Alcohol Use, Mental Health, and Functional Capacity as Predictors of Workplace Disability in a Cohort With Manifest Huntington’s Disease

Employment is important for financial security, social activity, personal satisfaction, and achievement (1). In contrast, extended work disability is associated with negative outcomes, including financial hardship, loss of self-esteem, social isolation, and increased mental health problems (2). Work disability is also associated with increased costs, such as health service use, sick leave, and indirect costs due to the loss of work productivity, wage replacement, retirement, and disability pensions. Overall, there is agreement that employment is beneficial for people economically and has physical and mental well-being benefits—and this is no different for people with cognitive impairment or dementia (3). Systematic reviews have reported health benefits for individuals with dementia or mild cognitive impairment who continue to engage in meaningful occupation (4). Moreover, psychologically complex and challenging work may have a preventive effect, reducing the impact or delaying the cognitive and functional decline associated with dementia (5).

The ability of individuals with neurodegenerative disorders to meet job expectations is a concern of employers, employees and their families, and clinicians and is a global public health, economic, and social issue. This is particularly so for those under age 65 who are diagnosed as having younger-onset dementia. In addition to financial consequences, changes in sense of identity; decreased self-worth, social contact, and meaningful occupation (6–10); and performance problems, coupled with potential personality changes, may result in difficult or traumatic transitions from employment (11). Loss of the work role often increases stress for the family, because of financial strain and increased working hours and stress for other family members. Additional stress can occur when the person with younger-onset cognitive impairment or dementia feels “out of place” as these transitions occur “out of time” in a “usual” life cycle, with symptoms occurring in midlife in contrast to the more well-known neurodegenerative disorders that become symptomatic later in life (such as late-onset Alzheimer’s disease).

Huntington’s disease (HD) is a neurodegenerative disease that often results in a younger-onset dementia. It is caused by mutations in the Huntingtin (HTT) gene, which involves an expanded and unstable DNA segment known as a CAG trinucleotide repeat (12). Symptoms include progressively worsening motor, cognitive, and psychiatric-behavioral symptoms. The onset of these symptoms and subsequent formal clinical diagnosis typically occur during the fourth or fifth decade of life, the age range when many individuals are at the peak of their careers and earning potential and when they often have significant financial commitments. The symptoms of HD have a strong impact on function and quality of life and affect a person’s ability to maintain daily functions, including work functions and occupational status, and eventually result in reduced work hours or cessation of work (13, 14). Indeed, difficulties maintaining employment have been reported as having the greatest impact on daily life for people with HD and their families (15).

Overall, there is a paucity of research on the factors associated with work disability in dementia; therefore, knowledge on how best to support individuals with their employment after diagnosis is limited (16) and is even more limited in cases of younger-onset dementias such as HD. One study of 220 employed and unemployed Enroll-HD participants at the Leiden University Medical Center, with and without a clinical motor diagnosis, found that HD mutation carriers with poorer cognitive performance and higher apathy scores were more likely to be unemployed, compared with HD mutation carriers with higher cognitive scores and no signs of apathy. Cognitive impairments, especially in the executive domain, and apathy were independent determinants of unemployment in HD mutation carriers. Motor disturbances, the clinical hallmark of HD, did not appear to be the most important predictor for work cessation (17).

We have previously examined factors related to workplace disability in individuals with premanifest HD and found that higher numbers of CAG repeats and more motor symptoms were associated with significantly higher odds of experiencing workplace impairment (18). In addition, several modifiable factors, including physical and mental health, were found to be related to workplace disability in people with premanifest HD. Building on this work, we aimed in the study reported here to identify significant factors associated with work impairment and disability in a cohort of employed, symptomatic individuals with HD. The focus of this study was thus on the following question: What are the predictors of workplace disability outcomes in people with manifest HD? We hypothesized that higher numbers of CAG repeats, more motor symptoms, greater cognitive impairment, and greater physical and mental health impairments would be associated with higher odds of experiencing workplace impairment.

