Standard Clinical Measures Research Articles

Quantitative muscle ultrasound and electrical impedance myography in late onset Pompe disease: A pilot study of reliability, longitudinal change and correlation with function

Background/objectivesLate-onset Pompe disease (LOPD) is slowly progressive, making it difficult to assess clinical change and response to interventions. In this study, quantitative muscle ultrasonography (QMUS) and electrical impedance myography (EIM) were evaluated as potential biomarkers. Methods25 patients with confirmed LOPD were recruited from the Duke Pompe Clinic and evaluated with standard clinical measures, QMUS, standard EIM (sEIM) and hand-held EIM (hEIM). Patients were evaluated at baseline, 12 months and 24 months. MUS, sEIM and hEIM were compared with the clinical data. Five patients were given hEIM devices to perform measurements at home. ResultsQMUS and hEIM had good reliability as measures of muscle structure and conduction properties. Home, patient-performed hEIM measurements did not differ significantly from those performed in the clinic setting. Thirteen patients completed all follow-up measures. Most measures did not change over the study period, however, vastus lateralis echointensity increased 27%, a sign of declining muscle health. Additionally, significant correlations between QMUS, hEIM and measures of muscle strength and function were present. ConclusionsQMUS and hEIM may provide useful outcome measures for future studies in LOPD with hEIM providing an opportunity to collect data at home. Larger, multicenter studies are needed to explore these possibilities.

A smartphone sensor-based digital outcome assessment of multiple sclerosis

Background: Sensor-based monitoring tools fill a critical gap in multiple sclerosis (MS) research and clinical care. Objective: The aim of this study is to assess performance characteristics of the Floodlight Proof-of-Concept (PoC) app. Methods: In a 24-week study (clinicaltrials.gov: NCT02952911), smartphone-based active tests and passive monitoring assessed cognition (electronic Symbol Digit Modalities Test), upper extremity function (Pinching Test, Draw a Shape Test), and gait and balance (Static Balance Test, U-Turn Test, Walk Test, Passive Monitoring). Intraclass correlation coefficients (ICCs) and age- or sex-adjusted Spearman’s rank correlation determined test–retest reliability and correlations with clinical and magnetic resonance imaging (MRI) outcome measures, respectively. Results: Seventy-six people with MS (PwMS) and 25 healthy controls were enrolled. In PwMS, ICCs were moderate-to-good (ICC(2,1) = 0.61–0.85) across tests. Correlations with domain-specific standard clinical disability measures were significant for all tests in the cognitive (r = 0.82, p < 0.001), upper extremity function (|r|= 0.40–0.64, all p < 0.001), and gait and balance domains (r = −0.25 to −0.52, all p < 0.05; except for Static Balance Test: r = −0.20, p > 0.05). Most tests also correlated with Expanded Disability Status Scale, 29-item Multiple Sclerosis Impact Scale items or subscales, and/or normalized brain volume. Conclusion: The Floodlight PoC app captures reliable and clinically relevant measures of functional impairment in MS, supporting its potential use in clinical research and practice.

Periodontal Disease and Breast Cancer Risk: Results from the Nurses' Health Study.

While periodontal disease has been linked to increased cancer risk, studies regarding an association with breast cancer are limited. We examined the relationship between self-reported diagnosis of periodontal bone loss and incidence of breast cancer in a large, prospective cohort study, the Nurses' Health Study (1998-2014). We calculated HRs using Cox proportional hazards modeling, adjusting for risk factors common to both periodontal disease and breast cancer. During 1,023,647 person-years of follow-up, 5,110 of breast cancer cases were reported. We observed no association between periodontal disease and overall breast cancer risk (HR, 1.02; 95% confidence interval: 0.94-1.10); the association was not modified by smoking status, or other breast cancer risk factors or by breast tumor subtypes. We did not observe any association between periodontal disease and breast cancer risk. Given inconsistent findings in the literature, further research with standardized clinical measures of periodontitis is warranted.

