Experimental laboratory models as tools for understanding modifiable dementia risk.

Experimental laboratory research has an important role to play in dementia prevention. Mechanisms underlying modifiable risk factors for dementia are promising targets for dementia prevention but are difficult to investigate in human populations due to technological constraints and confounds. Therefore, controlled laboratory experiments in models such as transgenic rodents, invertebrates and in vitro cultured cells are increasingly used to investigate dementia risk factors and test strategies which target them to prevent dementia. This review provides an overview of experimental research into 15 established and putative modifiable dementia risk factors: less early-life education, hearing loss, depression, social isolation, life stress, hypertension, obesity, diabetes, physical inactivity, heavy alcohol use, smoking, air pollution, anesthetic exposure, traumatic brain injury, and disordered sleep. It explores how experimental models have been, and can be, used to address questions about modifiable dementia risk and prevention that cannot readily be addressed in human studies. HIGHLIGHTS: Modifiable dementia risk factors are promising targets for dementia prevention. Interrogation of mechanisms underlying dementia risk is difficult in human populations. Studies using diverse experimental models are revealing modifiable dementia risk mechanisms. We review experimental research into 15 modifiable dementia risk factors. Laboratory science can contribute uniquely to dementia prevention.

Isolated rapid eye movement sleep behaviour disorder (iRBD) in the Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) Sleep Study: protocol and baseline characteristics.

Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a sleep disorder that is characterised by dream enactment episodes during REM sleep. It is the strongest known predictor of α-synuclein-related neurodegenerative disease (αNDD), such that >80% of people with iRBD will eventually develop Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy in later life. More research is needed to understand the trajectory of phenoconversion to each αNDD. Only five 'gold standard' prevalence studies of iRBD in older adults have been undertaken previously, with estimates ranging from 0.74% to 2.01%. The diagnostic recommendations for video-polysomnography (vPSG) to confirm iRBD makes prevalence studies challenging, as vPSG is often unavailable to large cohorts. In Australia, there have been no iRBD prevalence studies, and little is known about the cognitive and motor profiles of Australian people with iRBD. The Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) Sleep Study will investigate the prevalence of iRBD in Tasmania, an island state of Australia, using validated questionnaires and home-based vPSG. It will also explore several cognitive, motor, olfactory, autonomic, visual, tactile, and sleep profiles in people with iRBD to better understand which characteristics influence the progression of iRBD to αNDD. This paper details the ISLAND Sleep Study protocol and presents preliminary baseline results.

The use of virtual reality in screening for preclinical Alzheimer's disease: A scoping review protocol.

INTRODUCTION: Preclinical Alzheimer's disease (AD) represents the earliest phase of AD, often years before the onset of mild cognitive impairment (MCI). There is a pressing focus on identifying individuals in the preclinical AD phase to alter the trajectory or impact of the disease potentially. Increasingly, Virtual Reality (VR) technology is being used to support a diagnosis of AD. While VR technology has been applied to the assessment of MCI and AD, studies about how best to utilize VR as a screening tool for preclinical AD are limited and discordant. The objectives of this review are to synthesize the evidence pertaining to the use of VR as a screening tool for preclinical AD as well as to identify factors that need to be considered when utilizing VR to screen for preclinical AD. METHODS AND ANALYSIS: The methodological framework proposed by Arksey and O'Malley (2005) will be introduced to guide the conduction of the scoping review, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) (2018) will be used to organize and structure the review. PubMed, Web of Science, Scopus, ScienceDirect and Google Scholar will be used to search for literature. Obtained studies will be screened for eligibility based on predefined exclusion criteria. A narrative synthesis of eligible studies will be performed, after tabulating the extracted data from existing literature, to answer the research questions. ETHICS AND DISSEMINATION: Ethical approval is not required for this scoping review. Findings will be disseminated through conference presentations, publication in a peer-reviewed journal, and discussions among professional networks in the research domain combining neuroscience and information and communications technology (ICT). REGISTRATION DETAILS: This protocol has been registered on Open Science Framework (OSF). Relevant materials and potential following updates are available at https://osf.io/aqmyu.

Isolated REM sleep behaviour disorder: current diagnostic procedures and emerging new technologies.