Methods

Participants

Enroll-HD (ClinicalTrials.gov identifier NCT01574053) is a global clinical research platform designed to facilitate clinical research in HD. As of July 1, 2019, there were 18,845 active participants enrolled at 174 sites in 19 countries. Individuals with premanifest HD or manifest HD, genotype negative or unknown, family members, and community controls participate in the Enroll-HD study. The diagnosis of HD is based on two factors: investigator-determined status, including clinical signs and symptoms, and genotyping status. Participants are classified as manifest HD if they show evidence of clinically significant motor symptoms (diagnostic confidence level of 4 from the Unified Huntington’s Disease Rating Scale [UHDRS], which is associated with motor abnormalities that are considered unequivocal signs of HD, scored by the investigator).

All enrolled participants undergo an annual assessment using a core data set covering motor, cognitive, and behavioral symptoms, with assessments also exploring work productivity measures, quality of life, and physical functioning. All sites are required to obtain and maintain local Ethics Committee approvals, and the project conforms to the provisions of the Declaration of Helsinki. Written informed consent was obtained from all participants. Data are monitored for quality and accuracy by using a risk-based monitoring approach, and all participants are deidentified.

For this study, we analyzed the third Enroll-HD baseline data set, extracted from the database on October 31, 2016, and made available on December 15, 2016. The sample consisted of 316 participants who were classified as manifest HD, having a CAG repeat length range between 39 and 60, and currently engaged in paid full- or part-time employment, who provided data (at least one subscale total) about work disability outcomes as measured by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) questionnaire.

Assessments and Measures

Data were collected on the following measures from included participants.

Sociodemographic and lifestyle factors.

Data were collected on age, gender, region, marital status, smoking and alcohol consumption status, employment status, and years of education.

Clinical and neuropsychological measures.

Motor symptoms were assessed with the UHDRS Total Motor Scale (TMS) (19). The TMS score reflects the sum of ratings on 31 items in 15 domains of motor impairment, each rated on a 5-point scale, ranging from 0, normal, to 4, severest impairment. The motor items rate oculomotor functioning (six items), chorea (seven items), dystonia (five items), bradykinesia (11 items), and rigidity (two items). The maximum possible total score is 124. Functional assessment was conducted by using the UHDRS Total Functional Capacity (TFC) scale (19). Global cognitive functioning was examined with the Mini-Mental State Examination (MMSE) (20). Anxiety, depressive, and irritability symptoms were assessed with the Hospital Anxiety and Depression Scale (HADS) (21) and Snaith Irritability Scale (22). Overall physical and mental health was measured by using the 12-item Short-Form Health Survey (SF-12) (23). CAG repeat length was determined with laboratory genotyping.

Work productivity measure.

The impact of HD on work productivity was examined with the WPAI-SHP questionnaire (24), a self-report instrument used to assess work productivity loss due to general health or a specified health problem. The WPAI-SHP consists of four subscales, the total scores for which are calculated as impairment percentages (from 0% to 100%), with higher numbers indicating greater impairment and less productivity (i.e., worse outcomes). The first subscale, absenteeism (work time missed due to illness or disease), includes any time taken off from work due to HD. The second subscale, presenteeism, is the reported percentage of impairment while at work due to illness or disease. The third subscale, activity impairment, is a global assessment of any work-related activity impairment due to illness or disease. The fourth subscale, work productivity loss–overall work impairment, refers to the participant’s overall productivity (on average) on days at work. The WPAI-SHP is a robust measure of work productivity, which has been validated as a measure of work-related impairment for numerous diseases (e.g., 25, 26).

Statistical Analysis

Because cell sizes were small for certain categories of predictor variables, some of the predictor variable categories were combined prior to analysis. Region was combined into three categories: Australasia, Europe, and the Americas (North and Latin America). Years of education was combined into three categories: below diploma (International Standard Classification of Education [ISCED] levels 0, 1, 2, and 3), diploma-certificate (ISCED level 4), and tertiary studies (ISCED levels 5 and 6). Dichotomized variables were marital status (single versus married or in a partnership); residence (town or city versus rural or village), and smoking and drinking status (alcohol drinker versus nondrinker, smoker versus nonsmoker). Employment status was categorized as full-time, part-time, and self-employed. To address study aims (and because the WPAI-SHP data for our sample were zero inflated), the WPAI-SHP variables were dichotomized into presence or absence of any impairment for analysis by using binary logistic regression models, following the approach suggested in the literature (27).

