Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue.

The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural characterization of LBD Asyn fibrils and approaches for studying disease mechanisms, imaging agents and therapeutics targeting Asyn.

Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile.

BACKGROUND: An analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤ 10.0 % at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays. METHODS: Human serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n = 64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated. RESULTS: The CVs for all individual instruments and overall were ≤ 10.0 % for two manufacturers (Abbott CVpooled = 6.3 % and Beckman CVpooled = 7.0 %). One of four Siemens Atellica instruments yielded a CV > 10.0 % (CVpooled = 7.7 %), whereas 15 of 41 Roche instruments yielded CVs > 10.0 % at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) (CVpooled = 11.7 %). Four Roche instruments also yielded CVs > 10.0 % near the female URL of 14 ng/L used in the United States (CVpooled = 8.5 %). CONCLUSIONS: The number of instruments achieving a CV ≤ 10.0 % at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.

A case of fatal overdose involving both hydromorphone and kratom.

Kratom is a plant originating in Southeast Asia that has been used for its dose-dependent stimulant and opioid effects. The main active compound in kratom is mitragynine, an alkaloid with affinity for the mu-opioid receptor. Toxicity and fatalities related to kratom use have increased substantially in recent years. In this case report, we describe a 44-year-old man who was found deceased in bed. The only significant finding at autopsy was abdominal distension with >4 L of ascites. Toxicology testing was performed on femoral blood which showed 79 ng/mL of hydromorphone, 560 ng/mL of mitragynine, and 240 ng/mL of olanzapine. In addition, creatinine and urea in vitreous humor were significantly elevated, consistent with renal impairment. Death was attributed to hydromorphone toxicity with mitragynine being a contributing factor.

Resting state correlates of picture description informativeness in left vs. right hemisphere chronic stroke.

Introduction: Despite a growing emphasis on discourse processing in clinical neuroscience, relatively little is known about the neurobiology of discourse production impairments. Individuals with a history of left or right hemisphere stroke can exhibit difficulty with communicating meaningful discourse content, which implies both cerebral hemispheres play a role in this skill. However, the extent to which successful production of discourse content relies on network connections within domain-specific vs. domain-general networks in either hemisphere is unknown. Methods: In this study, 45 individuals with a history of either left or right hemisphere stroke completed resting state fMRI and the Cookie Theft picture description task. Results: Participants did not differ in the total number of content units or the percentage of interpretative content units they produced. Stroke survivors with left hemisphere damage produced significantly fewer content units per second than individuals with right hemisphere stroke. Intrinsic connectivity of the left language network was significantly weaker in the left compared to the right hemisphere stroke group for specific connections. Greater efficiency of communication of picture scene content was associated with stronger left but weaker right frontotemporal connectivity of the language network in patients with a history of left hemisphere (but not right hemisphere) stroke. No significant relationships were found between picture description measures and connectivity of the dorsal attention, default mode, or salience networks or with connections between language and other network regions. Discussion: These findings add to prior behavioral studies of picture description skills in stroke survivors and provide insight into the role of the language network vs. other intrinsic networks during discourse production.

Small-Volume Blood Collection Tubes to Reduce Transfusions in Intensive Care: The STRATUS Randomized Clinical Trial.

