Less spatial exploration is associated with poorer spatial memory in midlife adults.

Introduction: Despite its importance for navigation, very little is known about how the normal aging process affects spatial exploration behavior. We aimed to investigate: (1) how spatial exploration behavior may be altered early in the aging process, (2) the relationship between exploration behavior and subsequent spatial memory, and (3) whether exploration behavior can classify participants according to age. Methods: Fifty healthy young (aged 18-28) and 87 healthy midlife adults (aged 43-61) freely explored a desktop virtual maze, learning the locations of nine target objects. Various exploration behaviors (object visits, distance traveled, turns made, etc.) were measured. In the test phase, participants navigated from one target object to another without feedback, and their wayfinding success (% correct trials) was measured. Results: In the exploration phase, midlife adults exhibited less exploration overall compared to young adults, and prioritized learning target object locations over maze layout. In the test phase, midlife adults exhibited less wayfinding success when compared to the young adults. Furthermore, following principal components analysis (PCA), regression analyses indicated that both exploration quantity and quality components were associated with wayfinding success in the midlife group, but not the young adults. Finally, we could classify participants according to age with similar accuracy using either their exploration behavior or wayfinding success scores. Discussion: Our results aid in the understanding of how aging impacts spatial exploration, and encourages future investigations into how pathological aging may affect spatial exploration behavior.

Is Carer Management Style Associated with Longitudinal Functional Decline in Dementia?

BACKGROUND: Various intrinsic (related to dementia) and extrinsic (not related to dementia) factors have been suggested to contribute separately to disability in people living with dementia (PLwD). OBJECTIVE: To investigate if the combination of specific intrinsic and extrinsic factors at baseline is associated with longitudinal declines in activities of daily living (ADL) performance of PLwD at 12-month follow-up. METHODS: 141 community-dwelling PLwD-carer dyads were assessed on their global cognition (ACE-III), apathy (CBI-R), carer management styles (DMSS), medical comorbidities (CCI), and ADL performance (DAD) at baseline, and for a subset of participants (n = 53), at 12-month follow-up. Multiple linear regression models were run to assess: 1) the relationships between PLwD's DAD scores and the remaining variables at baseline and 2) whether these variables' scores at baseline were associated with longitudinal change in the PLwD's DAD scores. RESULTS: At baseline, having lower ACE-III (ß= 0.354, p < 0.001), higher CBI-R (ß= -0.284, p < 0.001), higher DMSS criticism (ß= -0.367, p = 0.013), lower DMSS encouragement (ß= 0.370, p = 0.014), and higher CCI scores (ß= -2.475, p = 0.023) were significantly associated with having lower DAD scores. The PLwD's DAD scores significantly declined from baseline to follow-up (p < 0.001, d = 1.15), however this decline was not associated with the baseline scores of any of the independent variables. Instead, it was associated with declines in the PLwD's ACE-III scores from baseline to follow-up (ß= 1.021, p = 0.001). CONCLUSIONS: In our limited sample, cognitive changes seem to be the main factor underlying longitudinal decline in ADL performance for PLwD. Carer management styles appear associated with current ADL performance but not with longitudinal ADL decline.

Predicting real world spatial disorientation in Alzheimer's disease patients using virtual reality navigation tests.

Spatial navigation impairments in Alzheimer's disease (AD) have been suggested to underlie patients experiencing spatial disorientation. Though many studies have highlighted navigation impairments for AD patients in virtual reality (VR) environments, the extent to which these impairments predict a patient's risk for spatial disorientation in the real world is still poorly understood. The aims of this study were to (a) investigate the spatial navigation abilities of AD patients in VR environments as well as in a real world community setting and (b) explore whether we could predict patients at a high risk for spatial disorientation in the community based on their VR navigation. Sixteen community-dwelling AD patients and 21 age/gender matched controls were assessed on their egocentric and allocentric navigation abilities in VR environments using the Virtual Supermarket Test (VST) and Sea Hero Quest (SHQ) as well as in the community using the Detour Navigation Test (DNT). When compared to controls, AD patients exhibited impairments on the VST, SHQ, and DNT. For patients, only SHQ wayfinding distance and wayfinding duration significantly predicted composite disorientation score on the DNT (ß = 0.422, p = 0.034, R2 = 0.299 and ß = 0.357, p = 0.046, R2 = 0.27 respectively). However, these same VR measures could not reliably predict which patients were at highest risk of spatial disorientation in the community (p > 0.1). Future studies should focus on developing VR-based tests which can predict AD patients at high risk of getting spatially disorientated in the real world.

