Assessing the newly proposed MRI criteria for diagnosing sporadic creutzfeldt-jakob disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a frequent differential diagnostic consideration in patients with rapidly progressive dementia (RPD). Fortunately, in the last 2 decades there has been substantial cumulative improvements in sCJD biomarkers, particularly those based on imaging and cerebrospinal fluid (CSF) interrogation. Brain MRI is a very frequently employed investigation in patients with RPD, often utilized quite early in the evaluation and thereby offering a potentially key role in prompting initial concerns for sCJD. Extant conventional MRI criteria for sCJD diagnosis are relatively stringent, requiring fluid attenuated inversion recovery (FLAIR) or diffusion weighted imaging (DWI) high signal changes in 2 or more cortical regions (excluding frontal) or in both the caudate and putamen. Challenging these conventional criteria, a recent publication described improved sensitivity and unchanged specificity if MRI criteria were arguably less rigorous, requiring DWI high signal changes in only 1 or more of 7 discrete brain regions: frontal, parietal, occipital or temporal cortices, as well as the caudate, putamen or thalamus. The aim of the current study was to test the diagnostic performance of this proposed change in MRI criteria in the Australian context and compare it with conventional criteria, as well as 2 other stringent sets of criteria, predicting that a similar improved sensitivity with unchanged specificity would be observed when the proposed criteria were utilized. Sixty-five definite sCJD cases were compared with 63 age- and sex-matched controls. Radiological review of all MRIs applying the different sets of MRI criteria was undertaken by a blinded neuroradiologist, very experienced in CJD interpretation, with independent assessment of 71 MRIs performed by a second blinded neuroradiologist less experienced in sCJD imaging findings. Our study found the sensitivity of the recently proposed MRI criteria (92.3%) to be comparable to that originally reported (90-95%) and also equivalent to the conventional MRI diagnostic criteria (92.3%), while the specificities were also quite similar between the conventional MRI criteria (87.3%) and proposed criteria (85.7%), with the latter lower than previously reported. Negative predictive values and positive predictive values were also very similar between the conventional and proposed MRI criteria. Other MRI criteria assessed were associated with unacceptably low sensitivity for clinical use. Inter-rater reliability as assessed by intra-class correlation coefficients (ICC) revealed moderate reliability for the conventional and proposed MRI criteria, modestly better in the former and when the frontal lobe was retained versus excluded in comparisons.

Optimizing exoskeleton assistance to improve walking speed and energy economy for older adults.

BACKGROUND: Walking speed and energy economy tend to decline with age. Lower-limb exoskeletons have demonstrated potential to improve either measure, but primarily in studies conducted on healthy younger adults. Promising techniques like optimization of exoskeleton assistance have yet to be tested with older populations, while speed and energy consumption have yet to be simultaneously optimized for any population. METHODS: We investigated the effectiveness of human-in-the-loop optimization of ankle exoskeletons with older adults. Ten healthy adults > 65 years of age (5 females; mean age: 72 ± 3 yrs) participated in approximately 240 min of training and optimization with tethered ankle exoskeletons on a self-paced treadmill. Multi-objective human-in-the-loop optimization was used to identify assistive ankle plantarflexion torque patterns that simultaneously improved self-selected walking speed and metabolic rate. The effects of optimized exoskeleton assistance were evaluated in separate trials. RESULTS: Optimized exoskeleton assistance improved walking performance for older adults. Both objectives were simultaneously improved; self-selected walking speed increased by 8% (0.10 m/s; p = 0.001) and metabolic rate decreased by 19% (p = 0.007), resulting in a 25% decrease in energetic cost of transport (p = 8e-4) compared to walking with exoskeletons applying zero torque. Compared to younger participants in studies optimizing a single objective, our participants required lower exoskeleton torques, experienced smaller improvements in energy use, and required more time for motor adaptation. CONCLUSIONS: Our results confirm that exoskeleton assistance can improve walking performance for older adults and show that multiple objectives can be simultaneously addressed through human-in-the-loop optimization.

Elastic energy-recycling actuators for efficient robots.

