establish MD as the most sensitive DTI marker for detecting fibre-tract alterations generally. The citing authors’ choice to use MD for all analyses is their own method, not a finding attributed to this source. (LLM, conf=0.86)
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Cerebral White Matter Integrity in Amnestic Mild Cognitive Impairment: A 1-Year Randomized Controlled Trial of Aerobic Exercise Training
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Altered Whole-Brain Structural Covariance of the Hippocampal Subfields in Subcortical Vascular Mild Cognitive Impairment and Amnestic Mild Cognitive Impairment Patients
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Regional Amyloid-β Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer’s Dementia
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A literature review of MRI techniques used to detect amyloid-beta plaques in Alzheimer’s disease patients
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Vitamin D Deficiency Disrupts Neuronal Integrity in Cognitively Impaired Patients
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Fascicle- and Glucose-Specific Deterioration in White Matter Energy Supply in Alzheimer’s Disease
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Synergism between fornix microstructure and beta amyloid accelerates memory decline in clinically normal older adults
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Connectome-derived diffusion characteristics of the fornix in Alzheimer's disease
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Retained executive abilities in mild cognitive impairment are associated with increased white matter network connectivity
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TSPO PET detects acute neuroinflammation but not diffuse chronically activated MHCII microglia in the rat
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Hippocampus-Based Dynamic Functional Connectivity Mapping in the Early Stages of Alzheimer’s Disease
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Fornix degeneration in risk factors of Alzheimer's disease, possible trigger of cognitive decline
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Association of deposition of tau and amyloid‐β proteins with structural connectivity changes in cognitively normal older adults and Alzheimer’s disease spectrum patients
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No relationship between fornix and cingulum degradation and within-network decreases in functional connectivity in prodromal Alzheimer’s disease
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Short‐term white matter alterations in Alzheimer's disease characterized by diffusion tensor imaging
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Long Longitudinal Tract Lesion Contributes to the Progression of Alzheimer's Disease
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Examining the relationship between nutrition and cerebral structural integrity in older adults without dementia
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Splenium tract projections of the corpus callosum to the parietal cortex classifies Alzheimer’s disease and mild cognitive impairment
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Posttraumatic Stress and Traumatic Brain Injury: Cognition, Behavior, and Neuroimaging Markers in Vietnam Veterans
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Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging
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“Reduced FA and increased MD in hippocampus were reported in many of these human studies, probably attributed to increased extracellular space volume and neurodegeneration (Muller et al., 2007; Cherubini et al., 2010; Hong et al., 2013; Nowrangi et al., 2013).”
Background
Exercise intervention on the brain structure and function of patients with mild cognitive impairment: systematic review based on magnetic resonance imaging studies
Xu, J., Yu, J., Gai, L., & Wang, Y. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1464159 · Cited by 12 · see citing works
Functional Imaging for Neurodegenerative Diseases
Chollet, F., & Payoux, P. (2022) · La Presse Médicale · doi:10.1016/j.lpm.2022.104121 · Cited by 10 · see citing works
Regional segmentation strategy for DTI analysis of human corpus callosum indicates motor function deficit in mild cognitive impairment
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Altered white matter functional pathways in Alzheimer’s disease
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Verbal memory and hippocampal volume predict subsequent fornix microstructure in those at risk for Alzheimer’s disease
Initiative, A. D. N., Yu, J., & Lee, T. M. C. (2019) · Brain Imaging and Behavior · doi:10.1007/s11682-019-00183-8 · Cited by 8 · see citing works
White matter microstructure associations to amyloid burden in adults with Down syndrome
Bazydlo, A., Zammit, M. D., Wu, M., Lao, P. J., Dean, D., Johnson, S. C., Tudorascu, D., Cohen, A. D., Cody, K. A., Ances, B. M., et al. (2021) · NeuroImage Clinical · doi:10.1016/j.nicl.2021.102908 · Cited by 8 · see citing works
Docetaxel-induced cognitive impairment in rats can be ameliorated by edaravone dexborneol: Evidence from the indicators of biological behavior and anisotropic fraction
Liu, P., Liu, H., Wei, L., Shi, X., Wang, W., Yan, S., Zhou, W., Zhang, J., & Han, S. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1167425 · Cited by 7 · see citing works
The application of diffusion tensor imaging in patients with mild cognitive impairment: a systematic review and meta-analysis
Zhao, X., You, M., Ren, W., Ji, L., Liu, Y., & Lu, M. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1467578 · Cited by 7 · see citing works
Mechanism of cognitive impairment in chronic patients with putaminal hemorrhage
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MRI-based comparative study of different mild cognitive impairment subtypes: protocol for an observational case–control study
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A review of brain research on T2DM-related cognitive dysfunction
Liu, Q., Dai, S., Li, X., Chen, Y., Wang, N., Wu, J., Zhou, Y., Yan, B., Guo, Y., & Liu, Y. (2025) · Open Medicine · doi:10.1515/med-2025-1253 · Cited by 4 · see citing works
Enhanced Integrity of White Matter Microstructure in Mind–Body Practitioners: A Whole-Brain Diffusion Tensor Imaging Study
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Regionally-specific diffusion tensor imaging in mild cognitive impairment and Alzheimer’s disease.
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Effectiveness of regional DTI measures in distinguishing Alzheimer’s disease, MCI, and normal aging
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Authors: Nowrangi, M. A., Lyketsos, C. G., Leoutsakos, J. S., Oishi, K., Albert, M., Mori, S., & Mielke, M. M.
Affiliations: Johns Hopkins University (US)
Mayo Clinic (US)
Corresponding author: Nowrangi, Milap A.
ORCID: Lyketsos, Constantine G.
Leoutsakos, Jeannie‐Marie S.
Oishi, Kenichi
Albert, Marilyn
Mori, Susumu
Mielke, Michelle M.
Venue: Alzheimer's & Dementia
Publisher: Wiley
Published: 2012-12-14
Volume: 9
Issue: 5
Pages: 519-528
ISSN: 1552-5260 (ISSN-L)
1552-5279
DOI: 10.1016/j.jalz.2012.05.2186
PMC: PMC3639296
OpenAlex: W2030309279
Cited by: 120
References: 64
Citations by year: 2026: 6 · 2025: 11 · 2024: 5 · 2023: 11 · 2022: 3 · 2021: 7 · 2020: 13 · 2019: 11 · 2018: 12 · 2017: 6 · 2016: 7 · 2015: 16 · 2014: 7 · 2013: 5
FWCI: 6.36
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Alzheimer s & Dementia (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: GlaxoSmithKline
National Institute on Aging (P50-AG005146, P50-AG021334, R21 AG033774)
National Institutes of Health (R21AG033774, P50AG005146)
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: mild cognitive impairment, Alzheimer's disease
MeSH terms: Aged, Alzheimer Disease, Brain, Female, Humans, Image Interpretation, Computer-Assisted, Longitudinal Studies, Male, Nerve Fibers, Myelinated, Anisotropy, Diffusion Magnetic Resonance Imaging, Cognitive Dysfunction

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Longitudinal, region-specific course of diffusion tensor imaging measures in mild cognitive impairment and Alzheimer’s disease

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