A clinical classification acknowledging neuropsychiatric and cognitive impairment in Huntington’s disease

Abstract

BackgroundInvoluntary movements, neuropsychiatric symptoms, and cognitive impairment are all part of the symptom triad in Huntington’s disease (HD). Despite the fact that neuropsychiatric symptoms and cognitive decline may be early manifestations of HD, the clinical diagnosis is conventionally based on the presence of involuntary movements and a positive genetic test for the HD CAG repeat expansion. After investigating the frequencies of the triad manifestations in a large outpatient clinical cohort of HD gene-expansion carriers, we propose a new clinical classification.MethodsIn this cross-sectional study, 107 gene-expansion carriers from a Danish outpatient clinic were recruited. All participants underwent neurological examination, psychiatric evaluation and neuropsychological testing. Participants were categorised according to motor symptoms, neuropsychiatric symptoms, the use of psychotropic medication, and cognitive impairment.ResultsAmong the motor manifest HD gene-expansion carriers, 51.8% presented with the full symptom triad, 25.0% were defined as cognitively impaired in addition to motor symptoms, and 14.3% had neuropsychiatric symptoms along with motor symptoms. Only 8.9% had isolated motor symptoms. Among gene-expansion carriers without motor symptoms, 39.2% had neuropsychiatric symptoms, were cognitively impaired, or had a combination of the two.ConclusionThis is the first study to report the frequencies of both motor symptoms, cognitive impairment, and neuropsychiatric symptoms in HD gene-expansion carriers in a national outpatient HD clinical cohort. We found that almost 40% of the gene-expansion carriers without motor symptoms had either neuropsychiatric symptoms, cognitive impairment or both, emphasising that these patients are not premanifest in psychiatric and cognitive terms, suggesting that the current clinical classification is neither necessarily suitable nor helpful for this patient group. Some premanifest gene-expansion carriers may have psychiatric and/or cognitive symptoms caused by reactive stress or other pathology than HD. Acknowledging this fact we, however, suggest classifying all HD gene-expansion carriers into three clinical categories: premanifest, non-motor manifest, and motor manifest.

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.…”

Determinants of functional disability in Huntington's disease: Role of cognitive and motor dysfunction

“…A related issue that often arises is to what extent there is a pure motor or pure cognitive “onset” of HD. This issue is reviewed in the Pausen et al article in this issue (SEE _____PAULSEN ARTICLE IN THIS ISSUE) and also discussed in Biglan et al and Vinther‐Jensen et al, so will not be discussed in detail here . Our impression is that though different individuals and families notice different aspects of the disorder, and different aspects of the disorder may be more pronounced at one time or another, it is very difficult to separate motor and cognitive features.…”

“…This issue is reviewed in the Pausen et al article in this issue (SEE _____PAULSEN ARTICLE IN THIS ISSUE) and also discussed in Biglan et al and Vinther-Jensen et al, so will not be discussed in detail here. 18,29 Our impression is that though different individuals and families notice different aspects of the disorder, and different aspects of the disorder may be more pronounced at one time or another, it is very difficult to separate motor and cognitive features. Many of the "cognitive" tests whose results are used to highlight the importance of cognition actually have major motor aspects (e.g., SDMT, Trail-Making, and certainly "tapping" tests), so this may be a function of measurement, but motor and cognitive ability do tend to decline together.…”

YKL-40 in cerebrospinal fluid in Huntington's disease – A role in pathology or a nonspecific response to inflammation?

“…The participants were all included in a cohort recruited from the Danish Dementia Research Centre HD outpatient clinic [4]. All participants underwent physical, neurological examination, neuropsychiatric and neuropsychological evaluation, a lumbar puncture and blood sampling.…”