Everyday Cognition in Prodromal Huntington Disease

The ability to complete daily tasks is diminished in Huntington disease (HD), an autosomal dominantly inherited neurodegenerative disorder resulting from an expansion in cytosine, adenine and guanine (CAG) bases in the HTT gene (Huntington's Disease Collaborative Research Group, 1993). Cognitive, behavioral, and motor changes all occur in HD, with cognitive changes identifiable prior to motor onset (Beglinger et al., 2010; Biglan et al., 2013; Duff et al., 2010), which is the period of prodromal HD. Functional impairment increases in prodromal HD as motor diagnosis approaches (Muthen & Muthen, 1998–2010; Paulsen et al., 2006, 2008, 2010; Tabrizi et al., 2009, 2011, 2012), impacting daily living skills, work functions, and interpersonal relationships (Downing et al., 2013; Downing, Williams, Leserman, & Paulsen, 2012; Paulsen, 2010; Williams, Downing, Vaccarino, Guttman, & Paulsen, 2011). Assessment of daily function changes in prodromal HD is important for clinical monitoring and management, as well as for tracking functional capacity in clinical trials (Beglinger et al., 2010; Paulsen et al., 2010). Previous work examining functional impairments in HD focused primarily on those who had already been given a motor diagnosis. Functional decline, as measured by the Total Functional Capacity (TFC) scale (Huntington Study Group, 1996), has been used widely in clinical trials as an outcome measure (Marder et al., 2000). Although motor impairments clearly lead to a variety of functional deficits (Brandt et al., 1984; Rothlind, Bylsma, Peyser, Folstein, & Brandt, 1993), many studies have shown cognitive and psychiatric impairments associated with HD significantly contribute to degree of functional impairment independent of motor impairments (Nehl, Paulsen, & Huntington Study Group, 2004). In particular, impairments in executive function have been associated with worsened activities of daily living (Hamilton et al., 2003). Additionally, greater degree of overall cognitive impairment has also been shown to predict rate of functional decline, such that those with greater cognitive impairment at study baseline show more rapid decline (Marder, et al., 2000). Such findings are consistent with the wider literature examining the important role of cognitive function in the ability to do daily tasks in normal aging as well as in Alzheimer disease (Benke et al., 2013; Martyr & Clare, 2012). Based on the finding that changes in everyday function can be observed in the prodromal stage of dementia – known as mild cognitive impairment (MCI) – it would be anticipated that functional changes likely accompany the very early cognitive changes occurring in prodromal HD. Indeed, recent research by our group demonstrates functional changes during the prodromal HD period (Downing et al., 2013; Paulsen et al., 2010). One obstacle to studying early functional changes in HD has been limitation of assessment methods. Instruments such as the TFC (Huntington Study Group, 1996) appear to be sensitive to changes following a motor diagnosis of HD (Marder et al., 2000) but may not have sufficient sensitivity to changes during prodromal HD (Downing et al., 2013; Paulsen et al., 2010). Further, given that cognitive impairments are among the very first signs of HD to emerge, there is a need for new functional assessment tools that specifically target cognitively-based functional abilities. Another issue relevant to measuring functional capacities in HD and prodromal HD is determining which method of ascertainment is most appropriate. Both companion and self-report of functional abilities have been used in HD and other populations. Due to the possibility of diminishing self-awareness as motor onset nears (Duff et al., 2010; Ho, Robbins, & Barker, 2006; Hoth et al., 2007), assessment from a companion may provide an important source of data. Discrepancies between participant and companion ratings in awareness of cognitive, behavioral and functional changes have been reported in those estimated to be closest to diagnosis (Downing et al., 2013; Duff et al., 2010). To address some of the gaps in knowledge about the nature of very early functional changes in prodromal HD, the present study examines self- and companion-rated everyday cognition in prodromal HD and compares ratings with the widely-used TFC. The four study aims were: (a) Compare the factor structure of the Everyday Cognition (ECog) scales (Farias et al., 2008) in a sample of people with prodromal HD to the factor structure of the original ECog using baseline data; (b) analyze baseline and longitudinal changes in participant and companion ratings of the ECog by disease progression groups; (c) compare participant and companion ratings over time in each disease progression group; and (d) assess the sensitivity of the ECog by comparison to the TFC for detecting change over the prodromal phase of HD. We hypothesized that the factor structure in the revised ECog would be similar to the original ECog. We anticipated that both participants and companions would report functional changes over time. However, we expected that companion ratings would diverge from participant ratings as participants become nearer to the time of diagnosis, owing to diminishing self-awareness in the participant group. Lastly, we expected that the ECog would be more sensitive than the TFC in detecting specific domains of daily cognitive function.