Longitudinal neuropsychological and genetic linkage analysis of persons at risk for Huntington's disease.
OBJECTIVE
To determine (1) whether the neuropsychological profiles of healthy individuals at risk (AR) for Huntington's disease who were positive (AR/+) or negative (AR/-) for the Huntington's disease genetic marker differed from those of symptomatic patients with Huntington's disease and normal control individuals and (2) whether the neuropsychological performance of the two AR groups differed from each other on three assessments during a 4-year span.


METHODS
Case-control, double-blind study, with AR status determined by genetic linkage analysis (G8 probe), in addition to examination of trinucleotide repeats for most AR subjects.


METHODS
The Neuropsychology Program in the Department of Psychiatry and the Department of Neurology at the University of Michigan Medical Center, Ann Arbor, a tertiary care center.


METHODS
Eight subjects matched as closely as possible for age, gender, and education in each of the following groups: AR/+, AR/-, normal control, and Huntington's disease.


METHODS
A battery of neuropsychological tasks, including measures of intelligence, memory, problem solving, and motor ability.


RESULTS
Although both AR groups demonstrated variability on select intellectual subtests relative to normal subjects, they did not differ from each other on the three assessments during a 4-year span. Patients with Huntington's disease performed more poorly than the other groups across a range of neuropsychological measures.


CONCLUSIONS
These results do not support previous evaluations concluding that AR/+ individuals demonstrate cognitive impairments as compared with AR/- individuals. Findings in earlier studies without genetic linkage analysis of lower performance of AR individuals, including children, as compared with normal controls may relate to extraneous environmental and familial issues that interfere with intellectual development.
Giordani
B
B
Department of Psychiatry, University of Michigan, Ann Arbor.
Berent
S
S
Boivin
M J
MJ
Penney
J B
JB
Lehtinen
S
S
Markel
D S
DS
Hollingsworth
Z
Z
Butterbaugh
G
G
Hichwa
R D
RD
Gusella
J F
JF
D004311:Double-Blind Method; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000523:psychology*; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests
D005819:Genetic Markers