Structural connectivity alterations along the Alzheimer’s disease continuum: reproducibility across two independent samples and correlation with cerebrospinal fluid Amyloid-β and tau.
Open accessAbstract
Background: Gray matter changes associated with the progression of Alzheimer’s disease (AD) have been thoroughly studied. However, alterations in white matter tracts have received less attention, particularly during early or preclinical stages of the disease. Objective: To identify the structural connectivity changes across the AD continuum. Methods: We performed probabilistic tractography in a total of 183 subjects on two independent samples that include control ( n = 68) and preclinical AD individuals ( n = 28), patients diagnosed with mild cognitive impairment (MCI) due to AD ( n = 44), and AD patients ( n = 43). We compared the connectivity between groups, and with CSF Aβ 42 and tau biomarkers. Results: We observed disconnections in preclinical individuals, mainly located in the temporal lobe. This pattern of disconnection spread to the parietal and frontal lobes at the MCI stage and involved almost all the brain in AD. These findings were not driven by gray matter atrophy. Discussion: Using tractography, we were able to identify white matter changes between subsequent disease stages and, notably, also in preclinical AD. Therefore, this method may be useful for detecting early and specific brain structural changes during preclinical AD stage.
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DTI metrics or structural connectome alterations showed correlations with amyloid burden or levels of cerebrospinal fluid amyloid and tau.
“Diffusion tensor imaging (DTI) metrics or structural connectome alterations showed correlations with amyloid burden (Racine et al., 2014) or levels of cerebrospinal fluid amyloid and tau (Tucholka et al., 2018).”
From Effects of Alzheimer’s and Vascular Pathologies on Structural Connectivity in Early- and Late-Onset Alzheimer’s Disease (2021) · cites this paper as Tucholka et al., 2018
The Results (‘Correlations of connections with biomarkers’; page not available) report correlations between structural connectivity and CSF Aβ42 in both samples. They also report a significant correlation with p-tau in one sample, but it was not reproduced in the other; the Discussion says tau-related associations were less consistent. Thus the citation supports the amyloid finding but overstates the tau finding if read as a general correlation. (LLM, conf=0.84)
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- Authors
- Tucholka, A., Grau-Rivera, O., Falcon, C., Rami, L., Sánchez-Valle, R., Lladó, A., Gispert, J. D., Molinuevo, J. L., & Initiative, F. T. A. D. N.
- Affiliations
- Pasqual Maragall Foundation (ES)
- Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain
- Hospital Clínic de Barcelona (ES)
- Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Corresponding author
- Gispert, Juan Domingo
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2018-01-23
- Volume
- 61
- Issue
- 4
- Pages
- 1575-1587
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC5798529
- OpenAlex
- W2793261759
- Cited by
- 29
- References
- 43
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 2
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- European Federation of Pharmaceutical Industries and Associations
- European Commission (115568)
- Innovative Medicines Initiative
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904)
- 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
- Alzheimer's disease, structural connectivity
- MeSH terms
- Aged, Alzheimer Disease, Atrophy, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Spain, Reproducibility of Results, Cohort Studies, Biomarkers, Case-Control Studies, Amyloid beta-Peptides, tau Proteins, Disease Progression, Cognitive Dysfunction, White Matter, Gray Matter
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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