A prospective evaluation of cognitive decline in early Huntington's disease

Bamford, Kathryn A.; Caine, Eric D.; Kido, D. K.; Cox, Christopher; Shoulson, Ira

doi:10.1212/wnl.45.10.1867

Cited by 114 publications

(59 citation statements)

References 4 publications

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“…The effect sizes for the mean of patients' regression scores for each measure was then tested for significance with α at 0.05 (two-tailed). As patients' successive performances over time was of interest, a healthy control group was not used [2,3].…”

Section: Discussionmentioning

confidence: 99%

Verbal fluency in Huntington’s disease: a longitudinal analysis of phonemic and semantic clustering and switching

Sahakian

Robbins

et al. 2002

Neuropsychologia

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Two underlying components of verbal fluency tasks have been identified as clustering (the ability to generate successive words within a sub-category) and switching (the ability to shift from one sub-category to another). Selective impairment of switching ability occurs in patients with frontostriatal pathology, whilst clustering ability is compromised with temporal lobe dysfunction. Letter fluency tasks have been shown to be especially sensitive to frontostriatal deficits, whereas, category fluency tasks tend to be compromised by temporal lobe pathology. This study examined two types of verbal fluency task (letter fluency and category fluency) using two levels of analysis (phonemic and semantic) for clustering and switching measures. The performance of 21 frontostriatally compromised Huntington's disease (HD) patients was followed over an average of 3.5 annual follow-up visits. HD patients showed a significant reduction of correctly generated words over time, together with a significant increase in word repetitions. Phonemic switching decreased significantly over time for both letter and category fluency. Semantic switching, however, remained stable over time for both verbal fluency tasks. Clustering (both semantic and phonemic) likewise remained stable and did not vary longitudinally for either letter or category fluency. Hence, phonemic switching alone drove verbal fluency performance and this selective impairment can be explained by the progressive involvement of frontostriatal circuitry in the natural progression of HD.

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Section: Discussionmentioning

confidence: 99%

Verbal fluency in Huntington’s disease: a longitudinal analysis of phonemic and semantic clustering and switching

Sahakian

Robbins

et al. 2002

Neuropsychologia

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“…These deficits worsen with the advancement of the disease and are also found in symptomatic HD patients (Bamford et al, 1995;Lawrence et al, 1999;Ho et al, 2003). In YAC128 mice, disease onset occurs at 3 months of age with hyperkinesia.…”

Section: Cognitive Deficits In Presymptomatic Yac128 Micementioning

confidence: 95%

Cognitive Dysfunction Precedes Neuropathology and Motor Abnormalities in the YAC128 Mouse Model of Huntington's Disease

Raamsdonk¹,

Pearson²,

Slow³

et al. 2005

J. Neurosci.

286

232

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Huntington's disease (HD) is an adult-onset neurodegenerative disorder involving motor dysfunction, cognitive deficits, and psychiatric disturbances that result from underlying striatal and cortical dysfunction and neuropathology. The YAC128 mouse model of HD reproduces both the motor deficits and selective degeneration observed in the human disease. However, the presence of cognitive impairment in this model has not been determined. Here, we report mild cognitive deficits in YAC128 mice that precede motor onset and progressively worsen with age. Rotarod testing revealed a motor learning deficit at 2 months of age that progresses such that by 12 months of age, untrained YAC128 mice are unable to learn the rotarod task. Additional support for cognitive dysfunction is evident in a simple swimming test in which YAC128 mice take longer to find the platform than wild-type (WT) controls beginning at 8 months of age. YAC128 mice also have deficits in open-field habituation and in a swimming T-maze test at this age. Strikingly, in the reversal phase of the swimming T-maze test, YAC128 mice take twice as long as WT mice to locate the platform, indicating a difficulty in changing strategy. At 12 months of age, YAC128 mice show decreased prepulse inhibition and habituation to acoustic startle. The clear pattern of cognitive dysfunction in YAC128 mice is similar to the symptoms and progression of cognitive deficits in human HD and provides both the opportunity to examine the relationship between cognitive dysfunction, motor impairment, and neuropathology in HD and to assess whether potential therapies for HD can restore cognitive function.

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“…A triad of progressive motor, cognitive, and emotional symptoms characterizes adult onset HD. Relatively few longitudinal studies to define the course of cognitive symptoms in HD patients have been performed [2][3][4][5][6][7][8][9]. Additionally, several of these studies investigated only a limited area of cognitive functioning [4,5,9] or were retrospective [6].…”

Section: Introductionmentioning

confidence: 99%

Cognitive changes in patients with Huntington?s disease (HD) and asymptomatic carriers of the HD mutation

et al. 2004

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A prospective evaluation of cognitive decline in early Huntington's disease

Cited by 114 publications

References 4 publications

Verbal fluency in Huntington’s disease: a longitudinal analysis of phonemic and semantic clustering and switching

Verbal fluency in Huntington’s disease: a longitudinal analysis of phonemic and semantic clustering and switching

Cognitive Dysfunction Precedes Neuropathology and Motor Abnormalities in the YAC128 Mouse Model of Huntington's Disease

Cognitive changes in patients with Huntington?s disease (HD) and asymptomatic carriers of the HD mutation

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