Beta Amyloid Peptide: Research Paper : Adaption and Preliminary Validation of the Addenbrooke's Cognitive Examination-III as a Screening Test for Mild Cognitive Impairment and Dementia in Hearing-Impaired Individuals

Adaption and Preliminary Validation of the Addenbrooke's Cognitive Examination-III as a Screening Test for Mild Cognitive Impairment and Dementia in Hearing-Impaired Individuals

Abstract

Background: A large proportion of older adults assessed for cognitive impairment likely have hearing loss, potentially affecting accuracy of cognitive performance estimations. This study aimed to develop a hearing-impaired version of the Addenbrooke's Cognitive Examination-III (HI-ACE-III) and to assess whether the HI-ACE-III can accurately distinguish people with Mild Cognitive Impairment (MCI) and dementia from cognitively intact controls.

Methods: The HI-ACE-III was developed by converting verbal instructions into a visual, timed PowerPoint presentation. 74 participants over the age of 60 were classified into three groups: 29 had MCI, 15 had mild to moderate dementia and 30 cognitively intact controls. Receiver Operating Characteristic (ROC) curves were graphed to test screening accuracy. Concurrent validity was examined through correlations between HI-ACE-III domain scores and relevant, visually presented standardised neuropsychological measures.

Results: ROC analysis for dementia revealed an Area Under the Curve (AUC) of 0.99, achieving excellent sensitivity (100%) and good specificity (93.3%) at an optimum cut-off of <87. The AUC for MCI was 0.86, achieving reasonable sensitivity (75.9%) and good specificity (86.7%) at an optimum cut-off of <92. HI-ACE-III subtests shared anticipated and statistically significant correlations with established measures of cognitive functioning. Internal consistency of the HI-ACE-III was excellent as verified with Cronbach's alpha (α = .904).

Conclusion: Preliminarily, the HI-ACE-III showed good reliability, validity and screening utility for MCI and dementia in older adults in a hearing-impairment context. The adapted HI-ACE-III may offer accurate and reliable indication of cognitive performance, supporting timely diagnosis and research examining links between hearing loss and cognitive decline.

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This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33486875/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : The CITIMERIVA Study: CITIcoline plus MEmantina plus RIVAstigmine in Older Patients Affected with Alzheimer's Disease

The CITIMERIVA Study: CITIcoline plus MEmantina plus RIVAstigmine in Older Patients Affected with Alzheimer's Disease

Abstract

Objective: Combined therapy of memantine or acetylcholinesterase inhibitors, with cholinergic precursors such as citicoline, can be effective in Alzheimer's disease. Indeed, they are able to increase the intrasynaptic levels of acetylcholine more than the single drug. Our aim was to evaluate the efficacy and safety of oral citicoline plus memantine plus rivastigmine in patients with Alzheimer's disease.

Methods: This was a multi-centric, retrospective case-control study conducted in Italian Centers for Cognitive Impairment and Dementia on consecutive patients aged 65 years or older affected with Alzheimer's disease. Overall, 104 patients were recruited (27% male, mean age 76.04 ± 4.92 years); 41 (39.42%) treated with citicolin 1000 mg/day given orally + memantine + rivastigmine (Cases) and 63 (60.58%) treated with memantine + rivastigmine (Controls). At baseline (T0), month 6 (T1) and month 12 (T2), cognitive functions were assessed by the Mini Mental State Examination (MMSE), functional dependence by basal Activities (ADL) and Instrumental Activities of Daily Living (IADL), comorbidity by the Cumulative Illness Rating Scale (CIRS), mood by the Geriatric Depression Scale (GDS), and behavioural disturbances by the Neuropsychiatric Inventory (NPI). Adverse events were reported during the study.

Results: The difference in MMSE score was not significant when comparing the two groups at T0, T1 or T2. However, in the case group, the MMSE total score showed a statistically significant difference at T0 versus T1 (13.63 ± 2.46 vs. 14.17 ± 2.24; p = 0.008), and at T0 versus T2 (13.63 ± 2.46 vs. 14.32 ± 2.53; p = 0.002). In the control group, no statistical differences were found at baseline (T0), T1 and T2. ADL, IADL, GDS and NPI total score did not improve during the study in either the case or the control group.

