Ratko Radakovic

Developing a new apathy measurement scale: Dimensional Apathy Scale

Apathy is both a symptom and syndrome prevalent in neurodegenerative disease, including motor system disorders, that affects motivation to display goal directed functions. Levy and Dubois (2006) suggested three apathetic subtypes, Cognitive, Emotional-affective and Auto-activation, all with discrete neural correlates and functional impairments. The aim of this study was to create a new apathy measure; the Dimensional Apathy Scale (DAS), which assesses apathetic subtypes and is suitable for use in patient groups with motor dysfunction. 311 healthy participants (mean=37.4, S.D.=15.0) completed a 45-item questionnaire. Horns parallel analysis of principal factors and Exploratory Factor Analysis resulted in 4 factors (Executive, Emotional, Cognitive Initiation and Behavioural Initiation) that account for 28.9% of the total variance. Twenty four items were subsequently extracted to form 3 subscales--Executive, Emotional and Behavioural/Cognitive Initiation. The subscale items show good internal consistency reliability. A weak to moderate relationship was found with depression using Becks Depression Inventory II. The DAS is a well-constructed method for assessing multidimensional apathy suitable for application to investigate this syndrome in different disease pathologies.

Multidimensional apathy in ALS: validation of the Dimensional Apathy Scale

Aim Apathy is a prominent symptom of amyotrophic lateral sclerosis (ALS), but measurement is confounded by physical disability. Furthermore, it has been traditionally measured as a unidimensional symptom despite research demonstrating a multifaceted construct. The new Dimensional Apathy Scale (DAS) has been specifically designed for patients with motor disability to measure 3 neurologically based subtypes of apathy: Executive, Emotional and Initiation. We aimed to explore this behavioural symptom by examining the substructure of apathy in ALS and to determine the reliability and validity of the DAS in patients and their carers. Method Patients and carers were recruited through the national Scottish Motor Neurone Disease Register and were asked to complete the DAS, the standardised Apathy Evaluation Scale, and the Geriatric Depression Scale-Short Form. 83 patients with ALS, 75 carers and 83 sex-matched, age-matched and education-matched controls participated. Results When compared with healthy controls, patients showed a significant increase in apathy on the Initiation subscale, and were significantly less apathetic on the Emotional subscale. Scores on the DAS patient and carer versions did not significantly differ. Internal consistency reliability, convergent and discriminant validity were found to be good for the DAS subscales. There was no association between the DAS and functional disability using the ALS Functional Rating Scale. Conclusions Apathy in ALS is characterised by a specific profile of increased initiation apathy and reduced emotional apathy. The DAS is a reliable and valid measure for the assessment of multidimensional apathy in ALS.

Apathy dimensions in Parkinson’s disease

Apathy is a prominent and disabling symptom in Parkinsons disease (PD) and is a multidimensional behaviour, but which dimensions are specifically affected is unclear. Therefore, the aim of this preliminary study was to determine the psychometric properties of the Dimensional Apathy Scale (DAS) and explore the multidimensional profile of apathy in PD patients.

Structural and functional papez circuit integrity in amyotrophic lateral sclerosis

Cognitive impairment in amyotrophic lateral sclerosis (ALS) is heterogeneous but now recognized as a feature in non-demented patients and no longer exclusively attributed to executive dysfunction. However, despite common reports of temporal lobe changes and memory deficits in ALS, episodic memory has been less explored. In the current study, we examined how the Papez circuit—a circuit known to participate in memory processes—is structurally and functionally affected in ALS patients (n = 20) compared with healthy controls (n = 15), and whether these changes correlated with a commonly used clinical measure of episodic memory. Our multimodal MRI approach (cortical volume, voxel-based morphometry, diffusion tensor imaging and resting state functional magnetic resonance) showed reduced gray matter in left hippocampus, left entorhinal cortex and right posterior cingulate as well as increased white matter fractional anisotropy and decreased mean diffusivity in the left cingulum bundle (hippocampal part) of ALS patients compared with controls. Interestingly, thalamus, mammillary bodies and fornix were preserved. Finally, we report a decreased functional connectivity in ALS patients in bilateral hippocampus, bilateral anterior and posterior parahippocampal gyrus and posterior cingulate. The results revealed that ALS patients showed statistically significant structural changes, but more important, widespread prominent functional connectivity abnormalities across the regions comprising the Papez circuit. The decreased functional connectivity found in the Papez network may suggest these changes could be used to assess risk or assist early detection or development of memory symptoms in ALS patients even before structural changes are established.

