Reduced care burden and improved quality of life in African American family caregivers: Positive impact of personalized assistive technology.

BACKGROUND: African Americans living with dementia are considered less likely to seek formal institutionalized elder care and more likely to be managed in the home by family-member caregivers. Assistive technologies (the use of smart visual devices like tablets and phones) can be used effectively to guide memory-impaired individuals with a sequence of pictures showing steps to complete activities of daily living, e.g., bathing, toileting, dressing. Assistive technology so far has not been generally embraced in African American communities. OBJECTIVES: Determine, if African American family caregivers, given the opportunity, would embrace the use of assistive technology and if they would perceive its use beneficial. METHODS: We assessed a group of eight family caregivers' overall care-burden scores, and their user-satisfaction scores after using assistive technology for three months. RESULTS: We found significant reduction in caregiver burden, positive changes in behavior and emotion scores, and high ratings on user satisfaction. CONCLUSIONS: The findings reported here comprise the first systematic study of the use of assistive technology by caregivers in an underserved population. They set the stage for exploring meaningful strategies and variables that will better engage underserved populations to take advantage of assistive technologies available in healthcare.

Personalized Visual Mapping Assistive Technology to Improve Functional Ability in Persons With Dementia: Feasibility Cohort Study.

BACKGROUND: Mobile health (mHealth) apps using novel visual mapping assistive technology can allow users to develop personalized maps that aid people living with cognitive impairment in the recall of steps needed to independently complete activities of daily living (ADLs), such as bathing, toileting, and dressing. OBJECTIVE: This study aims to determine the feasibility and preliminary impact of an mHealth assistive technology app providing guidance to aid individuals living with cognitive impairment in the recall of steps to independently complete ADLs. METHODS: A total of 14 Veterans (mean age 65 SD 9.5 years; 14/14, 100% male; 10/14, 71.4% Black) and 8 non-Veterans (mean age 78, SD 10.3 years; 5/8, 62.5% male; 8/8, 100% Black) were recruited and enrolled from the Department of Veterans Affairs (VA) and non-VA cognitive care clinics. A visual mapping software program, MapHabit, was used to generate a series of personalized visual map templates focused on ADLs created within the MapHabit app. The visual maps were accessed through a tablet device. A 19-item exit questionnaire was administered to the participants to assess perceived improvement in their functional ability after using the MapHabit system for 3 months. RESULTS: A total of 13 (93%) VA clinic participants and 8 (100%) non-VA clinic participants completed the 3-month study. Baseline cognitive testing indicated impaired to significantly impaired cognitive function. After 3 months of using the MapHabit system, VA clinic participants reported perceived improvement in social engagement (P=.01) and performance of ADLs (P=.05) compared to the baseline, whereas non-VA clinic participants reported improvements in the performance of ADLs (P=.02), mood (P=.04), social engagement (P=.02), and memory (P=.02). All study participants reported they would recommend the MapHabit system to a colleague, and 85% (11/14) of VA and 100% (8/8) of non-VA clinic participants reported a willingness to participate in a future study. CONCLUSIONS: Older VA and non-VA clinic participants with cognitive impairment were willing to use an mHealth app to assist with the completion of ADLs, and they reported positive preliminary effects. A larger study is warranted to assess the efficacy in the setting of a randomized controlled trial.

Device-Embedded Cameras for Eye Tracking-Based Cognitive Assessment: Implications for Teleneuropsychology.

Introduction:Widespread screening for cognitive decline is an important challenge to address as the aging population grows, but there is currently a shortage of clinical infrastructure to meet the demand for in-person evaluation. Remotely delivered assessments that utilize eye-tracking data from webcams, such as visual paired comparison (VPC) tasks, could increase access to remote, asynchronous neuropsychological screening for cognitive decline but further validation against clinical-grade eye trackers is required.Methods:To demonstrate equivalence between a novel automated scoring system for eye-tracking metrics acquired through a laptop-embedded camera and a gold-standard eye tracker, we analyzed VPC data from 18 subjects aged 50+ with normal cognitive function across three visits. The eye tracker data were scored by the manufacturer's software, and the webcam data were scored by a novel algorithm.Results:Automated scoring of webcam-based VPC data revealed strong correlations with the clinical-grade eye-tracking camera. Correlation of mean VPC performance across all time points was robust: r = 0.95 (T1 r = 0.97; T2 r = 0.88; T3 r = 0.97; p's < 0.001). Correlation of per-trial performance across time points was also robust: r = 0.88 (T1 r = 0.85; T2 r = 0.89; T3 r = 0.92; p's < 0.001). Mean differences between performance data acquired by each device were 0.00.Conclusion:These results suggest that device-embedded cameras are a valid and scalable alternative to traditional laboratory-based equipment for gaze-based tasks measuring cognitive function. The validation of this technique represents an important technical advance for the field of teleneuropsychology.