Importance: Blood collection for laboratory testing in intensive care unit (ICU) patients is a modifiable contributor to anemia and red blood cell (RBC) transfusion. Most blood withdrawn is not required for analysis and is discarded. Objective: To determine whether transitioning from standard-volume to small-volume vacuum tubes for blood collection in ICUs reduces RBC transfusion without compromising laboratory testing procedures. Design, Setting, and Participants: Stepped-wedge cluster randomized trial in 25 adult medical-surgical ICUs in Canada (February 5, 2019 to January 21, 2021). Interventions: ICUs were randomized to transition from standard-volume (n = 10 940) to small-volume tubes (n = 10 261) for laboratory testing. Main Outcomes and Measures: The primary outcome was RBC transfusion (units per patient per ICU stay). Secondary outcomes were patients receiving at least 1 RBC transfusion, hemoglobin decrease during ICU stay (adjusted for RBC transfusion), specimens with insufficient volume for testing, length of stay in the ICU and hospital, and mortality in the ICU and hospital. The primary analysis included patients admitted for 48 hours or more, excluding those admitted during a 5.5-month COVID-19-related trial hiatus. Results: In the primary analysis of 21 201 patients (mean age, 63.5 years; 39.9% female), which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference in RBC units per patient per ICU stay (relative risk [RR], 0.91 [95% CI, 0.79 to 1.05]; P = .19; absolute reduction of 7.24 RBC units/100 patients per ICU stay [95% CI, -3.28 to 19.44]). In a prespecified secondary analysis (n = 27 411 patients), RBC units per patient per ICU stay decreased after transition from standard-volume to small-volume tubes (RR, 0.88 [95% CI, 0.77 to 1.00]; P = .04; absolute reduction of 9.84 RBC units/100 patients per ICU stay [95% CI, 0.24 to 20.76]). Median decrease in transfusion-adjusted hemoglobin was not statistically different in the primary population (mean difference, 0.10 g/dL [95% CI, -0.04 to 0.23]) and lower in the secondary population (mean difference, 0.17 g/dL [95% CI, 0.05 to 0.29]). Specimens with insufficient quantity for analysis were rare (≤0.03%) before and after transition. Conclusions and Relevance: Use of small-volume blood collection tubes in the ICU may decrease RBC transfusions without affecting laboratory analysis. Trial Registration: ClinicalTrials.gov Identifier: NCT03578419.

A Novel Brain PET Radiotracer for Imaging Alpha Synuclein Fibrils in Multiple System Atrophy.

Abnormal α-synuclein (α-syn) aggregation characterizes α-synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy (MSA). However, no suitable positron emission tomography (PET) radiotracer for imaging α-syn in PD and MSA exists currently. Our structure-activity relationship studies identified 4-methoxy-N-(4-(3-(pyridin-2-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)phenyl)benzamide (4i) as a PET radiotracer candidate for imaging α-syn. In vitro assays revealed high binding of 4i to recombinant α-syn fibrils (inhibition constant (Ki) = 6.1 nM) and low affinity for amyloid beta (Aß) fibrils in Alzheimer's disease (AD) homogenates. However, [3H]4i also exhibited high specific binding to AD, progressive supranuclear palsy, and corticobasal degeneration tissues as well as PD and MSA tissues, suggesting notable affinity to tau. Nevertheless, the specific binding to pathologic α-syn aggregates in MSA post-mortem brain tissues was significantly higher than in PD tissues. This finding demonstrated the potential use of [11C]4i as a PET tracer for imaging α-syn in MSA patients. Nonhuman primate PET studies confirmed good brain uptake and rapid washout for [11C]4i.

Digitally Based Blood Pressure Self-Monitoring Program That Promotes Hypertension Self-Management and Health Education Among Patients With Low-Income: Usability Study.

BACKGROUND: According to evidence-based clinical guidelines, adults with hypertension are advised to self-monitor their blood pressure (BP) twice daily. Self-measured BP monitoring is a recommended strategy for improving hypertension management. OBJECTIVE: We aimed to determine the feasibility and acceptability of a digitally based BP self-monitoring program that promotes hypertension self-management and health education among low-income patients. We hypothesized that the program would be highly feasible and acceptable and that at least 50% of the patients would use the monitor at the rate required for the reimbursement of the device's cost (16 days of measurements in any 30-day period). METHODS: Withings BPM Connect was deployed to patients at Family Health Centers of San Diego. Program elements included training, SMS text message reminders, and physician communication. Compliance, use, mean BP, and BP control status were calculated. A Kaplan-Meier time-to-event analysis was conducted to compare time to compliance between a strict definition (≥16 days in any rolling 30-day window) and a lenient definition (≥1 day per week for 4 consecutive weeks). A log-rank test was performed to determine whether the difference in time to compliance between the definitions was statistically significant. Mean systolic BP (SBP) and diastolic BP (DBP) before the intervention and after the intervention and mean change in SBP and DBP across patients were calculated. Paired sample t tests (2-tailed) were performed to assess the changes in SBP and DBP from before to after the intervention. RESULTS: A total of 179 patients received the monitors. The mean changes in SBP and DBP from before to after the intervention were +2.62 (SE 1.26) mm Hg and +3.31 (SE 0.71) mm Hg, respectively. There was a statistically significant increase in both SBP and DBP after the intervention compared with before the intervention (P=.04 and P<.001). At the first and last measurements, 37.5% (63/168) and 48.8% (82/168) of the patients had controlled BP, respectively. During the observation period, 83.3% (140/168) of the patients had at least 1 controlled BP measurement. Use decreased over time, with 53.6% (90/168) of the patients using their monitor at week 2 and only 25% (42/168) at week 11. Although only 25.6% (43/168) achieved the strict definition of compliance, 42.3% (71/168) achieved the lenient definition of compliance. The median time to compliance was 130 days for the strict definition and 95 days for the lenient definition. The log-rank test showed a statistically significant difference in time to compliance between the compliance definitions (P<.001). Only 26.8% (45/168) complied with the measurement rate that would result in device cost reimbursement. CONCLUSIONS: Few patients used the monitors at a rate that would result in reimbursement, raising financial feasibility concerns. Plans for sustaining costs among low-income patients need to be further evaluated.

