BackgroundAs Huntington's disease (HD) is a progressive disease for which there is no cure yet, patients in the advanced stage of HD may benefit from palliative care.ObjectiveTo review the... Show moreBackgroundAs Huntington's disease (HD) is a progressive disease for which there is no cure yet, patients in the advanced stage of HD may benefit from palliative care.ObjectiveTo review the literature focusing on palliative care in advanced stage HD, and the level of evidence.MethodsPublications between 1993 and October 29th, 2021 from 8 databases (Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier, PMC PubMed Central and Pubmed) were included. The literature was deductively classified based on topics that are part of the definition of palliative care, or as care-related topics that emerged from the literature. Levels of evidence I (high) - V (low) were determined as defined by the Joanna Briggs Institute.ResultsOur search resulted in 333 articles, 38 of which were included. The literature covered four domains of palliative care: physical care, psychological care, spiritual care, and social care. Four other topics in the literature were: advance care planning, end-of-life needs assessments, pediatric HD care, and need for health care services. Most literature was underpinned by a low level of evidence, except for the topics on social care (Level III-V), advance care planning (Level II-V) and end-of-life needs assessments (Level II-III).ConclusionsTo deliver adequate palliative care in advanced HD, both general and HD-specific symptoms and problems need to be addressed. As the level of evidence in existing literature is low, further research is essential to improve palliative care and to meet patient's wishes and needs. Show less
Dementia is a progressive, life-limiting disease. A palliative approach to care, that focuses on the quality of life of people with dementia and their relatives, is therefore indicated. Advance... Show moreDementia is a progressive, life-limiting disease. A palliative approach to care, that focuses on the quality of life of people with dementia and their relatives, is therefore indicated. Advance care planning is core to palliative care. Relatives play a major role in this, because people with dementia often become unable to indicate their preferences for future care. Palliative dementia care is still sub optimally implemented, however. Nursing home staff and relatives of people with dementia need information about dementia and palliative care to ensure it is optimally implemented. Also, ongoing communication between everyone involved in the care of a person with dementia is required, including discussions about future care needs. This facilitates a palliative care approach in dementia. These conclusions result from a survey among elderly care physicians, a systematic review, care plan data in nursing homes and an intervention study in two nursing homes: the mySupport study. It appears that relatives want timely information about the end of life with dementia. That way they can prepare. Although physicians are usually the ones who educate relatives, nursing staff often have a stronger relationship with relatives. After training, they can play an important role in providing information. Show less
The current symptomatic treatment for cognitive dysfunction due to dementia (eg Alzheimer's disease) is moderately effective and causes dose limiting side effects. This thesis describes the phase 1... Show moreThe current symptomatic treatment for cognitive dysfunction due to dementia (eg Alzheimer's disease) is moderately effective and causes dose limiting side effects. This thesis describes the phase 1 development of new symptomatic treatments; Gln-1062 (pro-drug of galantamine) and HTL0009936 and HTL0018318 (both M1 muscarinic receptor partial agonists). Additionally, a new methodology was investigated, which can be applied when demonstrating pharmacological effects (biperiden challenge model), and a review of all biomarkers that were used to measure cholinergic effects is presented. Show less
Neurodegenerative diseases are hallmarked by protein inclusions and cell loss in disease-related brain regions, but the molecular mechanisms that lead to the pathological and symptomatic hallmarks... Show moreNeurodegenerative diseases are hallmarked by protein inclusions and cell loss in disease-related brain regions, but the molecular mechanisms that lead to the pathological and symptomatic hallmarks of neurodegeneration are still not fully understood. In this thesis, we make use of bioinformatics approaches to analyze a high-resolution spatial gene expression atlas of the healthy human brain generated by the Allen Institute of Brain Science. Spatial transcriptomics allows examining the molecular and functional organization of the human brain and can be combined with neuroimaging data to identify brain regions and anatomical structures that are vulnerable to cell loss in neurodegenerative diseases. By combining both data modalities, we examined healthy molecular functions in brain regions associated with disease vulnerability based on neuroimaging features, namely gray matter loss within brain networks in individuals with Parkinson’s disease, Huntington’s disease, and individuals at risk of schizophrenia. With this thesis, we have shown that by applying data-driven computational methods we can explore the whole genome and find gene expression patterns informative of regional brain vulnerability in neurodegenerative diseases. Our methods can similarly be applied to unravel the molecular mechanisms in other neurodegenerative diseases, and potentially even reveal shared mechanisms between neurological disorders. Show less
Glucocorticoid hormones have important effects on brain function in the context of acute and chronic stress. Many of these are mediated by the glucocorticoid receptor (GR). GR has transcriptional... Show moreGlucocorticoid hormones have important effects on brain function in the context of acute and chronic stress. Many of these are mediated by the glucocorticoid receptor (GR). GR has transcriptional activity which is highly context-specific and differs between tissues and even between cell types. The outcome of GR-mediated transcription depends on the interactome of associated coregulators. Selective GR modulators (SGRMs) are a class of GR ligands that can be used to activate only a subset of GR-coregulator interactions, thereby giving the possibility to induce a unique combination of agonistic and antagonistic GR properties. We describe SGRM action in animal models of brain function and pathology, and argue for their utility as molecular filters, to characterize context-specific GR interactome and transcriptional activity that are responsible for particular glucocorticoid-driven effects in cognitive processes such as memory consolidation. The ultimate objective of this approach is to identify molecular processes that are responsible for adaptive and maladaptive effects of glucocorticoids in the brain. Show less
Martino, P. di; Censi, R.; Gigliobianco, M.R.; Zerrillo, L.; Magnoni, F.; Agas, D.; ... ; Lupidi, G. 2017
this thesis investigates a family with autosomal dominant neuronal ceroid lipofuscinosis, with chapters on clinical neurology, neuropathology, neurogenetics, neurophysiology, auditory and visual... Show morethis thesis investigates a family with autosomal dominant neuronal ceroid lipofuscinosis, with chapters on clinical neurology, neuropathology, neurogenetics, neurophysiology, auditory and visual aspects. Show less