Conclusions: In our study we observed absence of a statistically significant difference between case and control groups for the MMSE total scores. However, in the case group in the MMSE total scores, there was a statistically significant increase between the baseline and the end of the study.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33484469/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Cognitive reserve and brain maintenance in aging and dementia: An integrative review

Cognitive reserve and brain maintenance in aging and dementia: An integrative review

Abstract

This research is an integrative review of scientific evidence differentiating between cognitive reserve (CR) and brain maintenance concepts. Thus, we have examined how CR socio-behavioral proxies (i.e. education, occupational attainment, and leisure activities) may help to cope with age-related cognitive decline and negative consequences of brain pathology. We also analyze lifestyle factors associated with brain maintenance or the relative absence of change in neural resources over time. Medline and Web of Science databases were used for the bibliographic search in the last 20 years. Observational cohort studies were selected to analyze the effect of different CR proxies on cognitive decline, including dementia incidence, whereas studies employing functional neuroimaging (fMRI) were used to display the existence of compensation mechanisms. Besides, structural MRI studies were used to test the association between lifestyle factors and neural changes. Our findings suggest that education, leisure activities, and occupational activity are protective factors against cognitive decline and dementia. Moreover, functional neuroimaging studies have verified the existence of brain networks that may underlie CR. Therefore, CR may be expressed either through a more efficient utilization (neural reserve) of brain networks or the recruitment of additional brain regions (compensation). Finally, lifestyle factors such as abstaining from smoking, lower alcohol consumption, and physical activity contributed to brain maintenance and were associated with the preservation of cognitive function. Advances in multimodal neuroimaging studies, preferably longitudinal design, will allow a better understanding of the neural mechanisms associated with the prevention of cognitive decline and preservation of neural resources in aging.

Keywords: Brain maintenance; cognitive aging; cognitive reserve; dementia; neuroimaging; socio-behavioral proxies.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33492168/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease

The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease

Abstract

Introduction: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals.

Methods: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants.

Results: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals.

Discussion: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.

Keywords: Alzheimer's disease; magnetic resonance imaging; phosphorylated tau; plasma biomarkers.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33491853/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Regional brain iron associated with deterioration in Alzheimer's disease: A large cohort study and theoretical significance

Regional brain iron associated with deterioration in Alzheimer's disease: A large cohort study and theoretical significance

Abstract

Objective: This paper is a proposal for an update of the iron hypothesis of Alzheimer's disease (AD), based on large-scale emerging evidence.

Background: Iron featured historically early in AD research efforts for its involvement in the amyloid and tau proteinopathies, APP processing, genetics, and one clinical trial, yet iron neurochemistry remains peripheral in mainstream AD research. Much of the effort investigating iron in AD has focused on the potential for iron to provoke the onset of disease, by promoting proteinopathy though increased protein expression, phosphorylation, and aggregation.

New/updated hypothesis: We provide new evidence from a large post mortem cohort that brain iron levels within the normal range were associated with accelerated ante mortem disease progression in cases with underlying proteinopathic neuropathology. These results corroborate recent findings that argue for an additional downstream role for iron as an effector of neurodegeneration, acting independently of tau or amyloid pathologies. We hypothesize that the level of tissue iron is a trait that dictates the probability of neurodegeneration in AD by ferroptosis, a regulated cell death pathway that is initiated by signals such as glutathione depletion and lipid peroxidation.

Major challenges for the hypothesis: While clinical biomarkers of ferroptosis are still in discovery, the demonstration of additional ferroptotic correlates (genetic or biomarker derived) of disease progression is required to test this hypothesis. The genes implicated in familial AD are not known to influence ferroptosis, although recent reports on APP mutations and apolipoprotein E allele (APOE) have shown impact on cellular iron retention. Familial AD mutations will need to be tested for their impact on ferroptotic vulnerability. Ultimately, this hypothesis will be substantiated, or otherwise, by a clinical trial of an anti-ferroptotic/iron compound in AD patients.

Linkage to other major theories: Iron has historically been linked to the amyloid and tau proteinopathies of AD. Tau, APP, and apoE have been implicated in physiological iron homeostasis in the brain. Iron is biochemically the origin of most chemical radicals generated in biochemistry and thus closely associated with the oxidative stress theory of AD. Iron accumulation is also a well-established consequence of aging and inflammation, which are major theories of disease pathogenesis.