Establishing quality indicators for point of care glucose testing: recommendations from the Canadian Society for Clinical Chemists Point of Care Testing and Quality Indicators Special Interest Groups.

OBJECTIVES: Monitoring quality indicators (QIs) is an important part of laboratory quality assurance (QA). Here, the Canadian Society of Clinical Chemists (CSCC) Point of Care Testing (POCT) and QI Special Interest Groups describe a process for establishing and monitoring QIs for POCT glucose testing. METHODS: Key, error prone steps in the POCT glucose testing process were collaboratively mapped out, followed by risk assessment for each step. Steps with the highest risk and ability to detect a non-conformance were chosen for follow-up. These were positive patient identification (PPID) and repeat of critically high glucose measurements. Participating sites were asked to submit aggregate data for these indicators from their site(s) for a one-month period. The PPID QI was also included as part of a national QI monitoring program for which fifty-seven sites submitted data. RESULTS: The percentage of POCT glucose tests performed without valid PPID ranged from 0-87%. Sites without Admission-Discharge-Transfer (ADT) connectivity to POCT meters were among those with the highest percentage of POCT glucose tests performed without valid PPID. The percentage repeated critically high glucose measurements ranged from 0-50%, indicating low compliance with this recommendation. A high rate of discordance was also noted when critically high POCT glucose measurements were repeated, demonstrating the importance of repeat testing prior to insulin administration. CONCLUSIONS: Here, a process for establishing these QIs is described, with preliminary data for two QIs chosen from this process. The findings demonstrate the importance of QIs for identification and comparative performance monitoring of non-conformances to improve POCT quality.

Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue.

The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. We developed and validated a novel method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and used solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise two protofilaments with pseudo-21 helical screw symmetry, very low twist and an interface formed by antiparallel beta strands of residues 85-93. The fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural landscape of LBD Asyn fibrils and inform further studies of disease mechanisms, imaging agents and therapeutics targeting Asyn.

Retrospective analysis of intra-patient laboratory variation demonstrates that the BD Vacutainer® Barricor™ blood collection tube reduces troponin variation.

OBJECTIVE: The BD Vacutainer® Barricor™ plasma blood collection tube uses a mechanical separator during centrifugation to separate plasma from the cellular elements of blood. Compared to use of plasma separator tubes (PST™) with gel, Barricor™ produces a cleaner sample with less residual cellular content. We sought to determine if Barricor™ reduces pre-analytical error compared to PST™. DESIGN & METHODS: We used a model previously published that utilizes serial differences between intra-patient measurements transformed into a Taylor series of variation vs time with the y-intercept equal to the sum of short-term analytic variation, preanalytic variation and biologic variation. The intra-patient variation of chloride, sodium, potassium, and troponin-T (hs-TnT) obtained from the Emergency Department of a large tertiary care center sampled with PST™ (May 2015-April 2018, n = 59,762 specimens) or Barricor™ (May 2018-May 2021, n = 61,512 specimens) was evaluated. All specimens were analyzed on either Roche Modular or Cobas® instruments. For each analyte, pairs of intra-patient results were tabulated and separated by 1 h intervals. The average between-pair variations were then regressed against time. We also determined the number of intra-patient outliers using the reference change value for each analyte. RESULTS: The Barricor™ hs-TnT y-intercept (-0.0132) was significantly lower than the PST™ intercept (0.9109; p = 0.022). This was also true for chloride (y-intercept = 1.0067 in Barricor™ and 1.3431 in PST™, p = 0.037). The percentage of hs-TnT outliers was significantly lower in Barricor™ (8.32 %) vs PST™ (12.2 %; p < 0.001). CONCLUSION: The analytical and biological variations are assumed to be steady over the study periods; we ascribe the difference in the y-intercept to the preanalytical effect of the Barricor™ tube reducing platelets and other cellular debris.