Using GPS Tracking to Investigate Outdoor Navigation Patterns in Patients With Alzheimer Disease: Cross-sectional Study.

BACKGROUND: Spatial disorientation is one of the earliest and most distressing symptoms seen in patients with Alzheimer disease (AD) and can lead to them getting lost in the community. Although it is a prevalent problem worldwide and is associated with various negative consequences, very little is known about the extent to which outdoor navigation patterns of patients with AD explain why spatial disorientation occurs for them even in familiar surroundings. OBJECTIVE: This study aims to understand the outdoor navigation patterns of patients with AD in different conditions (alone vs accompanied; disoriented vs not disoriented during the study) and investigate whether patients with AD experienced spatial disorientation when navigating through environments with a high outdoor landmark density and complex road network structure (road intersection density, intersection complexity, and orientation entropy). METHODS: We investigated the outdoor navigation patterns of community-dwelling patients with AD (n=15) and age-matched healthy controls (n=18) over a 2-week period using GPS tracking and trajectory mining analytical techniques. Here, for the patients, the occurrence of any spatial disorientation behavior during this tracking period was recorded. We also used a spatial buffer methodology to capture the outdoor landmark density and features of the road network in the environments that the participants visited during the tracking period. RESULTS: The patients with AD had outdoor navigation patterns similar to those of the controls when they were accompanied; however, when they were alone, they had significantly fewer outings per day (total outings: P<.001; day outings: P=.003; night outings: P<.001), lower time spent moving per outing (P=.001), lower total distance covered per outing (P=.009), lower walking distance per outing (P=.02), and lower mean distance from home per outing (P=.004). Our results did not identify any mobility risk factors for spatial disorientation. We also found that the environments visited by patients who experienced disorientation versus those who maintained their orientation during the tracking period did not significantly differ in outdoor landmark density (P=.60) or road network structure (road intersection density: P=.43; intersection complexity: P=.45; orientation entropy: P=.89). CONCLUSIONS: Our findings suggest that when alone, patients with AD restrict the spatial and temporal extent of their outdoor navigation in the community to successfully reduce their perceived risk of spatial disorientation. Implications of this work highlight the importance for future research to identify which of these individuals may be at an actual high risk for spatial disorientation as well as to explore the implementation of health care measures to help maintain a balance between patients' right to safety and autonomy when making outings alone in the community.

Machine learning detects altered spatial navigation features in outdoor behaviour of Alzheimer's disease patients.

Impairment of navigation is one of the earliest symptoms of Alzheimer's disease (AD), but to date studies have involved proxy tests of navigation rather than studies of real life behaviour. Here we use GPS tracking to measure ecological outdoor behaviour in AD. The aim was to use data-driven machine learning approaches to explore spatial metrics within real life navigational traces that discriminate AD patients from controls. 15 AD patients and 18 controls underwent tracking of their outdoor navigation over two weeks. Three kinds of spatiotemporal features of segments were extracted, characterising the mobility domain (entropy, segment similarity, distance from home), spatial shape (total turning angle, segment complexity), and temporal characteristics (stop duration). Patients significantly differed from controls on entropy (p-value 0.008), segment similarity (p-value [Formula: see text]), and distance from home (p-value [Formula: see text]). Graph-based analyses yielded preliminary data indicating that topological features assessing the connectivity of visited locations may also differentiate patients from controls. In conclusion, our results show that specific outdoor navigation features discriminate AD patients from controls, which has significant implication for future AD diagnostics, outcome measures and interventions. Furthermore, this work illustrates how wearables-based sensing of everyday behaviour may be used to deliver ecologically-valid digital biomarkers of AD pathophysiology.

Effectiveness of Interventions for Preventing People With Dementia Exiting or Getting Lost.