ECAS A-B-C: alternate forms of the Edinburgh Cognitive and Behavioural ALS Screen

Abstract Background: The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is a short assessment by which neuropsychological symptoms can be detected and quantified in people with ALS. To avoid potential practice effects with repeated administration, here we present alternative versions of the ECAS suitable for measuring change over time. Objective: To develop two alternate versions of the ECAS: ECAS-B and ECAS-C. Method: One hundred and forty-nine healthy adult participants were recruited. Thirty participants completed a pilot study in developing the alternate versions. Two groups of 40 participants were administered the ECAS-B or ECAS-C and compared to published data of the original ECAS (ECAS-A) to determine equivalence. An additional 39 participants were administered the ECAS consecutively, either repeating the original version (ECAS-A-A-A) serially or the different versions (ECAS-A-B-C) to determine potential practice effects. Recordings of assessments were scored by a second researcher to determine inter-rater reliability. Results: No significant differences were found between versions (A, B, C) of the composite performance measures of ALS Specific, ALS Non-Specific, and ECAS Total scores. Repeated serial administration of ECAS-A (A-A-A) produced some practice effects for composite scores, whereas no such effects were found when alternate versions were administered serially (A-B-C). Exceptionally high intra-class correlations were found for all three versions of the ECAS suggesting a high degree of rater agreement. Conclusion: The newly developed alternate forms of the ECAS are both highly equitable to the original ECAS-A and enable avoidance of practice effects, thus supporting their use in measuring cognition and behaviour over time.

A novel assessment and profiling of multidimensional apathy in Alzheimer's Disease

BACKGROUND Apathy is a complex multidimensional syndrome frequently reported in Alzheimers disease (AD) and is associated with impaired awareness. Here we present a psychometrically robust method to profile apathy in AD. OBJECTIVES To determine the validity and reliability of a multidimensional apathy measure, the Dimensional Apathy Scale (DAS), and explore the apathy subtype profile and its associations in AD. METHODS 102 people with AD and 55 healthy controls were recruited. Participants completed the DAS, the Apathy Evaluation Scale (AES), Geriatric Depression Short form (GDS-15), and Lawton Instrumental Activities of Daily Living (LIADL). Psychometric properties of the DAS were determined. AD-Control comparison was performed to explore group differences on the DAS. Latent Class Analysis (LCA) was used to explore the profile of apathy in AD. RESULTS The DAS had a good to excellent Cronbachs standardized alpha (self-rated = 0.85, informant/carer-rated = 0.93) and good convergent and divergent validity against standard apathy (AES) and depression (GDS-15) measures. Group comparison showed people with AD were significantly higher for all apathy subtypes than controls (p < 0.001), and lacking in awareness over all apathy subtype deficits. LCA showed three distinct AD subgroups, with 42.2% in the Executive-Initiation apathy, 28.4% in the Global apathy, and 29.4% in the Minimal apathy group. CONCLUSIONS The DAS is a psychometrically robust method of assessing multidimensional apathy in AD. The apathy profiles in AD are heterogeneous, with additional specific impairments relating to awareness dependent on apathy subtype.

Multidimensional apathy: evidence from neurodegenerative disease

Apathy is a demotivation syndrome common in neurodegenerative diseases and is fundamentally multidimensional in nature. Different methodologies have been used to identify and quantify these dimensions, which has resulted in multifarious concepts, ranging in the number and characteristics of apathy subtypes. This has created an ambiguity over the fundamental substructure of apathy. Here we review the multidimensional concepts of apathy and demonstrate that overlapping elements exist, pointing towards commonalities in apathy subtypes. These can be subsumed under a unified Dimensional Apathy Framework: a triadic structure of Initiation, Executive and Emotional apathy. Distinct cognitive processes may underlie these domains, while self-awareness interplays with all subtypes. Evidence from neurodegenerative diseases supports this distinction with differing apathy profiles in amyotrophic lateral sclerosis, Parkinsons disease and Alzheimers disease.