Enhanced Imaging and Language Assessments for Primary Progressive Aphasia.

BACKGROUND AND OBJECTIVES: It is widely agreed that primary progressive aphasia (PPA) is a clinical syndrome with at least 3 distinct variants that differ in phenotype, areas of atrophy, and most common underlying neurodegenerative disease. The distinction between logopenic variant PPA (lvPPA) and other variants is important for prognosis and medical management. However, differentiating logopenic from nonfluent agrammatic variant can be difficult. We aimed to identify a novel behavioral assessment that (1) distinguishes logopenic from the other variants with a high degree of accuracy and (2) correlates with left superior temporal-inferior parietal atrophy (previously shown to be associated with this variant). The location of atrophy was measured using a novel, clinically useful imaging analysis. METHODS: In this observational cohort study of 227 individuals with PPA, participants were administered sentence reading and repetition subtests from a standard battery. A subset of 41 participants were administered enhanced reading and repetition subtests with 5 longer sentences, of which 13 had brain imaging. Ratios of word-level and sentence-level accuracy in reading:repetition were calculated. We used one-way analysis of variance (ANOVA) to determine whether either or both ratios of reading:repetition independently discriminated between variants and t test to determine whether the ratios distinguished between nonfluent and logopenic variants. We identified receiver operating characteristics and Pearson correlations between the reading:repetition ratios and ratio of left:right superior temporal-inferior parietal volume. RESULTS: The sentence reading:repetition ratio using the new stimuli significantly differed across the 3 variants (p < 0.00001) and differed between nonfluent and logopenic variants (t(27) = 4.1; p = 0.0003). The area under the curve for distinguishing logopenic from other variants was 0.85 (0.71-0.99), and the diagnostic accuracy was 87.5%. The sentence reading:repetition ratio correlated with left:right superior temporal-inferior parietal volume (r = 0.69; p = 0.0087), but not with left:right volume of regions of interest associated with other variants. DISCUSSION: Results provide an efficient and reliable clinical assessment, and a novel imaging analysis, to distinguish the clinical syndrome of logopenic variant from other variants of PPA. Results also support the proposal that lvPPA reflects a defect in phonological short-term memory caused by atrophy in the superior temporal-inferior parietal cortex. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the sentence reading:repetition ratio distinguished logopenic PPA from other PPA variants.

Identification of cannabinoids in post-mortem blood samples from the province of New Brunswick before and after recreational cannabis legalization.

INTRODUCTION: Since recreational legalization of cannabis in Canada in 2018, self-reported use in New Brunswick (NB) has increased from 15.1% to 20.3%, the largest increase of any province. Current literature on the impact of recreational cannabis legislation in other jurisdictions is conflicting, though retail availability has often been delayed on enactment. Given the immediate availability of cannabis in NB after legalization, we sought to establish the effect this had on post-mortem cannabinoid detection. Furthermore, we wanted to investigate the impact that age, sex, and manner of death had on cannabis use. We also established if there were any increases in commonly detected drugs over the study period. METHODS: A retrospective chart review was conducted on all adult Coroner's cases with toxicology analysis in NB between January 2014 and May 2020 (n = 3060). Differences in the proportion of cannabinoid-positive samples pre- versus post-legalization in the overall cohort as well as within each demographic parameter were assessed using chi-square tests. The effects of demographic parameters on cannabis presence were further assessed by logistic regression. Lastly, chi-square tests for trend were performed to identify increasing trends in cannabis detection, as well as cocaine, ethanol, opiates/opioids, benzodiazepines, and amphetamines over the study period. RESULTS: After controlling for age, sex, and manner of death, participants that died after recreational legalization had higher odds of having cannabis present post-mortem than those that died pre-legalization. In addition, demographic sub-analysis identified a greater proportion of cannabinoid-positive samples post-legalization in 25- to 44-year-olds and in deaths classified as either suicide or accidental compared to pre-legalization. We also observed a significant increase in the presence of cocaine and amphetamines in post-mortem samples over the study period. CONCLUSION: This study demonstrates that cannabis use has increased post-legalization in NB, particularly within young adults and those dying by suicide or accidental means. It also highlights the need for future research into the impact that legalization has on cannabis use in other jurisdictions.

