Anosognosia in HD: Comparison of Self-report and Caregiver Ratings with Objective Performance Measures

Abstract

Introduction:

Individuals with Huntington’s disease (HD) commonly experience anosognosia, a lack of awareness of deficits. Thus, it is important to examine the accuracy of patient vs caregiver ratings on the basis of objective performance-based measures.

Methods:

The Anosognosia Scale (AS) was given to 33 patients with manifest HD and their caregivers. The AS consists of 8 items in which individuals rate their global abilities relative to same-aged peers. Scores range from very impaired to excellent. Caregiver and patient ratings were then correlated with objective measures.

Results:

Caregivers’ evaluations of patients’ cognitive and motoric abilities were more highly correlated with objective measures than patients’ ratings. Specifically, caregivers’ AS item scores were highly correlated with objective measures of walking (Unified Huntington Disease Rating Scale (UHDRS) tandem walking score [r=.57, p=.001] vs. patient [r=.39, p=.031]); dexterity (UHDRS pronation supination score [r=.55, p=.011] vs. patient [r=.18, p=.393]); speech (UHDRS dysarthria score [r=.55, p=.004] vs. patient [r=.03, p=.854]); memory (MoCA score [r=−.45, p=.048] vs. patient [r=−.11, p=.963]); attention (Trails Making Test A score [r=.58, p=.004] vs. patient [r=.08, p=.686]); and word retrieval (category fluency ([r=−.58, p=.004] vs. patient [r=−.02, p=1.00]). Moreover, both the UHDRS total motor score (TMS) (F(1,29)=7.50, p=.010) and the Mini Mental Status Exam (MMSE) (F(1,31)=5.40, p=.027) were significant predictors of patient levels of anosognosia.

Conclusions:

Our findings indicate that caregivers may be better able to rate HD patients’ cognitive and motor abilities than patients themselves. Both cognitive and motor severity are significant predictors of levels of anosognosia in HD.

Introduction

Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by abnormal expansion of the CAG trinucleotide repeat in the HTT gene and characterized by a combination of motor, cognitive, and behavioral features. Cognitive deficits associated with HD include cognitive slowing, along with poorer attention, memory, executive functioning, and visuospatial perception. Psychiatric comorbidities include depression, anxiety, cognitive rigidity, obsessive-compulsive behaviors, and behavioral outbursts [1].

Individuals with HD often experience symptoms of anosognosia, or the lack of insight or awareness of deficits and their impact [2–5]. HD patients exemplify a striking example of this unawareness as they can demonstrate lack of insight in relation to chorea as well as cognitive, emotional, and physical function [2]. Varying levels of anosognosia within the HD population can make it difficult to fully rely on patient self-report in clinical and research settings.

The Anosognosia Scale (AS), created by Deckel and Morrison [5], is commonly used to compare self-report to caregiver or clinician report, with a difference of six points or higher, indicating anosognosia [3–5]. Literature comparing self-report to clinical interview data is incredibly variable, especially with regard to anosognosia for cognitive and psychiatric symptoms. In one instance, individuals with HD were found to significantly overrate their ability to think, remember, and/or control their emotions [5]. Chatterjee et al. [7] found that individuals with HD and their caregivers tended to disagree with regard to patients’ levels of irritability but not depression; while Andrews et al. [8] found that early manifest participants reported less apathy and executive dysfunction than their informants. Additional findings indicated that individuals with HD significantly differed from clinicians when grading the level of their functional capacity [6, 9]. These studies all highlight the importance of further examination of the reliability and accuracy of patient versus clinician/caregiver ratings.

Reliability of self-report scales, especially, is a concern in HD due to anosognosia. Anosognosia has been observed at early, even premanifest, stages of HD [3, 4]. Therefore, we believe it is crucial to examine the accuracy of self-report symptoms by those living with HD. The majority of studies to date have compared patient ratings with those of their caregivers and/or clinicians. To our knowledge, no study has explored the accuracy of patient vs caregiver ratings on the basis of objective performance measures. Therefore, the primary aim of our study was to compare patient and caregiver report of cognitive and motoric symptoms versus objective performance measures of these abilities in individuals with HD to clarify the impact of anosognosia on self-report ratings.

Method

The AS [5] was given to 33 individuals with manifest HD and their caregivers who presented to the University of California, San Diego Huntington’s Disease Clinical Research Center (UCSD HDCRC) for a research visit. Our sample participants were on average 52.79 years of age, had 15.55 years of education, and 43.76 CAG repeats. Clinically the average total motor score was 36.74, average total functional capacity score was 8.88, average Montreal Cognitive Assessment score was 22.10, and the average Problem Behavior Assessment – short form score was 8.18.

The AS consists of 8 questions in which individuals are asked to rate their abilities to complete specific activities relative to their same-aged peers. These activities include physical movements (e.g., walking, speech, chorea, fine-motor dexterity), cognitive processes (e.g., memory, attention), and emotion regulation. Scores range from very impaired to excellent on a 5-point Likert scale.

