Treatment of a Whole Population Sample of Alzheimer’s Disease with Donepezil over a 4-Year Period: Lessons Learned

2008 ◽  
Vol 25 (3) ◽  
pp. 226-231 ◽  
Author(s):  
Sarah Lyle ◽  
Moni Grizzell ◽  
Sasi Willmott ◽  
Susan Benbow ◽  
Michael Clark ◽  
...  
2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 850-850
Author(s):  
Nicole Dawson ◽  
Heather Menne

Abstract The National Institute on Aging recognizes the importance of identifying promising non-pharmacological interventions (NPI) to promote health in individuals with Alzheimer’s disease and related dementias. Several systematic reviews have been completed investigating exercise in this population resulting in mixed evidence regarding efficacy across functional domains. It is critical to investigate the methodological factors from the original interventions for a true understanding of these findings as to not outright dismiss exercise as beneficial. One example is Ohio’s replication of Reducing Disability in Alzheimer’s Disease (n=508), which resulted in no significant improvements in physical performance for individuals with dementia ((gait speed (p=.81), balance (p=.82), functional reach (p=.58)). In this investigation, along with many others, researchers were not guided by key principles of exercise science leading to critical intervention design and methodological flaws. Thus, exercise interventions for individuals with dementia need to include interpretations of non-findings and report key factors affecting the outcomes.


Author(s):  
David Vaquero-Puyuelo ◽  
Concepción De-la-Cámara ◽  
Beatriz Olaya ◽  
Patricia Gracia-García ◽  
Antonio Lobo ◽  
...  

(1) Introduction: Dementia is a major public health problem, and Alzheimer’s disease (AD) is the most frequent subtype. Clarifying the potential risk factors is necessary in order to improve dementia-prevention strategies and quality of life. Here, our purpose was to investigate the role of the absence of hedonic tone; anhedonia, understood as the reduction on previous enjoyable daily activities, which occasionally is underdetected and underdiagnosed; and the risk of developing AD in a cognitively unimpaired and non-depressed population sample. (2) Method: We used data from the Zaragoza Dementia and Depression (ZARADEMP) project, a longitudinal epidemiological study on dementia and depression. After excluding subjects with dementia, a sample of 2830 dwellers aged ≥65 years was followed for 4.5 years. The geriatric mental state examination was used to identify cases of anhedonia. AD was diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. A multivariate survival analysis and Cox proportional hazards regression model were performed, and the analysis was controlled by an analysis for the presence of clinically significant depression. (3) Results: We found a significant association between anhedonia cases and AD risk in the univariate analysis (hazard ratio (HR): 2.37; 95% CI: 1.04–5.40). This association persisted more strongly in the fully adjusted model. (4) Conclusions: Identifying cognitively intact individuals with anhedonia is a priority to implement preventive strategies that could delay the progression of cognitive and functional impairment in subjects at risk of AD.


Neurology ◽  
2003 ◽  
Vol 61 (1) ◽  
pp. 7-8 ◽  
Author(s):  
P. M. Mathews ◽  
R. A. Nixon

Author(s):  
Ashok K. Datusalia ◽  
Gurpreet Singh ◽  
Nikita Yadav ◽  
Sachin Gaun ◽  
Moumita Manik ◽  
...  

: Alzheimer’s disease (AD) is one of the most common neurodegenerative disease, which affect millions of people worldwide. Accumulation of amyloid-β plaques and hyperphosphorylated neurofibrillary tangles are the key mechanisms involved in the etiopathogenesis of AD, characterized by memory loss and behavioural changes. Effective therapies targeting AD pathogenesis are limited, making it the largest unmet clinical need. Unfortunately, the available drugs provide symptomatic relief and primary care, with no substantial impact on the disease pathology. However, in recent years researchers are working hard on several potential therapeutic targets to combat disease pathogenesis and few drugs have also reached clinical trials. In addition, drugs are being repurposed both in the preclinical and clinical studies for the treatment of AD. For instance, montelukast is most commonly used leukotriene receptor antagonist, for treating asthma and seasonal allergy. Its leukotriene antagonistic action can also be beneficial for the reduction of detrimental effects of leukotriene against neuro-inflammation, an hallmark feature of AD. The available marketed formulations of montelukast present challenges such as poor bioavailability and reduced uptake, reflecting the lack of effectiveness of its desired action in the CNS. While on the other side targeted drug delivery is a satisfactory approach to surpass the challenges associated with the therapeutic agents. This review will discuss the enhancement of montelukast treatment efficacy and its access to CNS, by using new approaches like nano-formulation, nasal gel, solid lipid formulation, nano-structure lipid carrier (NSLC), highlighting lessons learned to target AD pathologies and hurdles that persist.


2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Yash Joshi ◽  
Domenico Praticò

AbstractAside from the well-known amyloid beta and tau pathologies found in Alzheimer’s disease (AD), neuroinflammation is a well-established aspect described in humans and animal models of the disease. Inflammatory perturbations are evident not only in neurons, but also in non-neuronal cells and cytokines in the AD brain. Although the amyloid hypothesis implicates amyloid beta (Aβ) as the prime initiator of the AD, brain inflammation in AD has a complex relationship between Aβ and tau. Using our work with the 5-lipoxygenase protein as an example, we suggest that at least in the case of AD, there is an interdependent and not necessarily hierarchical pathological relationship between Aβ, tau and inflammation.


2005 ◽  
Vol 2 (5) ◽  
pp. 255-260 ◽  
Author(s):  
Dale B. Schenk ◽  
Peter Seubert ◽  
Michael Grundman ◽  
Ron Black

Author(s):  
P.S. Aisen ◽  
R.J. Bateman ◽  
M. Carrillo ◽  
R. Doody ◽  
K. Johnson ◽  
...  

A diverse range of platforms has been established to increase the efficiency and speed of clinical trials for Alzheimer’s disease (AD). These platforms enable parallel assessment of multiple therapeutics, treatment regimens, or participant groups; use uniform protocols and outcome measures; and may allow treatment arms to be added or dropped based on interim analyses of outcomes. The EU/US CTAD Task Force discussed the lessons learned from the Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN-TU) platform trial and the challenges addressed by other platform trials that have launched or are in the planning stages. The landscape of clinical trial platforms in the AD space includes those testing experimental therapies such as DIAN-TU, platforms designed to test multidomain interventions, and those designed to streamline trial recruitment by building trial-ready cohorts. The heterogeneity of the AD patient population, AD drugs, treatment regimens, and analytical methods complicates the design and execution of platform trials, yet Task Force members concluded that platform trials are essential to advance the search for effective AD treatments, including combination therapies.


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