January 2013

Subcortical Morphology in Niemann Pick Type C

Striatal, hippocampal, thalamic and cerebellar MRI changes characterise NPC

In two recent papers, we have shown that Niemann-Pick type C (NPC) in adults is characterised by significant subcortical volumetric changes that correlate with various illness variables including cognition, ataxia and ocular-motor functioning. This expands on our suite of neuroimaging papers in NPC, the only group neuroimaging studies in this disorder, by further clarifying the relationships between brain changes and behaviour in this disorder. We have shown that volumetric changes are greatest in those regions that carry the largest neurofibrillary tangle burden and/or ganglioside excess based on neuropathological studies, and that these changes correlate with illness stage, cognition, ataxia measures and key ocular-motor saccadic measures. The first paper involved collaborating with Brian Patenaude (author of the FIRST toolbox in FSL, from the Oxford FMRIB group); the second utilised Freesurfer methodology to parcellate the cerebellum.

These two papers can be found
here and here.

Walterfang et al. Subcortical volumetric reductions in adult Niemann-Pick type C: a cross-sectional study.
Am J Neuroradiol in press.

Walterfang et al. Cerebellar volume correlates with saccadic gain and ataxia in adult Niemann-Pick type C.
Mol Genet Metab 108: 85-89, 2013.

Basal Ganglia Morphology Distinguishes Dementia Subtypes

Putaminal Morphology Reveals Frontostriatal “Axis” in FTD

With collaborators from the Australian National University and the University of California (Los Angeles), we have shown that, like the hippocampus, the putamen in the striatum can be used as a possible biomarker for dementia subtype. In comparing a well-characterised group of patients with frontotemporal dementia, Huntington’s disease Alzheimer’s disease and matched healthy controls, and using sophisticated shape analysis methodology from Paul Thompson’s group at UCLA, we showed that there are distinct atrophy “signatures” that occur in the putamen, a key grey matter structure in the basal ganglia. These signatures may be useful in aiding diagnosis, and for better understanding of some of the cognitive and behavioural disturbances that occur in these degenerative disorders.

The research also shows that, compared to a more typical basal ganglia disorder and a cortical disorder, frontotemporal dementia shares characteristics of both, adding to our previous work proposing a frontostriatal axis for many of the features of this illness.

The paper can be found

Looi et al. Differential putaminal morphology in Huntington’s disease, frontotemporal dementia and Alzheimer’s disease.
Aust NZ J Psychiatry 46: 1145-1158, 2012.