BACKGROUND AND OBJECTIVES: People with dementia are at risk of exiting premises unsupervised, eloping, or getting lost, potentially leading to harmful or distressing consequences. This review aimed to estimate the effectiveness of interventions for preventing people with dementia from exiting or getting lost. RESEARCH DESIGN AND METHODS: A systematic review of English sources was undertaken. Health care (EMBASE, BNI, Medline, PubMed, CINAHL, PsycINFO, AMED, HTA, CENTRAL) and gray literature (OpenGrey) databases were searched using prespecified search terms. Additional studies were identified by hand-searching bibliographies of relevant reviews and included studies. Wide inclusion criteria were set to capture a range of intervention types. Data extraction and risk of bias assessment were completed independently by two reviewers. Methods were preregistered on PROSPERO. RESULTS: Individual and overall risk of bias was too high for statistical meta-analyses. A narrative synthesis was therefore performed. Twenty-five studies with 814 participants were included, investigating a range of nonpharmacological interventions aiming to prevent exiting, facilitate retrieval, educate participants, or a combination of these. Seventeen (68%) of the included studies had critical risks of internal bias to outcomes, providing no useful evidence for the effectiveness of their respective interventions. The remaining 8 (32%) studies had serious risks of bias. Narrative synthesis of results yielded no overall robust evidence for the effectiveness of any interventions. DISCUSSION AND IMPLICATIONS: No evidence was found to justify the recommendation of any interventions included in this review. Future studies should focus on high-quality, controlled study designs.

Cognitive and neuroimaging markers for preclinical vascular cognitive impairment.

Detection of incipient cognitive impairment and dementia pathophysiology is critical to identify preclinical populations and target potentially disease modifying interventions towards them. There are currently concerted efforts for such detection for Alzheimer's disease (AD). By contrast, the examination of cognitive markers and their relationship to biomarkers for Vascular Cognitive Impairment (VCI) is far less established, despite VCI being highly prevalent and often concomitantly presenting with AD. Critically, vascular risk factors are currently associated with the most viable treatment options via pharmacological and non-pharmacological intervention, hence early identification of vascular factors have important implications for modifying dementia disease trajectories. The aim of this review is to examine the current evidence of cognitive marker correlates to VCI pathology. We begin by examining midlife risk factors that predict VCI. Next, discuss preclinical cognitive hallmarks of VCI informed by insights from neuropsychological assessment, network connectivity and ERP/EEG experimental findings. Finally, we discuss limitations of current cognitive assessments and the need for future cognitive test development to inform diagnostic assessment. As well as, intervention outcome measures for preclinical VCI. In turn, these tests will inform earlier detection of vascular changes and allow implementation of disease intervention approaches.

Impact of road network structure on dementia-related missing incidents: a spatial buffer approach.

Dementia-related missing incidents are a highly prevalent issue worldwide. Despite being associated with potentially life-threatening consequences, very little is still known about what environmental risk factors may potentially contribute to these missing incidents. The aim of this study was to conduct a retrospective, observational analysis using a large sample of police case records of missing individuals with dementia (n = 210). Due to the influence that road network structure has on our real world navigation, we aimed to explore the relationship between road intersection density, intersection complexity, and orientation entropy to the dementia-related missing incidents. For each missing incident location, the above three variables were computed at a 1 km radius buffer zone around these locations; these values were then compared to that of a set of random locations. The results showed that higher road intersection density, intersection complexity, and orientation entropy were all significantly associated with dementia-related missing incidents. Our results suggest that these properties of road network structure emerge as significant environmental risk factors for dementia-related missing incidents, informing future prospective studies as well as safeguarding guidelines.

Test-retest reliability of spatial navigation in adults at-risk of Alzheimer's disease.

