Assessing Impairment of Executive Function and Psychomotor Speed in Premanifest and Manifest Huntington’s Disease Gene-expansion Carriers

Abstract

Executive functions (EF) and psychomotor speed (PMS) has been widely studied in Huntington's disease (HD). Most studies have focused on finding markers of disease progression by comparing group means at different disease stages. Our aim was to investigate performances on nine measures of EF and PMS in a group of premanifest and manifest HD-gene expansion carriers and to investigate which measures were most sensitive for assessment of individual patients by analyzing frequencies of impaired performances relative to healthy controls. We recruited HD gene-expansion carriers, 48 manifest and 50 premanifest and as controls 39 healthy gene-expansion negative individuals. All participants underwent neurological examination and neuropsychological testing with nine cognitive measures. The frequency of impairment was investigated using cutoff scores. In group comparisons the manifest HD gene-expansion carriers scored significantly worse than controls on all tests and in classification of individual scores the majority of scores were classified as probably impaired (10th percentile) or impaired (5th percentile) with Symbol Digit Modalities Test (SDMT) being the most frequently impaired. Group comparisons of premanifest HD gene-expansion carriers and healthy controls showed significant differences on SDMT and Alternating fluency tests. Nevertheless the frequencies of probably impaired and impaired scores on individual tests were markedly higher for Alternating and Lexical fluency tests than for SDMT. We found distinct group differences in frequency of impairment on measures of EF and PMS in manifest and premanifest HD gene-expansion carriers. Our results indicate to what degree these measures can be expected to be clinically impaired.

Huntington's Disease: Premotor Phase

“…Similar results were also found in other studies [35,36], including a more detailed evaluation of executive dysfunction in premotor patients [37]. It is advisable to include executive dysfunction tests, as alternating fluency tests, in the cognitive assessment of premotor HD patients, as they seem to be more sensible for detecting early changes.…”

Social Cognition, Executive Functions and Self-Report of Psychological Distress in Huntington’s Disease

“…All patients had gone through genetic counseling and had been informed of their genetic status prior to (and independently from) study enrolment. We have previously published results from the same cohort2 , 4 , 5 , 21 also including premanifest HD carriers, but since we found no impairments in social cognitive functions in our premanifest subjects we did not include them in the present study.…”

“…Once onset of motor symptoms has occurred, cognitive and/or psychiatric symptoms also tend to be present 2 , 3 , 4 , 5. The cognitive deterioration in HD is thought to be related to dysfunction of the frontostriatal circuits due to gradual degeneration of the striatum6 , 7.…”

“…The cognitive deterioration in HD is thought to be related to dysfunction of the frontostriatal circuits due to gradual degeneration of the striatum6 , 7. Accordingly, the first signs of cognitive impairment are observed in cognitive functions associated with the prefrontal cortex such as executive functions and social cognitive functions4 , 8 , 9 , 10. Psychiatric symptoms are also commonly found even in the presymptomatic and earliest stages in HD, and a wide variety of psychiatric symptoms such as apathy, depression, irritability, anxiety, mania and obsessive compulsive symptoms can be seen11.…”

“…In two previous studies we have investigated performance on tests of executive functions and social cognition in a large cohort of HD patients in early-moderate disease stage and found a high frequency of impaired performances on tests of executive functions and social cognition2 , 4. Based on the associations between the presence of psychiatric symptoms and impairments in executive functions and social cognition found in other patient groups we wanted to investigate how subjective experience of psychological distress as reported by patients with Huntington’s disease is related to performance on tests of social cognition and executive functions.…”