Statistical Analysis

To avoid the negative values that are typically assigned to the Likert scale points (−2 to 2), the AS was recoded so that the Likert scale values ranged from 5 to 1, with 5 being very impaired and 1 being excellent. Item 8 on the AS assesses an individuals’ ability to regulate their emotions, which we did not feel had an objective performance-based correlate, and thus was not included in our analyses. The responses to questions 1 through 7 by the individuals with HD and their caregivers were then correlated with objective measures of physical movement and cognitive function. Pearson correlations were used for all item comparisons. Table 1 shows the performance-based measures used for correlational analysis with items on the AS. Objective measures of motoric functioning included The Unified Huntington’s Disease Rating Scale (UHDRS) tandem walking, finger tapping, dysarthria, and chorea scores [9]. Objective measures of cognition included the Montreal Cognitive Assessment (MoCA) Delayed Recall Score, Trail Making Test A (TMT A), and a Category Fluency (animals) task [10].

Table 1.

Performance Based Measures Used for Correlational Analysis with Anosognosia Scale (AS) Items

AS Item	Performance-Based Measure
AS Item 1. Walking	UHDRS Tandem Walking Score
AS Item 2. Accurately and Quickly Use Hands and Fingers (Fine-Motor Dexterity)	UHDRS Finger Tapping Score
AS Item 3. Speak Clearly	UHDRS Dysarthria Score
AS Item 4. Remember	MoCA Delayed Recall Score
AS Item 5. Concentrate and Attend	TMT A
AS Item 6. Sit “Still and Quietly”	UHDRS Chorea Score
AS Item 7. Say The Word You Are Thinking Of (retrieval)	Category Fluency (Animals)

UHDRS=Unified Huntington’s Disease Rating Scale; MoCA=Montreal Cognitive Assessment; TMT A=Trail Making Test A

Additionally, we ran a linear regression analysis to determine if cognitive or motoric objective measures were predictive of levels of anosognosia. We used the total Mini Mental State Examination (MMSE) score [11] and the Symbol Digit Modalities Test (SDMT), specific to executive functioning, for cognitive severity and the UHDRS Total Motor Score for motoric severity. Anosognosia levels were defined by the difference between caregiver report and patient report [2, 6, 7].

Results

Correlation coefficients for the associations between AS item ratings and their respective objective measures are shown in Table 2 for caregivers and individuals with HD.

Table 2 –

Correlations between Anosognosia Scale (AS) Items and Performance-Based Measures in Caregivers and in Individuals with Manifest HD

	UHDRS Tandem Walking	UHDRS Finger Tapping	UHDRS Dysarthria	MoCA Delayed Recall	Trail Making Test A	UHDRS Chorea	Category Fluency (Animals)
AS Item 1	.57 ** .39 *
AS Item 2		.61 ** .34
AS Item 3			.55 ** .03
AS Item 4				−.48* −.31
AS Item 5					.58 ** .08
AS Item 6						.43 * .29
AS Item 7							−.58** −.02

Correlations in bold are caregivers’ ratings correlated with performance-based measures Correlations in italics are HD individuals’ ratings correlated with performance-based measures UHDRS=Unified Huntington’s Disease Rating scale; MoCA=Montreal Cognitive Assessment

^*p<.05;

^**p<.01

Motor Results

Caregivers’ ratings of HD individuals’ ability to walk were moderately correlated with the UHDRS tandem walking score (r=.57, p=.001) with a moderate effect size (r² =.325). In comparison, HD individuals’ ratings of their ability to walk showed a smaller correlation (r=.39, p=.031) and a 53% smaller effect size (r² =.152). For dexterity, caregivers’ ratings of HD individuals were significantly correlated with the UHDRS finger tapping score (r=.61, p=.001) with a moderate effect size (r² =.372). HD individuals’ ratings were not significantly correlated with their UHDRS finger tapping score (r=.34, p=.058) and a 68% smaller effect size was observed (r² = .116). Caregivers’ ratings of HD individuals’ speech were significantly correlated with the UHDRS dysarthria scores (r=.55, p=.004) with a moderate effect size as well (r² = .303). On the other hand, HD individuals’ ratings of their speech were not significantly correlated with their UHDRS dysarthria scores (r=.03, p=.854) and a 99% smaller effect size was observed (r² = .001). Lastly, ratings from caregivers regarding HD individuals’ ability to sit still and quietly were significantly correlated with UHDRS chorea scores (r=.43, p=.037, r² = .185). Manifest HD individuals’ ratings of their chorea showed a smaller non-significant correlation in comparison to caregivers (r=.29, p=.113) and a 55% smaller effect size (r² = .084).

Cognitive Results

Caregivers’ ratings of HD individuals’ memory were strongly correlated with the MoCA delayed recall score (r=−.48; p=.012) with a moderate effect size (r² = .230). In comparison, HD individuals’ ratings of their memory were not significantly correlated with the MoCA (r = −.31, p = .090), and a 58% smaller effect size was observed (r² = .096). Ratings from caregivers on HD individual’s ability to attend and concentrate were moderately correlated with TMT A scores (r = .58, p = .004), with a moderate effect size as well (r² = .336). HD individuals’ ratings of their ability to attend and concentrate did not correlate with TMT A scores (r = .08, p=.686, r² = .006). With regard to verbal fluency, caregivers’ ratings of manifest HD individuals’ word retrieval abilities were significantly correlated with a categorical animal fluency task (r= −.58, p= .004, r² = .336). In contrast, HD individuals’ ratings of their word retrieval abilities were not correlated with the categorical animal fluency task (r= −.02, p= 1.000).

