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

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

Tranfa, Mario (författare): University of Naples Federico II,Academic Medical Center of University of Amsterdam (AMC)

Lorenzini, Luigi (författare): Amsterdam Neuroscience,Academic Medical Center of University of Amsterdam (AMC)

Collij, Lyduine E. (författare): 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)

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Vállez García, David (författare): Amsterdam Neuroscience,Academic Medical Center of University of Amsterdam (AMC)

Ingala, Silvia (författare): Copenhagen University Hospital,Academic Medical Center of University of Amsterdam (AMC),Amsterdam Neuroscience

Pontillo, Giuseppe (författare): Academic Medical Center of University of Amsterdam (AMC)

Pieperhoff, Leonard (författare): Academic Medical Center of University of Amsterdam (AMC),Amsterdam Neuroscience

Maranzano, Alessio (författare): Istituto Auxologico Italiano

Wolz, Robin (författare): IXICO Plc

Haller, Sven (författare): Uppsala University,Beijing Tiantan Hospital

Blennow, Kaj (författare): Sahlgrenska Academy,Sahlgrenska University Hospital

Frisoni, Giovanni (författare): Geneva University Hospital,Centro San Giovanni di Dio Fatebenefratelli

Sudre, Carole H. (författare): University College London,King's College London,Sahlgrenska Academy

Chételat, Gael (författare)

Ewers, Michael (författare): German Center for Neurodegenerative Diseases (DZNE), Bonn

Payoux, Pierre (författare): Toulouse University Hospital

Waldman, Adam (författare): Imperial College London,University of Edinburgh

Martinez-Lage, Pablo (författare)

Schwarz, Adam J. (författare): Indiana University

Ritchie, Craig W. (författare): University of Edinburgh

Wardlaw, Joanna M. (författare): University of Edinburgh

Gispert, Juan Domingo (författare): Hospital del Mar Medical Research Institute,Pompeu Fabra University,CIBER Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN)

Brunetti, Arturo (författare): University of Naples Federico II

Mutsaerts, Henk J.M.M. (författare): Amsterdam Neuroscience,Ghent University Hospital

Wink, Alle Meije (författare): Academic Medical Center of University of Amsterdam (AMC),Amsterdam Neuroscience

Barkhof, Frederik (författare): Academic Medical Center of University of Amsterdam (AMC),University College London

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Engelska.
Ingår i: Annals of Clinical and Translational Neurology. - 2328-9503.

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Objective: Alzheimer'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-ε4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults. Methods: Within 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 β1-42 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. Results: AD pathology, APOE-ε4, 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-ε4, 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. Interpretation: Our 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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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Neurologi

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Av lärosätet: Lunds universitet

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

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