In the data set, values were missing for 11 of the 22 variables, with the proportions ranging from 0.3% (residence and TMS) to 32.6% (overall work impairment). Of the 316 individuals who constituted the study cohort, 46.5% had one or more missing values, with the missing values in total accounting for 5.2% of the total values. Before the transformation of the four WPAI-SHP variables mentioned above and formal data analysis, we performed multiple imputation to address the missing data based on the assumption that data were missing at random (28–30). Specifically, we included all baseline variables of interest in the imputation model, selected “Automatic” imputation method, set the number of imputations as 35 (slightly larger than the highest proportion of missing values [32.6%] for the variable overall work impairment), and set constraints for all continuous variables to ensure that the imputed values would be within the normal range of the variables (29, 31). After creating 35 imputed data sets, we used standard statistical methods (logistical regression) to fit the model of interest to each of the imputed data sets. Estimated associations in each imputed data set were averaged together to give overall estimated associations between the predictor variables and outcome variables (28, 29).

We calculated mean values and SDs as well as frequencies and percentages for sociodemographic, lifestyle, clinical, and neuropsychological measures. To identify significant predictors of the four WPAI-SHP outcomes, we first conducted a series of univariate logistic regression analyses (“Enter” method) for each outcome variable using the imputed data sets. Variables with a p value <0.25 were included in a multivariable logistic regression analysis (“Enter” method) for each WPAI-SHP outcome (32). We also conducted the same regression analyses using the data set with missing data and found some different significant factors. Given that missing data, if not specified, can lead to the loss of power and potentially biased results, we reported the results of the imputed data sets (31).

Collinearity of all predictor variables were tested by using the linear regression procedure. Statistical significance was assessed using a p value <0.05 and a 95% confidence interval in logistic regression models. Odds ratios were used to quantify the association between independent and outcome variables. All analyses were performed using SPSS 22 (IBM Corporation, Armonk, N.Y.).

Results

Demographic Characteristics

Sociodemographic, lifestyle, clinical, and neuropsychological characteristics are summarized in Table 1. Most participants were male (52.5%), were married or in a partnership (61.7%), worked full-time (64.2%), and lived in a town or city (79.7%). The mean age of participants was 47.0 years (SD=10.5, range 22–76), and most were from Europe (64.2%), followed by the Americas (30.7%) and Australasia (5.1%).

Mean CAG repeat length was 44.5 (SD=3.4, range=39–60). Participants had a mean TMS score of 24.4 (SD=12.9, range=0–87), which suggested a wide variability in motor symptoms in the participants classified as manifest HD (the maximum possible total TMS score is 124). Nevertheless, all included participants had been classified clinically as having manifest HD by the Enroll-HD study investigators on the basis of the criteria described above. Higher scores on the TMS indicate more impaired motor function, and individuals with manifest HD are classified in Enroll-HD based on TMS scores >5 (as consistent with previous literature [33]). In our sample, 308 participants had a TMS score >5 (97.7% of our cohort).

Participants had a mean MMSE score of 27.2 out of a possible 30 (SD=2.4, range=20–30), indicating minimal cognitive impairment. The mean TFC score was close to the maximum level of functioning of 13 (11.5, SD=1.7, range=4–13). The mean total scores on both the HADS anxiety (HADS-A) and HADS depression (HADS-D) subscales were below the cutoff score of 7, indicating absence of clinically relevant symptoms of anxiety and depression (HADS-A: 6.8, SD=4.2, range=0–21; HADS-D: 6.0, SD=4.0, range=0–18). Likewise, participants fell significantly below the cutoff score of 14 points for irritability measured by the Snaith Irritability scale (6.6, SD=4.5, range=0–20). On the SF-12, the mean physical composite score (PCS) (50.7, SD=8.6) and the mean mental composite score (MCS) (44.2, SD=10.8) indicated an “average” level of physical and mental health in this sample, according to the normative mean of 50.

