A shared cognitive and neural basis underpinning cognitive apathy and planning in behavioural-variant frontotemporal dementia and Alzheimer's disease.

Apathy is the most common and disabling non-cognitive feature of dementia, affecting up to 90% of individuals over the disease course. Despite its prevalence, the underlying mechanisms of apathy remain elusive. This study aimed to investigate whether cognitive apathy and executive functioning have a shared cognitive and neural basis, in behavioural-variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). Seventy-one participants (31 bvFTD, 17 AD and 23 controls) were assessed on a neuropsychological battery of executive tasks including the Zoo Map Test, Modified Six Elements Test, Tower Test and verbal fluency. The Dimensional Apathy Scale (DAS) was used to quantify cognitive apathy. Principal components analysis identified a single component underpinning performance on the neuropsychological tests, with both bvFTD and AD showing significantly reduced "planning ability" compared to controls. On the DAS, 74% of bvFTD patients and 59% of AD patients showed clinically significant cognitive apathy. Importantly, linear regression revealed that lower planning ability significantly predicted increased cognitive apathy, even after controlling for cognitive impairment and disease duration. Voxel-based morphometry analyses revealed that planning ability and cognitive apathy were both associated with atrophy of the right frontal pole and orbitofrontal cortex, as well as the thalamus and putamen. From a theoretical perspective, our results reveal a shared mechanism underpinning both cognitive apathy and planning deficits in bvFTD and AD. Clinically, this knowledge will help to improve the identification of apathy in clinical syndromes and inform targeted interventions to improve independence and wellbeing for those living with dementia.

Environmental Enrichment Partially Repairs Subcortical Mapping Errors in Ten-m3 Knock-Out Mice during an Early Critical Period.

Environmental enrichment (EE) has been shown to improve neural function via the regulation of cortical plasticity. Its capacity to induce functional and/or anatomical repair of miswired circuits is unknown. Ten-m3 knock-out (KO) mice exhibit a highly stereotyped and profound miswiring of ipsilateral retinogeniculate axons and associated deficits in binocularly-mediated visual behavior. We determined whether, and when, EE can drive the repair of subcortical wiring deficits by analyzing Ten-m3 KO and wild-type (WT) mice that were enriched for six weeks from adulthood, weaning or birth in comparison to standard-housed (SE) controls. Six weeks of EE initiated from birth, but not later, induced a significant reduction in the area occupied by ipsilateral retinogeniculate terminals in KOs. No EE-induced correction of mistargeted axons was observed at postnatal day (P)7, indicating that this intervention impacts pruning rather than initial targeting of axons. This reduction was most prominent in the ventrolateral region of the dorsal lateral geniculate nucleus (dLGN), suggesting a preferential pruning of the most profoundly mistargeted axons. EE can thus partially repair a specific, subcortical axonal wiring deficit, but only during an early, developmentally-restricted time window.

Subcortical volumetric differences between clinical stages of young people with affective and psychotic disorders.

The aim of this study was to investigate differences in subcortical and hippocampal volumes between healthy controls, young people at an early stage of affective and psychotic disorders and those in more advanced stages, to identify markers associated with functional outcomes and illness severity. Young people presenting to youth mental health services with admixtures of depressive, manic and psychotic symptoms (n = 141), and healthy counterparts (n = 49), aged 18-25 were recruited. Participants underwent magnetic resonance imaging, clinical assessments and were rated as to their current clinical stage. Eighty-four patients were classified at the attenuated syndrome stage (Stage 1b) and 57 were classified as having discrete and persistent disorders (Stage 2+). Automated segmentation was performed using NeuroQuant® to determine volumes of subcortical and hippocampus structures which were compared between groups and correlated with clinical and functional outcomes. Compared to healthy controls, Stage 2+ patients showed significantly reduced right amygdala volumes. Whereas Stage 1b patients showed significantly reduced left caudate volumes compared to healthy controls. Smaller left caudate volume correlated with greater psychological distress and impaired functioning. This study shows a clinical application for an automated program to identify and track subcortical changes evident in young people with emerging psychopathology.