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  • Tranfa, MarioUniversity of Naples Federico II,Academic Medical Center of University of Amsterdam (AMC) (author)

Alzheimer's Disease and Small Vessel Disease Differentially Affect White Matter Microstructure

  • Article/chapterEnglish2024

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  • 2024

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  • LIBRIS-ID:oai:gup.ub.gu.se/339229
  • https://gup.ub.gu.se/publication/339229URI
  • https://doi.org/10.1002/acn3.52071DOI
  • https://lup.lub.lu.se/record/e61fb061-d9aa-4c5f-8214-2b0d9a4d2fdeURI

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  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

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  • ObjectiveAlzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non-invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE-epsilon 4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults.MethodsWithin the prospective European Prevention of Alzheimer's Dementia study, we selected 606 participants (64.9 +/- 7.2 years, 376 females) with baseline cerebrospinal fluid samples of amyloid beta 1-42 and p-Tau181 and MRI scans, including DTI scans. Longitudinal scans (mean follow-up time = 1.3 +/- 0.5 years) were obtained in a subset (n = 223). WM integrity was assessed by extracting fractional anisotropy and mean diffusivity in relevant tracts. To identify the determinants of WM disruption, we performed a multimodel inference to identify the best linear mixed-effects model for each tract.ResultsAD pathology, APOE-epsilon 4, cSVD burden, and cardiovascular risk were all associated with WM integrity within several tracts. While limbic tracts were mainly impacted by AD pathology and APOE-epsilon 4, commissural, associative, and projection tract integrity was more related to cSVD burden and cardiovascular risk. AD pathology and cSVD did not show any significant interaction effect.InterpretationOur results suggest that AD pathology and cSVD exert independent and spatially different effects on WM microstructure, supporting the role of DTI in disease monitoring and suggesting independent targets for preventive medicine approaches.

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  • Lorenzini, LuigiAmsterdam Neuroscience,Academic Medical Center of University of Amsterdam (AMC) (author)
  • Collij, Lyduine E.Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Amsterdam Neuroscience,Academic Medical Center of University of Amsterdam (AMC)(Swepub:lu)ly4120co (author)
  • Vallez Garcia, DavidAmsterdam Neuroscience,Academic Medical Center of University of Amsterdam (AMC) (author)
  • Ingala, SilviaCopenhagen University Hospital,Academic Medical Center of University of Amsterdam (AMC),Amsterdam Neuroscience (author)
  • Pontillo, GiuseppeAcademic Medical Center of University of Amsterdam (AMC) (author)
  • Pieperhoff, LeonardAcademic Medical Center of University of Amsterdam (AMC),Amsterdam Neuroscience (author)
  • Maranzano, AlessioIstituto Auxologico Italiano (author)
  • Wolz, RobinIXICO Plc (author)
  • Haller, SvenUppsala University,Beijing Tiantan Hospital (author)
  • Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy,Sahlgrenska University Hospital(Swepub:lu)med-kbw (author)
  • Frisoni, GiovanniGeneva University Hospital,Centro San Giovanni di Dio Fatebenefratelli (author)
  • Sudre, Carole H.University College London,King's College London,Sahlgrenska Academy (author)
  • Chetelat, Gael (author)
  • Ewers, MichaelGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Payoux, PierreToulouse University Hospital (author)
  • Waldman, AdamImperial College London,University of Edinburgh (author)
  • Martinez-Lage, Pablo (author)
  • Schwarz, Adam J.Indiana University (author)
  • Ritchie, Craig W.University of Edinburgh (author)
  • Wardlaw, Joanna M.University of Edinburgh (author)
  • Gispert, Juan DomingoHospital del Mar Medical Research Institute,Pompeu Fabra University,CIBER Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) (author)
  • Brunetti, ArturoUniversity of Naples Federico II (author)
  • Mutsaerts, Henk J. M. M.Amsterdam Neuroscience,Ghent University Hospital (author)
  • Wink, Alle MeijeAcademic Medical Center of University of Amsterdam (AMC),Amsterdam Neuroscience (author)
  • Barkhof, FrederikAcademic Medical Center of University of Amsterdam (AMC),University College London (author)
  • University of Naples Federico IIAcademic Medical Center of University of Amsterdam (AMC) (creator_code:org_t)

Related titles

  • In:ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY11:6, s. 1541-15562328-9503

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