Workplace Impairment and Associated Significant Factors

As shown in Table 1, the proportion of participants who reported having missed work due to HD symptoms was 20.3% (N=64). The proportion who reported experiencing impairment while working due to HD was 60.1% (N=190). In addition, 79.1% (N=250) reported having work-related activity impairment due to HD, and 60.8% (N=192) reported experiencing impairment in overall work productivity due to HD.

Based on the results of univariate logistic regression analyses using the significance level of 0.25, the potential significant predictors for each outcome were determined. For absenteeism, they were education (p=0.15), current alcohol use (p<0.001), TMS score (p=0.08), SF-12 MCS (p=0.01), TFC score (p<0.001), MMSE score (p=0.03), HADS-D score (p=0.01), irritability score (p=0.02), and SF-12 PCS (p=0.01). For presenteeism, they were region (p<0.01), current alcohol use (p=0.06), current smoker (p=0.06), TFC score (p=0.02), HADS-D score (p=0.11), irritability score (p=0.08), and SF-12 MCS (p=0.01). For activity impairment, they were current alcohol use (p=0.20), current smoker (p=0.15), TMS score (p=0.08), TFC score (p=0.06), HADS-A score (p<0.001), HADS-D score (p<0.001), irritability score (p<0.001), SF-12 PCS (p=0.026), and SF-12 MCS (p<0.001). For overall work impairment, they were region (p=0.12), current alcohol use (p=0.18), current smoker (p=0.12), TFC score (p=0.04), HADS-A score (p=0.24), irritability score (p=0.09), and SF-12 MCS (p=0.02),

On the basis of multivariable logistic regression analyses of the imputed data sets, we identified significant (p<0.05) factors associated with two outcomes (Table 2). For absenteeism, significant factors included current alcohol use (odds ratio=2.86, 95% CI=1.62, 5.03) and TFC score (odds ratio=0.76, 95% CI=0.64, 0.91). Significant factors for activity impairment included SF-12 MCS (odds ratio=0.95, 95% CI=0.897, 0.995). In contrast, no significant factors were identified for the other two outcomes—presenteeism and work productivity loss–overall work impairment.

No collinearity within the independent variables was identified based on the collinearity statistics (tolerance value above 0.2). The Hosmer-Lemeshow test was used to assess the goodness of fit, with a significant p value indicating poor model fit. Using this criterion, all regression models were assessed as having a good model fit.

Discussion

This cross-sectional study investigated significant factors associated with workplace impairment and disability in a cohort of employed individuals with HD with manifest motor symptoms. Almost eight in 10 participants reported having work-related activity impairment due to HD. Two in 10 reported missing work due to HD. Six in 10 participants reported both impairment while working due to HD and impairment in their overall work ability (work productivity loss) due to HD.

In terms of our hypotheses, the number of CAG repeats, motor symptoms, overall cognitive impairment, and physical impairments were not associated with higher odds of experiencing workplace impairment. However, we did find associations with mental health and functional status. Specifically, several significant predictors of absenteeism were identified. Individuals had 25% greater odds of missing work time (absenteeism) if they had a higher level of functional impairment. That is, participants with lower TFC scores were more likely to have missed work time (lower TFC scores reflect reduced functional capacity to work, handle finances, perform domestic chores and self-care tasks, and live independently). This was the finding of the analysis, even though most participants in this study fell within stages I and II of functional decline, indicating low levels of functional impairment (mean TFC score=11.5, SD=1.7, range=4–13). The strongest predictor of absenteeism was current alcohol use; current drinkers had almost three times greater odds of missing work, compared with nondrinkers (odds ratio=2.86, 95% CI=1.62, 5.03).

In terms of activity impairment, participants had 5% greater odds of experiencing impairment at work due to HD if they had a lower SF-12 MCS (indicating lower perceived mental health, including depression and anxiety symptoms and functional impairment as a consequence of psychological symptoms).

