Verbal episodic memory declines prior to diagnosis in Huntington's disease

Abstract

Previous studies of verbal episodic memory in pre-diagnostic Huntington's disease (HD) have yielded mixed results; some evidence suggests that memory decline is evident prior to the onset of pronounced neurological signs of HD, whereas other data indicate that memory function remains normal throughout the pre-diagnostic period. This study examines verbal episodic memory in a sample of CAG expanded individuals who have not yet been clinically diagnosed, and who represent a wide range of points along the continuum from health to disease. The Hopkins Verbal Learning Test-Revised (HVLT-R) was administered to 479 participants (428 with the HD CAG expansion and 51 without), and performance was compared to neurobiological indices of disease progression, including a DNA-based estimate of proximity to clinical diagnosis, magnetic resonance imaging (MRI) measures of striatal volume, and neurologist ratings of motor signs. Lower HVLT-R scores were associated with closer proximity to clinical diagnosis and smaller striatal volumes; these relationships were found even in groups with no neurological signs of HD. The CAG expanded groups, including those with only minimal neurological signs, had significantly lower HVLT-R scores than the control group, and performance was worse in sub-groups that had more neurological signs consistent with HD. These findings indicate that verbal episodic memory is affected in early pre-diagnostic HD and may decline as striatal volumes decrease and individuals approach the motor diagnostic threshold.

Figure 1

Bargraphs of HVLT-R performance by confidence level group. Confidence level ratings correspond to the following characterizations: 0 = normal (no abnormalities), 1 = non-specific motor abnormalities (less than 50% confidence), 2 = motor abnormalities that may be signs of HD (50–89% confidence), 3 = motor abnormalities that are likely signs of HD (90–98% confidence), 4 = motor abnormalities that are unequivocal signs of HD (≥ 99% confidence). As noted in the method section, individuals with confidence level ratings of 4 were excluded from all analyses. Bars represent means; error bars show standard error of the mean. Asterisks indicate differences from CAG-Norm group; * p ≤ .05, ** p ≤ .01, *** p ≤ .001