The findings suggest that the tool can be used to not only assess cognitive impairment in Huntington disease (HD) but also to detect brain atrophy patterns associated with cognitive status in these patients.
A widely used tool for assessing cognitive impairment may also offer indications of structural brain atrophy in prodromal/early Huntington disease (HD)—a disease that often presents with motor, cognitive, and psychiatric deficits. The findings were published in British Journal of Haematology.
Utilizing scores on the Montreal Cognitive Assessment (MoCA), the group found that in addition to bilateral caudate volume differences, total scores had correlations left amygdala volume differences. Traditionally associated with psychiatric symptoms, the amygdala has more recently been shown to have associations with worse visuomotor skills, slower processing speed, and emotional recognition.
“It is well known that striatal atrophy is the neuropathological hallmark of HD being the caudate volume differences considered as a biomarker of disease progression,” wrote the researchers.“Since the striatum is strongly associated with cognitive functioning, it was expected that the caudate volume differences correlated strongly with MoCA total score. Therefore, our results strengthen the previous evidence showing that caudate atrophy is associated with cognitive impairment evaluated by different neuropsychological tests.”
Taking this finding, the researchers suggested that progressive death of striatal spiny neurons is the primary driver of striatal atrophy’s impact on cognitive impairment, followed by disconnection of that nucleus with the frontal cortex due to axonal neurodegeneration of cortico-striatal tracts that have deep connections with regions of motor and associative networks.
Among the 22 patients with HD, imaging also showed extensive cortical thinning in the fronto-parietal and temporo-occipital cortices. According to the researchers, this finding corroborates previous research that has identified certain cognitive deficits in HD, such as attention and executive functions, that correlate with these cortical changes.
The study also included 22 healthy controls, allowing the researchers to confirm previous findings that the assessment can distinguish between prodromal/early HD patients and healthy patients. There were significant differences in MoCA scores between the 2 groups, with patients with HD having a mean score of 24.18 and healthy controls having mean scores of 27.90. More than half (59%) of patients with HD exhibited impaired cognition, with scores ranging between 14 and 25 points, falling short of the appropriate cut-off score of 26.
“This result support previous reports showing that symptomatic as well as prodromal HD patients exhibit cognitive decline assessed using brief screenings or comprehensive neuropsychological tests,” commented the researchers. “It should be noted that the MoCA test composition encompasses psychometric properties to detect cognitive impairment; therefore, this test is particularly useful for HD because the patients typically develop notably heterogeneous cognitive deficits with different degrees of impairment that weigh the presence of the global cognitive decline.”
Among patients with HD, MoCA scores had strong positive correlations with functional status and had significant negative correlations with motor performance. According to the researchers, this finding signals a strong linear relationship between the factors and is in alignment with previous studies of HD, which have shown that cognitive impairment is associated with functional and motor performance declines.
The researchers noted that in additional to functional status and motor performance, future research should also explore the correlations between HD and Diagnostic Confidence Level, the standard measure, based solely on motor evaluation, for diagnosing at-risk patients.
Early ML, Linton E, Bosch A, et al. The Montreal cognitive assessment as a cognitive screening tool in sickle cell disease: associations with clinically significant cognitive domains. Br J Haematol. Published April 6, 2022. doi:10.1111/bjh.18188