It is noteworthy that motor symptoms, the clinical hallmark of manifest HD, were not identified in this study as a predictor of workplace disability. This finding is consistent with a recent study that reported that motor symptoms did not predict unemployment in a sample of people with HD in The Netherlands (17). This might indicate that in people with HD, motor impairments may have less impact on occupational functioning than do functional capacity and mental well-being, both of which should be considered as a priority when evaluating workplace ability. Table 3 presents a comparison of data from the sample in our previous study of individuals with premanifest HD (18) and the sample in this study with manifest HD. Although the proportion of individuals reporting workplace disability was lower in the sample with premanifest HD, mental health problems were a significant factor in the same work disability outcome (activity impairment) in that sample. Unlike in the present study, alcohol use was not found to be a significant factor of any work disability outcomes in that asymptomatic cohort.

There is well-established evidence that alcohol use, and particularly episodic heavy drinking, increases the risk of unemployment and, for working persons, absenteeism, and many studies have also suggested that alcohol consumption may have more effect on job productivity than on the number of workdays missed (34). However, despite much evidence of the negative impact of alcohol on work, the exact nature of the relationship between alcohol and workplace disability remains poorly understood. One hypothesis posits that this relationship is likely governed less by drinking or not drinking, but rather by the amount of alcohol consumed and even more by the way it is consumed (e.g., binge drinking versus moderate levels of alcohol consumption) (35). Additionally, it is also well established that alcohol can have a major impact on mental health, and alcohol use has been found to be especially associated with poor mental health functioning (36). Indeed, being at risk of or experiencing symptoms of younger onset dementia can cause significant stress. Drinking alcohol may be a coping strategy, as having a neurodegenerative illness, particularly one such as HD that is strongly genetically transmitted and typically affects multiple members of one family, can cause anxiety about the future, particularly as symptoms occur “out of time” in a “usual” life cycle, at a time when the individual often has significant family and financial responsibilities.

Overall, our results indicate a high level of workplace disability among persons with symptomatic HD and that mental health, functional status, and drinking alcohol are significant predictors of workplace disability. These results were significant in a group of clinically symptomatic individuals with minimal cognitive impairment and minimal functional limitations; no clinically relevant symptoms of depression, anxiety, or irritability; and an “average” level of physical and mental health. Thus, even in a group still working and reporting a high level of capacity, individuals were reporting significant workplace disability, with consequences for employees, employers, and the economy. Results highlight the importance of research into factors related to workplace disability in HD and its role in creating an evidence base for interventions.

Implications for Individuals, Clinicians, Employers, and Policy Makers

A recent systematic review noted that early identification of persons with dementia in the workplace, reasonable adjustments for people with dementia, and provision of information to raise awareness and facilitate informed choice were key factors in good employee management (37). Several key predictors of work disability outcomes identified in our study (current alcohol use and mental well-being) are modifiable and are potentially responsive to interventions. For example, there are many effective pharmacological and nonpharmacological treatments for mental health disorders, particularly for depression and anxiety. Based on our results, in order to minimize and delay workplace disability for persons with HD, health promotion should be a target for workplace health interventions, even if individuals report that they are functioning well. These health promotion interventions should strategically target mental health and well-being. Psychoeducation and teaching effective coping strategies could be incorporated into these interventions, which may potentially reduce alcohol use as a coping mechanism and may also positively affect functional capacity. These workplace interventions would be useful for all employees (regardless of diagnosis) and in all workplaces. Appropriate workplace support and modifications for persons with HD would engender inclusivity and diversity of employees, retain experienced workers, and keep persons with HD functioning within society for longer. Then, if and when they choose to leave the workforce, it can be done with dignity and choice.

Limitations and Future Research

We were limited in our choice of variables to those collected by the Enroll-HD study, and thus we were unable to explore other potential significant factors associated with workplace disability, such as job-related stress, job demands, and type of occupation. Exploring differences between occupations, such as between those with a greater or lesser degree of physical, cognitive, or emotional demands, may highlight important differences and identify occupation-specific predictors of workplace disability. In addition, it should be acknowledged that the Enroll-HD study relies on self-reported data for most outcomes. Because participants in this study had manifest HD, difficulties with capacity and insight may have affected the quality of the data collected. It is also well known that alcohol consumption is underreported in self-reports (38). Collection of collateral information from family members and employers may help to overcome this issue in future.