Performance on the CVLT-2 during induced pain

Objective: Chronic pain patients frequently report cognitive problems including learning and memory. However, recent research involving induced pain has demonstrated an absence of reliably detectable decrements on several standard cognitive measures, suggesting that factors other than pain likely explain perceived cognitive deficits in chronic pain patients. This study examined potential effects of induced pain on verbal learning and memory as measured by the California Verbal Learning Test (CVLT-2). Potential effects of self-reported pain intensity were also evaluated. Method: Participants (111 non-clinical undergraduate students in the Southwestern United States) completed one version (Standard or Alternate) of the CVLT-2 under normal conditions, and then were administered the other version (Alternate or Standard) either while experiencing cold pressor-induced pain (Pain condition) or non-painful warm water immersion (Control condition). Results: For the Pain condition decrements in performance across most CVLT-2 variables were observed, including a mean T-score decrease of 10.98 (SD = 10.99) for Trials 1-5, whereas the comparable decrease in the Control condition was an average of 1.5 words (SD = 8.27). Self-reported pain intensity was significantly correlated with the degree of Time 1 to Time 2 performance decrement for Short-Delay Free Recall (r = −.51, p < .050), but not for Trials 1-5 (r = −.37, p = .160). Conclusion: Induced pain produces detectable decrements in performance on a standard clinical measure of verbal learning and memory performance, suggesting that pain in clinical populations may contribute to learning and memory deficits apart from potential neurological conditions.

Radiographic and plantar pressure assessment of pes planovalgus severity in children with cerebral palsy

BackgroundPes planovalgus is common in children with cerebral palsy. Although severity influences treatment, there still lacks standard clinical measurements to objectively quantify pes planovalgus in this population. The comparison of pedobarographic data and radiographic measurements to clinical evaluation has not been reported in this population. Methods395 feet were identified from a population of ambulatory pediatric patients with cerebral palsy. Each patient initially underwent clinical evaluation by an experienced physical therapist who classified feet as: 136 controls, 116 mild, 100 moderate, and 43 severe pes planovalgus. Quantitative measurements were then calculated from antero-posterior and lateral radiographs of the foot. Pedobarographic analysis included the arch index, center of pressure index, and a newly defined medial index. FindingsA multivariate analysis was performed on the radiographic and pedobarographic measurements collected. It identified seven variables that improved objective classification of pes planovalgus severity when utilized together. These include the foot progression angle, initial contact force, arch index, medial index, antero-posterior talonavicular coverage, lateral calcaneal pitch and lateral Meary's angle. While the lateral calcaneal pitch angle statistically differed amongst all severity classes, no pedobarographic value statistically differed between all severity classes. InterpretationOverall, the combination of radiographic and pedobarographic measurements provides valuable information for objectively classifying severity of pes planovalgus in children with cerebral palsy by utilizing these values together rather than independently. In a clinical setting, radiographs and pedobarographic data may be obtained to enhance assessment of severity and guide treatment.

Translational Value of Skilled Reaching Assessment in Clinical and Preclinical Studies on Motor Recovery After Stroke

Background Assessment of skilled reaching enables extensive analysis of upper limb function in clinical and preclinical studies on poststroke outcome. However, translational research if often limited by lack of correspondence between tests of human and rodent motor function. Objectives To determine (1) the translational value of skilled reaching performance for preclinical research by comparing the behavioral recovery profiles of skilled reaching characteristics between humans and rats recovering from stroke and (2) the relationship between skilled reaching performance and commonly used clinical outcome measures after stroke. Methods Twelve patients with ischemic or hemorrhagic stroke and 17 rats with photothrombotic stroke underwent an equivalent skilled reaching test at different time points, representing early to late subacute stages poststroke. Success scores and a movement element rating scale were used to measure the skilled reaching performance. The Fugl-Meyer Upper Extremity (FM-UE) assessment and the Action Research Arm Test (ARAT) were used as clinical outcome measures. Results Both species had muscle flaccidity at the early subacute stage after stroke and showed motor recovery following a proximal-distal principle toward the early subacute stage, albeit for rats within a shorter time course. Human skilled reaching scores and FM-UE and ARAT scores in the first 3 months poststroke were significantly correlated (P < .05). Conclusions Our study demonstrates that poststroke changes in skilled reaching performance are highly similar between rats and humans and correspond with standard clinical outcome measures. Skilled reaching testing therefore offers an effective and highly translational means for assessment of motor recovery in experimental and clinical stroke settings.

