The study investigated longitudinal change in cognitive
function in 87 patients with Huntington's disease
(HD), using a range of neuropsychological tests, which
tap mental manipulative abilities, memory, and frontal
executive skills. Over a 1-year period the largest changes
were noted in letter fluency, object recall, and Stroop
Test performance, whereas no changes were noted over more
than 3 years on the modified Wisconsin Card Sorting Test.
Contrary to expectation, greater change was evident over
1 year for tasks with low compared to high cognitive demands.
The differential sensitivity of tasks was attributed in
part to inherent characteristics of the tests themselves:
their capacity to detect minor gradations of change and
their vulnerability to practice effects. However, the greater
change for relatively automatic, speed-based tasks with
low cognitive demands was interpreted as reflecting the
evolution of HD, with a greater magnitude of change occurring
in basal ganglia than cortical function. One purpose of
the study was to identify tasks sensitive to the progression
of HD and hence most suitable for the evaluation of therapies.
Despite reaching statistical significance by virtue of
the large group size, numerical differences in test scores
over 1 year were very small, suggesting that the use of
such tests to evaluate change in individuals or small groups
of subjects would be problematic. The data highlight the
slow progression of HD, the limitations of standard cognitive
tests in detecting change over short periods, and the need
for therapeutic studies that encompass a relatively prolonged
time frame. (JINS, 2001, 7, 33–44.)
Volumetric MRI-Based Biomarkers in Huntington's Disease: An Evidentiary Review
