Neurological Dysfunction Detectable Before Huntington’s Diagnosis, Study Finds

Signs of neurological dysfunction can start long before a clinical diagnosis of Huntington’s disease, a study shows.

Early cognitive rehabilitation programs might be useful in the pre-manifest stage of the disease.

The study, “Task-switching abilities in pre-manifest Huntington’s disease subjects” was published in Parkinsonism and Related Disorders.

Although family history and DNA testing can confirm a diagnosis of Huntington’s, disease onset is only officially declared when neurological abnormalities — motor disturbances, cognitive decline and behavioral dysfunction — unequivocally attributed to the disease are diagnosed.

Huntington’s disease has a wide variation in onset age and is characterized by several phases. The first stage is called pre-manifest (pre-HD) and extends from birth to the prodromal (early) phase. This period is regarded as being asymptomatic, although symptoms such as mood swings are experienced and signs lincuding chorea — abnormal involuntary movements — are apparent upon examination.

In the prodromal stage, Huntington’s carrier subjects develop subjective cognitive/affective symptoms and early motor problems. The final, or manifest, phase occurs when patients exhibit cognitive, motor and/or psychiatric symptoms.

However, cognitive dysfunction begins many years before motor onset. During the pre-HD stage, difficulties in emotion recognition and awareness as well as executive functioning — cognitive processes that allow people to plan, organize, and complete tasks — may be evident. In manifest individuals, a more general and widespread cognitive deterioration can be present, including memory, attention, language, and disorientation until overt dementia.

The task-switching paradigm has been largely used to study executive functioning in neurodegenerative disorders, such as multiple sclerosis or Parkinson’s disease.

In this procedure, two tasks are performed in rapid succession and in a random sequence, so that the task to be executed can change from one trial to the next (switch trial), or can be repeated (repetition trial). This can show a person’s ability to adaptively shift attention and action.

Researchers investigated whether this type of procedure would be suitable to detect primary executive impairment in pre-HD individuals.

Thirty pre-manifest individuals were recruited at the LIRH Foundation and C.S.S. Mendel Institute in Rome and divided into two groups according to their total motor score (TMS), a measurement of motor impairment.

There were 15 pre-manifest HD participants (pre-HD1) and 15 prodromal disease participants (pre-HD2). Eighteen healthy controls were matched according to age, gender and education.

All groups received clinical and neuropsychological evaluation. Symptom checklist-90-R, a brief self-report questionnaire that assesses symptoms of psychopathology and distress, was included in the examinations. No significant differences were observed between pre-HD1 and pre-HD2 groups.

Reaction times for switch trials, repetition trials and switch cost (the difference between the two) were measured.

Overall, pre-HD individuals performed worse than the controls. Their reaction times in both switch and repetition trials were significantly higher.

The pre-HD2 group performed particularly poorly in terms of switch control, showing impaired switching abilities with reaction times slower than pre-HD1 and healthy controls.

In terms of accuracy, the pre-HD2 group showed a reduced error number in the execution of the task compared to the pre-HD1 group in switch trials.

“This phenomenon can be interpreted as a mechanism of behavioral compensation, since pre-HD2 could employ more time to make a decision compared to pre-HD1,” researchers said.

“Our study … highlighted that the task-switching protocol is a useful and comprehensive tool to detect early executive disorder in HD subjects without clear motor signs of the disease,” researchers said.

The authors hypothesized that the observed early impairment in executive control processes involved in task-switching may be linked to “an early longitudinal change in the fronto-striatal network (which mediates motor, cognitive, and behavioral functions), with deterioration over time, which could explain executive dysfunction and behavioral changes (i.e. perseveration, irritability) in the early phase of the disease.”