Head movement kinematics are altered during gaze stability exercises in vestibular schwannoma patients

Gaze stability is the ability of the eyes to fixate a stable point when the head is moving in space. Because gaze stability is impaired in peripheral vestibular loss patients, gaze stabilization exercises are often prescribed to facilitate compensation. However, both the assessment and prescription of these exercises are subjective. Accordingly, here we quantified head motion kinematics in patients with vestibular loss while they performed the standard of care gaze stability exercises, both before and after surgical deafferentation. We also correlate the head kinematic data with standard clinical outcome measures. Using inertial measurement units, we quantified head movements in patients as they transitioned through these two vestibular states characterized by different levels of peripheral damage. Comparison with age-matched healthy control subjects revealed that the same kinematic measurements were significantly abnormal in patients both pre- and post-surgery. Regardless of direction, patients took a longer time to move their heads during the exercises. Interestingly, these changes in kinematics suggest a strategy that existed preoperatively and remained symmetric after surgery although the patients then had complete unilateral vestibular loss. Further, we found that this kinematic assessment was a good predictor of clinical outcomes, and that pre-surgery clinical measures could predict post-surgery head kinematics. Thus, together, our results provide the first experimental evidence that patients show significant changes in head kinematics during gaze stability exercises, even prior to surgery. This suggests that early changes in head kinematic strategy due to significant but incomplete vestibular loss are already maladaptive as compared to controls.

Age-at-Onset and APOE-Related Heterogeneity in Pathologically Confirmed Sporadic Alzheimer Disease.

To characterize age-related clinical heterogeneity in Alzheimer disease (AD) and determine whether it is modified by APOE genotype or concomitant non-AD pathology, we analyzed data from 1,750 patients with sporadic, pathologically confirmed severe AD. In this retrospective cohort study, regression and mixed effects models assessed effects of estimated age at onset, APOE genotype, and their interaction on standardized clinical, cognitive, and pathologic outcome measures from the National Alzheimer's Coordinating Center database. A bimodal distribution of age at onset frequency in APOE ε4- cases showed best separation at age 63. Using this age cutoff, cases were grouped as ε4- early-onset AD (EOAD) (n = 169), ε4+ EOAD (n = 273), ε4- late-onset AD (LOAD) (n = 511), and ε4+ LOAD (n = 797). Patients with EOAD were more likely than patients with LOAD to present with noncognitive behavioral or motor symptoms or nonmemory cognitive complaints, and had more executive dysfunction, but less language impairment on objective cognitive testing. Age at onset and ε4- genotype were independently associated with lower baseline Mini-Mental State Examination scores and greater functional impairment and patients with EOAD had faster cognitive and functional decline than patients with LOAD regardless of APOE genotype. Patients with EOAD were more likely than patients with LOAD to receive a non-AD clinical diagnosis even though they were more likely to have pure AD without concomitant vascular or other non-AD neurodegenerative pathology. Early-onset sporadic AD is associated with a greater likelihood of an atypical, non-memory-dominant clinical presentation, especially in the absence of the APOE ε4 allele, which may lead to misattribution to non-AD underlying pathology.

Viral Rebound Kinetics Correlate with Distinct HIV Antibody Features.

