Executive and mnemonic functions in early Huntington's disease

Abstract

Eighteen patients with early Huntington's disease were compared with age- and IQ-matched control volunteers on tests of executive and mnemonic function taken from the Cambridge Neuropsychological Test Automated Battery. Tests of pattern and spatial recognition memory, spatial span, spatial working memory, spatial planning and visual discrimination learning/attentional set shifting were employed. These tests have previously been found to be sensitive to the later stages of Huntington's disease. Patients with early Huntington's disease were found to have a wide range of cognitive impairments encompassing both visuospatial memory and executive functions, a pattern distinct from those seen in other basal ganglia disorders. In contrast to patients with more advanced Huntington's disease, early Huntington's disease patients were not impaired at simple reversal learning, but were impaired at performing an extradimensional shift (EDS). The results will be discussed in relation to the hypothesized neuropathological staging of Huntington's disease and to the anatomical connectivity of the striatum.

Early Huntington’s disease affects movements in transformed sensorimotor mappings

“…More work will of course be needed to disentangle these contributions if possible. This hypothesis is compatible with impairments in attention and choice responses in these patients (Bradshaw et al, 1992;Hefter, Homberg, Lange, & Freund, 1987;Jahanshahi et al, 1993;Lawrence et al, 1996). The results are similar to the problems shown by HD patients in the Stroop task, in which an overlearned skill (word reading) interferes with an attention-demanding voluntary response (rapid color naming) (ex: Snowden et al, 2001).…”

Profiles of Cognitive Dysfunction in Chronic Amphetamine and Heroin Abusers

“…The EDS is formally equivalent to the category shift in the Wisconsin Card sorting Test. The EDS stage deficit has also been observed in patients with basal ganglia disorders, such as Huntington's disease (Lawrence et al 1996) and in neurosurgical patients with frontal, but not temporal lobe excision (Owen et al 1991). By contrast, the heroin group were less impaired on the EDS stage, although they were more impaired at earlier stages of the test, including the IDS, which involves abstraction and learning set.…”

“…At this stage, the subject had to learn that the previously irrelevant dimension was now relevant and the previously relevant dimension was now irrelevant in order to correspond correctly. The EDS stage is equivalent to a category shift in the WCST and has been shown to be sensitive to frontal lobe (Owen et al 1991) and basal ganglia dysfunction (Downes et al 1989;Lawrence et al 1996). The main measures of performance were the stage of the task successfully attained and errors made.…”

“…Tests shown to be sensitive to fronto-striatal or temporal lobe damage were employed from a standardized and computerised neuropsychological test battery (CANTAB) (Robbins et al 1994 together with other related variants (Iddon et al 1998;Owen et al 1995a). The CANTAB battery has been used in a wide variety of relevant patient groups, including patients with neurosurgical excisions of the prefrontal cortex or temporal lobe (Owen et al 1995b), basal ganglia disorders such as Parkinson's (e.g., Downes et al 1989;Owen et al 1992), and Huntington's disease (e.g., Lawrence et al 1996), as well as depression, schizophrenia (Elliott et al 1998), and dementia (Sahakian et al 1988). The battery has also been previously employed in psychopharmacological Elliott et al 1997;Robbins et al 1998) and toxicological (Maruff et al 1998) investigations.…”

Cortical dysfunction in patients with Huntington's disease during working memory performance

“…In line with the notion that WM processes are subserved by frontoparietal and striatal areas, WM deficits and frontostriatal dysfunction have also been demonstrated in other disorders of the basal ganglia, e.g., Parkinson's disease [PD] [Altgassen et al, 2007;Lewis et al, 2003;Monchi et al, 2000]. In HD, WM dysfunction is present during early stages of the illness [Lemiere et al, 2004] and has been demonstrated in both patients with manifest HD and individuals with the HD gene mutation who are presymptomatic for the motor symptoms of the disorder [pre-HD individuals] [Lawrence et al, 1996;Montoya et al, 2006;Nehl et al, 2001]. In a sample of pre-HD individuals, we have recently shown aberrant activation of the dorsolateral prefrontal cortex (DLPFC) during WM performance [Wolf et al, 2007b], demonstrating that DLPFC dysfunction may occur several years before the onset of manifest HD symptoms.…”