open access publication

Article, Early Access, 2024

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

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, ISSN 2328-9503, 2328-9503, 10.1002/acn3.52071

Contributors

Tranfa, Mario 0000-0002-4451-4746 (Corresponding author) [1] [2] [3] Lorenzini, Luigi 0000-0002-9756-881X [2] [3] Collij, Lyduine E. 0000-0001-6263-1762 [2] [3] [4] Vallez Garcia, David [2] [3] Ingala, Silvia 0000-0003-2199-385X [2] [3] [5] [6] [7] Pontillo, Giuseppe 0000-0001-5425-1890 [2] [3] Pieperhoff, Leonard [2] [3] Maranzano, Alessio 0000-0002-3642-9584 [8] Wolz, R. [9] Haller, Sven [10] [11] [12] Blennow, Kaj [13] [14] Frisoni, Giovanni [15] [16] Sudre, Carole H. 0000-0001-5753-428X [14] [17] [18] [19] Chetelat, Gael 0000-0002-4889-7932 [20] [21] Ewers, Michael 0000-0003-1240-0522 [22] [23] Payoux, Pierre 0000-0002-1374-1620 [21] [24] [25] [26] Waldman, Adam [27] [28] Martinez-Lage, Pablo 0000-0001-5404-9967 [29] Schwarz, Adam J. 0000-0002-9743-6171 [30] [31] [32] Ritchie, Craig W. [28] [33] Wardlaw, Joanna M. [28] Gispert, Juan Domingo [34] [35] [36] [37] [38] Brunetti, Arturo [1] Mutsaerts, Henk J. M. M. [2] [39] Wink, Alle Meije [2] [3] Barkhof, Frederick 0000-0003-3543-3706 [2] [3] [18] [19]

Affiliations

  1. [1] Univ Federico II, Dept Adv Biomed Sci, Via Pansini 5, I-80131 Naples, Italy
    2. [NORA names: Italy; Europe, EU; OECD];
  2. [2] Amsterdam Neurosci, Brain Imaging, Amsterdam, Netherlands
    3. [NORA names: Netherlands; Europe, EU; OECD];
  3. [3] Univ Amsterdam, Vrije Univ, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands
    4. [NORA names: Netherlands; Europe, EU; OECD];
  4. [4] Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Malmo, Sweden
    5. [NORA names: Sweden; Europe, EU; Nordic; OECD];
  5. [5] Cerebriu AS, Copenhagen, Denmark
    6. [NORA names: Other Companies; Private Research; Denmark; Europe, EU; Nordic; OECD];

Abstract

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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