Plasma viremia reoccurs in most HIV-infected individuals once antiretroviral therapy (ART) is interrupted. The kinetics of viral rebound, specifically the time until plasma virus becomes detectable, differ quite substantially between individuals, and associations with virological and immunological factors have been suggested. Standard clinical measures, like CD4 T-cell counts and plasma HIV RNA levels, however, are poor predictive markers. Antibody features, including Fc functionality and Fc glycosylation have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we analyzed HIV-specific antibody quantities and qualitative differences like antibody-mediated functions, Fc gamma receptor (FcγR) binding, and IgG Fc glycosylation as well as cytokine profiles and cellular HIV DNA and RNA levels in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders (≤4 weeks versus >4 weeks) and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. Specifically, individuals with early viral rebound exhibited higher levels of total HIV-specific IgGs carrying inflammatory Fc glycans, while delayed rebounders showed an enrichment of highly functional antibodies. Overall, only four features, including enhanced antibody-mediated NK cell activation in delayed rebounders, were necessary to discriminate the groups. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future ATI studies.IMPORTANCE Plasma viremia reoccurs in most HIV-infected individuals once antiretroviral therapy is interrupted, and interindividual differences in the kinetics of viral rebound have been associated with virological and immunological factors. Antibody features, including Fc functionality and Fc glycosylation, have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we systematically analyzed HIV-specific antibody quantities and qualitative differences in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future HIV eradication studies.

Test-Retest Reliability of Audiometric Assessment in Individuals With Mild Dementia

Accurate assessment of hearing is critically important regardless of a person's cognitive ability. The degree to which hearing can be reliably measured in adults with mild dementia has not been determined. To obtain quantitative measures of reliability to evaluate the degree to which audiologic testing can be accurately conducted in older adults with mild dementia. This repeated-measures cross-sectional study consisted of a comprehensive audiologic assessment on 2 occasions separated by 1 to 2 weeks performed in the department of otolaryngology at the Washington University School of Medicine from December 3, 2018, to March 4, 2020. Participants were 15 older adults with a verified diagnosis of mild dementia and 32 older adults without a verified diagnosis of mild dementia who were recruited from the Knight Alzheimer Disease Research Center at Washington University in St Louis. Test-retest reliability was assessed for tympanometry, acoustic reflex thresholds, otoacoustic emissions, hearing sensitivity, speech reception threshold, speech perception in noise, and hearing handicap, using standard clinical audiology measures. A total of 47 older adults (26 women; mean [SD] age, 74.8 [6.0] years [range, 53-87 years]), including 32 with normal cognitive function and 15 with very mild or mild dementia, completed the study protocol. For participants with mild dementia, high test-retest reliability (Spearman ρ > 0.80) was found for most measures typically included in a comprehensive audiometric evaluation. For acoustic reflex thresholds, agreement was moderate to high, averaging approximately 83% across frequencies for both groups. Scores for the screening Hearing Handicap Inventory for the Elderly at time 1 and time 2 were highly correlated for the group with normal cognitive function (r = 0.84 [95% CI, 0.70-0.93]) and for the group with mild dementia (r = 0.96 [95% CI, 0.88-0.99]). For hearing thresholds, all rank-order correlations were above 0.80 with 95% CIs at or below 15% in width, with the exception of a moderate correlation of bone conduction thresholds at 500 Hz for the group with normal cognitive function (r = 0.69 [95% CI, 0.50-0.84]) and slightly wider 95% CIs for low-frequency bone conduction thresholds for both groups. For speech reception thresholds, correlations were high for groups with normal cognitive function (r = 0.91 [95% CI, 0.84-0.95]) and mild dementia (r = 0.83 [95% CI, 0.63-0.94]). Test-retest reliability for hearing measures obtained from participants with mild dementia was comparable to that obtained from cognitively normal participants. These findings suggest that mild cognitive impairment does not preclude accurate audiologic assessment.

National learning health care system to advance early psychosis care, research

A national initiative aiming to create a collaborative learning health care system culture that values communication among patients, clinicians and stakeholder communities is seeking to link early psychosis care clinics through standard clinical measures, uniform data collection methods and data sharing agreements, according to the National Institute of Mental Health. The (NIMH) announced the launch Jan. 22 of the Early Psychosis Intervention Network (EPINET).

Advances in Retinal Oximetry.

Similar to other organs, the retina relies on tightly regulated perfusion and oxygenation. Previous studies have demonstrated that retinal blood flow is affected in a variety of eye and systemic diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Although measurement of peripheral oxygen saturation has become a standard clinical measurement through the development of pulse oximetry, developing a noninvasive technique to measure retinal oxygen saturation has proven challenging, and retinal oximetry technology currently remains inadequate for reliable clinical use. Here, we review current strategies and approaches, as well as several newer technologies in development, and discuss the future of retinal oximetry.