The Virtual Supermarket Task (VST) and Sea Hero Quest detect high-genetic-risk Alzheimer`s disease (AD). We aimed to determine their test-retest reliability in a preclinical AD population. Over two time points, separated by an 18-month period, 59 cognitively healthy individuals underwent a neuropsychological and spatial navigation assessment. At baseline, participants were classified as low-genetic-risk of AD or high-genetic-risk of AD. We calculated two-way mixed effects intraclass correlation coefficients (ICC) for task parameters and used repeated measures ANOVAS to determine whether genetic risk or sex contributed to test-retest variability. The egocentric parameter of the VST measure showed the highest test-retest reliability (ICC = .72), followed by the SHQ distance travelled parameter (ICC = .50). Post hoc longitudinal analysis showed that boundary-based navigation predicts worsening episodic memory concerns in high-risk (F = 5.01, P = 0.03), but in not low-risk, AD candidates. The VST and the Sea Hero Quest produced parameters with acceptable test-retest reliability. Further research in larger sample sizes is desirable.

Path Integration Changes as a Cognitive Marker for Vascular Cognitive Impairment?-A Pilot Study.

Path integration spatial navigation processes are emerging as promising cognitive markers for prodromal and clinical Alzheimer's disease (AD). However, such path integration changes have been less explored in Vascular Cognitive Impairment (VCI), despite neurovascular change being a major contributing factor to dementia and potentially AD. In particular, the sensitivity and specificity of path integration impairments in VCI compared to AD is unclear. In the current pilot study, we explore path integration performance in early-stage AD and VCI patient groups and hypothesize that: (i) medial parietal mediated egocentric processes will be more affected in VCI; and (ii) medial temporal mediated allocentric processes will be more affected in AD. This cross-sectional study included early-stage VCI patients (n = 9), AD patients (n = 10) and healthy age-matched controls (n = 20). All participants underwent extensive neuropsychological testing, as well as spatial navigation testing. The spatial navigation tests included the virtual reality "Supermarket" task assessing egocentric (body-based) and allocentric (map-based) navigation as well as the "Clock Orientation" test assessing egocentric and path integration processes. Results showed that egocentric integration processes are only impaired in VCI, potentially distinguishing it from AD. However, in contrast to our prediction, allocentric integration was not more impaired in AD compared to VCI. These preliminary findings suggest limited specificity of allocentric integration deficits between VCI and AD. By contrast, egocentric path integration deficits emerge as more specific to VCI, potentially allowing for more specific diagnostic and treatment outcome measures for vascular impairment in dementia.

Functional connectivity between the entorhinal and posterior cingulate cortices underpins navigation discrepancies in at-risk Alzheimer's disease.

Navigation processes that are selectively mediated by functional activity in the entorhinal cortex may be a marker of preclinical Alzheimer's disease (AD). Here, we tested if a short path integration paradigm can detect the strongest genetic-risk phenotype of AD in large sample of apolipoprotein E (APOE)-genotyped individuals. We also examined the associations between APOE-mediated navigation process, subjective cognitive decline, and rest-stating network connectivity. Navigation discrepancies classified 77% the APOE-genotyped cohort into their respective low-risk ε3ε3 and high-risk ε3ε4 categories. When connectivity strength between entorhinal and the posterior cingulate cortices (also a functional correlate of strongest APOE-dependant behavioral characteristics) was considered, this classification accuracy increased to 85%. Our findings present a whole picture of at-genetic-risk AD, including select impairment in path integration, self-report cognitive decline, and altered network activity that is reminiscent of the pathological spread of preclinical AD disease. These findings may have important implications for the early detection of AD.

Geospatial Analysis of Environmental Risk Factors for Missing Dementia Patients.

BACKGROUND: Dementia-related missing incidents are highly prevalent but still poorly understood. This is particularly true for environmental/geospatial risk factors, which might contribute to these missing incidents. OBJECTIVE: The study aimed to conduct a retrospective, observational analysis on a large sample of missing dementia patient case records provided by the police (n = 210), covering dates from January 2014 to December 2017. In particular, we wanted to explore 1) whether there were any hotspot regions of missing incidents and 2) the relationship between outdoor landmark density and missing incidents. METHODS: Global spatial autocorrelation (Moran's I) was used to identify the potential hotspot regions for missing incidents. Meanwhile, spatial buffer and regression modelling were used to determine the relationship between outdoor landmark density and missing incidents. RESULTS: Our demographics measures replicated and extended previous studies of dementia-related missing incidents. Meanwhile, no hotspot regions for missing incidents were identified, while higher outdoor landmark density led to increased missing incidents. CONCLUSION: Our results highlight that missing incidents do not occur in isolated hotspots of regions but instead are endemic in patients regardless of location. Higher outdoor landmark density emerges as a significant geospatial factor for missing incidents in dementia, which crucially informs future safeguarding/intervention studies.

