TY  - JOUR
AU  - Tranfa, Mario
AU  - Lorenzini, Luigi
AU  - Collij, Lyduine E
AU  - Vállez García, David
AU  - Ingala, Silvia
AU  - Pontillo, Giuseppe
AU  - Pieperhoff, Leonard
AU  - Maranzano, Alessio
AU  - Wolz, Robin
AU  - Haller, Sven
AU  - Blennow, Kaj
AU  - Frisoni, Giovanni
AU  - Sudre, Carole H
AU  - Chételat, Gael
AU  - Ewers, Michael
AU  - Payoux, Pierre
AU  - Waldman, Adam
AU  - Martinez-Lage, Pablo
AU  - Schwarz, Adam J
AU  - Ritchie, Craig W
AU  - Wardlaw, Joanna M
AU  - Gispert, Juan Domingo
AU  - Brunetti, Arturo
AU  - Mutsaerts, Henk J M M
AU  - Wink, Alle Meije
AU  - Barkhof, Frederik
TI  - Alzheimer's Disease and Small Vessel Disease Differentially Affect White Matter Microstructure.
JO  - Annals of Clinical and Translational Neurology
VL  - 11
IS  - 6
SN  - 2328-9503
CY  - Chichester [u.a.]
PB  - Wiley
M1  - DZNE-2024-00785
SP  - 1541 - 1556
PY  - 2024
AB  - 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.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.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.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.
KW  - Humans
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: diagnostic imaging
KW  - Female
KW  - Cerebral Small Vessel Diseases: diagnostic imaging
KW  - Cerebral Small Vessel Diseases: pathology
KW  - Male
KW  - White Matter: diagnostic imaging
KW  - White Matter: pathology
KW  - Aged
KW  - Diffusion Tensor Imaging
KW  - Middle Aged
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - Amyloid beta-Peptides: metabolism
KW  - Apolipoprotein E4: genetics
KW  - tau Proteins: cerebrospinal fluid
KW  - tau Proteins: metabolism
KW  - Prospective Studies
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Apolipoprotein E4 (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11187968
C6  - pmid:38757392
DO  - DOI:10.1002/acn3.52071
UR  - https://pub.dzne.de/record/270323
ER  -