Explore the vast range of titles available.

Abstract Competence in muscle biopsy evaluation is a core component of neuropathology practice. The practicing neuropathologist should be able to prepare frozen sections of muscle biopsies with minimal artifacts and identify key histopathologic features of neuromuscular disease in hematoxylin and eosin-stained sections as well as implement and interpret a basic panel of additional histochemical, enzyme histochemical, and immunohistochemical stains. Important to everyday practice is a working knowledge of normal muscle histology at different ages, muscle motor units, pitfalls of myotendinous junctions, nonpathologic variations encountered at traditional and nontraditional muscle sites, the pathophysiology of myonecrosis and regeneration, and approaches to distinguish muscular dystrophies from inflammatory myopathies and other necrotizing myopathies. Here, we provide a brief overview of what every neuropathologist needs to know concerning the muscle biopsy.

Abstract Social media use continues to grow among pathologists. Discussions of current topics, posts of educational information, and images of pathological entities are commonly found and distributed on popular sites such as Facebook and Twitter. However, little is known about the presence of neuropathology content in social media and the audience for such content. We designed and distributed a survey to assess the demographics of users viewing neuropathology content and their opinions about neuropathology in social media. User posts on the Facebook group, Surgical Neuropathology, were also analyzed. The results show that there is a demand for neuropathology content of high quality, curated by experts, and that this demand is present among both specialists and nonspecialists. These findings suggest that social media may be useful for rapid dissemination of information in the field of neuropathology. This format also offers a unique opportunity to extend the reach of information to nonneuropathologists who may not receive neuropathology journals or have access to specialty-level neuropathology training, to build networks between professionals, and potentially to influence public opinion of neuropathology on an international scale.

To understand the current state of neurology residents training in neuropathology, we electronically distributed a 16-item survey to 150 adult and 70 child neurology program directors (PDs). The survey inquired about their program characteristics, neuropathology curriculum and assessment methods, trainee performance, and attitudes. Descriptive analysis was used to summarize categorical variables as frequencies and percentages and continuous as means and standard deviations. We conducted a series of Mann-Whitney U and Fisher’s exact tests to evaluate differences between various program characteristics. Sixty-four (29%) PDs responded to the survey, including 45 (30%) adult and 19 (27%) child neurology PDs. Thirty-one programs required a dedicated neuropathology rotation. The majority (92%) used the Residency In-Service Training Examination (RITE) to assess trainee’s knowledge. Approximately 86% of the PDs agreed that neuropathology is essential and a defined curriculum is necessary during residency training. There was no difference in the RITE scores between programs. We conclude that a neuropathology rotation was felt to be essential even though the RITE scores did not differ between programs with and without a dedicated rotation. Alternative evaluation and training methods may need consideration. A future survey of all the stakeholders may be required to thoroughly understand and disseminate the neuropathology education well.

Few data on the pathology of cerebral vessel disease, dementia, and cognition are available. We examined the association of cerebral atherosclerosis and arteriolosclerosis neuropathology with probable and possible Alzheimer's disease dementia and cognitive function. This cross-sectional study included men and women aged 65 years or older who had yearly clinical assessments and had agreed to brain autopsy at the time of death, as part of one of two cohort studies of ageing (The Religious Orders Study and the Rush Memory and Aging Project). Individuals without dementia or with Alzheimer's disease dementia, and with complete neuropathological data, are included in our analyses. We used neuropsychological data proximate to death to create summary measures of global cognition and cognitive domains. Clinical data recorded between 1994 and 2015 were used to determine presence of Alzheimer's disease dementia. Systematic neuropathological assessments documented the severity of cerebral large vessel (atherosclerosis) and small vessel (arteriolosclerosis) disease. By use of regression analyses adjusted for demographics, gross and microscopic infarcts, and Alzheimer's disease pathology, we examined associations of vessel disease severity (mild, moderate, and severe) with odds of probable and possible Alzheimer's disease dementia and cognitive function. Study enrolment began in January, 1994, and two cohort studies are ongoing. 1143 individuals were included in our analyses (median age at death 88·8 years; 478 [42%] with Alzheimer's disease dementia). Moderate-to-severe atherosclerosis was present in 445 (39%) individuals, and arteriolosclerosis in 401 (35%) individuals. Each level increase in the severity of atherosclerosis or arteriolosclerosis was associated with significantly higher odds of Alzheimer's disease dementia (odds ratio [OR] for atherosclerosis 1·33, 95% CI 1·11–1·58; OR for arteriolosclerosis 1·20, 1·04–1·40). Atherosclerosis was associated with lower scores for global cognition (estimate −0·10 [SE 0·04], p=0·0096) and four cognitive domains (episodic memory −0·10 [0·04], p=0·017; semantic memory −0·11 [0·05], p=0·018; perceptual speed −0·14 [0·04], p=0·00080; and visuospatial abilities −0·13 [0·04], p=0·0080), but not working memory (−0·05 [0·04], p=0·21). Arteriolosclerosis was associated with lower scores for global cognition (estimate −0·10 [0·03], p=0·0015) and four domains (episodic memory −0·12 [0·04], p=0·00090; semantic memory −0·10 [0·04], p=0·013; working memory −0·07 [0·03], p=0·045; perceptual speed −0·12 [0·04], p=0·0012), and a non-significant association was noted for visuospatial abilities (−0·07 [0·03], p=0·052). Findings were unchanged in analyses controlling for the presence of APOE ε4 allele or vascular risk factors. Cerebral atherosclerosis and arteriolosclerosis are associated with Alzheimer's disease dementia, and are also associated with low scores in most cognitive domains. Cerebral vessel pathology might be an under-recognised risk factor for Alzheimer's disease dementia. US National Institutes of Health.

