Acceptance of and attitudes towards Alzheimer's disease screening in elderly German adults

2013 ◽  
Vol 26 (3) ◽  
pp. 425-434 ◽  
Author(s):  
Sarah R. Braun ◽  
Katinka Reiner ◽  
Christina Tegeler ◽  
Nina Bucholtz ◽  
Malaz A. Boustani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Factor Structure ◽  
Disease Screening ◽  
German Version ◽  
German Prism ◽  
Convenience Sample ◽  
Dementia Screening ◽  
Starting Point ◽  
Aging Study

ABSTRACTBackground:Considering the discussion on implementing routine dementia screening in Germany, the objective of the current study was to validate the German version of the Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC) questionnaire and to determine the acceptance of Alzheimer's disease screening in elderly German adults.Methods:The German version of the PRISM-PC was administered to a subsample of participants who attended the Berlin Aging Study II (n = 506). The questionnaire was validated by exploratory as well as confirmatory factor analysis.Results:Regarding acceptance of Alzheimer's disease screening (Section B) a single factor structure fitted best. In terms of attitudes regarding Alzheimer's disease (Section D), a hierarchical factor structure was modeled with the higher-order factor “Harms” covering the domains “Family Burden,” “Dependence,” “Emotional Suffering,” “Stigma,” and “Medical Care” on the one hand and the domain “Future Planning” on the other hand. Internal consistency of the different scales reached from α = 0.67 to α = 0.94. Overall, 71.2% of the participants indicated that they wanted to be screened for Alzheimer's disease on a regular basis.Conclusions:This study suggests that acceptance can reliably be assessed with the section “Acceptance of Alzheimer's disease screenings” of the German PRISM-PC questionnaire. Furthermore, the majority of elderly German adults would like to be screened for Alzheimer's disease regularly, which might be an effective starting point in order to implement routine dementia screenings. As the sample is a convenience sample of (relatively) healthy older adults, generalizability of these results is limited.

Consideration of a Pharmacological Combinatorial Approach to Inhibit Chronic Inflammation in Alzheimer’s Disease

2019 ◽  
Vol 16 (11) ◽  
pp. 1007-1017 ◽  
Author(s):  
James G. McLarnon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Chronic Inflammation ◽  
Preventive Strategy ◽  
Subsequent Work ◽  
Activated Microglia ◽  
Starting Point ◽  
Anti Inflammatory ◽  
Cocktail Approach

A combinatorial cocktail approach is suggested as a rationale intervention to attenuate chronic inflammation and confer neuroprotection in Alzheimer’s disease (AD). The requirement for an assemblage of pharmacological compounds follows from the host of pro-inflammatory pathways and mechanisms present in activated microglia in the disease process. This article suggests a starting point using four compounds which present some differential in anti-inflammatory targets and actions but a commonality in showing a finite permeability through Blood-brain Barrier (BBB). A basis for firstchoice compounds demonstrated neuroprotection in animal models (thalidomide and minocycline), clinical trial data showing some slowing in the progression of pathology in AD brain (ibuprofen) and indirect evidence for putative efficacy in blocking oxidative damage and chemotactic response mediated by activated microglia (dapsone). It is emphasized that a number of candidate compounds, other than ones suggested here, could be considered as components of the cocktail approach and would be expected to be examined in subsequent work. In this case, systematic testing in AD animal models is required to rigorously examine the efficacy of first-choice compounds and replace ones showing weaker effects. This protocol represents a practical approach to optimize the reduction of microglial-mediated chronic inflammation in AD pathology. Subsequent work would incorporate the anti-inflammatory cocktail delivery as an adjunctive treatment with ones independent of inflammation as an overall preventive strategy to slow the progression of AD.