Electric motors are widely used in robots but waste energy in many applications. We introduce an elastic energy-recycling actuator that maintains the versatility of motors while improving energy efficiency in cyclic tasks. The actuator comprises a motor in parallel with an array of springs that can be individually engaged and disengaged, while retaining stored energy, by pairs of low-power electroadhesive clutches. We developed a prototype actuator and tested it in five repetitive tasks with features common in robotic applications but difficult to perform efficiently. The actuator reduced power consumption by at least 50% in all cases and by 97% in the best case. Elastic energy recovery, controlled by low-power clutches, can improve the efficiency of mobile robots, assistive devices, and other engineered systems.

Lower limb biomechanics of fully trained exoskeleton users reveal complex mechanisms behind the reductions in energy cost with human-in-the-loop optimization.

Exoskeletons that assist in ankle plantarflexion can improve energy economy in locomotion. Characterizing the joint-level mechanisms behind these reductions in energy cost can lead to a better understanding of how people interact with these devices, as well as to improved device design and training protocols. We examined the biomechanical responses to exoskeleton assistance in exoskeleton users trained with a lengthened protocol. Kinematics at unassisted joints were generally unchanged by assistance, which has been observed in other ankle exoskeleton studies. Peak plantarflexion angle increased with plantarflexion assistance, which led to increased total and biological mechanical power despite decreases in biological joint torque and whole-body net metabolic energy cost. Ankle plantarflexor activity also decreased with assistance. Muscles that act about unassisted joints also increased activity for large levels of assistance, and this response should be investigated over long-term use to prevent overuse injuries.

Combining neuropsychological assessment and structural neuroimaging to identify early Alzheimer's disease in a memory clinic cohort.

INTRODUCTION: The current study examined the contributions of comprehensive neuropsychological assessment and volumetric assessment of selected mesial temporal subregions on structural magnetic resonance imaging (MRI) to identify patients with amnestic mild cognitive impairment (aMCI) and mild probable Alzheimer's disease (AD) dementia in a memory clinic cohort. METHODS: Comprehensive neuropsychological assessment and automated entorhinal, transentorhinal, and hippocampal volume measurements were conducted in 40 healthy controls, 38 patients with subjective memory symptoms, 16 patients with aMCI, 16 patients with mild probable AD dementia. Multinomial logistic regression was used to compare the neuropsychological and MRI measures. RESULTS: Combining the neuropsychological and MRI measures improved group membership prediction over the MRI measures alone but did not improve group membership prediction over the neuropsychological measures alone. CONCLUSION: Comprehensive neuropsychological assessment was an important tool to evaluate cognitive impairment. The mesial temporal volumetric MRI measures contributed no diagnostic value over and above the determinations made through neuropsychological assessment.

Lower-Limb Exoskeletons Appeal to Both Clinicians and Older Adults, Especially for Fall Prevention and Joint Pain Reduction.

Exoskeletons are a burgeoning technology with many possible applications to improve human life; focusing the effort of exoskeleton research and development on the most important features is essential for facilitating adoption and maximizing positive societal impact. To identify important focus areas for exoskeleton research and development, we conducted a survey with 154 potential users (older adults) and another survey with 152 clinicians. The surveys were conducted online and to ensure a consistent concept of an exoskeleton across respondents, an image of a hip exoskeleton was shown during exoskeleton-related prompts. The survey responses indicate that both older adults and clinicians are open to using exoskeletons, fall prevention and joint pain reduction are especially important features, and users are likely to wear an exoskeleton in the scenarios when it has the greatest opportunity to help prevent a fall. These findings can help inform future exoskeleton research and guide the development of devices that are accepted, used, and provide meaningful benefit to users.

Alzheimer's disease biomarker utilization at first referral enhances differential diagnostic precision with simultaneous exclusion of Creutzfeldt-Jakob disease.

