Complex relationships between cerebral blood flow and brain atrophy in early Huntington's disease

Abstract

Alterations in cerebral blood flow (CBF) may play an important role in the pathophysiology of neurodegenerative disorders such as Huntington's disease (HD). While a few reports have suggested reductions in CBF in HD, little is known about their extent and whether, or how, they might be related to atrophy and to clinical symptoms. We used pulsed arterial-spin labeling MRI in conjunction with high-resolution anatomical MRI to non-invasively measure regional CBF in 17 early stage HD subjects and 41 age- and gender-matched healthy controls. We found profound yet heterogeneous CBF reductions in the cortex, extending to the sensorimotor, paracentral, inferior temporal and lateral occipital regions, with sparing of the neighboring postcentral gyrus, insula and medial occipital areas. As expected, CBF in subcortical regions was also profoundly reduced, and to a similar degree. Unexpectedly, however, the association between CBF reductions and regional atrophy was complex, the two being directly associated in certain areas but not with others. In contrast, CBF was associated with performance on the Stroop, suggesting a potentially important role for alterations in CBF in cognitive deficits in HD. The work described here may have broad-reaching implications for our understanding of HD pathogenesis, progression and emerging therapies.