Suchergebnisse

AbstractSchool‐aged and adolescent children continue to demonstrate improvements in how they integrate and comprehend real‐time, auditory language over this developmental time period, which can have important implications for academic and social success. To better understand developmental changes in the neural processes engaged during language comprehension in this age group, we use electroencephalography to investigate how 8–9 year old, 12–13 year olds, and adults process semantics and syntax in naturally paced, auditory sentences. Participants listened to semantically and syntactically correct and incorrect sentences and were asked to complete an acceptability judgment task. When processing a semantic error, developmental differences were observed in theta, but not the N400, suggesting that the N400 may be too gross a measure to identify more subtle aspects of semantic development that occur in the school years. For the syntactic task, errors resulted in a larger P600 and greater beta decrease than correct sentences, but the amplitude and location of the P600 and amplitude of beta decreases differed as a function of age, suggesting specialization of syntactic skills is ongoing through adolescence. The current findings shed new light on the development of the neural oscillations supporting language comprehension and suggest that the neural substrates underlying semantic processing reach adult‐like levels at a younger age than those underlying syntactic processing.

Abstract

Background
Dementia results from multiple neuropathologies causing cognitive impairment sufficiently severe to affect functional status. However, these pathologies and functional impairment are common in persons without dementia. We examined the association of Alzheimer's disease (AD) and multiple other neuropathologies with instrumental and basic activities of daily living in persons with and without dementia.


Methods
Participants were 1 509 deceased from the Religious Orders Study or Rush Memory and Aging Project. Pathologic AD and 3 other AD indices were examined, in addition to 4 non-AD neurodegenerative pathologies: cerebral amyloid angiopathy (CAA), hippocampal sclerosis, TDP-43, and Lewy bodies, and 4 cerebrovascular pathologies: gross- and microinfarctions, athero- and arteriolosclerosis. Functional assessment included Lawton and Katz Index Instrumental and Basic Activities of Daily Living (IADL and BADL). Ordinal regression models adjusted for age, sex, and education were used to examine the association of neuropathologies with IADL and BADL.


Results
Alzheimer's disease and the other neuropathologies were associated with impaired IADL (all ps < .001) and with impaired BADL (ps < .01), except for atherosclerosis and CAA, which were not associated with BADL. The effects of most neuropathologies were largely affected by dementia. However, small effects on IADL remained for PHF-tau tangles after adjusting models for dementia. Direct effects of gross infarcts on IADL and BADL and of microinfarcts on BADL remained unchanged after adjusting the models for dementia.


Conclusions
Alzheimer's disease and all other neuropathologies are strongly associated with functional disability. The association of most neuropathologies with disability was eliminated or attenuated by dementia, except for gross infarcts and microinfarcts.

Abstract

Background
Mild cognitive impairment (MCI) and parkinsonism affect many older adults. The objective of this study was to determine the sequence of their occurrence and associated risk of death.


Methods
A total of 1255 community-dwelling unimpaired participants from 2 epidemiological cohorts were examined annually. MCI was based on neuropsychological testing and parkinsonism was based on the motor portion of the modified Unified Parkinson's Disease Rating Scale. A multistate Cox proportional hazards model simultaneously examined incidences of MCI, parkinsonism, and death.


Results
The average age at baseline was 76.5 years (standard deviation [SD] = 7.2) and 73% were female. Incident MCI occurred almost as commonly as incident parkinsonism, yet compared with no impairment, the risk of death was higher for MCI (hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.34, 2.47), but it was not different for parkinsonism (HR = 1.29; 95% CI =0.95, 1.75). The risk of death for participants with incident MCI who progressed to parkinsonism (40%) was not significantly different from those with MCI alone (HR = 1.25, 95% CI = 0.93, 1.69). However, the risk of death for participants with incident parkinsonism who progressed to MCI (51%) was significantly higher than those who did not progress (HR = 1.67, 95% CI = 1.27, 2.18), indicating that the risk of death is highest with the incidence of MCI.


Conclusions
The varied patterns of sequential occurrence of cognitive and motor impairment and associated risk of death suggest much greater heterogeneity than previously recognized. Further work is needed to determine the biology underlying the temporal evolution of these phenotypes, and if identification of the various subtypes improves risk stratification.

INTRODUCTION: In recent years, there has been growing discussion to better understand the pathophysiological mechanisms of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) and how they may be linked to an increased risk of neurodegenerative diseases including Alzheimer's disease (AD) in veterans. METHODS: Building on that discussion, and subsequent to a special issue of Alzheimer's & Dementia published in June, 2014, which focused on military risk factors, the Alzheimer's Association convened a continued discussion of the scientific community on December 1, 2016. RESULTS: During this meeting, participants presented and evaluated progress made since 2012 and identified outstanding knowledge gaps regarding factors that may impact veterans' risk for later life dementia. DISCUSSION: The following is a summary of the invited presentations and moderated discussions of both the review of scientific understanding and identification of gaps to inform further investigations.

Introduction: In recent years, there has been growing discussion to better understand the pathophysiological mechanisms of traumatic brain injury and post-traumatic stress disorder and how they may be linked to an increased risk of neurodegenerative diseases including Alzheimer's disease in veterans. Methods: Building on that discussion, and subsequent to a special issue of Alzheimer's & Dementia published in June 2014, which focused on military risk factors, the Alzheimer's Association convened a continued discussion of the scientific community on December 1, 2016. Results: During this meeting, participants presented and evaluated progress made since 2012 and identified outstanding knowledge gaps regarding factors that may impact veterans' risk for later life dementia. Discussion: The following is a summary of the invited presentations and moderated discussions of both the review of scientific understanding and identification of gaps to inform further investigations.

The Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the "A, T, N System" (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development. In addition, challenges and barriers to the potential adoption of this new framework will be discussed. Finally, future directions for research will be proposed.