Assistive technology: Visual mapping combined with mobile software can enhance quality of life and ability to carry out activities of daily living in individuals with impaired memory.

BACKGROUND: There is growing evidence that assistive digital technology can enhance quality of life (QOL) for individuals with various forms of cognitive impairment, including dementia. OBJECTIVE: Assess whether the use of a visual mapping software program to manage activities of daily living would have a positive impact on QOL scores and on cognitive scores in a group of dementia residents in an adult living community. METHODS: We compared quality-of-life scores and cognitive function scores before and after using the assistive technology for three months. RESULTS: 1. QOL scores significantly improved in the memory impaired residents, as measured by a self-report questionnaire. 2. Caregivers also reported significantly improved QOL scores in the residents, and the caregivers reported more improved scores than the residents did. 3. Net Promoter Scores for residents and caregivers showed that using visual maps was highly satisfying; they would continue using this technology. 4. Memory-impaired residents showed significantly improved scores in cognitive areas reflecting improved ability to focus and pay attention. CONCLUSIONS: In addition to the positive findings in QOL and cognition, assistive technologies applied to dementia care are easy to access, easy to use, have little risk of side effects, and are relatively low in cost.

Device-Embedded Cameras for Eye Tracking-Based Cognitive Assessment: Validation With Paper-Pencil and Computerized Cognitive Composites.

BACKGROUND: As eye tracking-based assessment of cognition becomes more widely used in older adults, particularly those at risk for dementia, reliable and scalable methods to collect high-quality data are required. Eye tracking-based cognitive tests that utilize device-embedded cameras have the potential to reach large numbers of people as a screening tool for preclinical cognitive decline. However, to fully validate this approach, more empirical evidence about the comparability of eyetracking-based paradigms to existing cognitive batteries is needed. OBJECTIVE: Using a population of clinically normal older adults, we examined the relationship between a 30-minute Visual Paired Comparison (VPC) recognition memory task and cognitive composite indices sensitive to a subtle decline in domains associated with Alzheimer disease. Additionally, the scoring accuracy between software used with a commercial grade eye tracking camera at 60 frames per second (FPS) and a manually scored procedure used with a laptop-embedded web camera (3 FPS) on the VPC task was compared, as well as the relationship between VPC task performance and domain-specific cognitive function. METHODS: A group of 49 clinically normal older adults completed a 30-min VPC recognition memory task with simultaneous recording of eye movements by a commercial-grade eye-tracking camera and a laptop-embedded camera. Relationships between webcam VPC performance and the Preclinical Alzheimer Cognitive Composite (PACC) and National Institutes of Health Toolbox Cognitive Battery (NIHTB-CB) were examined. Inter-rater reliability for manually scored tests was analyzed using Krippendorff's kappa formula, and we used Spearman's Rho correlations to investigate the relationship between VPC performance scores with both cameras. We also examined the relationship between VPC performance with the device-embedded camera and domain-specific cognitive performance. RESULTS: Modest relationships were seen between mean VPC novelty preference and the PACC (r=.39, P=.007) and NIHTB-CB (r=.35, P=.03) composite scores, and additional individual neurocognitive task scores including letter fluency (r=.33, P=.02), category fluency (r=.36, P=.01), and Trail Making Test A (-.40, P=.006). Robust relationships were observed between the 60 FPS eye tracker and 3 FPS webcam on both trial-level VPC novelty preference (r=.82, P<.001) and overall mean VPC novelty preference (r=.92 P<.001). Inter-rater agreement of manually scored web camera data was high (kappa=.84). CONCLUSIONS: In a sample of clinically normal older adults, performance on a 30-minute VPC task correlated modestly with computerized and paper-pencil based cognitive composites that serve as preclinical Alzheimer disease cognitive indices. The strength of these relationships did not differ between camera devices. We suggest that using a device-embedded camera is a reliable and valid way to assess performance on VPC tasks accurately and that these tasks correlate with existing cognitive composites.

Web Camera Based Eye Tracking to Assess Visual Memory on a Visual Paired Comparison Task.

