Oropharyngeal dysphagia is a common condition after stroke, Parkinson’s disease (PD), and Alzheimer’s disease (AD), and can cause serious complications including malnutrition, aspiration pneumonia, ...and premature mortality. Despite its high prevalence among the elderly and associated serious complications, dysphagia is often overlooked and under-diagnosed in vulnerable patient populations. This systematic review aimed to improve understanding and awareness of the prevalence of dysphagia in susceptible patient populations. MEDLINE, EMBASE, the Cochrane library, PROSPERO, and disease-specific websites were systematically searched for studies reporting oropharyngeal dysphagia prevalence or incidence in people with stroke, PD, AD, traumatic brain injury, and community-acquired pneumonia, from the USA, Canada, France, Germany, Italy, Spain, UK, Japan, China, and regional studies. The quality of study descriptions were assessed based on STROBE guidelines. A total of 1207 publications were identified and 33 met inclusion criteria: 24 in stroke, six in PD, two in traumatic brain injury, and one in patients with traumatic brain injury. Dysphagia was reported in 8.1–80 % of stroke patients, 11–81 % of PD, 27–30 % of traumatic brain injury patients, and 91.7 % of patients with community-acquired pneumonia. No relevant studies of dysphagia in AD were identified. This review demonstrates that dysphagia is highly prevalent in these populations, and highlights discrepancies between studies, gaps in dysphagia research, and the need for better dysphagia management starting with a reliable, standardized, and validated method for oropharyngeal dysphagia identification.
We have previously shown delayed poststroke dementia in elderly (≥75 years old) stroke survivors is associated with medial temporal lobe atrophy; however, the basis of the structural and functional ...changes is unknown.
Using 3-dimensional stereological methods, we quantified hippocampal pyramidal neuronal volumes and densities in a total of 95 postmortem samples from demented and nondemented poststroke survivors within our prospective Cognitive Function after Stroke study and subjects pathologically diagnosed with vascular dementia, Alzheimer disease, and mixed Alzheimer disease and vascular dementia syndrome.
Hippocampal CA1 but not CA2 subfield neuron density was affected in poststroke, Alzheimer disease, vascular dementia, and mixed dementia groups relative to control subjects (P<0.05). Neuronal volume was reduced in the poststroke dementia relative to poststroke nondemented group in both CA1 and CA2, although there were no apparent differences in neuronal density. Poststroke nondemented neuronal volumes were similar to control subjects but greater than in all dementias (P<0.05). Neuronal volumes positively correlated with global cognitive function and memory function in both CA1 and CA2 in poststroke subjects (P<0.01). Degrees of neuronal atrophy and loss were similar in the poststroke dementia and vascular dementia groups. However, in the entorhinal cortex layer V, neuronal volumes were only impaired in the mixed and Alzheimer disease groups (P<0.05).
Our results suggest hippocampal neuronal atrophy is an important substrate for dementia in both cerebrovascular and neurodegenerative disease.
Objectives
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by strategic white matter (WM) hyperintensities on MRI. Pathological ...features include WM degeneration, arteriolosclerosis, lacunar infarcts, and the deposition of granular osmiophilic material. Based on the hypothesis that the gliovascular unit is compromised, we assessed the nature of astrocyte damage in the deep WM of CADASIL subjects.
Methods
We evaluated post‐mortem brains from CADASIL, cerebral small vessel disease, similar age cognitively normal and older control subjects. Standard immunohistochemical, immunofluorescent, and unbiased stereological methods were used to evaluate the distribution of astrocytes, microvessels, and autophagy markers in five different brain regions.
Results
Compared to the controls, the deep WM of CADASIL subjects overall showed increased numbers of glial fibrillary acidic protein (GFAP)‐positive clasmatodendritic astrocytes (P=0.037) and a decrease in the percentage of normal appearing astrocytes (P=0.025). In accord with confluent WM hyperintensities, the anterior temporal pole contained abundant clasmatodendritic astrocytes with displaced aquaporin 4 immunoreactivity. Remarkably, we also found strong evidence for the immunolocalization of autophagy markers including microtubule‐associated protein 1, light chain 3 (LC3), and sequestosome 1/p62 and Caspase‐3 in GFAP‐positive clasmatodendritic cells, particularly within perivascular regions of the deep WM. LC3 was co‐localized in more than 90% of the GFAP‐positive clasmatodendrocytes.