Linear Regression Results

The UHDRS TMS, a measure of motor severity, was a significant predictor of anosognosia levels [F (1,29) = 7.50, p=.01, R² = .21]. Motor severity accounted for 21% of the variance of anosognosia levels. Additionally, the MMSE, a measure of global cognitive functioning, was also a significant predictor of anosognosia levels [F (1,31) = 5.40, p=.02, R² = .15. The SDMT, included as a specific indicator of executive dysfunction, was a significant predictor of anosognosia levels [F (1, 30) = 5.968, p=.0207, R² = .17]. Global cognitive severity accounted for 15% of the variance in anosognosia levels, while executive dysfunction accounted for 17% of the variance.

Power Analysis

A post-hoc power analysis, utilizing the Pearson correlation between individuals with HD and caregivers’ ratings, revealed power to be at .965. Power is thus high enough to detect true statistical effects.

Discussion

In this study, we found that caregivers’ individual item ratings of manifest HD individuals’ motoric and cognitive abilities were more strongly correlated overall with objective measures of these individuals’ functioning. In some instances, HD individual’s ratings of their cognitive and motor capabilities were very minimally correlated, often lower than r=.10, with objective measures. These findings highlight the importance of a collateral informant in clinical settings when collecting subjective measures of functioning from individuals with HD. Our findings suggest that caregivers may be more reliable in their ratings of HD patients’ abilities in these areas.

Additionally, we found that motor and cognitive severity are significant predictors of levels of anosognosia in manifest HD individuals. These findings indicate that, as motoric ability and cognition worsen, anosognosia levels increase. Therefore, in individuals with HD who have higher levels of motor severity and worsening cognition, it is important to assess for anosognosia and gather collateral information to ensure reliability of the clinical presentation.

Individuals with HD often experience varying levels of anosognosia in motoric, cognitive, and psychiatric areas of functioning. These anosognostic features are not only distressing to family and caregivers of individuals with HD but also challenge the reliability of self-report measures among this population. Therefore, questionnaires such as the AS [5] are essential for assessing for the presence of anosognosia among HD individuals. The AS allows a caregiver, family member, or clinician to rate an individual with HD in comparison to the individual’s own self-ratings of their abilities. In general, studies have found that caregiver or clinician ratings tend to be more reliable than HD individuals’ self-ratings [2, 12]. However, while these patient versus caregiver/clinician ratings can divulge a disconnect in perceptions of the individuals’ abilities, they are still subjective in nature. Thus, the goal of our study was to not only examine HD individuals versus caregivers’ ratings, but to additionally compare these ratings to objective measures of an individual’s cognitive and motor functioning, which we believe is the first study of its kind.

Limitations of this study include the relatively modest sample size of manifest HD individuals and caregivers. Future research could additionally examine group differences in anosognosia between premanifest and manifest individuals with differing levels of disease severity. Additionally, although we found that motoric and cognitive severity were predictors of anosognosia levels, they were only predictive of a limited percentage of the total variance of anosognosia (e.g., 21% and 15%, respectively). Further examination of additional predictors of anosognosia is warranted. Finally, our analysis did not explore anosognosia for psychiatric symptoms due to constrained AS items in this regard and no obvious performance-based correlate for Item #8, ability to regulate emotions. Future studies should clearly address anosognosia for psychiatric symptoms since this is an area of vital importance for establishing a global understanding of how HD symptoms are impacted by anosognosia.

Overall, these findings reveal several important issues to consider when assessing individuals with manifest HD in the clinical or research setting. First, reliance on self-report measures within this population should be done with caution, recognizing that anosognosia levels may skew symptom reports in some individuals. Involving an additional informant, such as a caregiver or family member, especially concerning individual’s cognitive and motoric functioning, can help to ensure a more valid representation of a person’s abilities. Additionally, these findings should dissuade against using self-report instruments as outcome measures in clinical HD research unless there is a matching companion form to account for varying levels of patient anosognosia.

Conclusion

Our study examined whether ratings of cognitive and motoric functioning provided by individuals with manifest HD vs their caregivers were more closely aligned with objective measures of performance. We found that caregivers’ ratings of manifest HD individuals were more highly associated with performance based measures, likely in part due to patients’ levels of anosognosia. Moreover, we found that patients’ motor and cognitive severity were significant predictors of their levels of anosognosia. These findings suggest that the use of a collateral informant, either caregiver or close family member, in clinical or research settings is necessary to ensure the reliability of symptom reports in individuals with HD.

Highlights.

• Caregiver-ratings of HD functioning better correlate with objective measures.

• Anosognosia impairs HD self-report of cognitive and motoric abilities.

• Cognitive and motoric severity are predictors of anosognosia levels in HD.