Cognitive manifestations of Huntington disease in relation to genetic structure and clinical onset
G. W. Jason, O. Suchowersky, E. M. Pajurkova, L. Graham, M. L. Klimek, A. T. Garber and D. Poirier-Heine
Department of Psychology, Foothills Hospital, Calgary, Alberta.
OBJECTIVE: To examine the cognitive manifestations of Huntington disease
(HD) with respect to age, clinical onset, progression, and genetic
analyses. DESIGN: Case series of people with HD or at risk (AR) for HD.
SETTING: Movement disorders and medical genetics clinics. PARTICIPANTS:
Volunteer sample of 50 patients with HD and 127 AR adults. MEASURES:
Neuropsychological evaluation was conducted with multiple measures of
cognitive function (intelligence, memory, attention, executive, spatial,
language), strength, manual speed/dexterity, somatosensory function, and
mood. Quantitative molecular genetic analysis by means of polymerase chain
reaction was conducted on 31 patients with HD and 86 AR subjects. RESULTS:
In clinical HD, cognitive impairment correlated with number of years
affected but not age at onset. The linear regression had a negative
intercept, suggesting impaired cognitive function by the time of onset. In
AR gene carriers, lower cognitive performance correlated with more
trinucleotide repeats. In clinical HD, trinucleotide repeats interacted
with disease chronicity such that more repeats were associated with worse
performance over time; the overall effect of this was small compared with
the effect of disease chronicity alone. Except for one AR subject, mood
state was not associated with cognitive performance in either patients with
HD or AR subjects. CONCLUSIONS: Cognitive decline appears to start before
clinical onset of HD and is correlated with the number of trinucleotide
repeats. Subsequent cognitive decline is primarily a function of number of
years affected, although there is evidence that the presence of more
trinucleotide repeats is associated with faster deterioration.
The association of CAG repeat length with clinical progression in Huntington disease
Rosenblatt et al.
Neurology 2006;66:1016-1020.
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Huntington's disease: Clinical correlates of disability and progression
Mahant et al.
Neurology 2003;61:1085-1092.
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Cognitive and Motor Functioning in Gene Carriers for Huntington's Disease: A Baseline Study
Witjes-Ane et al.
J. Neuropsychiatry Clin. Neurosi. 2003;15:7-16.
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PACSIN 1 interacts with huntingtin and is absent from synaptic varicosities in presymptomatic Huntington's disease brains
Modregger et al.
Hum Mol Genet 2002;11:2547-2558.
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Swan and Carmelli
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Neurology 2001;57:658-662.
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Flint
Brain 1999;122:2015-2032.
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Dujardin et al.
J. Neurol. Neurosurg. Psychiatry 1999;67:323-328.
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Genetic Structure and Cognitive Function in Huntington Disease
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