Multidimensional apathy and executive dysfunction in amyotrophic lateral sclerosis

Abstract

Apathy and cognitive dysfunction are prominent symptoms of Amyotrophic lateral sclerosis (ALS). More specifically ALS patients show increased Initiation apathy-a lack of motivation for self-generation of thoughts as assessed by the Dimensional Apathy Scale. This study aimed to investigate the cognitive underpinnings of apathy subtypes in ALS. We hypothesized that increased Initiation apathy would be associated deficits on tests of intrinsic response generation, such as verbal fluency. We also explored the relationship of other apathy subtypes to cognitive processes, in particular emotional apathy with emotional and social cognition deficits and executive apathy with planning and goal management deficits. ALS patients, and their carers (N = 30), and healthy matched controls, and their informants (N = 29) were recruited. All participants completed self- and informant/carer-rated Dimensional Apathy Scale, to quantify apathy subtypes (Executive, Emotional and Initiation), along with standard apathy and depression measures. Patients and controls completed the Edinburgh Cognitive and behavioural ALS Screen, and a comprehensive neuropsychological battery including emotional recognition, social cognition, intrinsic response generation tasks (verbal fluency and random number generation) and a new ecologically valid, computerised measure of planning and goal management. The results demonstrated that increased Initiation apathy was the only significantly elevated subtype in ALS (self-rated p < .05, informant/carer-rated p < .01). Initiation apathy was found to be significantly associated with verbal fluency deficit, while Emotional apathy was significantly associated with emotional recognition deficits. No associations were found between apathy subtypes and depression or in controls. This is the first study to show specific associations between apathy subtypes (Emotional and Initiation) and executive and emotional cognitive dysfunction, indicating possible distinct underlying mechanisms to these demotivational symptoms.

ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS

“… 5 , 29 Neuropsychological studies have shown that letter fluency impairment may represent a difficulty in cognitive initiation, 4 , 35 which in turn is related to the high frequency of apathy in ALS. 36 Similar to executive functioning and letter fluency, apathy has been associated with reduced fractional anisotropy in the right anterior cingulate cortex 37 and the dorsolateral and orbitomedial prefrontal cortex. 38 Pathologic TAR DNA-binding protein 43 inclusions have been suggested to spread predictably in ALS, 39 beginning in the primary motor cortex, spinal cord, and cranial nerves and spreading to the reticular formation of the brainstem, prefrontal cortex, and finally hippocampus.…”

Relationship between neuropsychiatric disorders and cognitive and behavioural change in MND

“…Apathy or demotivation is the most common behavioural impairment in ALS 36 37. Although some symptoms of depression and apathy may overlap, a dissociation in ALS has been demonstrated,37 and the distinct profile of initiation apathy found in ALS has been related to a cognitive failure to initiate as demonstrated by verbal fluency deficits 38. Early signs of apathy may have been captured as premorbid mood disorders on the CARE-MND platform.…”

Sexuality and intimacy in ALS: systematic literature review and future perspectives

“…Probably, the higher prevalence of negative/inhibited behaviours with respect to positive/disinhibited ones makes aberration of sexual activities less present and described. In fact, apathy is the most frequently reported symptom occurring in around 50% of patients,43 with consequent reductions in sexual interest and activities that could be less recorded and investigated, even if with a relevant impact on the patient–carer relationship. Maybe the issue of apathy-related diminished sexual interest and activities should be investigated as distinct from emotional-driven inhibition as described above, with the possible development of different interventions when appropriate.…”