A Novel Ecological Approach Reveals Early Executive Function Impairments in Huntington's Disease

Abstract

Introduction: Impairments in executive functions are common in neurogenetic disorders such as Huntington's disease (HD) and are thought to significantly influence the patient's functional status. Reliable tools with higher ecological validity that can assess and predict the impact of executive dysfunction in daily-life performance are needed. This study aimed to develop and validate a novel non-immersive virtual reality task ("EcoKitchen") created with the purpose of capturing cognitive and functional changes shown by HD carriers without clinical manifestations of the disease (Premanifest HD), in a more realistic setting. Materials and Methods: We designed a virtual reality task with three blocks of increasing executive load. The performance of three groups (Controls, CTRL; Premanifest HD individuals, HP; Early Manifest HD patients, HD) was compared in four main components of the study protocol: the EcoKitchen; a subjective (self-report) measure - "The Adults and Older Adults Functional Assessment Inventory (IAFAI)"; the "Behavioural Assessment of Dysexecutive Syndrome battery (BADS)"; and a conventional neuropsychological test battery. We also examined statistical associations between EcoKitchen and the other executive, functional and clinical measures used. Results: The HD group showed deficits in all the assessment methods used. In contrast, the HP group was only found to be impaired in the EcoKitchen task, particularly in the most cognitively demanding blocks, where they showed a higher number of errors compared to the CTRL group. Statistically significant correlations were identified between the EcoKitchen, measures of the other assessment tools, and HD clinical features. Discussion: The EcoKitchen task, developed as an ecological executive function assessment tool, was found to be sensitive to early deficits in this domain. Critically, in premanifest HD individuals, it identifies dysfunction prior to symptom onset. Further it adds a potential tool for diagnosis and management of the patients' real-life problems.

Keywords: Huntington’s disease; activities of daily living; ecological validity; executive functions; virtual reality.

FIGURE 1

EcoKitchen task design. EcoKitchen included three different blocks (each preceded by a practice trial), with increasing executive demands. In Block 1, the participant had to prepare a cup of coffee with milk – Task A. In Block 2, while performing Task A, the participant had to turn off a boiling kettle that burst at several random moments. In Block 3, the participant had to perform the tasks previously described, whilst preparing toasts with butter (Task B).

FIGURE 2

EcoKitchen Number of Total Errors per minute of Performance Time Task A and Number of Total Errors per minute of Performance Time Task B (mean) and significant differences between groups. Boxplots: central mark – median; edges of box – 25th and 75th percentiles; whiskers – most extreme data points (minimum and maximum). ^ΦHP≠Control (Mann–Whitney, p < 0.05); ^¥HD≠Control (Mann–Whitney, p < 0.05).

FIGURE 3

EcoKitchen Performance Time Task A (A) and Performance Time Task B (B) and significant differences between groups. Boxplots: central mark – median; edges of box – 25th and 75th percentiles; whiskers – most extreme data points (minimum and maximum). ^¥HD≠Control (Mann–Whitney, p < 0.05); ^#HD ≠ HP (Mann–Whitney, p < 0.05).

FIGURE 4

EcoKitchen Reaction Time per Block (A) and Reaction Time per Cue (B) – Stove, Kettle, and Toaster (mean of the three blocks) and significant differences between groups. Boxplots: central mark – median; edges of box – 25th and 75th percentiles; whiskers – most extreme data points (minimum and maximum). ^¥HD≠Control (Mann–Whitney, p < 0.05); ^#HD≠HP (Mann–Whitney, p < 0.05).