The experience of dementia

2020 ◽  
pp. 409-426
Author(s):  
Keith Oliver ◽  
Hilary Doxford ◽  
Louise Lafortune ◽  
Carol Brayne ◽  
June Hennell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
The Third ◽  
Early Stages ◽  
Timely Diagnosis ◽  
Living Well ◽  
The Moment ◽  
The Impact

This chapter consists of four sections that consider various aspects of the journey through dementia. The first two parts (by Keith Oliver and Hilary Doxford) describe the early stages of dementia, the process of getting a diagnosis, and the challenges of living well with dementia. The third section (Louise Lafortune and Carol Brayne) discusses the tensions between ‘early’ and ‘timely’ diagnosis, and also the issues that arise from having biomarkers that potentially enable us to diagnose conditions like Alzheimer’s disease before a person has any concerns or symptoms. At the moment, there is little evidence that people stand to benefit greatly in a diagnosis before the emergence of clinical symptoms. June Hennell concludes the chapter by describing her journey as a carer and adjusting to life after bereavement. The chapter thus provides a balanced and authentic view of how people respond to the impact of diagnosis and life afterwards.

scholarly journals Hyperactivity Induced by Soluble Amyloid-β Oligomers in the Early Stages of Alzheimer's Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Audrey Hector ◽  
Jonathan Brouillette
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Epileptiform Activity ◽  
Amyloid Β ◽  
Gamma Oscillations ◽  
Synaptic Activity ◽  
Early Stages ◽  
The Impact

Soluble amyloid-beta oligomers (Aβo) start to accumulate in the human brain one to two decades before any clinical symptoms of Alzheimer's disease (AD) and are implicated in synapse loss, one of the best predictors of memory decline that characterize the illness. Cognitive impairment in AD was traditionally thought to result from a reduction in synaptic activity which ultimately induces neurodegeneration. More recent evidence indicates that in the early stages of AD synaptic failure is, at least partly, induced by neuronal hyperactivity rather than hypoactivity. Here, we review the growing body of evidence supporting the implication of soluble Aβo on the induction of neuronal hyperactivity in AD animal models, in vitro, and in humans. We then discuss the impact of Aβo-induced hyperactivity on memory performance, cell death, epileptiform activity, gamma oscillations, and slow wave activity. We provide an overview of the cellular and molecular mechanisms that are emerging to explain how Aβo induce neuronal hyperactivity. We conclude by providing an outlook on the impact of hyperactivity for the development of disease-modifying interventions at the onset of AD.

scholarly journals Unraveling Aβ-Mediated Multi-Pathway Calcium Dynamics in Astrocytes: Implications for Alzheimer’s Disease Treatment From Simulations

2021 ◽  
Vol 12 ◽  
Author(s):  
Langzhou Liu ◽  
Huayi Gao ◽  
Alexey Zaikin ◽  
Shangbin Chen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Ryanodine Receptors ◽  
Amyloid Β ◽  
Calcium Oscillations ◽  
Resting Membrane Potential ◽  
Amyloid Β Peptide ◽  
Channel Blockers ◽  
The Impact

The accumulation of amyloid β peptide (Aβ) in the brain is hypothesized to be the major factor driving Alzheimer’s disease (AD) pathogenesis. Mounting evidence suggests that astrocytes are the primary target of Aβ neurotoxicity. Aβ is known to interfere with multiple calcium fluxes, thus disrupting the calcium homeostasis regulation of astrocytes, which are likely to produce calcium oscillations. Ca2+ dyshomeostasis has been observed to precede the appearance of clinical symptoms of AD; however, it is experimentally very difficult to investigate the interactions of many mechanisms. Given that Ca2+ disruption is ubiquitously involved in AD progression, it is likely that focusing on Ca2+ dysregulation may serve as a potential therapeutic approach to preventing or treating AD, while current hypotheses concerning AD have so far failed to yield curable therapies. For this purpose, we derive and investigate a concise mathematical model for Aβ-mediated multi-pathway astrocytic intracellular Ca2+ dynamics. This model accounts for how Aβ affects various fluxes contributions through voltage-gated calcium channels, Aβ-formed channels and ryanodine receptors. Bifurcation analysis of Aβ level, which reflected the corresponding progression of the disease, revealed that Aβ significantly induced the increasing [Ca2+]i and frequency of calcium oscillations. The influence of inositol 1,4,5-trisphosphate production (IP3) is also investigated in the presence of Aβ as well as the impact of changes in resting membrane potential. In turn, the Ca2+ flux can be considerably changed by exerting specific interventions, such as ion channel blockers or receptor antagonists. By doing so, a “combination therapy” targeting multiple pathways simultaneously has finally been demonstrated to be more effective. This study helps to better understand the effect of Aβ, and our findings provide new insight into the treatment of AD.

