Accumulation of neurofibrillary tangles and activated microglia is associated with lower neuron densities in the aphasic variant of Alzheimer’s disease

The neurofibrillary tangles (NFT) and amyloid‐ß plaques (AP) that comprise Alzheimer’s disease (AD) neuropathology are associated with neurodegeneration and microglial activation. Activated microglia exist on a dynamic spectrum of morphologic subtypes that include resting, surveillant microglia capable of converting to activated, hypertrophic microglia closely linked to neuroinflammatory processes and AD neuropathology in amnestic AD. However, quantitative analyses of microglial subtypes and neurons are lacking in non‐amnestic clinical AD variants, including primary progressive aphasia (PPA‐AD). PPA‐AD is a language disorder characterized by cortical atrophy and NFT densities concentrated to the language‐dominant hemisphere. Here, a stereologic investigation of five PPA‐AD participants determined the densities and distributions of neurons and microglial subtypes to examine how cellular changes relate to AD neuropathology and may contribute to cortical atrophy. Adjacent series of sections were immunostained for neurons (NeuN) and microglia (HLA‐DR) from bilateral language and non‐language regions where in vivo cortical atrophy and Thioflavin‐S‐positive APs and NFTs were previously quantified. NeuN‐positive neurons and morphologic subtypes of HLA‐DR‐positive microglia (i.e., resting [ramified] microglia and activated [hypertrophic] microglia) were quantified using unbiased stereology. Relationships between neurons, microglia, AD neuropathology, and cortical atrophy were determined using linear mixed models. NFT densities were positively associated with hypertrophic microglia densities (P < 0.01) and inversely related to neuron densities (P = 0.01). Hypertrophic microglia densities were inversely related to densities of neurons (P < 0.01) and ramified microglia (P < 0.01). Ramified microglia densities were positively associated with neuron densities (P = 0.02) and inversely related to cortical atrophy (P = 0.03). Our findings provide converging evidence of divergent roles for microglial subtypes in patterns of neurodegeneration, which includes hypertrophic microglia likely driving a neuroinflammatory response more sensitive to NFTs than APs in PPA‐AD. Moreover, the accumulation of both NFTs and activated hypertrophic microglia in association with low neuron densities suggest they may collectively contribute to focal neurodegeneration characteristic of PPA‐AD.     

Is there a bit of autism in all of us? Autism spectrum traits are related to cortical thickness differences in both autism and typical development

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in communication and social interaction, as well as repetitive behaviors and interests. However, these traits are highly variable across individuals with ASD and are also present in the typically developing population. Brain structural correlates of ASD are also heterogeneous. Recent findings have indicated that ASD traits as measured by the autism quotient (AQ) are reflected in white matter structural differences in a continuous way across both typically-developed and ASD individuals. Here, we tested for the first time, how ASD traits are related to gray matter structural differences (and particularly cortical thickness) in both ASD and typically developing adults. The present results show that ASD traits are primarily correlated with reductions in cortical thickness in a continuous fashion across ASD and typically developing adults in social brain areas and the default mode network including the orbitofrontal cortex, postcentral gyrus, and lingual gyrus. These findings provide new evidence that ASD traits are primarily reflected in neural structure that exists along a continuum extending into the typically developing population.     

Changes in energy metabolism after induction therapy in patients with severe or moderate ulcerative colitis

We investigated the changes in energy expenditure during induction therapy in patients with severe or moderate ulcerative colitis. Thirteen patients (10 men, 3 women; mean age, 36.5 years) with ulcerative colitis admitted to the Shiga University Hospital were enrolled in this study. We measured the resting energy expenditure and respiratory quotients of these patients before and after induction therapy with indirect calorimetry. We analyzed the changes of nutritional status and serum inflammatory cytokine levels and also evaluated the relationship between energy metabolism and disease activity by using the Seo index and Lichtiger index. The resting energy expenditure was 26.3 ± 3.8 kcal/kg/day in the active stage and significantly decreased to 23.5 ± 2.4 kcal/kg/day after induction therapy (p<0.01). The resting energy expenditure changed in parallel with the disease activity index and C-reactive protein and inflammatory cytokine levels. The respiratory quotient significantly increased after induction therapy. Thus, moderate to severe ulcerative colitis patients had a hyper-metabolic status, and the energy metabolism of these patients significantly changed after induction therapy. Therefore, we recommend that nutritional management with 30–34 kcal/kg/day (calculated as measured resting energy expenditure × activity factor, 1.3) may be optimal for hospitalized ulcerative colitis patients.     

