DOI: 10.5061/dryad.gb5mkkx3g
title: The insidious degeneration of white matter and cognitive decline in Fabry disease

description: Fabry disease is a rare X-linked deficiency of lysosomal
 alpha-galactosidase that causes glycolipid accumulation in tissues,
 including the brain. The most common neurologic sequelae of Fabry are
 cognitive decline and white matter lesions (WMLs) on brain magnetic
 resonance imaging (MRI). In the at-large population, however, WMLs are
 non-specific, highly prevalent, and most are clinically silent. Thus, we
 compared Fabry to typical brain aging to identify factors unique to
 Fabry-related cognitive decline. Twenty adult Fabry patients (75% female;
 median age 36.4 yrs, range: 19.8-63.2 yrs; 95% on enzyme replacement
 therapy) without a history of stroke or other neurologic diseases and 20
 age/sex-matched healthy controls were enrolled in a case-control study.
 All participants underwent a neurocognitive assessment and a 3.0 T MRI
 study of the brain that used structural MRI (e.g., fluid-attenuated
 inversion recovery, FLAIR), semi-quantitative MRI (e.g., normalized FLAIR
 signal intensity), and quantitative MRI (diffusion tensor imaging,
 bound-pool fraction imaging). During a blinded review of structural MRIs,
 a neuroradiologist’s categorization of case-control status did not
 correspond to disease status (Fisher’s test, P&gt;0.99) but rather to
 age (P=0.004), indicating qualitative changes associated with Fabry were
 similar to normal age-related brain alterations. Using quantitative MRI,
 however, we detected evidence of microstructural damage in the white
 matter of younger Fabry adults (&lt;40 yrs). With age, WML severity
 increased and the corpus callosum atrophied in Fabry, phenomena absent in
 controls and consistent with progressive tissue damage. Neurocognitive
 assessments identified trends for lower verbal intelligence quotient and
 executive function in the younger Fabry participants, which became
 statistically significant in the older Fabry patients. Our data suggest
 that the early onset of microstructural damage in Fabry drives the
 insidious degeneration of white matter, leading to impaired cognition.
 Aging Fabry patients may benefit from serial cognitive assessments to
 identify unmet therapeutic needs.
description: # The insidious degeneration of white matter and cognitive decline in
 Fabry disease Dataset DOI:
 [10.5061/dryad.gb5mkkx3g](https://doi.org/10.5061/dryad.gb5mkkx3g) ##
 Description of the data and file structure Magnetic resonance imaging
 files for each study participant are located in the participant's
 study ID folder.            F = Fabry participant, C = healthy control
 participant Data in DICOM format is available in the subfolder that
 contains the following strings:           DTI = diffusion tensor imaging  
         FLAIR = fluid attenuated inversion recovery           T2W =
 T2-weighted            MP_Rage = magnetization prepared rapid acquisition
 gradient echo           MT = magnetization transfer:                    
 4000 = off-resonance of 4 kHz                     8000 = off-resonance of
 8 kHz                     96000 = off-resonance of 96 kHz           VFA =
 variable flip angle:                     3 = 3 degree flip angle          
           10 = 10 degree flip angle                     15 = 15 degree
 flip angle Because DICOM format does not permit complex numbers, data used
 to generate B0 and B1 maps are shared in matrix format (i.e., RAW data in
 .mat format) in the "B0_Map"  and "B1_Map"
 subdirectories, respectively.  To access a participant's B0 data
 using Matlab, change the Matlab directory to the participant's
 "B0_Map" folder, and type at the Matlab prompt:                 
     load("b0map_masked.mat") Three matrices (each of size
 128x128x60) will open:           (1) S0 and (2) S1, which can be used to
 compute B0 using the dual-TE phase method governed by the following Matlab
 equations:                     B0 = 0.5*angle((S1.*conj(S0).^2);          
           B0 = B0*180/pi;           (3) B0 is the computed B0 field after
 3D smoothing. To access a participant's B1 data using Matlab, change
