Executive Impairment in Huntington's Disease: Insights From a Systematic Review of the Literature

TL;DR

This study reviews how executive function declines in Huntington's disease at different stages, linking cognitive changes to brain changes like striatal atrophy and prefrontal cortex dysfunction.

Contribution

The study provides a systematic synthesis of executive dysfunction patterns in HD, linking early cognitive changes to neurobiological markers across disease stages.

Findings

Early HD stages show deficits in psychomotor speed, cognitive flexibility, inhibition, and working memory updating.

Later stages involve broader impairments in planning and attention, alongside striatal atrophy and frontostriatal disconnection.

Prefrontal cortex activation during executive tasks is reduced in HD patients.

Abstract

This systematic review examines executive dysfunction in Huntington's disease (HD), an inherited neurodegenerative disorder characterized by cognitive alterations that may emerge years before the onset of motor symptoms. The objective of this review is to provide an updated and comprehensive synthesis of executive function deficits observed across the clinical spectrum of HD—from presymptomatic to the more advanced symptomatic phases—and to examine how these deficits relate to underlying neurobiological changes identified through neuroimaging and neurophysiological studies.

A systematic review was conducted encompassing studies published up to November 2024 and listed on PubMed database. Inclusion criteria focused on clinical and experimental studies involving executive functions in HD at different stages. A total of 3487 articles were screened, of which 115 met the eligibility criteria. The present review synthesizes recent longitudinal and multimodal findings, with a specific focus on the presymptomatic and prodromal phases, offering an integrative perspective that links cognitive, structural, and functional markers of executive dysfunction.

The findings reveal a selective, stage‐dependent pattern of executive dysfunction. Early alterations are most consistently observed in psychomotor speed, cognitive flexibility, response inhibition, and working memory updating, whereas later stages exhibit broader impairments in planning and attention, accompanied by overall functional decline. Among neuroimaging markers, striatal atrophy, frontostriatal disconnection, and reduced prefrontal activation during executive tasks emerge as the most robust correlates of executive dysfunction.

These results underscore the relevance of early cognitive assessment for detecting subtle executive changes prior to overt motor symptoms, and the need for longitudinal, multimodal and computational approaches integrating behavioral, neuroimaging, and electrophysiological data. Future research should prioritize prospective tracking of presymptomatic individuals, the standardization of executive function measures, and the identification of biologically markers to inform early interventions and monitor treatment efficacy.

Executive dysfunction in Huntington's disease follows a selective, stage‐dependent pattern, with early deficits in psychomotor speed, cognitive flexibility, inhibition, and working‐memory updating. Progression is associated with broader impairments in planning and attention. These cognitive changes parallel striatal atrophy, frontostriatal disconnection, and reduced prefrontal activation. Early, multimodal assessment is crucial for detecting subtle executive alterations prior to motor onset.

DLPFC, dorsolateral prefrontal cortex; VLPFC, ventrolateral prefrontal cortex.

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