Profiles of motivational impairment and their relationship to functional decline in frontotemporal dementia.

Motivational disturbances are pervasive in frontotemporal dementia (FTD) and impact negatively on everyday functioning. Despite mounting evidence of anhedonia in FTD, it remains unclear how such changes fit within the broader motivational symptom profile of FTD, or how anhedonia relates to functional outcomes. Here we sought to comprehensively characterize motivational disturbances in FTD and their respective relationships with functional impairment. A cross-sectional study design was used including 211 participants-68 behavioral-variant FTD (bvFTD), 32 semantic dementia (SD), 43 Alzheimer's disease (AD), and 68 healthy older control participants. Anhedonia severity was measured using the Snaith-Hamilton Pleasure Scale while severity of apathy was assessed across Emotional, Executive, and Initiation dimensions using the Dimensional Apathy Scale. Functional impairment was established using the FTD Functional Rating Scale (FRS). Distinct motivational profiles emerged in each dementia syndrome: a domain-general motivational impairment in bvFTD; a predominantly anhedonic profile in SD; and more pronounced initiation and executive apathy in AD. Correlation analyses revealed differential associations between motivational symptoms and severity of functional impairment in each group. Executive apathy was associated with functional impairment in bvFTD, while anhedonia was strongly correlated with functional decline in SD. Finally, executive and emotional apathy were associated with functional decline in AD. Our study indicates distinct profiles of apathy and anhedonia in FTD syndromes, which in turn are differentially associated with functional decline. This detailed characterization of motivational phenotypes can inform patient stratification for targeted interventions to improve functional outcomes.

The Role of Apathy in Spontaneous Verbal and Nonverbal Behaviors: A Transdiagnostic Pilot Study in Neurodegeneration.

BACKGROUND: Apathy, characterized by a quantifiable reduction in motivation or goal-directed behavior, is a multidimensional syndrome that has been observed across many neurodegenerative diseases. OBJECTIVE: To develop a novel task measuring spontaneous action initiation (ie, a nonverbal equivalent to spontaneous speech tasks) and to investigate the association between apathy and executive functions such as the voluntary initiation of speech and actions and energization (ie, ability to initiate and sustain a response). METHOD: We compared the energization and executive functioning performance of 10 individuals with neurodegenerative disease and clinically significant apathy with that of age-matched healthy controls (HC). We also investigated the association between self-reported scores on the Apathy Evaluation Scale (AES) and performance on energization tasks. RESULTS: The individuals with apathy made significantly fewer task-related actions than the HC on the novel spontaneous action task, and their scores on the AES were negatively correlated with spontaneous task-related actions, providing preliminary evidence for the task's construct validity. In addition, the individuals with apathy performed more poorly than the HC on all of the energization tasks, regardless of task type or stimulus modality, suggesting difficulty in sustaining voluntary responding over time. Most of the tasks also correlated negatively with the AES score. However, the individuals with apathy also performed more poorly on some of the executive function tasks, particularly those involving self-monitoring. CONCLUSION: Our work presents a novel experimental task for measuring spontaneous action initiation-a key symptom of apathy-and suggests a possible contribution of apathy to neuropsychological deficits such as poor energization.

Post-stroke apathy: A case series investigation of neuropsychological and lesion characteristics.

Apathy is a multi-dimensional syndrome associated with reduced initiation, executive function and emotion toward goal-directed behaviour. Affecting ∼30% of stroke patients, apathy can negatively impact rehabilitation outcomes and increase caregiver burden. However, relatively little is known about the multi-dimensional nature of post-stroke apathy and whether these dimensions map onto neuropsychological and neuroanatomical correlates. The present study aimed to address this question in a case series of stroke patients with apathy. 65 patients with acute stroke were assessed on a comprehensive battery of neuropsychological tasks and 12 patients were identified as having clinically significant apathy on one or more domains on the Dimensional Apathy Scale. Individual scores were compared to a group of healthy controls and normative data where available. Lesion mapping was completed from clinical CT and MRI scans to characterise the extent and locations of each patient's lesion. All participants performed significantly poorer than controls on one or more tasks. Difficulties with inhibition were observed across all dimensions. Prospective memory deficits were also common, while speed and social cognition were only reduced in initiation and emotional apathy, respectively. Verbal fluency was not impaired in any of the patients, despite previously established relationships with apathy. Lesions were predominantly located in right subcortical regions, with some additional frontal, temporal and cerebellar/brainstem involvement. There was substantial overlap in lesion locations within and between dimensions, such that similar apathy symptoms occurred in patients with very different lesion sites. Overall, our results suggest that neuropsychological and lesion profiles of apathy in stroke patients may be more complex and heterogenous than in neurodegenerative disease, possibly due to functional changes occurring beyond the lesion site.

Evidence against benefits from cognitive training and transcranial direct current stimulation in healthy older adults.

Cognitive training and brain stimulation show promise for ameliorating age-related neurocognitive decline. However, evidence for this is controversial. In a Registered Report, we investigated the effects of these interventions, where 133 older adults were allocated to four groups (left prefrontal cortex anodal transcranial direct current stimulation (tDCS) with decision-making training, and three control groups) and trained over 5 days. They completed a task/questionnaire battery pre- and post-training, and at 1- and 3-month follow-ups. COMT and BDNF Val/Met polymorphisms were also assessed. Contrary to work in younger adults, there was evidence against tDCS-induced training enhancement on the decision-making task. Moreover, there was evidence against transfer of training gains to untrained tasks or everyday function measures at any post-intervention time points. As indicated by exploratory work, individual differences may have influenced outcomes. But, overall, the current decision-making training and tDCS protocol appears unlikely to lead to benefits for older adults.