We also transformed some variables and combined some variable categories, leading to the loss of information. In addition, the size of the study cohort meant that it was not feasible to examine the interactions of variables associated with the outcomes. In future, we recommend longitudinal studies that examine time-dependent predictor variables to identify determinants of work disability outcomes in individuals with manifest HD and studies with larger samples so that interactions of variables can be investigated.

There is evidence that apathy is one of the most disabling behavioral symptoms for patients and caregivers, affecting up to 90% of individuals with HD (39). Greater levels of apathy have also been found to be related to less independence, increased motor impairment, and more clinician-rated behavioral problems (i.e., anger, irritability, and depression) (40). In addition, a recently published systematic review found that the most common significant factors associated with decreased functional capacity were depression and apathy (41). Given the prevalence of apathy among persons with HD reported in the literature and a recent study finding that apathy was an independent determinant of unemployment in HD mutation carriers (17), future research should include a measure of apathy in the methodology and analyses. This is particularly pertinent because our most significant predictors were related to absenteeism from work, which may be related to apathy manifesting as a reduction in the goal-directed behavior of attending work.

This study dichotomized participants into drinkers and nondrinkers because of small cell sizes, but it is also worth exploring the amount and type of alcohol consumption. There is a need to explore the extent of mental health problems in relation to alcohol consumption in order to guide interventions that decrease risk and improve psychological well-being and workplace ability of people with HD, particularly because substance abuse (including alcohol abuse) has been found to have a strong effect on the age at onset of motor symptoms in patients with HD in the Enroll-HD study (42). In addition, there are reports of positive aspects of leaving work, such as the sense of relief (43), which should be explored.

We used raw MMSE scores in our analysis, because we wished to directly compare findings in a premanifest and manifest cohort (Table 3), and previous studies have also found problems in the interpretation of transformed MMSE scores in specific populations (44). When we conducted an analysis after transforming MMSE scores to Z scores using established normative data (published 26 years ago) (45) to ascertain the potential influence of this approach to MMSE score interpretation on the study results, we observed two differences in the results of the multivariate regression following this analysis. Significant predictors of work productivity loss–overall work impairment included TFC score (odds ratio=−0.51, 95% CI=0.37, 0.96). In addition, where participants resided in the world (region) was a significant predictor of presenteeism (when workers come to work when they are unwell or attend work but work at levels that are less than optimal). The North and South American region had an odds ratio of 2.46 (95% CI=2.6, 77.8), and the European region had an odds ratio of 1.60 (95% CI=1.06, 23.3). All other results were the same. There is evidence to suggest that that the use of Z scores results in a loss of the meaningfulness of the raw score and standard deviation and may magnify certain effects and diminish others (46). Furthermore, we do not feel it is justified to transform MMSE raw scores into Z scores because age and education may influence not only MMSE scores but also other predictor variables employed in our study. Therefore, we elected to present the study results using raw MMSE scores. In addition, the participants represented a global cohort, with participants from Europe (64.2%), North and South America (30.7%), and Australasia (5.1%).

Although this study focused on worldwide predictors of workplace disability, it is known that the context of people’s lives determines their health. Future research should further investigate the social and economic determinants of employment and of health in HD, since the current literature is scarce in this area.

Conclusions

This study explored workplace disability in people with manifest HD in a sample of diverse, international participants. Almost eight in 10 participants reported having work-related activity impairment due to HD, highlighting the importance of research such as this into further understanding workplace disability in this cohort. Overall functioning, mental health, and alcohol use were established as important predictors of workplace disability in individuals with manifest HD. A better understanding of those who report workplace disability and of specific predictors or markers of occupational impairment is crucial to inform work accommodations and other strategies that may promote and facilitate continuing employment for those with manifest HD and inform the development of interventions and strategies to enhance engagement at work. Such findings may improve the international understanding of HD, and results may be useful in clinical evaluation, informing future policy, or developing strategies, which will help to delay unemployment and workplace disability and maintain individuals with HD in the workplace for as long as they wish and are able.