 the Matlab directory to the participant's "B1_Map" folder,
 and type at the Matlab prompt:                     
 load("b1map_masked.mat") Three matrices (each of size
 128x128x60) will open:           (1) S1 and (2) S2, which can be used to
 compute B1 using the actual flip-angle imaging method governed by the
 following Matlab equations:                     tr1 = 25 ms; % TR1
 acquisition parameter                     tr2 = 125 ms; % TR2 acquisition
 parameter                     alpha = 60; % acquisition flip-angle        
             r = S2./S1;                     n = tr2 / tr1;               
       act_alpha = acos((r*n - 1)./(n - r)) * 180/pi;                    
 B1 = real(act_alpha/alpha;                      B1(isnan(b1)) = 0;        
             B1(isinf(b1)) = 0;           (3) B1 is the computed B1 field
 after 3D smoothing. All DICOM header files have been anonymized using
 Matlab's "dicomwrite" command to convert a 2D matrix to
 DICOM file. All DICOM and RAW data image files have undergone skull
 stripping using Matlab morphology operators. ### Files and variables ####
 File: F980.tar.gz **Description:** Fabry participant #### File:
 F921.tar.gz **Description:** Fabry participant #### File: F878.tar.gz
 **Description:** Fabry participant #### File: F888.tar.gz
 **Description:** Fabry participant #### File: F768.tar.gz
 **Description:** Fabry participant #### File: F632.tar.gz
 **Description:** Fabry participant #### File: F876.tar.gz
 **Description:** Fabry participant #### File: F592.tar.gz
 **Description:** Fabry participant #### File: F605.tar.gz
 **Description:** Fabry participant #### File: F589.tar.gz
 **Description:** Fabry participant #### File: F576.tar.gz
 **Description:** Fabry participant #### File: F543.tar.gz
 **Description:** Fabry participant #### File: F467.tar.gz
 **Description:** Fabry participant #### File: F372.tar.gz
 **Description:** Fabry participant #### File: F444.tar.gz
 **Description:** Fabry participant #### File: F342.tar.gz
 **Description:** Fabry participant #### File: F333.tar.gz
 **Description:** Fabry participant #### File: F146.tar.gz
 **Description:** Fabry participant #### File: F123.tar.gz
 **Description:** Fabry participant #### File: F222.tar.gz
 **Description:** Fabry participant #### File: C93.tar.gz
 **Description:** Healthy control participant #### File: C99.tar.gz
 **Description:** Healthy control participant #### File: C87.tar.gz
 **Description:** Healthy control participant #### File: C85.tar.gz
 **Description:** Healthy control participant #### File: C77.tar.gz
 **Description:** Healthy control participant #### File: C76.tar.gz
 **Description:** Healthy control participant #### File: C63.tar.gz
 **Description:** Healthy control participant #### File: C61.tar.gz
 **Description:** Healthy control participant #### File: C64.tar.gz
 **Description:** Healthy control participant #### File: C51.tar.gz
 **Description:** Healthy control participant #### File: C44.tar.gz
 **Description:** Healthy control participant #### File: C33.tar.gz
 **Description:** Healthy control participant #### File: C32.tar.gz
 **Description:** Healthy control participant #### File: C55.tar.gz
 **Description:** Healthy control participant #### File: C42.tar.gz
 **Description:** Healthy control participant #### File: C27.tar.gz
 **Description:** Healthy control participant #### File: C16.tar.gz
 **Description:** Healthy control participant #### File: C62.tar.gz
 **Description:** Healthy control participant #### File: C13.tar.gz
 **Description:** Healthy control participant #### File: C11.tar.gz
 **Description:** Healthy control participant ## Code/software A DICOM
 viewer is necessary to visualize the data in DICOM format. To access the
 B0 and B1 data, a Matlab license is necessary. ## Human subjects data The
 magnetic resonance images were anonymized by using the participant's
 randomly-generated study identifier instead of the participant's name
 at the time of image acquisition. The images do not contain any personally
 identifiable information (PII; e.g., name, date of birth, etc.). All
 participants consented to publish the de-identified data in the public
 domain.