Conclusions
Our novel findings show astrocytes undergo autophagy‐like cell death in CADASIL, with the anterior temporal pole being highly vulnerable. We propose astrocytes transform from normal appearing type A to hypertrophic type B and eventually to clasmatodendritic type C cells. These observations also suggest the gliovascular unit of the deep WM is severely impaired in CADASIL.
ABSTRACTHippocampal atrophy is widely recognized in Alzheimer disease (AD). Whether neurons within hippocampal subfields are similarly affected in other aging-related dementias, particularly after ...stroke, remains an open question. We investigated hippocampal CA3 and CA4 pyramidal neuron volumes and densities using 3-dimensional stereologic techniques in postmortem samples from a total of 67 subjectspoststoke demented (PSD; n = 11), nondemented stroke survivors (PSND) and PSD patients from the CogFAST (Cognitive Function After Stroke) cohort (n = 13), elderly controls (n = 12), and subjects diagnosed as having vascular dementia (n = 11), AD (n = 10), and mixed AD and vascular dementia (n = 10). We found that CA3 and CA4 neuron volumes were reduced in PSD samples compared with those in PSND samples. The CA3 and CA4 neuron volumes were positively correlated with poststroke global cognitive function but were not associated with the burden of AD pathology. There were no differences in total neuron densities in either subfield in any of the groups studied. Our results indicate that selective reductions in CA4 and to a lesser extent CA3 neuron volumes may be related to post stroke cognitive impairment and aging-related dementias. These data suggest that CA4 neurons are vulnerable to disease processes and support our previous finding that a reduction in hippocampal neuron volume predominantly reflects vascular mechanisms as contributing to dementia after stroke.
Background: Delayed post-stroke dementia (PSD) affects up to 50% of all stroke survivors, developing months or years after the initial stroke. However, the underlying mechanisms which cause PSD are ...unclear. Hippocampal atrophy is associated with PSD and vascular dementia, and hippocampal neurons are known to be particularly vulnerable in stroke and cerebrovascular disease. This work aimed to identify neuropathological characteristics and mechanisms contributing to cognitive decline in post-stroke survivors, focusing on the involvement of regional specific hippocampal neurons. Methods: Post-mortem brain tissue from the prospective CogFAST study was analyzed to compare pathological changes in stroke survivors who developed PSD with those who maintained normal cognitive function (PSND). Tissue from elderly controls and pathologically defined dementia groups lzheimer’s disease ( D) vascular dementia (VaD), mixed AD with VaD (MD); were also analysed for comparison with different disease aetiologies. Histological and immunohistochemical staining with quantitative image analysis and 3D morphometric analysis was carried out in paraffin-embedded sections, and protein immunoblotting was used in frozen hippocampal tissue. Key findings: Neuronal volumes in hippocampal subfields CA1-4 were reduced in PSD, VaD and AD subjects compared to elderly controls and PSND. Neuronal volume was also related to post-stroke cognitive function. There were no differences in dendritic length-density, hippocampal myelin loss, or autophagy markers between PSD and PSND. However, neuronal volumes were related to hippocampal tau pathology burden, reactive astrocyte density and myelin density in the alveus. Interestingly, the PSND subjects had greater burden of hippocampal amyloid-β than PSD. There were no quantitative differences in markers for astrocytes or microglia between the post-stroke groups. Conclusion: These findings suggest that neuronal volume loss is associated with post- stroke and ageing-related dementia. There were no relationships between the observed neuronal changes and AD pathology in stroke survivors, suggesting an important role for cerebrovascular disease processes.
