Background: Anosognosia, or unawareness of symptoms, is common in Huntington's disease (HD), but the neuroanatomical basis of this is unknown.
Objective: To identify neuroanatomical correlates of HD anosognosia using structural MRI data.
Methods: We leveraged a pre-processed dataset of 570 HD participants across the well-characterized PREDICT-HD and TRACK-HD cohort studies. Anosognosia index was operationalized as the score discrepancies between HD participants and their caregivers on the Frontal Systems Behavior Scale (FrSBe).
Results: Univariate correlation analyses identified volumes of globus pallidus, putamen, caudate, basal forebrain, substantia nigra, angular gyrus, and cingulate cortex as significant correlates of anosognosia after correction for multiple comparisons. A multivariable model constructed with stepwise regression that included volumetric data showed globus pallidus volume alone explained more variance in anosognosia severity than motor impairment or CAP score alone.
Conclusions: Anosognosia appears to be related to degeneration affecting both cortical and subcortical areas. Globus pallidus neurodegeneration in particular appears to be a key process of importance.
Keywords: Anosognosia; FrSBe; Huntington’s disease; PREDICT-HD; TRACK-HD; globus pallidus.