Journal of Alzheimer's disease : JAD
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Neurocognitive disorders create important challenges for patients, their families, and clinicians who provide their health care. Early/timely detection in daily clinical practice allows for diagnosis and adequate treatment, psychosocial support, education, and engagement in shared decision-making related to health care, life planning, involvement in research, and financial matters. However, neurocognitive disorders, when present, are not detected or not diagnosed and not documented, in more than half of patients seen by primary care physicians. The aim of this paper is to highlight the strategies and the perspectives to improve the early/timely detection of neurocognitive disorders in daily clinical practice.
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Cataract surgery substantially improves patient quality of life. Despite the rising prevalence of dementia in the US, little is known about use of cataract surgery among this group. ⋯ US Medicare patients with dementia are less likely to undergo cataract surgery than those without dementia. This finding has implications for quality of care and dementia progression. More information is necessary to understand why rates of cataract surgery are lower for these patients, and to identify conditions where benefits of surgery may outweigh risks.
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Instrumental activities of daily living (IADL) impairment and apathy occur in early-stage Alzheimer's disease (AD) and are associated with regional atrophy and hypometabolism in vivo and greater tau burden at autopsy. ⋯ This exploratory study suggests that IADL impairment in AD is associated with medial temporal and frontal tau, especially in individuals with elevated amyloid, while apathy may be associated with right frontal tau.
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Ubiquitin Specific Protease-13 (USP13) is a de-ubiquinating enzyme that regulates protein ubiquitination and clearance. The role of USP13 is largely unknown in neurodegeneration. In this study we aim to demonstrate whether tau accumulation and/or clearance depends on ubiquitination/de-ubiquitination via USP-13. ⋯ Clearance of p-tau appears to be mediated by autophagy in these animal models. Taken together, these data suggest that USP13 knockdown reduces p-tau accumulation via regulation of ubiquitination/de-ubiquitination and mediates its clearance via autophagy and/or the proteasome. These results suggest that USP13 inhibition may be a therapeutic strategy to reduce accumulation of plaques and toxic p-tau in AD and human tauopathies.
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Alzheimer's disease (AD) is an age-related progressive form of dementia that features neuronal loss, intracellular tau, and extracellular amyloid-β (Aβ) protein deposition. Neurodegeneration is accompanied by neuroinflammation mainly involving microglia, the resident innate immune cell population of the brain. During AD progression, microglia shift their phenotype, and it has been suggested that they express matricellular proteins such as secreted protein acidic and rich in cysteine (SPARC) and Hevin protein, which facilitate the migration of other immune cells, such as blood-derived dendritic cells. ⋯ SPARC is highly expressed in AD brain and collocates to Aβ protein deposits, thus contributing actively to cerebral inflammation and subsequent tissue repair, and Hevin may be downregulated in the diseased state. However, further research is needed to reveal the exact roles of SPARC and Hevin proteins and associated signaling pathways in AD-related neuroinflammation. Nevertheless, normalizing SPARC/Hevin protein expression such as interdicting heightened SPARC protein expression may confer a novel therapeutic opportunity for modulating AD progression.