Joint Effect of ABCA7 rs4147929 and Body Mass Index on Progression from Mild Cognitive Impairment to Alzheimer’s Disease: The Shanghai Aging Study

2020 ◽  
Vol 17 (2) ◽  
pp. 185-195
Author(s):  
Jianxiong Xi ◽  
Ding Ding ◽  
Qianhua Zhao ◽  
Xiaoniu Liang ◽  
Li Zheng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Body Mass Index ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Body Mass ◽  
Joint Effect ◽  
Genome Wide Association Studies ◽  
Risk Genotype ◽  
Aging Study

Background: Approximately 40 independent Single Nucleotide Polymorphisms (SNPs) have been associated with Alzheimer’s Disease (AD) or cognitive decline in genome-wide association studies. Methods: We aimed to evaluate the joint effect of genetic polymorphisms and environmental factors on the progression from Mild Cognitive Impairment (MCI) to AD (MCI-AD progression) in a Chinese community cohort. Conclusion: Demographic, DNA and incident AD diagnosis data were derived from the follow-up of 316 participants with MCI at baseline of the Shanghai Aging Study. The associations of 40 SNPs and environmental predictors with MCI-AD progression were assessed using the Kaplan-Meier method with the log-rank test and Cox regression model. Results: Rs4147929 at ATP-binding cassette family A member 7 (ABCA7) (AG/AA vs. GG, hazard ratio [HR] = 2.43, 95% confidence interval [CI] 1.24-4.76) and body mass index (BMI) (overweight vs. non-overweight, HR = 0.41, 95% CI 0.22-0.78) were independent predictors of MCI-AD progression. In the combined analyses, MCI participants with the copresence of non-overweight BMI and the ABCA7 rs4147929 (AG/AA) risk genotype had an approximately 6-fold higher risk of MCI-AD progression than those with an overweight BMI and a non-risk genotype (HR = 6.77, 95% CI 2.60-17.63). However, a nonsignificant result was found when participants carried only one of these two risk factors (nonoverweight BMI and AG/AA of ABCA7 rs4147929). Conclusion: ABCA7 rs4147929 and BMI jointly affect MCI-AD progression. MCI participants with the rs4147929 risk genotype may benefit from maintaining an overweight BMI level with regard to their risk for incident AD.

scholarly journals Identification of Novel Cathepsin B Inhibitors with Implications in Alzheimer’s Disease: Computational Refining and Biochemical Evaluation

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1946
Author(s):  
Nitin Chitranshi ◽  
Ashutosh Kumar ◽  
Samran Sheriff ◽  
Veer Gupta ◽  
Angela Godinez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hydrogen Bond ◽  
Virtual Screening ◽  
Cathepsin B ◽  
Amyloid Β ◽  
Proteolytic Degradation ◽  
Hydrogen Bond Acceptor ◽  
Starting Point ◽  
The Brain

Amyloid precursor protein (APP), upon proteolytic degradation, forms aggregates of amyloid β (Aβ) and plaques in the brain, which are pathological hallmarks of Alzheimer’s disease (AD). Cathepsin B is a cysteine protease enzyme that catalyzes the proteolytic degradation of APP in the brain. Thus, cathepsin B inhibition is a crucial therapeutic aspect for the discovery of new anti-Alzheimer’s drugs. In this study, we have employed mixed-feature ligand-based virtual screening (LBVS) by integrating pharmacophore mapping, docking, and molecular dynamics to detect small, potent molecules that act as cathepsin B inhibitors. The LBVS model was generated by using hydrophobic (HY), hydrogen bond acceptor (HBA), and hydrogen bond donor (HBD) features, using a dataset of 24 known cathepsin B inhibitors of both natural and synthetic origins. A validated eight-feature pharmacophore hypothesis (Hypo III) was utilized to screen the Maybridge chemical database. The docking score, MM-PBSA, and MM-GBSA methodology was applied to prioritize the lead compounds as virtual screening hits. These compounds share a common amide scaffold, and showed important interactions with Gln23, Cys29, His110, His111, Glu122, His199, and Trp221. The identified inhibitors were further evaluated for cathepsin-B-inhibitory activity. Our study suggests that pyridine, acetamide, and benzohydrazide compounds could be used as a starting point for the development of novel therapeutics.

