Cut-off scores for mild and moderate dementia on the Addenbrooke's Cognitive Examination-III and the Mini-Addenbrooke's Cognitive Examination compared with the Mini-Mental State Examination.

AIMS AND METHOD: We aimed to establish cut-off scores to stage dementia on the Addenbrooke's Cognitive Examination-III (ACE-III) and the Mini-Addenbrooke's Cognitive Examination (M-ACE) compared with scores traditionally used with the Mini-Mental State Examination (MMSE). Our cross-sectional study recruited 80 patients and carers from secondary care services in the UK. RESULTS: A score ≤76 on the ACE-III and ≤19 on the M-ACE correlated well with MMSE cut-offs for mild dementia, with a good fit on the receiver operating characteristic analysis for both the ACE-III and M-ACE. The cut-off for moderate dementia had lower sensitivity and specificity. There were low to moderate correlations between the cognitive scales and scales for everyday functioning and behaviour. CLINICAL IMPLICATIONS: Our findings allow an objective interpretation of scores on the ACE-III and the M-ACE relative to the MMSE, which may be helpful for clinical services and research trials.

Spatial orientation - a stable marker for vascular cognitive impairment?

Vascular cognitive impairment (VCI) is the second most prevalent form of dementia, but little is known about the early cognitive and neuroimaging markers. Spatial navigation deficits are an emerging marker for Alzheimer's disease (AD), yet less is known about spatial orientation deficits sensitive to VCI. This case report follows up on the first VCI patient identified to have an egocentric orientation deficit. The study aimed to examine the patient's spatial deficits three years on and gain insights from the addition of the patient's MRI brain scan. A battery of spatial navigation tasks were administered following neuropsychological assessment. Results continue to show spatial orientation deficits. Critically, these changes appear stable and are sensitive to novel spatial tests. Whereas conventional screening tools demonstrate patient recovery. MRI DTI analysis indicates a non-significant trend towards loss of structural integrity to the posterior tracts of the longitudinal superior fasciculus (SLF), while the medial temporal lobe, typically implicated in spatial navigation, is unaffected. This finding potentially reflects reduced network connectivity in posterior to anterior white matter tracts co-existing with spatial orientation deficits. Findings have clinical utility and show spatial orientation as a potential sensitive cognitive marker for VCI.

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.

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.

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.