A comparison of clinical outcomes in PPMS in the INFORMS original trial data set

Background: The expanded disability status scale (EDSS) is the standard clinical outcome measure in primary progressive multiple sclerosis (PPMS), even though the timed 25-foot walk (T25FW), nine-hole peg test (NHPT) or combinations of these measures may be more useful. The paced auditory serial addition test (PASAT) is a widely used cognitive measure in MS, but little is known about change in PASAT scores over time in PPMS. Objective: The objective of this study is to compare clinical outcome measures in a large PPMS trial data set. Methods: We determined significant worsening events on the EDSS, T25FW and NHPT, and PASAT scores over the course of this 3-year trial. We compared unconfirmed, confirmed and sustained disability worsening and contrasted disability worsening with similarly defined improvement. We examined the association of baseline characteristics with the risk of disability worsening at 12, 24 and 36 months with logistic regression models. Results: The EDSS and T25FW showed most worsening events, while only few patients worsened on the NHPT. Adding the NHPT to a combined outcome added only few further worsening events. PASAT scores slightly increased over time, possibly due to a practice effect. Conclusion: Both the EDSS and T25FW, but not NHPT or PASAT, appear to be useful outcome measures in PPMS.

Validation of the Yale Food Addiction Scale 2.0 in Patients Seeking Bariatric Surgery.

The Yale Food Addiction Scale (YFAS) was developed in 2009 to assess food addiction (FA); a revised version was released in 2016 (YFAS 2.0). The objective of this study was to determine the statistical and clinical validity of the YFAS 2.0 in adults seeking bariatric surgery. Patients who underwent a preoperative psychological evaluation in preparation for bariatric surgery from 2015 to 2018 were included. The YFAS 2.0 was administered as part of routine clinical care and validated against an assessment battery of standardized clinical measures. Statistical analyses included chi-square and Wilcoxon rank sum tests and calculation of Spearman's rank correlation coefficients. Overall, 1061 patients were included. Mean age and BMI were 47.5 ± 12.9years and 46.9 ± 13.4kg/m2, respectively. There were 196 (18%) patients who screened positive on the YFAS 2.0 (21% mild, 23% moderate, and 56% severe FA). The YFAS 2.0 demonstrated strong convergent validity where patients who met criteria for FA had significantly increased levels of binge eating (p < 0.001), emotional eating (p < 0.001), and lower self-efficacy (p < 0.001). Discriminant validity was demonstrated by lack of association with alcohol use (p = 0.319). The YFAS 2.0 was significantly correlated with total scores for depression (p < 0.001), anxiety (p < 0.001), bipolar disorder symptoms (p < 0.001), and trauma history (p < 0.001). The prevalence of FA in a large sample of patients seeking bariatric surgery was consistent with previous literature. These data suggest that the YFAS 2.0 is psychometrically valid, demonstrating strong construct validity, and is a clinically useful measure of FA severity in patients pursuing bariatric surgery.

American Academy of Sports Physical Therapy Platform Presentation Abstracts SPL1–SPL82

American Academy of Sports Physical Therapy Platform Presentation Abstracts SPL1–SPL82

The SE-AssessWrist for robot-aided assessment of wrist stiffness and range of motion: Development and experimental validation.

IntroductionPhysical human-robot interaction offers a compelling platform for assessing recovery from neurological injury; however, robots currently used for assessment have typically been designed for the requirements of rehabilitation, not assessment. In this work, we present the design, control, and experimental validation of the SE-AssessWrist, which extends the capabilities of prior robotic devices to include complete wrist range of motion assessment in addition to stiffness evaluation.MethodsThe SE-AssessWrist uses a Bowden cable-based transmission in conjunction with series elastic actuation to increase device range of motion while not sacrificing torque output. Experimental validation of robot-aided wrist range of motion and stiffness assessment was carried out with five able-bodied individuals.ResultsThe SE-AssessWrist achieves the desired maximum wrist range of motion, while having sufficient position and zero force control performance for wrist biomechanical assessment. Measurements of two-degree-of-freedom wrist range of motion and stiffness envelopes revealed that the axis of greatest range of motion and least stiffness were oblique to the conventional anatomical axes, and approximately parallel to each other.ConclusionsSuch an assessment could be beneficial in the clinic, where standard clinical measures of recovery after neurological injury are subjective, labor intensive, and graded on an ordinal scale.

