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Background and ObjectivesMost primary progressive aphasia (PPA) literature is based on English language users. Linguistic features that vary from English, such as logographic writing systems, are underinvestigated. The current study characterized the dysgraphia phenotypes of patients with PPA who write in Chinese and investigated their diagnostic utility in classifying PPA variants.MethodsThis study recruited 40 participants with PPA and 20 cognitively normal participants from San Francisco, Hong Kong, and Taiwan. We measured dictation accuracy using the Chinese Language Assessment for PPA (CLAP) 60-character orthographic dictation test and examined the occurrence of various writing errors across the study groups. We also performed voxel-based morphometry analysis to identify the gray matter regions correlated with dictation accuracy and prevalence of writing errors.ResultsAll PPA groups produced significantly less accurate writing responses than the control group and no significant differences in dictation accuracy were noted among the PPA variants. With a cut score of 36 out of 60 in the CLAP orthographic dictation task, the test achieved sensitivity and specificity of 90% and 95% in identifying Chinese participants with PPA vs controls. In addition to a character frequency effect, dictation accuracy was affected by homophone density and the number of strokes in semantic variant PPA and logopenic variant PPA groups. Dictation accuracy was correlated with volumetric changes over left ventral temporal cortices, regions known to be critical for orthographic long-term memory. Individuals with semantic variant PPA frequently presented with phonologically plausible errors at lexical level, patients with logopenic variant PPA showed higher preponderance towards visual and stroke errors, and patients with nonfluent/agrammatic variant PPA commonly exhibited compound word and radical errors. The prevalence of phonologically plausible, visual, and compound word errors was negatively correlated with cortical volume over the bilateral temporal regions, left temporo-occipital area, and bilateral orbitofrontal gyri, respectively.DiscussionThe findings demonstrate the potential role of the orthographic dictation task as a screening tool and PPA classification indicator in Chinese language users. Each PPA variant had specific Chinese dysgraphia phenotypes that vary from those previously reported in English-speaking patients with PPA, highlighting the importance of language diversity in PPA.

Diagnostic criteria for dyslexia describe specific reading difficulties, and single-deficit models, including the phonological deficit theory, have prevailed. Children seeking diagnosis, however, do not always show phonological deficits, and may present with strengths and challenges beyond reading. Through extensive neurological, neuropsychological, and academic evaluation, we describe four children with visuospatial, socio-emotional, and attention impairments and spared phonology, alongside long-standing reading difficulties. Diffusion tensor imaging revealed white matter alterations in inferior longitudinal, uncinate, and superior longitudinal fasciculi versus neurotypical children. Findings emphasize that difficulties may extend beyond reading in dyslexia and underscore the value of deep phenotyping in learning disabilities.

Developmental dyscalculia (DD) is an heterogenous neurodevelopmental learning disability that manifests as persistent difficulties in learning mathematics. DD can occur in isolation but is often diagnosed as a co-occurring difficulty in children with language-based learning disabilities. Basic cognitive and neuroimaging findings suggest different subtypes of dyscalculia exist. However, a comprehensive theoretical framework that provides accepted terminology and clinical criteria to design appropriate interventions is still lacking. We developed a comprehensive battery of cognitive tests, the UCSF Dyscalculia Subtyping Battery (DSB), aiming at identifying deficits in four distinct mathematical domains: number processing, arithmetical procedures, arithmetic facts retrieval, and geometrical abilities. The mathematical abilities of a cohort of 75 children aged 7 to 16, referred to the UCSF Dyslexia Center for a language-based neurodevelopmental disorder, were initially evaluated using a behavioral neurology approach. A team of professional clinicians classified children with difficulties in mathematics in four groups, depending on their parents’ and teachers’ reported symptoms and clinical history, in one of the following domains: number processing, arithmetical procedures, arithmetic facts retrieval and geometrical abilities. The 75 children and 18 typically developing control children were then evaluated with the DSB to identify which subtests of the battery better represented each group. We describe the detailed profiles of four cases, each of them representative of deficits in one of the four domains, and report the pattern of impairment in the overall cohort. Our results show that a neuroscience-based DD evaluation battery enables identification of subtypes acknowledging the multidimensional nature of the disorder. If corroborated in large samples, these findings can pave the way for novel diagnostic approaches, consistent subtype classification, and ultimately personalized interventions.