Background: Web cameras are increasingly part of the standard hardware of most smart devices. Eye movements can often provide a noninvasive "window on the brain," and the recording of eye movements using web cameras is a burgeoning area of research. Objective: This study investigated a novel methodology for administering a visual paired comparison (VPC) decisional task using a web camera.To further assess this method, we examined the correlation between a standard eye-tracking camera automated scoring procedure [obtaining images at 60 frames per second (FPS)] and a manually scored procedure using a built-in laptop web camera (obtaining images at 3 FPS). Methods: This was an observational study of 54 clinically normal older adults.Subjects completed three in-clinic visits with simultaneous recording of eye movements on a VPC decision task by a standard eye tracker camera and a built-in laptop-based web camera. Inter-rater reliability was analyzed using Siegel and Castellan's kappa formula. Pearson correlations were used to investigate the correlation between VPC performance using a standard eye tracker camera and a built-in web camera. Results: Strong associations were observed on VPC mean novelty preference score between the 60 FPS eye tracker and 3 FPS built-in web camera at each of the three visits (r = 0.88-0.92). Inter-rater agreement of web camera scoring at each time point was high (κ = 0.81-0.88). There were strong relationships on VPC mean novelty preference score between 10, 5, and 3 FPS training sets (r = 0.88-0.94). Significantly fewer data quality issues were encountered using the built-in web camera. Conclusions: Human scoring of a VPC decisional task using a built-in laptop web camera correlated strongly with automated scoring of the same task using a standard high frame rate eye tracker camera.While this method is not suitable for eye tracking paradigms requiring the collection and analysis of fine-grained metrics, such as fixation points, built-in web cameras are a standard feature of most smart devices (e.g., laptops, tablets, smart phones) and can be effectively employed to track eye movements on decisional tasks with high accuracy and minimal cost.

Progressive cognitive deficit, motor impairment and striatal pathology in a transgenic Huntington disease monkey model from infancy to adulthood.

One of the roadblocks to developing effective therapeutics for Huntington disease (HD) is the lack of animal models that develop progressive clinical traits comparable to those seen in patients. Here we report a longitudinal study that encompasses cognitive and motor assessment, and neuroimaging of a group of transgenic HD and control monkeys from infancy to adulthood. Along with progressive cognitive and motor impairment, neuroimaging revealed a progressive reduction in striatal volume. Magnetic resonance spectroscopy at 48 months of age revealed a decrease of N-acetylaspartate (NAA), further suggesting neuronal damage/loss in the striatum. Postmortem neuropathological analyses revealed significant neuronal loss in the striatum. Our results indicate that HD monkeys share similar disease patterns with HD patients, making them potentially suitable as a preclinical HD animal model.

Temporal evolution of ischemic lesions in nonhuman primates: a diffusion and perfusion MRI study.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) and perfusion MRI were used to examine the spatiotemporal evolution of stroke lesions in adult macaques with ischemic occlusion. METHODS: Permanent MCA occlusion was induced with silk sutures through an interventional approach via the femoral artery in adult rhesus monkeys (n = 8, 10-21 years old). The stroke lesions were examined with high-resolution DWI and perfusion MRI, and T2-weighted imaging (T2W) on a clinical 3T scanner at 1-6, 48, and 96 hours post occlusion and validated with H&E staining. RESULTS: The stroke infarct evolved via a natural logarithmic pattern with the mean infarct growth rate = 1.38 ± 1.32 ml per logarithmic time scale (hours) (n = 7) in the hyperacute phase (1-6 hours). The mean infarct volume after 6 hours post occlusion was 3.6±2.8 ml (n = 7, by DWI) and increased to 3.9±2.9 ml (n = 5, by T2W) after 48 hours, and to 4.7±2.2ml (n = 3, by T2W) after 96 hours post occlusion. The infarct volumes predicted by the natural logarithmic function were correlated significantly with the T2W-derived lesion volumes (n = 5, r = 0.92, p = 0.01) at 48 hours post occlusion. The final infarct volumes derived from T2W were correlated significantly with those from H&E staining (r = 0.999, p < 0.0001, n = 4). In addition, the diffusion-perfusion mismatch was visible generally at 6 hours but nearly diminished at 48 hours post occlusion. CONCLUSION: The infarct evolution follows a natural logarithmic pattern in the hyperacute phase of stroke. The logarithmic pattern of evolution could last up to 48 hours after stroke onset and may be used to predict the infarct volume growth during the acute phase of ischemic stroke. The nonhuman primate model, MRI protocols, and post data processing strategy may provide an excellent platform for characterizing the evolution of acute stroke lesion in mechanistic studies and therapeutic interventions of stroke disease.