Negative Fusional Vergence Is Abnormal in Children with Symptomatic Convergence Insufficiency.

Deficits of disparity divergence found with objective eye movement recordings may not be apparent with standard clinical measures of negative fusional vergence (NFV) in children with symptomatic convergence insufficiency. This study aimed to determine whether NFV is normal in untreated children with symptomatic convergence insufficiency and whether NFV improves after vergence/accommodative therapy. This secondary analysis of NFV measures before and after office-based vergence/accommodative therapy reports changes in (1) objective eye movement recording responses to 4° disparity divergence step stimuli from 12 children with symptomatic convergence insufficiency compared with 10 children with normal binocular vision (NBV) and (2) clinical NFV measures in 580 children successfully treated in three Convergence Insufficiency Treatment Trial studies. At baseline, the Convergence Insufficiency Treatment Trial cohort's mean NFV break (14.6 ± 4.8Δ) and recovery (10.6 ± 4.2Δ) values were significantly greater (P < .001) than normative values. The post-therapy mean improvements for blur, break, and recovery of 5.2, 7.2, and 1.3Δ, respectively, were statistically significant (P < .0001). Mean pre-therapy responses to 4° disparity divergence step stimuli were worse in the convergence insufficiency group compared with the NBV group for peak velocity (P < .001), time to peak velocity (P = .01), and response amplitude (P < .001). After therapy, the convergence insufficiency group showed statistically significant improvements in mean peak velocity (11.63°/s; 95% confidence interval [CI], 6.6 to 16.62°/s), time to peak velocity (-0.12 seconds; 95% CI, -0.19 to -0.05 seconds), and response amplitude (1.47°; 95% CI, 0.83 to 2.11°), with measures no longer statistically different from the NBV cohort (P > .05). Despite clinical NFV measurements that seem greater than normal, children with symptomatic convergence insufficiency may have deficient NFV when measured with objective eye movement recordings. Both objective and clinical measures of NFV can be improved with vergence/accommodative therapy.

Laser induced breakdown spectroscopy with machine learning reveals lithium-induced electrolyte imbalance in the kidneys

Lithium is a major psychiatric medication, especially as long-term maintenance medication for Bipolar Disorder. Despite its effectiveness, lithium has side-effects, such as on renal function. In this study, lithium was administered to adult rats. This animal model of renal function was validated by measuring blood lithium, urea nitrogen (BUN), and thyroxine (T4) using inductively-coupled plasma mass spectrometry and enzyme-linked immunosorbent assay. The kidneys were analyzed by laser induced breakdown spectroscopy (LIBS) with 1064 nm ablation and 300–900 nm detection. Principal components analysis (PCA), radial visualization, and random forest classification were performed on the LIBS spectra for multi-element prediction and classification. Lithium at 0.34 mmol/L was detected in the blood of lithium treated subjects only. BUN was increased (6.6 vs. 5.3 mmol/L) and T4 decreased (58.12 vs. 51.4 mmol/L) in the blood of lithium subjects compared with controls, indicating renal abnormalities. LIBS detected lithium at 2.3 mmol/kg in the kidneys of lithium subjects only. Calcium was also observed to be reduced in lithium subjects, compared with controls. Subsequent PCA observed a change in the balance of sodium and potassium in the kidneys. These are key electrolytes in the body. Importantly, partial least squares regression showed that standard clinical measurements, such as the blood tests, can be used to predict kidney electrolyte measurements, which typically cannot be performed in humans. Overall, lithium accumulates in the kidneys and adversely affects renal function. The effects are likely related to electrolyte imbalance. LIBS with machine learning analysis has potential to improve clinical management of renal side-effects in patients on lithium medication.