Fine particulate matter (PM

Clinical understanding of primary progressive aphasia (PPA) has been established based on English-speaking population. The lack of linguistic diversity in research hinders the diagnosis of PPA in non-English speaking patients. This case report describes the tonal and orthographic deficits of a multilingual native Cantonese-speaking woman with nonfluent/agrammatic variant PPA (nfvPPA) and progressive supranuclear palsy. Our findings suggest that Cantonese-speaking nfvPPA patients exhibit tone production impairments, tone perception deficits at the lexical selection processing, and linguistic dysgraphia errors unique to logographic script writer. These findings suggest that linguistic tailored approaches offer novel and effective tools in identifying non-English speaking PPA individuals.

BackgroundAneurysm of proximal thoracic aorta (pTAA) is an often indolent, yet fatal disease. Although advancements in aneurysmal repair techniques have increased long-term survival rates, studies have proven that there are increases in perioperative risk for stroke incidence after pTAA surgery. Conversely, there is little evidence regarding the long-term stroke incidence in pTAA individuals, which strongly influences the morbidity, mortality, and usage of antithrombotic agents.MethodsUsing the Taiwan National Health Insurance Research Database, a nationwide population-based cohort, we recruited 3013 pTAA survivors hospitalized from 1 January 2000 to 31 December 2012. To ensure study cohort quality, only patients aged 20 years and above who underwent aneurysmal repair surgery are included. The control cohort is identified by matching background features (comorbidities, age, gender) at a 1:4 ratio through the use of frequency matching. The primary outcomes include incidence of ischemic stroke and intracranial hemorrhage one month after aneurysmal repair surgery.ResultsThe mortality of pTAA survivors is nearly twice of the matched controls despite aneurysmal repair (28.5 % vs. 15.2%, p ConclusionsDespite the advancement of aneurysmal repair surgery, this study suggests that pTAA patients may still face an increased risk of hemorrhage stroke. Further investigation is warranted to provide better long-term care for the pTAA population.

PURPOSE OF REVIEW: Knowledge on primary progressive aphasia (PPA) has expanded rapidly in the past few decades. Clinical characteristics, neuroimaging correlates, and neuropathological features of PPA are better delineated. This facilitates scientific studies on the disease pathophysiology and allows speech and language therapy to be more precisely targeted. This review article begins with a summary of the current understanding of PPA and discusses how PPA can serve as a model to promote scientific discovery in neurodegenerative diseases. RECENT FINDINGS: Studies on the different variants of PPA have demonstrated the high compatibility between clinical presentations and neuroimaging features, and in turn, enhances the understanding of speech and language neuroanatomy. In addition to the traditional approach of lesion-based or voxel-based mapping, scientists have also adopted functional connectivity and network topology approaches that permits a more multidimensional understanding of neuroanatomy. As a result, pharmacological and cognitive therapeutic strategies can now be better targeted towards specific pathological/molecular and cognitive subtypes. SUMMARY: Recent scientific advancement in PPA potentiates it to be an optimal model for studying brain network vulnerability, neurodevelopment influences and the effects of nonpharmacological intervention in neurodegenerative diseases.

Clinical phenotyping of primary progressive aphasia has largely focused on speech and language presentations, leaving other cognitive domains under-examined. This study investigated the diagnostic utility of visuospatial profiles and examined their neural basis among the three main primary progressive aphasia variants. We studied the neuropsychological performances of 118 primary progressive aphasia participants and 30 cognitively normal controls, across 11 measures of visuospatial cognition, and investigated their neural correlates via voxel-based morphometry analysis using visuospatial composite scores derived from principal component analysis. The principal component analysis identified three main factors: visuospatial-executive, visuospatial-memory and visuomotor components. Logopenic variant primary progressive aphasia performed significantly worst across all components; nonfluent/agrammatic variant primary progressive aphasia showed deficits in the visuospatial-executive and visuomotor components compared with controls; and the semantic variant primary progressive aphasia scored significantly lower than nonfluent/agrammatic variant primary progressive aphasia and control in the visuospatial-memory component. Grey matter volumes over the right parieto-occipital cortices correlated with visuospatial-executive performance; volumetric changes in the right anterior parahippocampal gyrus and amygdala were associated with visuospatial-memory function, and visuomotor composite scores correlated significantly with the grey matter volume at the right precentral gyrus. Discriminant function analysis identified three visuospatial measures: Visual Object and Space Perception and Benson figure copy and recall test, which classified 79.7% (94/118) of primary progressive aphasia into their specific variant. This study shows that each primary progressive aphasia variant also carries a distinctive visuospatial cognitive profile that corresponds with grey matter volumetric changes and in turn can be largely represented by their performance on the visuomotor, visuospatial-memory and executive functions.

Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer’s disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD.

Prions diseases are uniformly fatal neurodegenerative diseases that occur in sporadic, genetic, and acquired forms. Acquired prion diseases, caused by infectious transmission, are least common. Most prion diseases are not infectious, but occur spontaneously through misfolding of normal prion proteins or genetic mutations in the prion protein gene. Although most prion diseases are not caused by infection, they can be transmitted accidentally. Certain infection control protocols should be applied when handling central nervous system and other high-risk tissues. New diagnostic methods are improving premortem and earlier diagnosis. Treatment trials have not shown improved survival, but therapies may be available soon.

Importance The US aging population is rapidly becoming more racially and ethnically diverse. Early diagnosis of dementia is a health care priority. Objective To examine the associations between race/ethnicity and timeliness of dementia diagnosis and comprehensiveness of diagnostic evaluation. Design, Setting, and Participants This retrospective cross-sectional study used 2013-2015 California Medicare fee-for-service data to examine the associations of race/ethnicity, individual factors, and contextual factors with the timeliness and comprehensiveness of dementia diagnosis. Data from 10 472 unique beneficiaries were analyzed. The sample was selected on the basis of the following criteria: presence of 1 or more claims; no diagnoses of dementia or mild cognitive impairment in 2013 to 2014; continuous enrollment in Medicare Parts A and B; Asian, Black, Hispanic, or White race/ethnicity; and incident diagnoses of dementia or mild cognitive impairment in January through June 2015. Data analyses were conducted from November 1, 2019, through November 10, 2020. Main Outcomes and Measures Timeliness of diagnosis, defined as incident diagnosis of mild cognitive impairment vs dementia, and comprehensiveness of diagnostic evaluation, defined as presence of the following services in claims within 6 months before or after the incident diagnosis date: specialist evaluation, laboratory testing, and neuroimaging studies. Results The sample comprised 10 472 unique Medicare beneficiaries with incident diagnoses of dementia or mild cognitive impairment (6504 women [62.1%]; mean [SD] age, 82.9 [8.0] years) and included 993 individuals who identified as Asian (9.5%), 407 as Black (3.9%), 1255 as Hispanic (12.0%), and 7817 as White (74.6%). Compared with White beneficiaries, those who identified as Asian (odds ratio, 0.46; 95% CI, 0.38-0.56), Black (odds ratio, 0.73; 95% CI, 0.56-0.94), or Hispanic (odds ratio, 0.62; 95% CI, 0.52-0.72) were less likely to receive a timely diagnosis. Asian beneficiaries (incidence rate ratio, 0.81; 95% CI, 0.74-0.87) also received fewer diagnostic evaluation elements. These associations remained significant after adjusting for age, sex, comorbidity burden, neighborhood disadvantage, and rurality. Conclusions and Relevance These findings highlight substantial disparities in the timeliness and comprehensiveness of dementia diagnosis. Public health interventions are needed to achieve equitable care for people living with dementia across all racial/ethnic groups.

Background Little is known about the distribution of medical comorbidities in Alzheimer's disease (AD). Objective We aimed to describe the comorbidity pattern of AD in a nested case-control study. Methods Incident AD cases were identified by International Classification of Diseases codes in a random sample of 2 million individuals in Taiwan National Health Insurance program during 2001-2011. We further restricted cases to those treated with AD drugs of approved reimbursement. We sampled a set of age- and sex-matched control subjects (2:1 ratio) and employed conditional logistic regression to estimate the associations between pre-specified 14 comorbidities and AD. The clusters of multiple chronic diseases were then identified by exploratory factor analysis. Results A total of 2,618 AD cases were identified during 2001-2011 with a mean age of 76.1 years and female preponderance (59%). The most common 5 comorbidities in AD were hypertension (55.1%), osteoarthritis (38.2%), depression (32.3%), diabetes mellitus (DM) (25.7%), and cerebrovascular disease (CVD) (22.7%). After adjusting for age and sex, DM, osteoporosis, depression, and CVD were significantly associated with AD. The number of comorbidity was 3-fold greater in the AD group. The cluster of hypertension, DM, and hyperlipidemia was the most common combination in old age, whereas the cluster osteoarthritis and osteoporosis was the only multimorbidity pattern significantly associated with AD. Conclusion Multimorbidity is common in AD. Depression, CVD, osteoporosis, and DM are associated with incident AD, supporting that their co-existence is a typical feature of AD at old age. Comorbidity care should be integrated into current management for patients with AD.