Structural neuroimaging differentiates vulnerability from disease manifestation in colombian families with Huntington's disease

Introduction The volume of the striatal structures has been associated with disease progression in individuals with Huntington's disease (HD) from North America, Europe, and Australia. However, it is not known whether the gray matter (GM) volume in the striatum is also sensitive in differentiating vulnerability from disease manifestation in HD families from a South‐American region known to have high incidence of the disease. In addition, the association of enlarged brain perivascular spaces (PVS) with cognitive, behavioral, and motor symptoms of HD is unknown. Materials and Methods We have analyzed neuroimaging indicators of global atrophy, PVS burden, and GM tissue volume in the basal ganglia and thalami, in relation to behavioral, motor, and cognitive scores, in 15 HD patients with overt disease manifestation and 14 first‐degree relatives not genetically tested, which represent a vulnerable group, from the region of Magdalena, Colombia. Results Poor fluid intelligence as per the Raven's Standard Progressive Matrices was associated with global brain atrophy (p = 0.002) and PVS burden (p ≤ 0.02) in HD patients, where the GM volume in all subcortical structures, with the exception of the right globus pallidus, was associated with motor or cognitive scores. Only the GM volume in the right putamen was associated with envy and MOCA scores (p = 0.008 and 0.015 respectively) in first‐degree relatives. Conclusion Striatal GM volume, global brain atrophy and PVS burden may serve as differential indicators of disease manifestation in HD. The Raven's Standard Progressive Matrices could be a cognitive test worth to consider in the differentiation of vulnerability versus overt disease in HD. The volume of gray matter in the basal ganglia and thalami is a sensitive differential indicator of disease manifestation versus vulnerability in HD families from a South‐American region with high incidence of this disease. This is the first study that analyzed and found that the burden of brain enlarged perivascular spaces is associated with less fluid intelligence in HD patients and not in their first‐degree relatives; and that the Raven's Standard Progressive Matrices discriminated overt HD versus vulnerability after accounting for age, biological sex, and years of education; thus suggesting their usefulness in the study of HD.