Dysconnectivity of the medio-dorsal thalamic nucleus in drug-naïve first episode schizophrenia: diagnosis-specific or trans-diagnostic effect?

Converging lines of evidence implicate the thalamocortical network in schizophrenia. In particular, the onset of the illness is associated with aberrant functional integration between the medio-dorsal thalamic nucleus (MDN) and widespread prefrontal, temporal and parietal cortical regions. Because the thalamus is also implicated in other psychiatric illnesses including post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), the diagnostic specificity of these alterations is unclear. Here, we determined whether aberrant functional integration between the MDN and the cortex is a specific feature of schizophrenia or a trans-diagnostic feature of psychiatric illness. Effective connectivity (EC) between the MDN and rest of the cortex was measured by applying psychophysiological interaction analysis to resting-state functional magnetic resonance imaging data of 50 patients with first episode schizophrenia (FES), 50 patients with MDD, 50 patients with PTSD and 122 healthy controls. All participants were medication-naïve. The only significant schizophrenia-specific effect was increased EC between the right MDN and the right pallidum (p < 0.05 corrected). In contrast, there were a number of significant trans-diagnostic alterations, with both right and left MDN displaying trans-diagnostic increased EC with several prefrontal and parietal regions bilaterally (p < 0.05 corrected). EC alterations between the MDN and the cortex are not specific to schizophrenia but are a trans-diagnostic feature of psychiatric disorders, consistent with emerging conceptualizations of mental illness based on a single general psychopathology factor. Therefore, dysconnectivity of the MDN could potentially be used to assess the presence of general psychopathology above and beyond traditional diagnostic boundaries.

Frontostriatal grey matter atrophy in amyotrophic lateral sclerosis A visual rating study.

Amyotrophic lateral sclerosis (ALS) is characterised by frontostriatal grey matter changes similar to those in frontotemporal dementia (FTD). However, these changes are usually detected at a group level, and simple visual magnetic resonance imaging (MRI) cortical atrophy scales may further elucidate frontostriatal changes in ALS. OBJECTIVE: To investigate whether frontostriatal changes are detectable using simple visual MRI atrophy rating scales applied at an individual patient level in ALS. METHODS: 21 ALS patients and 17 controls were recruited and underwent an MRI scan. Prefrontal cortex sub-regions of the medial orbitofrontal cortex (MOFC), lateral orbitofrontal cortex (LOFC) and anterior cingulate cortex (ACC), striatal sub-regions of the caudate nucleus (CN) and nucleus accumbens (NAcc) were rated using visual grey matter atrophy 5-point Likert scales. RESULTS: Significantly higher atrophy ratings in the bilateral MOFC only in ALS patients versus controls was observed (p<.05). Patients with greater MOFC atrophy had significantly higher atrophy of the CN (p<.05) and LOFC (p<.05). CONCLUSION: Use of simple visual atrophy rating scales on an individual level reliably detects frontostriatal deficits specific to ALS, showing MOFC atrophy differences with associated CN and LOFC atrophy. This is an applicable method that could be used to support clinical diagnosis and management.

