Search

The logopenic variant of primary progressive aphasia (lvPPA) is a neurodegenerative syndrome characterized linguistically by gradual loss of repetition and naming skills, resulting from left posterior temporal and inferior parietal atrophy. Here, we sought to identify which specific cortical loci are initially targeted by the disease (epicenters) and investigate whether atrophy spreads through pre-determined networks. First, we used cross-sectional structural MRI data from individuals with lvPPA to define putative disease epicenters using a surface-based approach paired with an anatomically-fine-grained parcellation of the cortical surface (i.e., HCP-MMP1.0 atlas). Second, we combined cross-sectional functional MRI data from healthy controls and longitudinal structural MRI data from individuals with lvPPA to derive the epicenter-seeded resting-state networks most relevant to lvPPA symptomatology and ascertain whether functional connectivity in these networks predicts longitudinal atrophy spread in lvPPA. Our results show that two partially distinct brain networks anchored to the left anterior angular and posterior superior temporal gyri epicenters were preferentially associated with sentence repetition and naming skills in lvPPA. Critically, the strength of connectivity within these two networks in the neurologically-intact brain significantly predicted longitudinal atrophy progression in lvPPA. Taken together, our findings indicate that atrophy progression in lvPPA, starting from inferior parietal and temporo-parietal junction regions, predominantly follows at least two partially non-overlapping pathways, which may influence the heterogeneity in clinical presentation and prognosis.

Background and ObjectivesMotor speech function, including speech timing, is a key domain for diagnosing nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard assessments use subjective, specialist-dependent evaluations, undermining reliability and scalability. Moreover, few studies have examined relevant anatomo-clinical alterations in patients with pathologically confirmed diagnoses. This study overcomes such caveats using automated speech timing analyses in a unique cohort of autopsy-proven cases.MethodsIn a cross-sectional study, we administered an overt reading task and quantified articulation rate, mean syllable and pause duration, and syllable and pause duration variability. Neuroanatomical disruptions were assessed using cortical thickness and white matter (WM) atrophy analysis.ResultsWe evaluated 22 persons with nfvPPA (mean age: 67.3 years; 13 female patients) and confirmed underlying 4-repeat tauopathy, 15 persons with semantic variant primary progressive aphasia (svPPA; mean age: 66.5 years; 8 female patients), and 10 healthy controls (HCs; 70 years; 5 female patients). All 5 speech timing measures revealed alterations in persons with nfvPPA relative to both the HC and svPPA groups, controlling for dementia severity. The articulation rate robustly discriminated individuals with nfvPPA from HCs (area under the ROC curve [AUC] = 0.95), outperforming specialist-dependent perceptual measures of dysarthria and apraxia of speech severity. Patients with nfvPPA exhibited structural abnormalities in left precentral and middle frontal as well as bilateral superior frontal regions, including their underlying WM. The articulation rate correlated with atrophy of the left pars opercularis and supplementary/presupplementary motor areas. Secondary analyses showed that, controlling for dementia severity, all measures yielded greater deficits in patients with nfvPPA and corticobasal degeneration (nfvPPA-CBD, n = 12) than in those with progressive supranuclear palsy pathology (nfvPPA-PSP, n = 10). The articulation rate robustly discriminated between individuals in each subgroup (AUC = 0.82). More widespread cortical thinning was observed for the nfvPPA-CBD than the nfvPPA-PSP group across frontal regions.DiscussionAutomated speech timing analyses can capture specific markers of nfvPPA while potentially discriminating between patients with different tauopathies. Thanks to its objectivity and scalability; this approach could support standard speech assessments.Classification of EvidenceThis study provides Class III evidence that automated speech analysis can accurately differentiate patients with nonfluent PPA from normal controls and patients with semantic variant PPA.

Background: Preventive care for adults with hypertension and diabetes has improved over the recent decade. This study aims to identify trends of these and other comorbidities for patients with stroke-related hospitalizations in California from 2000 to 2013. Methods: This retrospective study is based on patient discharge information compiled by the California Office of Statewide Health and Planning Development from 2000 to 2013. The study population is comprised of residents, and represents over 31.68 million hospital events. Stroke hospitalizations were identified using the first listed diagnoses in the hospital records, ICD-9-CM codes 430 to 436. Comorbidities were identified using ICD-9-CM codes in 24 other diagnostic fields in each stroke hospitalization, aided by AHRQ’s Clinical Classification Software. Cochran Armitage trend test was employed to identify comorbidity trends from 2000 to 2013. Stroke hospitalizations were adjusted for sex, age, race/ethnicity and insurance type using multivariable logistic regression for each of the comorbidities analyzed. Results: Over 1 million hospitalizations and 77,908 in-hospital mortalities for stroke were identified from 2000 to 2013. Disorders of lipid metabolism among stroke-related hospitalizations rose by 230.5% from 16.7% in 2000 to 55.1% in 2013. Diabetes mellitus increased by 45.1% from 27.0% in 2000 to 39.2% in 2013. Cardiac dysrhythmia rose by 36.6% from 21.0% in 2000 to 28.7% in 2013 while hypertension rose by 22.0% from 67.7% in 2000 to 82.6% in 2013. The trend test showed significant upward trends (p After adjusting for patient demographics and insurance type, all four comorbidities had a positive association with stroke-related hospitalizations: diabetes mellitus (AOR 1.247; 95% CI=1.228-1.267), hypertension (AOR 2.685;[95% CI=2.631-2.740), disorders of lipid metabolism (AOR 2.095; 95% CI=2.063-2.127) and cardiac dysrhythmias (AOR 1.193; 95% CI=1.172-1.213). Conclusion: Diabetes mellitus, hypertension, disorders of lipid metabolism and cardiac dysrhythmia are positively associated with stoke-related hospitalizations.

Background: We examined stroke-related hospitalizations and in-hospital mortality trends by sex and age in California from 2000 to 2013. Methods: This retrospective analysis is based on data compiled by the California Office of Statewide Health and Planning Development from 2000 to 2013. Over 31.68 million inpatient events were studied, with cases from hospital discharge records identified as using the first listed diagnoses as ICD-9-CM codes 430 to 436. Hospitalization rates were expressed as the number of hospitalizations per 10,000 population and in-hospital mortality per 100,000 population, with the age and sex standardized to the year 2000 U.S. population. Results: We identified 1,060,006 hospitalizations and 77,908 in-hospital mortalities that were stroke-related from 2000 to 2013. Hospitalization rates standardized for age and sex, significantly declined from 56.15 in year 2000 to 37.17 in year 2013, representing a 51.1% reduction (Rate Ratio (RR) 1.511; p In-hospital mortality rates standardized for age and sex, significantly declined from 43.0 in 2000 to 25.0 in 2013, representing a 70.0% reduction (Rate Ratio (RR) 1.700; p Conclusion: Stroke-related hospitalizations and in-hospital mortality declined substantially for both sexes, but at a greater rate among females over the 14 year study period. Although rates are declining overall for both sexes and most age groups, rates of stroke-related hospitalization and in-hospital mortality rose for males age 35 to 59.