Quantifying regional α -synuclein, amyloid ß, and tau accumulation in lewy body dementia.

OBJECTIVE: Parkinson disease (PD) is defined by the accumulation of misfolded α-synuclein (α-syn) in Lewy bodies and Lewy neurites. It affects multiple cortical and subcortical neuronal populations. The majority of people with PD develop dementia, which is associated with Lewy bodies in neocortex and referred to as Lewy body dementia (LBD). Other neuropathologic changes, including amyloid ß (Aß) and tau accumulation, occur in some LBD cases. We sought to quantify α-syn, Aß, and tau accumulation in neocortical, limbic, and basal ganglia regions. METHODS: We isolated insoluble protein from fresh frozen postmortem brain tissue samples for eight brains regions from 15 LBD, seven Alzheimer disease (AD), and six control cases. We measured insoluble α-syn, Aß, and tau with recently developed sandwich ELISAs. RESULTS: We detected a wide range of insoluble α-syn accumulation in LBD cases. The majority had substantial α-syn accumulation in most regions, and dementia severity correlated with neocortical α-syn. However, three cases had low neocortical levels that were indistinguishable from controls. Eight LBD cases had substantial Aß accumulation, although the mean Aß level in LBD was lower than in AD. The presence of Aß was associated with greater α-syn accumulation. Tau accumulation accompanied Aß in only one LBD case. INTERPRETATION: LBD is associated with insoluble α-syn accumulation in neocortical regions, but the relatively low neocortical levels in some cases suggest that other changes contribute to impaired function, such as loss of neocortical innervation from subcortical regions. The correlation between Aß and α-syn accumulation suggests a pathophysiologic relationship between these two processes.

Pseudoword spelling ability predicts response to word spelling treatment in acquired dysgraphia.

Although rehabilitation of acquired dysgraphia can be quite effective, identifying predictors of responsiveness to treatment is useful for prognosis and individualization of treatment protocols. This study examined whether various features of treatment response were predicted by the integrity of one or more of the central cognitive components of spelling: orthographic long-term memory, orthographic working memory, and phoneme-grapheme conversion. Twenty dysgraphic individuals received 12 weeks of bi-weekly, individualized, lexically-based spelling rehabilitation using a spell-study-spell paradigm. Linear multiple regression modelling examined whether the type and severity of the dysgraphic deficit, assessed before rehabilitation, predicted the magnitude and rate of improvement, generalization to untrained items and maintenance of treatment gains. The results revealed that pseudoword spelling accuracy - indexing the integrity of the phoneme-grapheme conversion system - was the only factor examined that significantly predicted the rate of accuracy gains for trained words as well as the extent of generalization to untrained words. Pre-treatment pseudoword spelling accuracy also predicted retention of gains for trained and untrained words at 3-month follow-up. These findings reveal that the integrity of the phoneme-grapheme conversion system prior to dysgraphia rehabilitation may play a key role in rehabilitation-driven recovery, even when the treatment approach targets lexical rather than pseudoword spelling processes.

Evaluation of BD Barricor™ and PST™ blood collection tubes compared to serum for testing 11 therapeutic drugs on a Roche Cobas® 8000 platform.

