No abstract

Obesity is recognized as a significant risk factor for Alzheimer's disease (AD). Studies have supported that obesity accelerates AD-related pathophysiology and memory impairment in mouse models of AD. However, the nature of the brain structure-behaviour relationship mediating this acceleration remains unclear. In this manuscript we evaluated the impact of adolescent obesity on the brain morphology of the triple transgenic mouse model of AD (3xTg) and a non-transgenic control model of the same background strain (B6129s) using longitudinally acquired structural magnetic resonance imaging (MRI). At 8 weeks of age, animals were placed on a high-fat diet (HFD) or an ingredient-equivalent control diet (CD). Structural images were acquired at 8, 16, and 24 weeks. At 25 weeks, animals underwent the novel object recognition (NOR) task and the Morris water maze (MWM) to assess short-term non-associative memory and spatial memory, respectively. All analyses were carried out across four groups: B6129s-CD and -HFD and 3xTg-CD and -HFD. Neuroanatomical changes in MRI-derived brain morphology were assessed using volumetric and deformation-based analyses. HFD-induced obesity during adolescence exacerbated brain volume alterations by adult life in the 3xTg mouse model in comparison to control-fed mice and mediated volumetric alterations of select brain regions, such as the hippocampus. Further, HFD-induced obesity aggravated memory in all mice, lowering certain memory measures of B6129s control mice to the level of 3xTg mice maintained on a CD. Moreover, decline in the volumetric trajectories of hippocampal regions for all mice were associated with the degree of spatial memory impairments on the MWM. Our results suggest that obesity may interact with the brain changes associated with AD-related pathology in the 3xTg mouse model to aggravate brain atrophy and memory impairments and similarly impair brain structural integrity and memory capacity of non-transgenic mice. Further insight into this process may have significant implications in the development of lifestyle interventions for treatment of AD.

Background Recently, artificial intelligence-powered devices have been put forward as potentially powerful tools for the improvement of mental healthcare. An important question is how these devices impact the physician-patient interaction. Aims Aifred is an artificial intelligence-powered clinical decision support system (CDSS) for the treatment of major depression. Here, we explore the use of a simulation centre environment in evaluating the usability of Aifred, particularly its impact on the physician–patient interaction. Method Twenty psychiatry and family medicine attending staff and residents were recruited to complete a 2.5-h study at a clinical interaction simulation centre with standardised patients. Each physician had the option of using the CDSS to inform their treatment choice in three 10-min clinical scenarios with standardised patients portraying mild, moderate and severe episodes of major depression. Feasibility and acceptability data were collected through self-report questionnaires, scenario observations, interviews and standardised patient feedback. Results All 20 participants completed the study. Initial results indicate that the tool was acceptable to clinicians and feasible for use during clinical encounters. Clinicians indicated a willingness to use the tool in real clinical practice, a significant degree of trust in the system's predictions to assist with treatment selection, and reported that the tool helped increase patient understanding of and trust in treatment. The simulation environment allowed for the evaluation of the tool's impact on the physician–patient interaction. Conclusions The simulation centre allowed for direct observations of clinician use and impact of the tool on the clinician–patient interaction before clinical studies. It may therefore offer a useful and important environment in the early testing of new technological tools. The present results will inform further tool development and clinician training materials.

Animal models of Alzheimer's disease (AD) can be used to determine the progressive neurodegeneration characteristics of AD in vivo using magnetic resonance imaging (MRI). Given the need for therapeutic interventions before the onset of frank AD, it is critical to examine if AD models demonstrate neuroanatomical remodeling in an equivalent preclinical phase. This manuscript examines the trajectories of brain and behavioural changes in the Triple transgenic mouse model (3xTg) prior to the development of AD-like behaviours. The 3xTg mimics both β-amyloid plaques and neurofibrillary tangles through three mutations associated with familial AD, namely: PS1, APP, and tau transgenes. We performed detailed investigation using longitudinal structural MRI at 6, 8, 12, 16, 20, and 24 weeks old to assess neuroanatomical changes using volumetric and deformation-based analyses. Learning- and memory-related behaviour were assessed through the Morris water maze at 9, 17, and 25 weeks of age. There was the absence of major memory deficits with the notable exception of water maze conducted at 17 weeks old, where 3xTg group spent significantly less time in the quadrant of interest in the probe trial. Through volumetric and deformation-based analyses, we observed relative decrease over time in the 3xTg group in the third ventricle, piriform cortex, fornix, and fimbria relative to the control group. We also observed decreases over time in the control mice in the hippocampus, entorhinal cortex, cerebellum, and olfactory bulb. In many of these cases, we note a delay in the attainment of peak volume in the 3xTgs relative to the control group, suggesting a possible neurodevelopmental and maturational delay given the likely over-expression of AD-related pathology from birth. Importantly, neuroanatomical alterations are observed prior to the manifestation of AD-like behaviours, suggesting that mutated amyloid and tau are, indeed, sufficient to cause changes in the neuroanatomy in 3xTg mice, but potentially insufficient to be responsible for behavioural changes in the earlier stages of life.