Background: Delayed post-stroke dementia (PSD) affects up to 50% of all stroke survivors, developing months or years after the initial stroke. However, the underlying mechanisms which cause PSD are ...unclear. Hippocampal atrophy is associated with PSD and vascular dementia, and hippocampal neurons are known to be particularly vulnerable in stroke and cerebrovascular disease. This work aimed to identify neuropathological characteristics and mechanisms contributing to cognitive decline in post-stroke survivors, focusing on the involvement of regional specific hippocampal neurons. Methods: Post-mortem brain tissue from the prospective CogFAST study was analyzed to compare pathological changes in stroke survivors who developed PSD with those who maintained normal cognitive function (PSND). Tissue from elderly controls and pathologically defined dementia groups lzheimer’s disease ( D) vascular dementia (VaD), mixed AD with VaD (MD); were also analysed for comparison with different disease aetiologies. Histological and immunohistochemical staining with quantitative image analysis and 3D morphometric analysis was carried out in paraffin-embedded sections, and protein immunoblotting was used in frozen hippocampal tissue. Key findings: Neuronal volumes in hippocampal subfields CA1-4 were reduced in PSD, VaD and AD subjects compared to elderly controls and PSND. Neuronal volume was also related to post-stroke cognitive function. There were no differences in dendritic length-density, hippocampal myelin loss, or autophagy markers between PSD and PSND. However, neuronal volumes were related to hippocampal tau pathology burden, reactive astrocyte density and myelin density in the alveus. Interestingly, the PSND subjects had greater burden of hippocampal amyloid-β than PSD. There were no quantitative differences in markers for astrocytes or microglia between the post-stroke groups. Conclusion: These findings suggest that neuronal volume loss is associated with post- stroke and ageing-related dementia. There were no relationships between the observed neuronal changes and AD pathology in stroke survivors, suggesting an important role for cerebrovascular disease processes.
Obituaries: Jean Arthur Gemmell Gemmell, Elizabeth
BMJ. British medical journal (International ed.),
01/2001, Letnik:
322, Številka:
7277
Journal Article
Recenzirano
Former medical superintendent the Maternity Hospital, Aden, and medical officer to the Women's Medical Service of India (b 1904; q Edinburgh 1929), d 10 November 2000.
The New Zealand collembolan genus Holacanthella contains the largest species of springtails (Collembola) in the world. Using Illumina technology we have sequenced and assembled a draft genome and ...transcriptome from Holacanthella duospinosa (Salmon). We have used this annotated assembly to investigate the genetic basis of a range of traits critical to the evolution of the Hexapoda, the phylogenetic position of H. duospinosa and potential horizontal gene transfer events.
Our genome assembly was ~375 Mbp in size with a scaffold N50 of ~230 Kbp and sequencing coverage of ~180×. DNA elements, LTRs and simple repeats and LINEs formed the largest components and SINEs were very rare. Phylogenomics (370,877 amino acids) placed H. duospinosa within the Neanuridae. We recovered orthologs of the conserved sex determination genes thought to play a role in sex determination. Analysis of CpG content suggested the absence of DNA methylation, and consistent with this we were unable to detect orthologs of the DNA methyltransferase enzymes. The small subunit rRNA gene contained a possible retrotransposon. The Hox gene complex was broken over two scaffolds. For chemosensory ability, at least 15 and 18 ionotropic glutamate and gustatory receptors were identified, respectively. However, we were unable to identify any odorant receptors or their obligate co-receptor Orco. Twenty-three chitinase-like genes were identified from the assembly. Members of this multigene family may play roles in the digestion of fungal cell walls, a common food source for these saproxylic organisms. We also detected 59 and 96 genes that blasted to bacteria and fungi, respectively, but were located on scaffolds that otherwise contained arthropod genes.
The genome of H. duospinosa contains some unusual features including a Hox complex broken over two scaffolds, in a different manner to other arthropod species, a lack of odorant receptor genes and an apparent lack of environmentally responsive DNA methylation, unlike many other arthropods. Our detection of candidate horizontal gene transfer candidates confirms that this phenomenon is occurring across Collembola. These findings allow us to narrow down the regions of the arthropod phylogeny where key innovations have occurred that have facilitated the evolutionary success of Hexapoda.
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