In a world with an ageing population, dementia has become an urgent threat to global health and wellbeing. Psychosocial and lifestyle factors, such as higher socioeconomic positions, longer times spent in education, greater occupational complexity, reduced stress at work, and engagement in mental, physical, and social activities, have been hypothesised to supply resilience against dementia. Although questions remain surrounding the role of these factors in the development of dementia, scientific advancements have considerably expanded our understanding of modifiable psychosocial and lifestyle factors and their neuroprotective and compensatory influences over a life course. Evidence from observational studies is robust enough to suggest that stimulating psychosocial and lifestyle factors are protective against dementia. And, although the corresponding evidence from intervention studies is still scarce, public health campaigns promoting psychosocial and lifestyle factors might improve the health and wellbeing of people aged 60 years and older.

Chronic traumatic encephalopathy (CTE) is a neurodegeneration characterized by the abnormal accumulation of hyperphosphorylated tau protein within the brain. Like many other neurodegenerative conditions, at present, CTE can only be definitively diagnosed by post-mortem examination of brain tissue. As the first part of a series of consensus panels funded by the NINDS/NIBIB to define the neuropathological criteria for CTE, preliminary neuropathological criteria were used by 7 neuropathologists to blindly evaluate 25 cases of various tauopathies, including CTE, Alzheimer’s disease, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy, and parkinsonism dementia complex of Guam. The results demonstrated that there was good agreement among the neuropathologists who reviewed the cases (Cohen’s kappa, 0.67) and even better agreement between reviewers and the diagnosis of CTE (Cohen’s kappa, 0.78). Based on these results, the panel defined the pathognomonic lesion of CTE as an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern. The group also defined supportive but non-specific p-tau-immunoreactive features of CTE as: pretangles and NFTs affecting superficial layers (layers II–III) of cerebral cortex; pretangles, NFTs or extracellular tangles in CA2 and pretangles and proximal dendritic swellings in CA4 of the hippocampus; neuronal and astrocytic aggregates in subcortical nuclei; thorn-shaped astrocytes at the glial limitans of the subpial and periventricular regions; and large grain-like and dot-like structures. Supportive non-p-tau pathologies include TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures in the hippocampus, anteromedial temporal cortex and amygdala. The panel also recommended a minimum blocking and staining scheme for pathological evaluation and made recommendations for future study. This study provides the first step towards the development of validated neuropathological criteria for CTE and will pave the way towards future clinical and mechanistic studies.

Background Neuropsychiatric symptoms (NPS) are prevalent in individuals with Alzheimer's disease (AD), impacting disease progression and patient quality of life. AD pathology (amyloid and tau) and related TDP‐43 neuropathology may contribute to NPS. The National Alzheimer's Coordinating Center (NACC) database was used to explore the relationship between NPS and AD, TDP‐43 neuropathology and clinical diagnosis. Method A total of 1391 participants from the NACC database were included in the analysis, with data available on NPS (NPI‐Q domains), clinical diagnosis (normal cognition, impaired‐not‐MCI, MCI, and dementia) and neuropathology. Logistic and linear regression models assessed associations between NPS presence or absence, severity and interactions involving clinical diagnosis and AD and TDP‐43 neuropathology, including their co‐occurrence. Age, sex, education, cognitive scores, and APOE e4 status were adjusted for in all models. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to quantify the effects. Result The regression models for several NPS domains were statistically significant with clinical diagnosis being the most consistent across domains (Table 1). The clinical diagnosis and neuropathology were significantly associated with apathy (OR = 2.80, 95% CI [2.13, 3.66], p < .001; OR = 1.74, 95% CI [1.09, 2.80], p = .021, respectively) and delusions (OR = 2.71, 95% CI [1.44, 5.09], p = .002; OR = 3.12, 95% CI [1.14, 8.54], p = .026, respectively). Interaction effects were also observed for apathy (OR = 0.88, 95% CI [0.77, 1.00], p = .049) and delusions (OR = 0.75, 95% CI [0.58, 0.98], p = .038). Clinical diagnosis also influenced NPS severity in nighttime behaviors (β = 1.14, 95% CI [0.02, 0.26], p = .018) and apathy (β = 0.16, 95% CI [0.01, 0.32], p = .039). Age, sex, education, cognitive scores, and APOE e4 status had domain‐specific effects. Conclusion The findings highlight the role of clinical diagnosis on NPS across domains, with AD and TDP‐43 neuropathology and demographic factors exerting domain‐specific effects, most notably in delusions and apathy. Interaction effects between neuropathology and clinical diagnosis were only seen in apathy, suggesting that pathology and clinical diagnosis may have independent effects on NPS. Future research is warranted to examine these effects longitudinally.