A fast multiparameter MRI approach for acute stroke assessment on a 3T clinical scanner: preliminary results in a non-human primate model with transient ischemic occlusion.

Many MRI parameters have been explored and demonstrated the capability or potential to evaluate acute stroke injury, providing anatomical, microstructural, functional, or neurochemical information for diagnostic purposes and therapeutic development. However, the application of multiparameter MRI approach is hindered in clinic due to the very limited time window after stroke insult. Parallel imaging technique can accelerate MRI data acquisition dramatically and has been incorporated in modern clinical scanners and increasingly applied for various diagnostic purposes. In the present study, a fast multiparameter MRI approach including structural T1-weighted imaging (T1W), T2-weighted imaging (T2W), diffusion tensor imaging (DTI), T2-mapping, proton magnetic resonance spectroscopy, cerebral blood flow (CBF), and magnetization transfer (MT) imaging, was implemented and optimized for assessing acute stroke injury on a 3T clinical scanner. A macaque model of transient ischemic stroke induced by a minimal interventional approach was utilized for evaluating the multiparameter MRI approach. The preliminary results indicate the surgical procedure successfully induced ischemic occlusion in the cortex and/or subcortex in adult macaque monkeys (n=4). Application of parallel imaging technique substantially reduced the scanning duration of most MRI data acquisitions, allowing for fast and repeated evaluation of acute stroke injury. Hence, the use of the multiparameter MRI approach with up to five quantitative measures can provide significant advantages in preclinical or clinical studies of stroke disease.

A two years longitudinal study of a transgenic Huntington disease monkey.

BACKGROUND: A two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington's disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human polyubiquitin C promoter was used together with four age-matched wild-type control monkeys. This is the first study on a primate model of human HD based on longitudinal clinical measurements. RESULTS: Changes in striatal and hippocampal volumes in rHD1 were observed with progressive impairment in motor functions and cognitive decline, including deficits in learning stimulus-reward associations, recognition memory and spatial memory. The results demonstrate a progressive cognitive decline and morphometric changes in the striatum and hippocampus in a transgenic HD monkey. CONCLUSIONS: This is the first study on a primate model of human HD based on longitudinal clinical measurements. While this study is based a single HD monkey, an ongoing longitudinal study with additional HD monkeys will be important for the confirmation of our findings. A nonhuman primate model of HD could complement other animal models of HD to better understand the pathogenesis of HD and future development of diagnostics and therapeutics through longitudinal assessment.

A behavioral task predicts conversion to mild cognitive impairment and Alzheimer's disease.

BACKGROUND/RATIONALE: Currently, we cannot reliably differentiate individuals at risk of cognitive decline, for example, mild cognitive impairment (MCI), Alzheimer's disease (AD), from those individuals who are not at risk. METHODS: A total of 32 participants with MCI and 60 control (CON) participants were tested on an innovative, sensitive behavioral assay, the visual paired comparison (VPC) task using infrared eye tracking. The participants were followed for 3 years after testing. RESULTS: Scores on the VPC task predicted, up to 3 years prior to a change in clinical diagnosis, those patients with MCI who would and who would not progress to AD and CON participants who would and would not progress to MCI. CONCLUSIONS: The present findings show that the VPC task can predict impending cognitive decline. To our knowledge, this is the first behavioral task that can identify CON participants who will develop MCI or patients with MCI who will develop AD within the next few years.

Detecting cognitive impairment by eye movement analysis using automatic classification algorithms.

The Visual Paired Comparison (VPC) task is a recognition memory test that has shown promise for the detection of memory impairments associated with mild cognitive impairment (MCI). Because patients with MCI often progress to Alzheimer's Disease (AD), the VPC may be useful in predicting the onset of AD. VPC uses noninvasive eye tracking to identify how subjects view novel and repeated visual stimuli. Healthy control subjects demonstrate memory for the repeated stimuli by spending more time looking at the novel images, i.e., novelty preference. Here, we report an application of machine learning methods from computer science to improve the accuracy of detecting MCI by modeling eye movement characteristics such as fixations, saccades, and re-fixations during the VPC task. These characteristics are represented as features provided to automatic classification algorithms such as Support Vector Machines (SVMs). Using the SVM classification algorithm, in tandem with modeling the patterns of fixations, saccade orientation, and regression patterns, our algorithm was able to automatically distinguish age-matched normal control subjects from MCI subjects with 87% accuracy, 97% sensitivity and 77% specificity, compared to the best available classification performance of 67% accuracy, 60% sensitivity, and 73% specificity when using only the novelty preference information. These results demonstrate the effectiveness of applying machine-learning techniques to the detection of MCI, and suggest a promising approach for detection of cognitive impairments associated with other disorders.

