Caregiver burden is a complex construct involving the caregiver’s feelings about the emotional/physical health, social life and financial status that they suffer as a result of caring for their relatives [10]. Caregiving was shown to have an adverse effect on the physical and psychological health of caregivers [11]. Although advancing ALS undoubtedly causes high levels of caregiver distress, few studies have focused on the contributory factors [12-14]. Caregiver burden, depression and anxiety appear inter-related, and associated with the ALS patients’ physical disability [15]. Also, neurobehavioral symptoms have a negative impact on caregivers’ psychological status [16]. Given the high rate of cognitive deficits and neuropsychiatric symptoms found in ALS patients [2,17,18], it is clearly germane to examine whether caregiver burden is associated with behavioral changes over and above the physical disability of patients with ALS.

ALS patients’ mean age was 63.5±9years, with a median of disease duration of 3years (interquartile range 2–5). The mean ALSFRS-R total score was 30.4 (S.D. 9.7). Distribution of patients by motor onset showed a predominance of limb (73.6%) over bulbar (26.4%) onset. The age range and pattern of disease onset (limb vs. bulbar) mirrors closely that found in large cohorts [26-28].

Behavioral symptoms, as measured by the Frontal Systems Behavioral Scale (FrSBe), have previously been reported to be associated to higher caregiver burden, [16,18] although only one study has considered variables related to caregivers [16]. We have confirmed this association using the Cambridge Behavioural Inventory - Revised and, importantly, found that the strongest predictor of caregiver burden was the patient’s abnormal behavior. It should be noted that, as in other studies, apathy was the most common behavioral change [2,18,29], but this factor did not enter the model of caregiver burden. Stereotypical behaviors were also reported at similar levels to abnormal behavior, but again, this factor did not explain caregiver burden. Specific changes in behavior, notably disinhibition and impulsivity, are particularly distressing for caregivers. We suspect that many clinicians involved in the management of ALS patients are unaware of the high rate of these changes and their impact on family relationships. Specific interventions targeting carers and developing their coping skills have been shown to be successful in FTD [30] and may have a successful place in the management of ALS dyads.

A number of studies have shown that caregivers of patients with ALS report high levels of burden, anxiety and depression in association with the patient’s loss of physical functions [14,15]. In our study, somewhat surprisingly, burden was not associated with changes in physical function, as measured by the ALSFRS-R. One possible explanation for this lack of association may be that behavioral changes which overshadow the lesser influence of physical disability in a log regression model. Moderate or worse depressive symptoms were present in 23% of caregivers, with similar rates of stress. These symptoms did not, however, enter the model explaining caregiver burden. The reported rate of caregiver depression in caregivers of people with ALS has varied from 11 to 61% [31,32] which almost certainly reflects the use of different instruments, the threshold used to determine depression and the level of disability of patients in the cohorts. It is interesting that caregiver depression had lesser role in the genesis of caregiver burden than seen in pure FTD, despite the overlap in behavioral symptoms between bvFTD and ALS [12,13].

The levels of anxiety and stress (around 20%) in our caregivers were lower than reported previously [33,34]. Again, the variability probably reflects the use of different instruments. Caregivers’ state anxiety has been previously related to their trait anxiety more than external factors [34]. Stress rather than depression and anxiety was the main psychological caregiver variable contributing to caregiver burden. This is clearly relevant to management since can be addressed in MND clinics and are potentially amenable to intervention.

A longitudinal study identified that, initially, caregiver distress was best predicted by the psychosocial impact of ALS symptoms and emotional lability. Later, caregiver distress related to satisfaction with social relationships and social support [13] rather than behavioral changes, although these were limited to dysexecutive symptoms rather than the FTD-like features explored by the CBI. Future longitudinal studies should investigate the role of specific behavioral changes, caregiver variables, and disease progression especially given the fact that caregiver burden seems to increase over time. A limitation of this study was the nature of the survey via the MND Association, where carers who responded to the invitation to the research study were likely to be those willing to respond the questionnaires. Still, our results corroborated those published previously, and the patients’ characteristics mirrored those in large cohorts.

Dr. Mioshi serves on the editorial board of Dementia and Geriatric Cognitive Disorders and is a recipient of a National Health and Medical Research Council of Australia Early Career Fellowship and an Motor Neurone Disease Research Institute of Australia Grant.

Prof Hodges is funded by the Australian Research Council Federation Fellowship, FF0776229.