Although Alzheimer disease and related dementias (ADRDs) have long been considered nonpreventable and even an inevitable consequence of aging, recent findings from longitudinal studies indicate a downtrend in age-adjusted incidence and prevalence of ADRDs in Western countries. This remarkable trend might be the result of improved management of so-called modifiable risk factors. The aim of this review is to present evidence of modifiable factors of ADRDs in a life-course approach. A PubMed database search was conducted between November and December 2020 to identify relevant studies evaluating the role of modifiable risk factors in the development of ADRDs. Key words (Alzheimer's disease and modifiable risk factors) were used and specific inclusion and exclusion criteria applied. This review identifies modifiable factors for ADRDs divided into early-life, middle-life, and late-life risk factors, depending on the available window of preventive action. According to life course exposure, factors can be protective or deleterious for ADRDs that participate in the underlying pathophysiologic complexity of these diseases as well as the complexity for public health measures implementations. The available evidence derived from epidemiologic, preclinical, interventional studies suggest that modifiable risk factors for ADRDs offer opportunities for therapeutic and preventive actions.

The term chronic traumatic encephalopathy (CTE) has recently entered public consciousness via media reports and even a Hollywood movie. However, in contrast to general impressions, the incidence of CTE is unknown, the clinical diagnostic criteria have not been agreed upon and the current neuropathological characterization of CTE is acknowledged as preliminary. Additionally, few studies have compared the pathologies of CTE with those of other neurodegenerative disorders or of age-matched controls. Consequently, disagreement continues about the neuropathological aspects that make CTE unique. Furthermore, CTE is widely considered to be a consequence of exposure to repeated head blows, but evidence suggests that a single moderate or severe traumatic brain injury can also induce progressive neuropathological changes. These unresolved aspects of CTE underlie disparate claims about its clinical and pathological features, leading to confusion among the public and health-care professionals alike.In this Perspectives article, Smith et al. address the misconceptions about the clinical and pathological features of chronic traumatic encephalopathy that cause confusion and controversy not only in the public but also among health-care professionals.

Alzheimer disease (AD) is the leading cause of dementia, and is set to rise in prevalence with the growth in the global elderly population. Here, Reitz and colleagues provide a comprehensive overview of our current understanding of AD epidemiology. The authors also examine the diagnostic criteria for this disease, and discuss the use of various biomarkers to improve the accuracy of AD detection and risk prediction. The global prevalence of dementia is estimated to be as high as 24 million, and is predicted to double every 20 years through to 2040, leading to a costly burden of disease. Alzheimer disease (AD) is the leading cause of dementia and is characterized by a progressive decline in cognitive function, which typically begins with deterioration in memory. Before death, individuals with this disorder have usually become dependent on caregivers. The neuropathological hallmarks of the AD brain are diffuse and neuritic extracellular amyloid plaques—which are frequently surrounded by dystrophic neurites—and intracellular neurofibrillary tangles. These hallmark pathologies are often accompanied by the presence of reactive microgliosis and the loss of neurons, white matter and synapses. The etiological mechanisms underlying the neuropathological changes in AD remain unclear, but are probably affected by both environmental and genetic factors. Here, we provide an overview of the criteria used in the diagnosis of AD, highlighting how this disease is related to, but distinct from, normal aging. We also summarize current information relating to AD prevalence, incidence and risk factors, and review the biomarkers that may be used for risk assessment and in diagnosis. Key Points The unprecedented level of aging occurring in developed nations will lead to an enormous burden of Alzheimer disease (AD) The primary pathological hallmarks in AD brain tissue—diffuse and neuritic extracellular amyloid plaques and intracellular neurofibrillary tangles—are well known, but the underlying etiologies of these pathologies remain unclear The diagnosis of AD in living patients is based on clinical examination—no definite diagnostic test is currently available—but may be supported by the use of clinical biomarkers AD heritability varies from 58–79% depending on age at onset; however, only a portion of the likely substantial genetic contribution to this disease has been determined Several nongenetic factors (including recognized vascular risk factors) have been associated with AD, but the underlying mechanisms linked to these factors are uncertain