Peripheral artery disease and physical function in women with and without HIV

Objectives: Peripheral artery disease (PAD) is associated with decreased physical function and increased mortality in the general population. We previously found that PAD is common in middle-aged women with and without HIV infection, but its association with functional decline is unclear. We examine the contribution of PAD to functional decline in the Women’s Interagency HIV Study, controlling for traditional cardiovascular risk factors and HIV-related factors. Methods: Analysis included 1839 participants (72% with HIV) with measured ankle – brachial index (ABI) and 4 m gait speed. ABI values categorized PAD severity. Linear models with repeated measures estimated the association of PAD severity with log-transformed gait speed after controlling for demographic, behavioral, and metabolic risk factors, and HIV/hepatitis C virus status. Results: Median age was 50 years and more than 70% were Black. Compared with normal ABI, there was a dose – response relationship between increasing PAD severity and slower gait speed in univariable analyses: 6% slower gait speed for low-normal ABI [95% confidence interval (CI): 4 – 9%], 10% for borderline PAD (95% CI: 6 – 13%), 14% for mild PAD (95% CI: 9 – 18%), and 16% for moderate – severe PAD (95% CI: 5 – 25%). PAD severity remained associated with slower gait speed in multivariable analyses. HIV/hepatitis C virus co-infection was independently associated with 9% (95% CI: 4 – 14%) slower gait speed compared with those with neither infection. Among women with HIV, neither CD4þ cell count nor HIV-RNA level was associated with gait speed. Conclusion: In middle-aged women with and without HIV infection, greater PAD severity is associated with progressively slower gait speed. Early detection of subclinical PAD may decrease the risk of lower extremity functional impairment and its long-term health consequences

A proposed staging system for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by progressive loss of upper and lower motor neurons, with a median survival of 2–3 years. Although various phenotypic and research diagnostic classification systems exist and several prognostic models have been generated, there is no staging system. Staging criteria for amyotrophic lateral sclerosis would help to provide a universal and objective measure of disease progression with benefits for patient care, resource allocation, research classifications and clinical trial design. We therefore sought to define easily identified clinical milestones that could be shown to occur at specific points in the disease course, reflect disease progression and impact prognosis and treatment. A tertiary referral centre clinical database was analysed, consisting of 1471 patients with amyotrophic lateral sclerosis seen between 1993 and 2007. Milestones were defined as symptom onset (functional involvement by weakness, wasting, spasticity, dysarthria or dysphagia of one central nervous system region defined as bulbar, upper limb, lower limb or diaphragmatic), diagnosis, functional involvement of a second region, functional involvement of a third region, needing gastrostomy and non-invasive ventilation. Milestone timings were standardized as proportions of time elapsed through the disease course using information from patients who had died by dividing time to a milestone by disease duration. Milestones occurred at predictable proportions of the disease course. Diagnosis occurred at 35% through the disease course, involvement of a second region at 38%, a third region at 61%, need for gastrostomy at 77% and need for non-invasive ventilation at 80%. We therefore propose a simple staging system for amyotrophic lateral sclerosis. Stage 1: symptom onset (involvement of first region); Stage 2A: diagnosis; Stage 2B: involvement of second region; Stage 3: involvement of third region; Stage 4A: need for gastrostomy; and Stage 4B: need for non-invasive ventilation. Validation of this staging system will require further studies in other populations, in population registers and in other clinic databases. The standardized times to milestones may well vary between different studies and populations, although the stages themselves and their meanings are likely to remain unchanged

Contributions of HIV, hepatitis C virus, and traditional vascular risk factors to peripheral artery disease in women

Objectives:HIV and hepatitis C virus (HCV) have been associated with cardiovascular disease (CVD), but it is unclear whether HIV and HCV are also associated with peripheral artery disease (PAD). We examined the association of HIV, HCV, and traditional CVD risk factors with PAD in the Women's Interagency HIV Study, a multicenter US cohort.Methods:In this cross-sectional study, ankle-brachial index was estimated using Doppler ultrasound and manual sphygmomanometer in 1899 participants aged more than 40 years with HIV/HCV coinfection, HCV or HIV monoinfection, or neither infection. Multivariable logistic regression was used to estimate the odds of PAD (ankle-brachial index ≤0.9) after controlling for demographic, behavioral, and CVD risk factors.Results:Over two-thirds were African-American, median age was 50 years, and PAD prevalence was 7.7% with little difference by infection status. After multivariable adjustment, neither HIV nor HCV infection was associated with greater odds of PAD. Factors associated with PAD included older age [adjusted odds ratio (aOR): 2.01 for age 61-70 vs. 40-50 years; 95% confidence interval (CI): 1.04, 3.87], Black race (aOR: 2.30; 95% CI: 1.15, 4.63), smoking (aOR: 1.27 per 10-pack-year increment; 95% CI: 1.09, 1.48), and higher SBP (aOR: 1.14 per 10 mmHg; 95% CI: 1.01, 1.28).Conclusion:The high PAD prevalence in this nationally representative cohort of women with or at risk for HIV is on par with general population studies in individuals a decade older than our study's median age. HIV and HCV infection are not associated with greater PAD risk relative to uninfected women with similar risk factors. Modifiable traditional CVD risk factors may be important early intervention targets in women with and at risk for HIV

Novel image–novel location object recognition task sensitive to age-related cognitive decline in nondemented elderly