Eye tracking during a visual paired comparison task as a predictor of early dementia.

The authors present findings from a behavioral task (visual paired comparison) using infrared eye-tracking that could potentially be useful in predicting the onset of Alzheimer's disease. Delay intervals of 2 seconds and 2 minutes were used between the initial viewing of a picture and when the picture was displayed alongside a novel picture. Eye-tracking revealed that at the 2-second delay, 6 patients with mild cognitive impairment, 15 matched control participants (normal control), and 4 neurological control participants with Parkinson's disease performed comparably, viewing the novel picture greater than 71% of the time. When the delay increased to 2 minutes, patients with mild cognitive impairment viewed the novel picture only 53% of the time (P < .05), while control participants and participants with Parkinson's disease remained above 70%. These findings demonstrate the usefulness of this task for assessing normal as well as impaired memory function.

Towards a transgenic model of Huntington's disease in a non-human primate.

Non-human primates are valuable for modelling human disorders and for developing therapeutic strategies; however, little work has been reported in establishing transgenic non-human primate models of human diseases. Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor impairment, cognitive deterioration and psychiatric disturbances followed by death within 10-15 years of the onset of the symptoms. HD is caused by the expansion of cytosine-adenine-guanine (CAG, translated into glutamine) trinucleotide repeats in the first exon of the human huntingtin (HTT) gene. Mutant HTT with expanded polyglutamine (polyQ) is widely expressed in the brain and peripheral tissues, but causes selective neurodegeneration that is most prominent in the striatum and cortex of the brain. Although rodent models of HD have been developed, these models do not satisfactorily parallel the brain changes and behavioural features observed in HD patients. Because of the close physiological, neurological and genetic similarities between humans and higher primates, monkeys can serve as very useful models for understanding human physiology and diseases. Here we report our progress in developing a transgenic model of HD in a rhesus macaque that expresses polyglutamine-expanded HTT. Hallmark features of HD, including nuclear inclusions and neuropil aggregates, were observed in the brains of the HD transgenic monkeys. Additionally, the transgenic monkeys showed important clinical features of HD, including dystonia and chorea. A transgenic HD monkey model may open the way to understanding the underlying biology of HD better, and to the development of potential therapies. Moreover, our data suggest that it will be feasible to generate valuable non-human primate models of HD and possibly other human genetic diseases.

Neural correlates of knowledge: stable representation of stimulus associations across variations in behavioral performance.

Behavioral responses to a sensory stimulus are often guided by associative memories. These associations remain intact even when other factors determine behavior. The substrates of associative memory should therefore be identifiable by neuronal responses that are independent of behavioral choices. We tested this hypothesis using a paired-associates task in which monkeys learned arbitrary associations between pairs of visual stimuli. We examined the activity of neurons in inferior temporal cortex as the animals prepared to choose a remembered stimulus from a visual display. The activity of some neurons (22%) depended on the monkey's behavioral choice; but for a novel class of neurons (54%), activity reflected the stimulus that the monkey was instructed to choose, regardless of the behavioral response. These neurons appear to represent memorized stimulus associations that are stable across variations in behavioral performance. In addition, many neurons (74%) were modulated by the spatial arrangement of the stimuli in the display.

Selective neurotoxic amygdala lesions in monkeys disrupt reactivity to food and object stimuli and have limited effects on memory.

Monkeys with bilateral neurotoxic amygdala lesions and normal monkeys were administered tests of emotional reactivity, recognition memory, and reward association memory. There were 3 main findings. First, monkeys with amygdala lesions performed differently than normal monkeys on initial administrations of the emotional reactivity tests and on retests that were given 21-23 months after surgery. Second, they performed like normal monkeys on tests of recognition memory. Third, they were initially impaired on a test of reward association memory, but they were not impaired on a retest that was given 16 months after surgery. These findings underscore the role of the amygdala in aspects of emotional reactivity and reward association memory, but not in recognition memory. In addition, at least some of the behavioral effects of amygdala damage can be long lasting.