Racial comparisons of MRI and PiB PET in acute stroke

AbstractBackgroundStroke and Alzheimer disease share risk factors and often co‐occur, and both have been reported to have a higher prevalence in African‐Americans. However, the interaction of race, stroke, and Alzheimer disease has not been established.MethodWe compared MRI and PiB PET biomarkers of non‐demented participants with and without acute ischemic stroke (total n=243, age 65‐101), with a focus on comparing African‐Americans (n=42 with stroke, n=84 without) to Non‐Hispanic Whites (n=39 with stroke, n=78 without). Our assessment included radiologic reads of the number of large infarcts, small infarcts, microbleeds, and leukoaraiosis; a PET measure of amyloid binding; quantitative measures of hippocampal volume and white matter hyperintensities; and longitudinal Mini Mental State Exam (MMSE) scores. Statistical analysis used logistic regression models to predict each biomarker using race and stroke status, while controlling for age, family history, APOE4, education, sex, and high blood pressure.ResultPiB PET did not differ significantly by stroke status or by race, with 23.6% of participants being classified as amyloid positive (Figure 1). As expected in stroke, the acute stroke participants were more likely to have large infarcts, small infarcts, microbleeds, and non‐zero Fazekas scores. MMSE showed racial differences at baseline (mean 26.8 for African‐Americans, 27.9 for Non‐Hispanic Whites, p=0.03), but not longitudinally. Overall, African‐Americans were more likely to have microbleeds (32.8% vs 22.6%, p=0.04). Within the stroke group African‐Americans were more likely to have small infarcts (75.6% vs 56.8%, p=0.049). Combined, African‐Americans were also more likely to have more than 5 microbleeds ‐ the cutoff for many Alzheimer clinical trials (15.2% vs 9.6%, p=0.04).ConclusionPreclinical Alzheimer disease does not appear to be a risk factor for stroke and did not differ by race in our sample. Standard clinical MRI measures differed by stroke status, but showed few racial differences. The observed lower MMSE scores in African‐Americans has been reported previously and may arise for a variety of reasons. In individuals with stroke, African‐Americans may have more severe pathology as evidenced by greater numbers of small infarcts and microbleeds. African‐Americans may be more likely to be excluded from Alzheimer disease clinical trials due to having 5 or more microbleeds.

Predicting Neuropsychological Impairment in Relapsing Remitting Multiple Sclerosis: The Role of Clinical Measures, Treatment, and Neuropsychiatry Symptoms

This retrospective observational study aimed to define neuropsychological impairment (NI) profiles and determine the influence of clinical, demographic, and neuropsychiatric measures in specific cognitive domains in a cohort of relapsing-remitting multiple sclerosis (RRMS) patients. Ninety-one RRMS patients underwent a neurological examination and a brief neuropsychological assessment. Patients were classified according to the disease-modifying therapies (DMTs) received (platform or high-efficacy). Differences between groups and multiple regression analyses were performed to determine the predictive value of the assessed measures in cognitive performance. More than two-thirds of the patients showed NI. Specifically, mild to moderate NI was presented in approximately half of the participants. Paced Auditory Serial Addition Test (PASAT-3) and Symbol Digit Modalities Test (SDMT) were the most frequently impaired cognitive tests (45.3% and 41.3%, respectively) followed by phonemic verbal fluency (PVF) (27.8%). Expanded Disability Status Scale (EDSS), age, depressive symptoms, and disease duration were the best predictors of SDMT (R2=.34; p<.01), whereas disease duration, EDSS, and anxiety-state levels predicted PASAT-3 (R2=.33, p<.01). Educational level, age, EDSS, and depressive symptoms demonstrated the strongest association with PVF (R2=.31, p<.01). Our results indicated a significant prevalence of NI in RRMS patients that was not dependent on the DMT type. In addition to the meaningful working memory (PASAT-3) and information processing speed (SDMT) impairments found, PVF deficits may also be an important marker of cognitive impairment in RRMS patients. This study supports the relevance of standard clinical measures and reinforces the importance of quantifying clinical and neuropsychiatric symptoms to predict subsequent cognitive performance on a similar multiple sclerosis phenotype and disease stage.