The Japanese version of the Rapid Dementia Screening Test is effective compared to the clock-drawing test for detecting patients with mild Alzheimer's disease

2015 ◽  
Vol 16 (4) ◽  
pp. 233-239 ◽  
Author(s):  
Yasushi Moriyama ◽  
Aihide Yoshino ◽  
Kaori Yamanaka ◽  
Motoichiro Kato ◽  
Taro Muramatsu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Screening Test ◽  
Japanese Version ◽  
Clock Drawing Test ◽  
Clock Drawing ◽  
Dementia Screening ◽  
Drawing Test

scholarly journals Perphenazine-macrocycle conjugates divert Aβ42 towards non-toxic aggregates by monomer sequestration

2020 ◽  
Author(s):  
Sarah R Ball ◽  
Julius S P Adamson ◽  
Michael A Sullivan ◽  
Manuela R Zimmermann ◽  
Victor Lo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nmr Spectroscopy ◽  
Kinetic Analysis ◽  
Amyloid Β ◽  
Dimensional Structure ◽  
Amyloid Β Peptide ◽  
Monomeric Form ◽  
Starting Point ◽  
The Impact

AbstractThe amyloid-β peptide, the main protein component of amyloid plaques in Alzheimer’s disease, plays a key role in the neurotoxicity associated with the condition through the formation of small toxic oligomer species which mediate the disruption of calcium and glutamate homeostasis. The lack of therapeutic benefit associated with removal of mature amyloid-β fibrils has focused attention on the toxic oligomeric species formed during the process of fibril assembly. Here, we present the design and synthesis of a family of perphenazine-macrocyle conjugates. We find that two-armed perphenazine-cyclam conjugates divert the monomeric form of the amyloid-β peptide away from the amyloidogenic pathway into amorphous aggregates that are not toxic to differentiated SH-SY5Y cells in vitro. This strategy prevents the formation of damaging amyloid oligomers. Kinetic analysis of the effects of these compounds on the assembly pathway, together with NMR spectroscopy, identifies rapid monomer sequestration as the underlying neuroprotective mechanism. The ability to specifically target the monomeric form of amyloid-β allows for further understanding of the impact of the multiple species formed between peptide biogenesis and plaque deposition. The modular, three-dimensional structure of these compounds provides a starting point for the design of more potent modulators of this amyloid-forming peptide, and can be adapted to probe the protein self-assembly pathways associated with other proteinopathies.Significance statementThe aggregation pathway of the amyloid-β (Aβ) peptide in Alzheimer’s disease is complex and involves multiple different species. An inability to isolate and study the impact of distinct Aβ species has undermined efforts to develop effective therapies. To address this issue, we have developed a series of molecules that specifically sequester the monomeric form of the highly aggregation-prone Aβ42 peptide. Interaction with these molecules diverts Aβ42 from the amyloidogenic pathway and prevents formation of toxic oligomeric species. We use kinetic analysis and NMR spectroscopy to identify rapid monomer sequestration as the underlying neuroprotective mechanism. Future rational development of these molecules and characterisation of their interactions with Aβ will delineate the impact of different Aβ oligomers on neurobiology and pathology.

Toward a More Nuanced Perception of Alzheimer’s Disease

2012 ◽  
Vol 27 (6) ◽  
pp. 388-396 ◽  
Author(s):  
Baldwin Van Gorp ◽  
Tom Vercruysse ◽  
Jan Van den Bulck
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Experimental Design ◽  
Fear Of Death ◽  
The Public ◽  
Starting Point

Starting point of this study was the assumption that Alzheimer’s disease is made worse for the person who has the disease by the negative regard in which the illness is held by society. The aim was to test by means of a campaign advertisement whether more nuanced counterframes could have an impact while remaining credible and comprehensible to the public. A sample of thousand people living in Belgium evaluated the campaign in an experimental design. This revealed that all the versions tested achieved a high average evaluation. The ad in which the heading referred to the fear of death and degeneration was judged to be most attention-grabbing, easier to understand, and more credible than the alternative heading with the idea that someone with Alzheimer’s could still enjoy playing cards. Together, these findings provided a basis for the use of counterframes to generating a more nuanced image of Alzheimer’s disease.