慢加急性肝衰竭患者的能量代谢状况

目的：探讨慢加急性肝衰竭（ ACLF）患者住院期间的动态能量代谢状况,为个体化的临床营养支持提供理论依据。方法应用美国MedGraphics CCM／D营养代谢测试系统（代谢车）测定24例好转的ACLF患者（存活组）及9例死亡的ACLF患者（死亡组）入院、住院期间、出院／死亡时的能量代谢指标及生化指标。结果存活组出院时REE／pREE与入院比较差异无统计学意义。死亡组住院期间REE／pREE与存活组比较差异有统计学意义（P＝0.008）。入院时两组呼吸商（RQ）值、碳水化合物氧化率（CHO％）均偏低,差异无统计学意义。存活组出院时RQ值及CHO％均有所上升,与入院时比较差异有统计学意义（ P＜0.05）。死亡组死亡时RQ值及CHO％均降低,RQ、CHO％与存活组出院时比较差异有统计学意义（ P＝0.006）。 Pearson相关分析显示, REE／pREE与直接胆红素、总胆汁酸、白细胞计数呈正相关,与凝血酶原活动度呈负相关。 RQ、CHO％与凝血酶原活动度、总胆固醇呈正相关,与直接胆红素、白细胞计数呈负相关。结论 ACLF患者治疗过程中趋于低代谢的状态有助于病情恢复,有利于改善患者预后;呼吸商及三大营养底物氧化比例的变化比静息能量代谢更敏感,是ACLF营养干预治疗中重要的、较好的监测指标;PTA及TC与代谢指标变化一致且灵敏,可间接体现患者的能量代谢状态。     

皮质下失语症的临床表现及机制

近年来,随着影像学技术的不断发展,由皮质下结构损害所致的失语症越来越常见。本文综述近年有关皮质下失语的文献,重点讨论皮质下结构的解剖特点、皮质下失语的临床特点及发病机制。     

Setting a Research Agenda to Inform Intensive Comprehensive Aphasia Programs

Abstract

Research into intensive comprehensive aphasia programs (ICAPs) has yet to show that this service delivery model is efficacious, effective, has cost utility, or can be broadly implemented. This article describes a phased research approach to the study of ICAPs and sets out a research agenda that considers not only the specific issues surrounding ICAPs, but also the phase of the research. Current ICAP research is in the early phases, with dosing and outcome measurement as prime considerations as well as refinement of the best treatment protocol. Later phases of ICAP research are outlined, and the need for larger scale collaborative funded research is recognized. The need for more rapid translation into practice is also acknowledged, and the use of hybrid models of phased research is encouraged within the ICAP research agenda.     

Participants’ perceptions of an aphasia-friendly occupational therapy home program

Background: Upper extremity impairments post-stroke impact participation in valued occupations. Home programs are used to extend the frequency and amount of upper extremity practice for people post-stroke, but novel ways of increasing adherence to these programs is needed to ensure intense repetitive practice.

Objectives: The purpose of this process evaluation, was to examine the perceptions of people with aphasia as it relates to modifications to home programs that could influence participation, specifically listening to music and aphasia-friendly adaptations of written materials.

Methods: Seven people with chronic aphasia completed an upper extremity home program that included the use of music and aphasia-friendly modified materials (ClinicalTrials.gov ID:2016/06/18). After the home program, participants completed semi-structured interviews to understand their perceptions of the program and the modifications.

Results: Five themes were identified including (1) music, (2) activities, (3) instructions, (4) logistics, and (5) progress. Most participants perceived music as helpful, but a few reported it being distracting. Participants found the variety of activities helpful as well as specific characteristics of the instructions such as photographs and images. Some participants expressed elements of the home program to be barriers to practice such as using the activity monitors and logbook, which required assistance at times. Finally, participants noted their own progress resulting from the program and liked that they could adjust the intensity of the program as they progressed.

Conclusions: Overall participants in this study with aphasia perceived the modifications to home programs including aphasia friendly written instructions and music to facilitate successful home practice.     

Verbal planning in a case of ‘Dynamic Aphasia’: An impairment at the level of macroplanning

Patients with ‘dynamic aphasia’ exhibit reduced spontaneous speech despite well preserved basic language functions. This disorder may allow insights into the conceptual preparation of messages. Various cognitive approaches have located the patients' impairment at the level of preverbal message generation, including verbal planning, loss of inhibition of lexical concepts, and, most recently, generation of sequences of novel thoughts. We report the case of HK who presented with dynamic aphasia. The study had two goals: first, as HK was assessed over a longer period of time, changes in his performances could be documented which were relevant for the interpretation of the underlying disorder. The present study is the first to document changes across time and improvements of some of the skills involved in language production. Second, further investigations were carried out to clarify HK's underlying deficits. He was unimpaired on a number of ‘verbal planning’ tasks which argues for the preservation of those specific processes of verbal planning which Levelt (1989) Levelt, W. J. M. 1989. Speaking: From intention to articulation, Cambridge, MA: MIT Press.  [Google Scholar] termed ‘microplanning’. It is suggested that HK's performance may be best described as an impairment at the level of ‘macroplanning’. The deficit may lie in the generation of novel thoughts though minor modifications of this recent approach are being suggested.     

Opportunities to say ‘yes’: Rare speech automatisms in a case of progressive nonfluent aphasia and apraxia

We describe the investigation of speech automatisms in a man with progressive nonfluent aphasia and apraxias. Occurrence of the automatisms yes and right, were analysed across a range of speech tasks varying in length, propositionality, lexical and articulatory complexity, whether tasks engaged internal generation or external triggering and articulatory distortions, and while completing pantomimes/gestures. No differences were found in occurrence across most tasks but there was a significant interaction between automatism production and apraxic speech errors and during limb praxic tasks, suggesting that production of the automatism was unrelated to linguistic or lexical variables, but was related to the presence of speech apraxia coupled with disinhibition.