Isolated REM sleep behaviour disorder (iRBD) is characterised by dream enactment behaviours, such as kicking and punching while asleep, and vivid/violent dreams. It is now acknowledged as a prodromal phase of neurodegenerative disease-approximately 80% of people with iRBD will develop dementia with Lewy Bodies, Parkinson's disease or another degenerative brain disease within 10 years. It is important that neurologists and other clinicians understand how to make an early accurate diagnosis of iRBD so that affected people can have the opportunity to take part in clinical trials. However, making a diagnosis can be clinically challenging due to a variety of reasons, including delayed referral, symptom overlap with other disorders, and uncertainty about how to confirm a diagnosis. Several methods of assessment are available, such as clinical interview, screening questionnaires and video polysomnography or 'sleep study'. This review aims to support clinical neurologists in assessing people who present with symptoms suggestive of iRBD. We describe the usefulness and limitations of each diagnostic method currently available in clinical practice, and present recent research on the utility of new wearable technologies to assist with iRBD diagnosis, which may offer a more practical assessment method for clinicians. This review highlights the importance of thorough clinical investigation when patients present with suspected iRBD and emphasises the need for easier access to diagnostic procedures for accurate and early diagnosis.

Lateral entorhinal cortex lesions impair both egocentric and allocentric object-place associations.

During navigation, landmark processing is critical either for generating an allocentric-based cognitive map or in facilitating egocentric-based strategies. Increasing evidence from manipulation and single-unit recording studies has highlighted the role of the entorhinal cortex in processing landmarks. In particular, the lateral (LEC) and medial (MEC) sub-regions of the entorhinal cortex have been shown to attend to proximal and distal landmarks, respectively. Recent studies have identified a further dissociation in cue processing between the LEC and MEC based on spatial frames of reference. Neurons in the LEC preferentially encode egocentric cues while those in the MEC encode allocentric cues. In this study, we assessed the impact of disrupting the LEC on landmark-based spatial memory in both egocentric and allocentric reference frames. Animals that received excitotoxic lesions of the LEC were significantly impaired, relative to controls, on both egocentric and allocentric versions of an object-place association task. Notably, LEC lesioned animals performed at chance on the egocentric version but above chance on the allocentric version. There was no significant difference in performance between the two groups on an object recognition and spatial T-maze task. Taken together, these results indicate that the LEC plays a role in feature integration more broadly and in specifically processing spatial information within an egocentric reference frame.

Distance- rather than location-based temporal judgments are more accurate during episodic recall in a real-world task.

Definitions of episodic memory typically emphasise the importance of spatiotemporal frameworks in the contextual reconstruction of episodic retrieval. However, our ability to retrieve specific temporal contexts of experienced episodes is poor. This has bearing on the prominence of temporal context in the definition and evaluation of episodic memory, particularly among non-human animals. Studies demonstrating that rats rely on elapsed time (distance) rather than specific timestamps (location) to disambiguate events have been used to suggest that human episodic memory is qualitatively different to other species. We examined whether humans were more accurate using a distance- or location-based method for judging when an event happened. Participants (n = 57) were exposed to a series of events and then asked either when (e.g., 1:03 pm) or how long ago (HLA; e.g., 33 min) a specific event took place. HLA judgements were significantly more accurate, particularly for the most recently experienced episode. Additionally, a significantly higher proportion of participants making HLA judgements accurately recalled non-temporal episodic features across all episodes. Finally, for participants given the choice of methods for making temporal judgements, a significantly higher proportion chose to use HLA judgements. These findings suggest that human and non-human temporal judgements are not qualitatively different.

Lateral Entorhinal Cortex Lesions Impair Local Spatial Frameworks.

A prominent theory in the neurobiology of memory processing is that episodic memory is supported by contextually gated spatial representations in the hippocampus formed by combining spatial information from medial entorhinal cortex (MEC) with non-spatial information from lateral entorhinal cortex (LEC). However, there is a growing body of evidence from lesion and single-unit recording studies in rodents suggesting that LEC might have a role in encoding space, particularly the current and previous locations of objects within the local environment. Landmarks, both local and global, have been shown to control the spatial representations hypothesized to underlie cognitive maps. Consequently, it has recently been suggested that information processing within this network might be organized with reference to spatial scale with LEC and MEC providing information about local and global spatial frameworks respectively. In the present study, we trained animals to search for food using either a local or global spatial framework. Animals were re-tested on both tasks after receiving excitotoxic lesions of either the MEC or LEC. LEC lesioned animals were impaired in their ability to learn a local spatial framework task. LEC lesioned animals were also impaired on an object recognition (OR) task involving multiple local features but unimpaired at recognizing a single familiar object. Together, this suggests that LEC is involved in associating features of the local environment. However, neither LEC nor MEC lesions impaired performance on the global spatial framework task.