Structural connectivity networks in prodromal and clinical Huntington's disease

C. Sanchez-Castañeda, H. Baggio, U. Sabatini, F. Squitieri, C. Junque (Barcelona, Spain)

Meeting: 2016 International Congress

Abstract Number: 1128

Keywords: Chorea (also see specific diagnoses, etc): Anatomy, Huntingtons disease, Magnetic resonance imaging(MRI)

Session Information

Date: Wednesday, June 22, 2016

Session Time: 12:00pm-1:30pm

Objective: To investigate how structural connectivity correlates with the number of CAG repeats, disease evolution and clinical measures in presymptomatic (preHD) and clinical Huntington Disease (HD) patients.

Background: Huntington disease is an autosomal-dominant disease determined by a CAG expansion mutation in the gene encoding the protein huntingtin. Graph theory analysis represents anatomical brain regions as nodes are linked edges, that are the structural connections of white matter tracts (1). We can define a node by its degree of connectivity (nº of edges linked to it), its centrality (nº of shortest paths between any two nodes), its efficiency and its clustering coefficient (probability of forming a group with the neighbouring nodes) (1,2). Mapping these structural networks may help to understand how the neurodegenerative process spreads across structurally interconnected brain regions.

Methods: 84 mutation carriers (31 PreHD and 53 HD patients (stage I-II)) and 76 matched control subjects underwent high-resolution T1-weighted imaging (MDEFT sequence: TR/TE=7.92/2.4ms, FoV=256, voxel-size=1mm3) and Diffusion-weighted imaging (spin-echo EPI sequence: TE/TR=89/8500 ms, voxel size 1.8mm3, 30 isotropically distributed orientations at b=1000 and 6 b=0 images) on a 3T Siemens scanner. Patients were examined by the Unified Huntington’s Disease Rating Scale (UHDRS; Huntington Study Group, 1996). The details of the image processing and network computation can be found in Baggio et al. (2). We used the CAP index (CAP=Age*CAG-33.66) to test the effect of mutation toxicity, corrected by the length of exposure to the mutation toxicity. Pearson correlation test was used.

Table 1. Demographic and clinical characteristics of the sample
	Controls (n=76)	PreHD (n=31)	HD (n=53)	X2/t	p-value
Gender (M:F)	41:35	20:11	33:20	5.63	NS
Age	44.5 (13.0)	38.2 (7.2)	48.1 (13.4)	5.57	0.025 Cnt < PreHD
CAG Repeat Length	NA	42.9 (2.2)	46.3 (5.8)	-2.95	0.004
Disease duration (years)	NA	NA	7.10 (5.5)	NA	NA
TIV	1408291 (130506.6)	13933948 (102824.9)	1321324 (120073.4)	7.78	<0.0001 Cnt > HD
MMSE	NA	28 (1.4)	24.4 (3.9)	4.06	<0.0001
UHDRS Motor*	NA	5.7 (5.3)	38.4 (14.8)	-10.6	<0.0001
UHDRS Cognitive	NA	260.3 (43.2)	136.6 (46.3)	10.2	<0.0001
UHDRS Behavioral*	NA	7.2 (8)	18.36 (9.1)	-4.97	<0.0001
UHDRS Functional	NA	25 (0)	17.5 (6)	6.15	<0.0001
TFC	NA	13 (0)	8.1 (2.6)	9.42	<0.0001
Independence scale	NA	100 (0)	77.2 (13.4)	8.34	<0.0001
Disease burden	NA	297.9 (65.2)	454.8 (117.3)	-4.6	<0.0001

Values expressed as mean (S.D.) with the exception of gender. Pearson’s Chi-square. T-student. Bonferroni correction. Abbreviations: Cnt, Control subjects; HD, Huntington’s disease; MMSE, mini-mental state examination; NA, not applicable; NS, not significant; PreHD, presymptomatic Huntington’s disease; TIV, total intracranial volume; TFC, total functional capacity *lower punctuations mean fewer symptoms“

Results: All general measures of structural connectivity correlated with the CAP index (p<0.005) and disease evolution (p<0.008).

Table 2. Structural connectivity measures’ correlation with disease evolution
		Disease Evolution
Strength	Pearson correlation	-0.445
	Sig. (bilateral)	<0.0001
Modularity	Pearson correlation	0.298
	Sig. (bilateral)	0.008
Global clustering	Pearson correlation	-0.460
	Sig. (bilateral)	<0.0001
Global efficiency	Pearson correlation	-0.475
	Sig. (bilateral)	<0.0001
Mean node degree	Pearson correlation	-0.340
	Sig. (bilateral)	0.002
Small worldness	Pearson correlation	0.251
	Sig. (bilateral)	0.026
Path length	Pearson correlation	0.450
	Sig. (bilateral)	<0.0001

Also, global efficiency significantly correlated with all clinical scales: UHDRS motor, cognitive, behavioural and functional scale, total functional capacity and cognitive measures (p<0.001).

Conclusions: These results provide evidence that the number of CAG repeats together with the time of exposure to the mutation (CAP index) determine the integrity of structural connectivity. Also, structural connectivity measures are correlated with disease evolution. Finally, the efficiency of these connections is related to the clinical scales: the most efficient, the better performance in motor and cognitive scales.

To cite this abstract in AMA style:

C. Sanchez-Castañeda, H. Baggio, U. Sabatini, F. Squitieri, C. Junque. Structural connectivity networks in prodromal and clinical Huntington’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/structural-connectivity-networks-in-prodromal-and-clinical-huntingtons-disease/. Accessed June 15, 2025.

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