No Untoward Effect of Long-Term Ketoconazole Administration on Electrocardiographic QT Interval in Patients with Cushing's Disease.

Ketoconazole is listed among drugs that prolong QT interval and may increase the risk of torsade de pointes, a severe ventricular arrhythmia. This compound has recently been approved for treatment of Cushing's syndrome, a severe endocrine disorder. These patients harbour several risk factors for prolonged QT interval, for example hypokalaemia and left ventricular hypertrophy, but no study has evaluated whether administration of ketoconazole affects their QT interval. The aim of this study was to assess the QT interval in patients with Cushing's disease during long-term administration of ketoconazole. Electrocardiograms from 15 patients with Cushing's disease (12 women, 3 men, age: 37.8 ± 2.66 years) on ketoconazole treatment (100 mg-800 mg qd) for 1 month to 12 years were reviewed retrospectively. QT interval was measured and corrected for heart rate (QTc). Measurements before and during ketoconazole treatment were compared and any abnormal QTc value recorded. Concurrent medical therapies were also documented. On average, QTc was superimposable before and during ketoconazole treatment (393.2 ± 7.17 versus 403.3 ± 6.05 msec. in women; 424.3 ± 23.54 versus 398.0 ± 14.93 msec. in men, N.S.). QTc normalized on ketoconazole in one man with prolonged QTc prior to treatment; no abnormal QTc was observed in any other patient during the entire observation period, even during concurrent treatment with other QT-prolonging drugs. In conclusion, long-term ketoconazole administration does not appear to be associated with significant prolongation of QT interval in patients with Cushing's disease. ECG monitoring can follow recommendations drawn for other low-risk QT-prolonging drugs with attention to specific risk factors, for example hypokalaemia and drug interactions

“Positive Bike” – An immersive biking experience for combined physical and cognitive training of elderly patients

Previous evidence shows that combined cognitive and physical exercises (dual-task intervention, (I-DT)) potentiates cognitive performance more than either type of single training alone (Lauenroth et al., 2015). Here, we describe the rationale, the design and the implementation of the “Positive Bike”, a fully-immersive virtual reality biking experience for implementing I-DT training protocols in older patients. The system consists of a cycle-ergometer positioned within a Cave Automatic Virtual Environment (CAVE). The system also features a cloud-based platform which allows the therapist to configure the exercise parameters (i.e, duration and load). Using the Positive Bike, the patient can take a virtual ride by physically pedalling at variable paces within a simulated scenario (i.e., a park). During the virtual ride, the patient can be presented with different interactive cognitive exercises (attentional, memory etc). In one of such exercises, for example, the patient has to recognize different animals appearing on the route sides and press a button if such animal has a name beginning with a specific letter. Potential applications of Positive Bike in geriatric wellness and rehabilitation are discussed

Building Embodied Spaces for Spatial Memory Neurorehabilitation with Virtual Reality in Normal and Pathological Aging

Along with deficits in spatial cognition, a decline in body-related information is observed in aging and is thought to contribute to impairments in navigation, memory, and space perception. According to the embodied cognition theories, bodily and environmental information play a crucial role in defining cognitive representations. Thanks to the possibility to involve body-related information, manipulate environmental stimuli, and add multisensory cues, virtual reality is one of the best candidates for spatial memory rehabilitation in aging for its embodied potential. However, current virtual neurorehabilitation solutions for aging and neurodegenerative diseases are in their infancy. Here, we discuss three concepts that could be used to improve embodied representations of the space with virtual reality. The virtual bodily representation is the combination of idiothetic information involved during virtual navigation thanks to input/output devices; the spatial affordances are environmental or symbolic elements used by the individual to act in the virtual environment; finally, the virtual enactment effect is the enhancement on spatial memory provided by actively (cognitively and/or bodily) interacting with the virtual space and its elements. Theoretical and empirical findings will be presented to propose innovative rehabilitative solutions in aging for spatial memory and navigation

The reference site collaborative network of the european innovation partnership on active and healthy ageing

Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, and the development of sustainable economic growth and the creation of jobs

ObReco-2: Two-step validation of a tool to assess memory deficits using 360° videos

Traditional neuropsychological evaluations are usually carried out using psychometric paper and pencil tests. Nevertheless, there is a continuous discussion concerning their efficacy to capture life-like abilities. The introduction of new technologies, such as Virtual Reality (VR) and 360° spherical photos and videos, has improved the ecological validity of the neuropsychological assessment. The possibility of simulating realistic environments and situations allows clinicians to evaluate patients in realistic activities. Moreover, 360° photos and videos seem to provide higher levels of graphical realism and technical user-friendliness compared to standard VR, regardless of their limitations in terms of interactivity. We developed a novel 360° tool, ObReco-2 (Object Recognition version 2), for the assessment of visual memory which simulates a daily situation in a virtual house. More precisely, patients are asked to memorize some objects that need to be moved for a relocation. After this phase, they are asked to recall them after 15 min and later to recognize them in the same environment. Here we present a first study about the usability of ObReco-2, and a second one exploring its clinical efficacy and updated usability data. We focused on Free Recall and Recognition scores, comparing the performances obtained by the participants in the standard and the 360° test. The preliminary results support the use of 360° technology for enhancing the ecological value of standard memory assessment tests

Bodily and Visual-Cognitive Navigation Aids to Enhance Spatial Recall in Mild Cognitive Impairment

Background: Individuals with mild cognitive impairment (MCI) syndrome often report navigation difficulties, accompanied by impairments in egocentric and allocentric spatial memory. However, studies have shown that both bodily (e.g., motor commands, proprioception, vestibular information) and visual-cognitive (e.g., maps, directional arrows, attentional markers) cues can support spatial memory in MCI. Objective: We aimed to assess navigation cues for innovative spatial training in aging. Methods: Fifteen MCI patients were recruited for this study. Their egocentric and allocentric memory recall performances were tested through a navigation task with five different virtual reality (VR) assistive encoding navigation procedures (bodily, vision only, interactive allocentric map, reduced executive load, free navigation without cues). Bodily condition consisted of an immersive VR setup to engage self-motion cues, vision only condition consisted of passive navigation without interaction, in the interactive allocentric map condition patients could use a bird-view map, in the reduced executive load condition directional cues and attentional markers were employed, and during free navigation no aid was implemented. Results: Bodily condition improved spatial memory compared to vision only and free navigation without cues. In addition, the interactive allocentric map was superior to the free navigation without cues. Surprisingly, the reduced executive load was comparable to vison only condition. Moreover, a detrimental impact of free navigation was observed on allocentric memory across testing trials. Conclusions: These findings challenge the notion of an amodal representation of space in aging, suggesting that spatial maps can be influenced by the modality in which the environment was originally encoded

Prognostic relevance of gait-related cognitive functions for dementia conversion in amnestic mild cognitive impairment

BackgroundIncreasing research suggests that gait abnormalities can be a risk factor for Alzheimer's Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up.MethodsFour hundred two individuals with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests.ResultsWhile controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abnormal gait (HR = 1.7), MMSE (HR = 1.09), and DSST (HR = 1.03) covariates showed a higher impact on AD dementia conversion.ConclusionsThe importance of the link between gait and related cognitive functions in terms of diagnosis, prognosis, and rehabilitation in aMCI is critical. We showed that in aMCI gait abnormalities lead to executive functions/attention deterioration and conversion to AD dementia