Traditional tests used in the clinic to identify dementia, such as the mini-mental state examination (MMSE), are useful to identify severe cognitive impairments but might be less sensitive to detect more subtle age-related cognitive changes. Previously, the novel image–novel location (NINL) object recognition test was shown to be sensitive to detect effects of apolipoprotein E4, a risk factor for developing age-related cognitive decline and Alzheimer’s disease, in nondemented elderly. In the present longitudinal study, performance on the MMSE and the NINL tests were compared over a 4-year period. Individual NINL scores over this period were highly correlated. In addition, while MMSE scores did not change over the 4-year period, NINL scores did. In a final testing session of a subset of the participants, NINL scores correlated with logical memory and word recall lists, cognitive tasks used to detect dementia in the clinic, as well as clinical dementia rating scales. These results support that the NINL might be a valuable tool to assess age-related cognitive decline

Dusty: an assistive mobile manipulator that retrieves dropped objects for people with motor impairments

People with physical disabilities have ranked object retrieval as a high priority task for assistive robots. We have developed Dusty, a teleoperated mobile manipulator that fetches objects from the floor and delivers them to users at a comfortable height. In this paper, we first demonstrate the robot's high success rate (98.4%) when autonomously grasping 25 objects considered important by people with amyotrophic lateral sclerosis (ALS). We tested the robot with each object in five different configurations on five types of flooring. We then present the results of an experiment in which 20 people with ALS operated Dusty. Participants teleoperated Dusty to move around an obstacle, pick up an object, and deliver the object to themselves. They successfully completed this task in 59 out of 60 trials (3 trials each) with a mean completion time of 61.4 seconds (SD=20.5 seconds), and reported high overall satisfaction using Dusty (7-point Likert scale; 6.8 SD=0.6). Participants rated Dusty to be significantly easier to use than their own hands, asking family members, and using mechanical reachers (p < 0.03, paired t-tests). 14 of the 20 participants reported that they would prefer using Dusty over their current methods

Amyotrophic Lateral Sclerosis Multiprotein Biomarkers in Peripheral Blood Mononuclear Cells

Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments.We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC), a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%), and from patients with neurological disorders that may resemble ALS (91%), between two levels of disease severity (90%), and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing.Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Longitudinal clinical and biomarker characteristics of non-manifesting LRRK2 G2019S carriers in the PPMI cohort

We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually with comprehensive motor and non-motor scales, dopamine transporter (DAT) imaging, and biofluid biomarkers. The latter included cerebrospinal fluid (CSF) Abeta, total tau and phospho-tau; serum urate and neurofilament light chain (NfL); and urine bis(monoacylglycerol) phosphate (BMP). At baseline, LRRK2 G2019S NMCs had a mean (SD) age of 62 (7.7) years and were 56% female. 13% had DAT deficit (defined as <65% of age/sex-expected lowest putamen SBR) and 11% had hyposmia (defined as ≤15th percentile for age and sex). Only 5 of 176 LRRK2 NMCs developed PD during follow-up. Although NMCs scored significantly worse on numerous clinical scales at baseline than HCs, there was no longitudinal change in any clinical measures over 2 years or in DAT binding. There were no longitudinal differences in CSF and serum biomarkers between NMCs and HCs. Urinary BMP was significantly elevated in NMCs at all time points but did not change longitudinally. Neither baseline biofluid biomarkers nor the presence of DAT deficit correlated with 2-year change in clinical outcomes. We observed no significant 2-year longitudinal change in clinical or biomarker measures in LRRK2 G2019S NMCs in this large, well-characterized cohort even in the participants with baseline DAT deficit. These findings highlight the essential need for further enrichment biomarker discovery in addition to DAT deficit and longer follow-up to enable the selection of NMCs at the highest risk for conversion to enable future prevention clinical trials

Tossing and Turning in Bed: Nocturnal Movements in Parkinson's Disease

Background: Sleep disturbances and nocturnal hypokinesia are common in Parkinson's disease (PD). Recent work using wearable technologies showed fewer nocturnal movements in PD when compared with controls. However, it is unclear how these manifest across the disease spectrum. Objectives: We assessed the prevalence of sleep disturbances and nocturnal hypokinesia in early and advanced PD and their relation to nonmotor symptoms and dopaminergic medication. Methods: A total of 305 patients with PD with diverse disease severity (Hoehn and Yahr [H&amp;Y] stage 1 = 47, H&amp;Y stage 2 = 181, H&amp;Y stage 3 = 77) and 205 healthy controls continuously wore a tri-axial accelerometer on the lower back for at least 2 days. Lying, turning, and upright -time at night were extracted from the acceleration signals. Percent upright time and nighttime walking were classified as sleep interruptions. The number, velocity, time, side, and degree of rotations in bed were used to evaluate nocturnal movements. Results: Nocturnal lying time was similar among all groups (healthy controls, 7.5 \ub1 1.2 hours; H&amp;Y stage 1, 7.3 \ub1 0.9 hours; H&amp;Y stage 2, 7.2 \ub1 1.3 hours; H&amp;Y stage 3, 7.4 \ub1 1.6 hours; P = 0.501). However, patients with advanced PD had more upright periods, whereas the number and velocity of their turns were reduced (P 64 0.021). Recently diagnosed patients (&lt;1 year from diagnosis) were similar to controls in the number of nocturnal turns (P = 0.148), but showed longer turning time (P = 0.001) and reduced turn magnitude (P = 0.002). Reduced nocturnal movements were associated with increased PD motor severity and worse dysautonomia and cognition and with dopaminergic medication. Conclusions: Using wearable sensors for continuous monitoring of movement at night may offer an unbiased measure of disease severity that could enhance optimal nighttime dopaminergic treatment and utilization of turning strategies. \ua9 2020 International Parkinson and Movement Disorder Society