Most suspected Creutzfeldt-Jakob disease (CJD) cases are eventually diagnosed with other disorders. We assessed the utility of investigating Alzheimer's disease (AD) biomarkers and neurofilament light (NfL) in patients when CJD is suspected. The study cohort consisted of cerebrospinal fluid (CSF) samples referred for CJD biomarker screening wherein amyloid beta 1-42 (Aß1-42), phosphorylated tau 181 (p-tau181), and total tau (t-tau) could be assessed via Elecsys immunoassays (n = 419) and NfL via enzyme-linked immunosorbent assay (ELISA; n = 161). In the non-CJD sub cohort (n = 371), 59% (219/371) had A+T- (abnormal Aß1-42 only) and 21% (79/371) returned A+T+ (abnormal Aß1-42 and p-tau181). In the 48 CJD subjects, a similar AD biomarker profile distribution was observed. To partially address the prevalence of likely pre-symptomatic AD, NfL was utilized to assess for neuronal damage. NfL was abnormal in 76% (25/33) of A+T- subjects 40 to 69 years of age, 80% (20/25) of whom had normal t-tau. This study reinforces AD as an important differential diagnosis of suspected CJD, highlighting that incorporating AD biomarkers and NfL at initial testing is worthwhile.

Genome wide association study of clinical duration and age at onset of sporadic CJD.

Human prion diseases are rare, transmissible and often rapidly progressive dementias. The most common type, sporadic Creutzfeldt-Jakob disease (sCJD), is highly variable in clinical duration and age at onset. Genetic determinants of late onset or slower progression might suggest new targets for research and therapeutics. We assembled and array genotyped sCJD cases diagnosed in life or at autopsy. Clinical duration (median:4, interquartile range (IQR):2.5-9 (months)) was available in 3,773 and age at onset (median:67, IQR:61-73 (years)) in 3,767 cases. Phenotypes were successfully transformed to approximate normal distributions allowing genome-wide analysis without statistical inflation. 53 SNPs achieved genome-wide significance for the clinical duration phenotype; all of which were located at chromosome 20 (top SNP rs1799990, pvalue = 3.45x10-36, beta = 0.34 for an additive model; rs1799990, pvalue = 9.92x10-67, beta = 0.84 for a heterozygous model). Fine mapping, conditional and expression analysis suggests that the well-known non-synonymous variant at codon 129 is the obvious outstanding genome-wide determinant of clinical duration. Pathway analysis and suggestive loci are described. No genome-wide significant SNP determinants of age at onset were found, but the HS6ST3 gene was significant (pvalue = 1.93 x 10-6) in a gene-based test. We found no evidence of genome-wide genetic correlation between case-control (disease risk factors) and case-only (determinants of phenotypes) studies. Relative to other common genetic variants, PRNP codon 129 is by far the outstanding modifier of CJD survival suggesting only modest or rare variant effects at other genetic loci.

Comparing optimized exoskeleton assistance of the hip, knee, and ankle in single and multi-joint configurations.

Exoskeletons that assist the hip, knee, and ankle joints have begun to improve human mobility, particularly by reducing the metabolic cost of walking. However, direct comparisons of optimal assistance of these joints, or their combinations, have not yet been possible. Assisting multiple joints may be more beneficial than the sum of individual effects, because muscles often span multiple joints, or less effective, because single-joint assistance can indirectly aid other joints. In this study, we used a hip-knee-ankle exoskeleton emulator paired with human-in-the-loop optimization to find single-joint, two-joint, and whole-leg assistance that maximally reduced the metabolic cost of walking. Hip-only and ankle-only assistance reduced the metabolic cost of walking by 26 and 30% relative to walking in the device unassisted, confirming that both joints are good targets for assistance (N = 3). Knee-only assistance reduced the metabolic cost of walking by 13%, demonstrating that effective knee assistance is possible (N = 3). Two-joint assistance reduced the metabolic cost of walking by between 33 and 42%, with the largest improvements coming from hip-ankle assistance (N = 3). Assisting all three joints reduced the metabolic cost of walking by 50%, showing that at least half of the metabolic energy expended during walking can be saved through exoskeleton assistance (N = 4). Changes in kinematics and muscle activity indicate that single-joint assistance indirectly assisted muscles at other joints, such that the improvement from whole-leg assistance was smaller than the sum of its single-joint parts. Exoskeletons can assist the entire limb for maximum effect, but a single well-chosen joint can be more efficient when considering additional factors such as weight and cost.