Hippocampal dysfunction defines disease onset in Huntington's disease

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Huntington's disease (HD) is a neurodegenerative disorder with motor, psychiatric, and cognitive symptoms.
• Cognitive deficits in HD are often linked to frontostriatal network disruption.
• Emerging evidence suggests early cognitive deficits in HD may originate in the hippocampus.

Purpose of the Study:

• To investigate the role of the hippocampus in early cognitive deficits in Huntington's disease.
• To bridge findings from rodent models of HD to clinical practice.
• To assess hippocampal integrity in patients with early and premanifest HD.

Main Methods:

• 94 participants, including early HD, premanifest HD, and controls, underwent cognitive assessments.
• Utilized a virtual reality Morris water maze to evaluate spatial learning and memory.
• Administered the Cambridge Neuropsychological Test Automated Battery (CANTAB) paired associates learning task.

Main Results:

• Patients with early HD demonstrated impaired performance on both the virtual Morris water maze and CANTAB paired associates learning.
• Cognitive deficits correlated with the estimated years to diagnosis in premanifest HD participants.
• Hippocampal impairments were identified as an early feature of HD.

Conclusions:

• Hippocampal impairments are an early characteristic of Huntington's disease in patients, consistent with animal models.
• Cognitive assessments targeting the hippocampus can aid in early diagnosis of HD.
• These hippocampal assessments may serve as valuable outcome measures for future Huntington's disease therapeutic trials.