INTRODUCTION: The type of blood collection tube used when obtaining samples for therapeutic drug monitoring (TDM) has important implications on the accuracy of results. Serum tubes without a gel separator are currently considered best practice. We sought to evaluate the performance of Barricor™, a novel plasma tube that utilizes an inert mechanical separator, as well as a gel-based tube (PST™) for testing acetaminophen, digoxin, gentamicin, methotrexate, phenobarbital, phenytoin, salicylate, vancomycin, valproic acid, carbamazepine, and theophylline on a Roche Cobas® 8000 platform. METHODS: Paired patient samples were collected from individuals taking at least one of the medications evaluated. These were supplemented with spiked specimens to ensure a minimum of 40 paired samples per drug. All drugs were measured within two hours of collection on Roche e602 or c502 instruments. Deming regression was used to assess bias between Barricor™ vs serum and PST™ vs serum. Seven-day refrigerated stability was also assessed in Barricor™, PST™, and serum tubes in a subset of samples (n = 10) for each drug. RESULTS: Drug concentrations in Barricor™ were similar to serum for each drug assessed. In contrast, a negative bias was observed in PST™ compared to serum tubes for carbamazepine (-7.6%) and phenytoin (-6.8%) although this did not surpass our total allowable error goal of 10%. All drugs recovered within ±10% of baseline value when samples were stored refrigerated for 7 days except for carbamazepine, phenytoin, and phenobarbital where significant analyte loss was observed within the first day in PST™ tubes. CONCLUSION: Barricor™ tubes are a suitable alternative to serum for TDM on the Roche Cobas® 8000 platform.

Written Discourse Task Helps to Identify Progression from Mild Cognitive Impairment to Dementia.

PURPOSE: We aimed to investigate: (1) the clinical, diagnostic value of a written discourse task, and (2) the relationship between executive functions and written discourse within the spectrum of individuals with mild cognitive impairment (MCI). METHOD: To determine whether written discourse performance predicts clinical course among individuals with MCI, we retrospectively classified individuals with MCI as converters (N = 26) who were later diagnosed with dementia or as a stable MCI group (N = 45). We quantified core word measures from written discourse samples obtained from the Cookie Theft picture description task. RESULT: Written discourse measures differentiated converters from the stable MCI group. Converters produced a fewer number of core words than the stable MCI group. A measure of executive function significantly predicted performance on the production of core words in written discourse for the converters. In a multivariable regression, production of core words remained the only explanatory variable closely associated with the progression to dementia in MCI. CONCLUSION: Written discourse tasks can predict the likelihood of MCI progressing to dementia, independently of recall and an executive function measure. Correlational results suggest that written discourse performance was associated with executive function as measured by the Trail Making Test. Our findings emphasize the usefulness of including written discourse tasks in language assessment batteries targeting preclinical dementia populations.

Characterizing subtypes and neural correlates of receptive aprosodia in acute right hemisphere stroke.

INTRODUCTION: Speakers naturally produce prosodic variations depending on their emotional state. Receptive prosody has several processing stages. We aimed to conduct lesion-symptom mapping to determine whether damage (core infarct or hypoperfusion) to specific brain areas was associated with receptive aprosodia or with impairment at different processing stages in individuals with acute right hemisphere stroke. We also aimed to determine whether different subtypes of receptive aprosodia exist that are characterized by distinctive behavioral performance patterns. METHODS: Twenty patients with receptive aprosodia following right hemisphere ischemic stroke were enrolled within five days of stroke; clinical imaging was acquired. Participants completed tests of receptive emotional prosody, and tests of each stage of prosodic processing (Stage 1: acoustic analysis; Stage 2: analyzing abstract representations of acoustic characteristics that convey emotion; Stage 3: semantic processing). Emotional facial recognition was also assessed. LASSO regression was used to identify predictors of performance on each behavioral task. Predictors entered into each model included 14 right hemisphere regions, hypoperfusion in four vascular territories as measured using FLAIR hyperintense vessel ratings, lesion volume, age, and education. A k-medoid cluster analysis was used to identify different subtypes of receptive aprosodia based on performance on the behavioral tasks. RESULTS: Impaired receptive emotional prosody and impaired emotional facial expression recognition were both predicted by greater percent damage to the caudate. The k-medoid cluster analysis identified three different subtypes of aprosodia. One group was primarily impaired on Stage 1 processing and primarily had frontotemporal lesions. The second group had a domain-general emotion recognition impairment and maximal lesion overlap in subcortical areas. Finally, the third group was characterized by a Stage 2 processing deficit and had lesion overlap in posterior regions. CONCLUSIONS: Subcortical structures, particularly the caudate, play an important role in emotional prosody comprehension. Receptive aprosodia can result from impairments at different processing stages.