Fasu-Net: Fast Alzheimer’s Disease Screening with Undersampled MRI Using Convolutional Neural Networks

2021 ◽  
Vol 11 (8) ◽  
pp. 2211-2221
Author(s):  
Yuanbo Xie ◽  
Haitao Jiang ◽  
Hongwei Du ◽  
Jinzhang Xu ◽  
Bensheng Qiu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Mri ◽  
Potential Method ◽  
Disease Screening ◽  
Acquisition Time ◽  
Mr Images ◽  
Brain Mr Images ◽  
Magnetic Resonance Imaging Mri ◽  
Questionnaire Method

Alzheimer’s Disease (AD) is a progressive and irreversible neurodegenerative condition, which results in dementia. Mild Cognitive Impairment (MCI) is an intermediate state between normal aging and AD. Instead of traditional questionnaire method, magnetic resonance imaging (MRI) can be used by radiologists to diagnose and screening AD recently, but long acquisition time is not conducive to screening AD and MCI. To solve this problem, we develop a Fasu-Net (Fast Alzheimer’s disease Screening neural network with Undersampled MRI) for AD and MCI clinical classification. The network uses undersampled structural MRI with a shorter acquisition time to improve the screening and diagnosis efficiency of AD. For achieving the best classification result, three axial planes of brain MR images were feed into the Fasu-Net with transfer learning method. The experiment results on undersampled 3D T1-weighted images database (ADNI) show that in the AD versus MCI versus HC (Healthy Controls) classification, the Fasu-Net achieved the accuracy of 91.41%, thus can be a potential method for fast clinical screening of AD.

scholarly journals Effect of Severe External Airborne Agents’ Exposure on Dementia

2020 ◽  
Vol 9 (12) ◽  
pp. 4069
Author(s):  
Seunghyun Lee ◽  
Joon Yul Choi ◽  
Jin-Ha Yoon ◽  
Wanhyung Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Elderly Population ◽  
Standardized Incidence Ratio ◽  
Dementia Screening ◽  
Confounding Variables ◽  
Occupational And Environmental Exposure ◽  
The Impact ◽  
International Awareness ◽  
Incidence Of Dementia

The impact of occupational and environmental exposure to external airborne agents on cognitive function, especially in incidence of dementia, is understudied. The present study was conducted to elucidate the association between severe external airborne agents’ exposure and incidence of dementia among an elderly population and to explore the effects of exposure to severe external airborne agents on preclinical dementia using the screening test of dementia. From the National Health Insurance Service-Health Screening Cohort (NHIS-HealS, 2002–2015), 514,580 participants were used for data analysis. We estimated the standardized incidence ratio (SIR) according to the exposure to external airborne agents. Of the total participants (n = 514,580), 1340 (0.3%) experienced severe external airborne agents exposure, and 26,050 (5.1%) had been diagnosed with dementia. The SIRs (95%CI) of dementia in Alzheimer’s disease, vascular dementia, dementia in other diseases, and unspecific dementia were 1.24 (1.01–1.49), 0.88 (0.37–1.32), 1.16 (0.01–2.77), and 0.69 (0.36–1.02), respectively. The risk of testing positive in the dementia screening significantly increased with exposure to severe external airborne agents after adjusting for all confounding variables. This study found that exposure to severe external airborne agents is a potential risk factor for dementia, especially in Alzheimer’s disease. It is essential to create international awareness regarding the effect of airborne agents’ exposure on dementia.

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