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@ARTICLE{Tranfa:270323,
      author       = {Tranfa, Mario and Lorenzini, Luigi and Collij, Lyduine E
                      and Vállez García, David and Ingala, Silvia and Pontillo,
                      Giuseppe and Pieperhoff, Leonard and Maranzano, Alessio and
                      Wolz, Robin and Haller, Sven and Blennow, Kaj and Frisoni,
                      Giovanni and Sudre, Carole H and Chételat, Gael and Ewers,
                      Michael and Payoux, Pierre and Waldman, Adam and
                      Martinez-Lage, Pablo and Schwarz, Adam J and Ritchie, Craig
                      W and Wardlaw, Joanna M and Gispert, Juan Domingo and
                      Brunetti, Arturo and Mutsaerts, Henk J M M and Wink, Alle
                      Meije and Barkhof, Frederik},
      title        = {{A}lzheimer's {D}isease and {S}mall {V}essel {D}isease
                      {D}ifferentially {A}ffect {W}hite {M}atter
                      {M}icrostructure.},
      journal      = {Annals of Clinical and Translational Neurology},
      volume       = {11},
      number       = {6},
      issn         = {2328-9503},
      address      = {Chichester [u.a.]},
      publisher    = {Wiley},
      reportid     = {DZNE-2024-00785},
      pages        = {1541 - 1556},
      year         = {2024},
      abstract     = {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.},
      keywords     = {Humans / Alzheimer Disease: pathology / Alzheimer Disease:
                      diagnostic imaging / Female / Cerebral Small Vessel
                      Diseases: diagnostic imaging / Cerebral Small Vessel
                      Diseases: pathology / Male / White Matter: diagnostic
                      imaging / White Matter: pathology / Aged / Diffusion Tensor
                      Imaging / Middle Aged / Amyloid beta-Peptides: cerebrospinal
                      fluid / Amyloid beta-Peptides: metabolism / Apolipoprotein
                      E4: genetics / tau Proteins: cerebrospinal fluid / tau
                      Proteins: metabolism / Prospective Studies / Amyloid
                      beta-Peptides (NLM Chemicals) / Apolipoprotein E4 (NLM
                      Chemicals) / tau Proteins (NLM Chemicals)},
      cin          = {Clinical Research (Munich)},
      ddc          = {610},
      cid          = {I:(DE-2719)1111015},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC11187968},
      pubmed       = {pmid:38757392},
      doi          = {10.1002/acn3.52071},
      url          = {https://pub.dzne.de/record/270323},
}