Keywords: Alzheimer's disease; cognitive decline; iron; neurodegeneration; pathology.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33491917/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Cultural adaptation of Alzheimer's disease assessment scale-cognitive subscale for use in India and validation of the Tamil version for South Indian population

Cultural adaptation of Alzheimer's disease assessment scale-cognitive subscale for use in India and validation of the Tamil version for South Indian population

Abstract

Objective: Currently no standardized tools are available in the Indian languages to assess changes in cognition. Our objectives are to culturally adapt the Alzheimer's disease Assessment Scale-Cognitive Subscale (ADAS-Cog) for use in India and to validate the Tamil version in an urban Tamil-speaking older adult population.

Methods: Two panels of key stakeholders and a series of qualitative interviews informed the cultural and linguistic adaptation of the ADAS-Cog-Tamil. Issues related to levels of literacy were considered during the adaptation. Validation of the ADAS-Cog-Tamil was completed with 107 participants - 54 cases with a confirmed diagnosis of mild-moderate dementia, and 53 age, gender and education matched controls. Concurrent validity was examined with the Vellore Screening Instrument for Dementia (VSID) in Tamil. Internal consistency using Cronbach's alpha, sensitivity and specificity data using the Area under the Receiver Operating Characteristics (AUROC) curve values were computed. Inter-rater reliability was established in a subsample.

Results: The ADAS-Cog-Tamil shows good internal consistency (α = 0.91), inter-rater reliability and concurrent validity (with VSID-Patient version: r = -0.84 and with VSID-Caregiver version: r = -0.79). A cut-off score of 13, has a specificity of 89% and sensitivity of 90% for the diagnosis of dementia.

Conclusion: ADAS-Cog-Tamil, derived from a rigorous, replicable linguistic and cultural adaptation process involving service users and experts, shows good psychometric properties despite the limitations of the study. It shows potential for use in clinical settings with urban Tamil speaking populations. The English version of the tool derived from the cultural adaptation process could be used for further linguistic adaptation across South Asia.

Keywords: ADAS-Cog; India; South Asia; Tamil; adaptation; cognition; dementia; validation.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33491464/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Screening of Alzheimer's disease by facial complexion using artificial intelligence

Screening of Alzheimer's disease by facial complexion using artificial intelligence

Abstract

Despite the increasing incidence and high morbidity associated with dementia, a simple, non-invasive, and inexpensive method of screening for dementia is yet to be discovered. This study aimed to examine whether artificial intelligence (AI) could distinguish between the faces of people with cognitive impairment and those without dementia.121 patients with cognitive impairment and 117 cognitively sound participants were recruited for the study. 5 deep learning models with 2 optimizers were tested. The binary differentiation of dementia / non-dementia facial image was expressed as a "Face AI score". Xception with Adam was the model that showed the best performance. Overall sensitivity, specificity, and accuracy by the Xception AI system and AUC of the ROC curve were 87.31%, 94.57%, 92.56%, and 0.9717, respectively. Close and significant correlations were found between Face AI score and MMSE (r = -0.599, p < 0.0001). Significant correlation between Face AI score and chronological age was also found (r = 0.321, p < 0.0001). However, MMSE score showed significantly stronger correlation with Face AI score than chronological age (p < 0.0001). The study showed that deep learning programs such as Xception have the ability to differentiate the faces of patients with mild dementia from that of patients without dementia, paving the way for future studies into the development of a facial biomarker for dementia.

Keywords: artificial intelligence; dementia; face; machine learning.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33495415/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Gossypol, a novel modulator of VCP, induces autophagic degradation of mutant huntingtin by promoting the formation of VCP/p97-LC3-mHTT complex

Gossypol, a novel modulator of VCP, induces autophagic degradation of mutant huntingtin by promoting the formation of VCP/p97-LC3-mHTT complex

Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by toxic aggregates of mutant huntingtin protein (mHTT) in the brain. Decreasing mHTT is a potential strategy for therapeutic purpose of HD. Valosin-containing protein (VCP/p97) is a crucial regulator of proteostasis, which regulates the degradation of damaged protein through proteasome and autophagy pathway. Since VCP has been implicated in pathogenesis of HD as well as other neurodegenerative diseases, small molecules that specifically regulate the activity of VCP may be of therapeutic benefits for HD patients. In this study we established a high-throughput screening biochemical assay for VCP ATPase activity measurement and identified gossypol, a clinical approved drug in China, as a novel modulator of VCP. Gossypol acetate dose-dependently inhibited the enzymatic activity of VCP in vitro with IC50 of 6.53±0.6 μM. We further demonstrated that gossypol directly bound to the interface between the N and D1 domains of VCP. Gossypol acetate treatment not only lowered mHTT levels and rescued HD-relevant phenotypes in HD patient iPS-derived Q47 striatal neurons and HD knock-in mouse striatal cells, but also improved motor function deficits in both Drosophila and mouse HD models. Taken together, gossypol acetate acted through a gain-of-function way to induce the formation of VCP-LC3-mHTT ternary complex, triggering autophagic degradation of mHTT. This study reveals a new strategy for treatment of HD and raises the possibility that an existing drug can be repurposed as a new treatment of neurodegenerative diseases.