A esclerose lateral amiotrófica (ELA) é caracterizada por alterações na substância cinzenta frontostriatal, semelhantes às da demência frontotemporal (DFT). No entanto, essas alterações geralmente são detectadas em nível de grupo, e as escalas simples de atrofia cortical por ressonância magnética visual (MRI) podem elucidar ainda mais as alterações frontostriatais na ELA. OBJETIVO: Investigar se as alterações frontostriatais são detectáveis usando escalas de classificação de atrofia MRI visuais simples aplicadas em um nível de paciente individual em ELA. MÉTODOS: 21 pacientes com ELA e 17 controles foram recrutados e submetidos a uma ressonância magnética. Sub-regiões do córtex pré-frontal do córtex orbitofrontal medial (MOFC), córtex orbitofrontal lateral (LOFC) e córtex cingulado anterior (ACC), sub-regiões estriadas do núcleo caudado (NC) e nucleus accumbens (NAcc) foram classificadas usando escalas de atrofia de substância cinzenta visuais de Likert de 5 pontos. RESULTADOS: Observações de atrofia significativamente maiores no MOFC bilateral em pacientes com ELA versus controles foram observadas apenas (p <0,05). Pacientes com maior atrofia do MOFC tiveram atrofia significativamente maior do CN (p <0,05) e LOFC (p <0,05). CONCLUSÃO: O uso de escalas de avaliação de atrofia visuais simples em um nível individual detecta de forma confiável déficits frontostriatais específicos para ELA, mostrando diferenças de atrofia MOFC com atrofia associada de CN e LOFC. Este é um método aplicável que pode ser usado para apoiar o diagnóstico e o gerenciamento clínico.

Frontostriatal grey matter atrophy in amyotrophic lateral sclerosis: a visual rating study / Atrofia da massa cinzenta frontostriatal na esclerose lateral amiotrófica: um estudo de avaliação visual antes da publicação

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is characterised by frontostriatal grey matter changes similar to those in frontotemporal dementia (FTD). However, these changes are usually detected at a group level, and simple visual magnetic resonance imaging (MRI) cortical atrophy scales may further elucidate frontostriatal changes in ALS. Objective: To investigate whether frontostriatal changes are detectable using simple visual MRI atrophy rating scales applied at an individual patient level in ALS. Methods: 21 ALS patients and 17 controls were recruited and underwent an MRI scan. Prefrontal cortex sub-regions of the medial orbitofrontal cortex (MOFC), lateral orbitofrontal cortex (LOFC) and anterior cingulate cortex (ACC), striatal sub-regions of the caudate nucleus (CN) and nucleus accumbens (NAcc) were rated using visual grey matter atrophy 5-point Likert scales. Results: Significantly higher atrophy ratings in the bilateral MOFC only in ALS patients versus controls was observed (p<.05). Patients with greater MOFC atrophy had significantly higher atrophy of the CN (p<.05) and LOFC (p<.05). Conclusion: Use of simple visual atrophy rating scales on an individual level reliably detects frontostriatal deficits specific to ALS, showing MOFC atrophy differences with associated CN and LOFC atrophy. This is an applicable method that could be used to support clinical diagnosis and management.

RESUMO: A esclerose lateral amiotrófica (ELA) é caracterizada por alterações na substância cinzenta frontostriatal, semelhantes às da demência frontotemporal (DFT). No entanto, essas alterações geralmente são detectadas em nível de grupo, e as escalas simples de atrofia cortical por ressonância magnética visual (MRI) podem elucidar ainda mais as alterações frontostriatais na ELA. Objetivo: Investigar se as alterações frontostriatais são detectáveis usando escalas de classificação de atrofia MRI visuais simples aplicadas em um nível de paciente individual em ELA. Métodos: 21 pacientes com ELA e 17 controles foram recrutados e submetidos a uma ressonância magnética. Sub-regiões do córtex pré-frontal do córtex orbitofrontal medial (MOFC), córtex orbitofrontal lateral (LOFC) e córtex cingulado anterior (ACC), sub-regiões estriadas do núcleo caudado (NC) e nucleus accumbens (NAcc) foram classificadas usando escalas de atrofia de substância cinzenta visuais de Likert de 5 pontos. Resultados: Observações de atrofia significativamente maiores no MOFC bilateral em pacientes com ELA versus controles foram observadas apenas (p <0,05). Pacientes com maior atrofia do MOFC tiveram atrofia significativamente maior do CN (p <0,05) e LOFC (p <0,05). Conclusão: O uso de escalas de avaliação de atrofia visuais simples em um nível individual detecta de forma confiável déficits frontostriatais específicos para ELA, mostrando diferenças de atrofia MOFC com atrofia associada de CN e LOFC. Este é um método aplicável que pode ser usado para apoiar o diagnóstico e o gerenciamento clínico.