scholarly journals Fiber Tracts Anomalies in APPxPS1 Transgenic Mice Modeling Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
H. Chen ◽  
S. Epelbaum ◽  
B. Delatour
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Clinical Symptoms ◽  
Anterior Commissure ◽  
Fiber Tract ◽  
Fiber Tracts ◽  
Age Related ◽  
The Impact ◽  
The Brain

Amyloid beta (A) peptides are known to accumulate in the brain of patients with Alzheimer's disease (AD). However, the link between brain amyloidosis and clinical symptoms has not been elucidated and could be mediated by secondary neuropathological alterations such as fiber tracts anomalies. In the present study, we have investigated the impact of A overproduction in APPxPS1 transgenic mice on the integrity of forebrain axonal bundles (corpus callosum and anterior commissure). We found evidence of fiber tract volume reductions in APPxPS1 mice that were associated with an accelerated age-related loss of axonal neurofilaments and a myelin breakdown. The severity of these defects was neither correlated with the density of amyloid plaques nor associated with cell neurodegeneration. Our data suggest that commissural fiber tract alterations are present in A-overproducing transgenic mice and that intracellular A accumulation preceding extracellular deposits may act as a trigger of such morphological anomalies.

scholarly journals The Impact of COVID-19 Quarantine on Patients With Dementia and Family Caregivers: A Nation-Wide Survey

2021 ◽  
Vol 12 ◽  
Author(s):  
Innocenzo Rainero ◽  
Amalia C. Bruni ◽  
Camillo Marra ◽  
Annachiara Cagnin ◽  
Laura Bonanni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family Caregivers ◽  
Odds Ratio ◽  
Protective Factor ◽  
Clinical Symptoms ◽  
Lewy Bodies ◽  
Behavioral Symptoms ◽  
Nation Wide Survey ◽  
The Impact

IntroductionPrevious studies showed that quarantine for pandemic diseases is associated with several psychological and medical effects. The consequences of quarantine for COVID-19 pandemic in patients with dementia are unknown. We investigated the clinical changes in patients with Alzheimer’s disease and other dementias, and evaluated caregivers’ distress during COVID-19 quarantine.MethodsThe study involved 87 Italian Dementia Centers. Patients with Alzheimer’s Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD), and Vascular Dementia (VD) were eligible for the study. Family caregivers of patients with dementia were interviewed by phone in April 2020, 45 days after quarantine declaration. Main outcomes were patients’ changes in cognitive, behavioral, and motor symptoms. Secondary outcomes were effects on caregivers’ psychological features.Results4913 patients (2934 females, 1979 males) fulfilled the inclusion criteria. Caregivers reported a worsening in cognitive functions in 55.1% of patients, mainly in subjects with DLB and AD. Aggravation of behavioral symptoms was observed in 51.9% of patients. In logistic regression analysis, previous physical independence was associated with both cognitive and behavioral worsening (odds ratio 1.85 [95% CI 1.42–2.39], 1.84 [95% CI 1.43–2.38], respectively). On the contrary, pandemic awareness was a protective factor for the worsening of cognitive and behavioral symptoms (odds ratio 0.74 [95% CI 0.65–0.85]; and 0.72 [95% CI 0.63–0.82], respectively). Approximately 25.9% of patients showed the onset of new behavioral symptoms. A worsening in motor function was reported by 36.7% of patients. Finally, caregivers reported a high increase in anxiety, depression, and distress.ConclusionOur study shows that quarantine for COVID-19 is associated with an acute worsening of clinical symptoms in patients with dementia as well as increase of caregivers’ burden. Our findings emphasize the importance to implement new strategies to mitigate the effects of quarantine in patients with dementia.

p35 Deficiency Accelerates HMGB-1-mediated Neuronal Death in the Early Stages of an Alzheimer’s disease Mouse Model

2013 ◽  
Vol 10 (8) ◽  
pp. 829-843 ◽  
Author(s):  
Ahram Jang ◽  
Hyunjeong Liew ◽  
Yun-Mi Kim ◽  
Heesoon Choi ◽  
Saeromi Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Neuronal Death ◽  
Early Stages
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