Clinical neuropsychology in the management of myotonic dystrophy

In a previous issue of Muscle & Nerve, we outlined how psychological processes interact with biological and social factors to affect quality of life in muscle disorders. We then described the use of psychological interventions—focusing mainly on talking therapies—for improving quality of life, mood, and general functioning. As in the case of well-cited reviews describing the clinical management of myotonic dystrophy, neuropsychological assessment and cognitive rehabilitation were not described in detail in our article. The work by Fujino et al. in this issue of the Journal suggests that, in the care of patients with myotonic dystrophy (type 1) at least, our lack of attention to cognitive rehabilitation may have been an oversight. Therefore, in this editorial, we discuss the clinical implications presented by Fujino et al., taking the opportunity to describe the potential for cognitive rehabilitation for myotonic dystrophy. Fujino and colleagues observed that a large proportion of their participants had quite severe myotonic dystrophy and demonstrated impairment in at least 1 cognitive domain (i.e., scores at least 2 standard deviations from population averages). Impairment occurred most frequently in the domains of executive functioning, processing speed, attention, and visuoconstruction. Although their study included no controls for the impact of marked motor impairment, this finding adds to a body of work showing that many people with myotonic dystrophy type 1 have cognitive difficulties. Consistent with existing work, a significant proportion of participants in the sample recruited by Fujino et al. demonstrated comorbid behavioral symptoms/changes—with higher levels of apathy and depression apparent in the sample. The etiology of cognitive and behavioral symptoms in Fujino et al.’s sample was unclear. Other studies found an association between unstable cytosine–thymine–guanine (CTG) repeat expansion size and cognitive test performance and behavior changes in myotonic dystrophy. This is unsurprising given that, in myotonic dystrophy type 1, a positive association exists between brain pathology and CTG repeat expansion, whereas the extent of white-matter lesions is positively correlated with cognitive impairment and behavioral symptoms. In addition, other contextual factors—which may be less dependent on underlying brain pathology— may also affect cognitive functioning. Reactive depression, perhaps resulting from difficulties adjusting to physical symptoms, may worsen performance on cognitive testing; fatigue, sleepiness, or pain may also lead to problems with effort. Importantly, Fujino et al. demonstrated that performance on several cognitive tests was positively correlated with psychosocial aspects of quality of life. Their cross-sectional design did not allow us to disentangle the direction of influence between these variables. Yet, this observation does raise the possibility that an improvement in cognitive symptoms, or their impact on functioning, could lead to an improvement in quality of life. Although a caveat is that some reduced insight may be protective of mood, cognitive rehabilitation may offer a means to improve outcomes for many people with myotonic dystrophy.

Cognitive ability does not predict objectively measured sedentary behaviour: evidence from three older cohorts

Higher cognitive ability is associated with being more physically active. Much less is known about the associations between cognitive ability and sedentary behavior. Ours is the first study to examine whether historic and contemporaneous cognitive ability predicts objectively measured sedentary behavior in older age. Participants were drawn from 3 cohorts (Lothian Birth Cohort, 1936 [LBC1936] [n = 271]; and 2 West of Scotland Twenty-07 cohorts: 1950s [n = 310] and 1930s [n = 119]). Regression models were used to assess the associations between a range of cognitive tests measured at different points in the life course, with sedentary behavior in older age recorded over 7 days. Prior simple reaction time (RT) was significantly related to later sedentary time in the youngest, Twenty-07 1950s cohort (p = .04). The relationship was nonsignificant after controlling for long-standing illness or employment status, or after correcting for multiple comparisons in the initial model. None of the cognitive measures were related to sedentary behavior in either of the 2 older cohorts (LBC1936, Twenty-07 1930s). There was no association between any of the cognitive tests and the number of sit-to-stand transitions in any of the 3 cohorts. The meta-analytic estimates for the measures of simple and choice RT that were identical in all cohorts (n = 700) were also not significant. In conclusion, we found no evidence that objectively measured sedentary time in older adults is associated with measures of cognitive ability at different time points in life, including cognitive change from childhood to older age.

Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function

Neurodegenerative disorders are associated with impaired cognitive function and worse physical health outcomes. This study aims to test whether polygenic risk for Alzheimer’s disease, Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) is associated with cognitive function and physical health in the UK Biobank, a cohort of healthy individuals. Group-based analyses were then performed to compare the top and bottom 10% for the three neurodegenerative polygenic risk scores; these groups were compared on the cognitive and physical health variables. Higher polygenic risk for AD, ALS, and FTD was associated with lower cognitive performance. Higher polygenic risk for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS. The results suggest some overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health.