Keywords: Huntington disease; LC3; VCP; autophagic degradation; drug reposition; gossypol acetate; mutant huntingtin protein.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33495516/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : The proteome of granulovacuolar degeneration and neurofibrillary tangles in Alzheimer's disease

The proteome of granulovacuolar degeneration and neurofibrillary tangles in Alzheimer's disease

Abstract

Granulovacuolar degeneration (GVD) is a common feature in Alzheimer's disease (AD). The occurrence of GVD is closely associated with that of neurofibrillary tangles (NFTs) and GVD is even considered to be a pre-NFT stage in the disease process of AD. Currently, the composition of GVD bodies, the mechanisms associated with GVD and how GVD exactly relates to NFTs is not well understood. By combining immunohistochemistry (IHC) and laser microdissection (LMD) we isolated neurons with GVD and those bearing tangles separately from human post-mortem AD hippocampus (n = 12) using their typical markers casein kinase (CK)1δ and phosphorylated tau (AT8). Control neurons were isolated from cognitively healthy cases (n = 12). 3000 neurons per sample were used for proteome analysis by label free LC-MS/MS. In total 2596 proteins were quantified across samples and a significant change in abundance of 115 proteins in GVD and 197 in tangle bearing neurons was observed compared to control neurons. With IHC the presence of PPIA, TOMM34, HSP70, CHMP1A, TPPP and VXN was confirmed in GVD containing neurons. We found multiple proteins localizing specifically to the GVD bodies, with VXN and TOMM34 being the most prominent new protein markers for GVD bodies. In general, protein groups related to protein folding, proteasomal function, the endolysosomal pathway, microtubule and cytoskeletal related function, RNA processing and glycolysis were found to be changed in GVD neurons. In addition to these protein groups, tangle bearing neurons show a decrease in ribosomal proteins, as well as in various proteins related to protein folding. This study, for the first time, provides a comprehensive human based quantitative assessment of protein abundances in GVD and tangle bearing neurons. In line with previous functional data showing that tau pathology induces GVD, our data support the model that GVD is part of a pre-NFT stage representing a phase in which proteostasis and cellular homeostasis is disrupted. Elucidating the molecular mechanisms and cellular processes affected in GVD and its relation to the presence of tau pathology is highly relevant for the identification of new drug targets for therapy.

Keywords: Alzheimer´s disease; Granulovacuolar degeneration; Neurofibrillary tangles; Neuropathology; Proteomics; Tau.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33492460/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Brain Asymmetry Detection and Machine Learning Classification for Diagnosis of Early Dementia

Brain Asymmetry Detection and Machine Learning Classification for Diagnosis of Early Dementia

Abstract

Early identification of degenerative processes in the human brain is considered essential for providing proper care and treatment. This may involve detecting structural and functional cerebral changes such as changes in the degree of asymmetry between the left and right hemispheres. Changes can be detected by computational algorithms and used for the early diagnosis of dementia and its stages (amnestic early mild cognitive impairment (EMCI), Alzheimer's Disease (AD)), and can help to monitor the progress of the disease. In this vein, the paper proposes a data processing pipeline that can be implemented on commodity hardware. It uses features of brain asymmetries, extracted from MRI of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, for the analysis of structural changes, and machine learning classification of the pathology. The experiments provide promising results, distinguishing between subjects with normal cognition (NC) and patients with early or progressive dementia. Supervised machine learning algorithms and convolutional neural networks tested are reaching an accuracy of 92.5% and 75.0% for NC vs. EMCI, and 93.0% and 90.5% for NC vs. AD, respectively. The proposed pipeline offers a promising low-cost alternative for the classification of dementia and can be potentially useful to other brain degenerative disorders that are accompanied by changes in the brain asymmetries.

Keywords: SVM; asymmetry detection; brain MRI; brain asymmetry; deep learning; dementia; machine learning methods.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33498908/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.