O4-08-02: Prevention of Postmenopausal Alzheimer's Disease and Cognitive Loss with Replacement Estrogen (PREPARE) Study Results

Abstract Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Efforts to determine risk factors for the development of AD are important for risk stratification and early diagnosis. Furthermore, there are no standardized practices for memory screening. Lack of knowledge on AD, perception of memory loss as part of normal aging, and poor socioeconomic conditions may also be implicated in the current situation of dementia. Objective: To evaluate knowledge of AD in a literate population of elders and correlate these findings with sociodemographic characteristics. Methods: A descriptive survey design study enrolled 994 volunteers from September 2007 to May 2008 in the city of Santos, São Paulo, Brazil, to answer a brief questionnaire consisting of 8 simple questions about knowledge of AD and worries about memory loss. Results: Greater knowledge about AD was associated with eight or more years of education, female gender and age between 60 and 70 years. Also, 52.8% of responders (95% CI - 49.5-56.0%) answered that memory loss is part of normal aging and 77.5% (95% CI - 74.7-80.1%) had never sought a doctor to evaluate their memories. Conclusion: Our study results reinforced that the first line of preventing late diagnosis of dementia is to act in health promotion, especially by targeting subjects older than 70 years of male gender and with lower educational level. It also provided evidence that strategies to promote physician initiative in treating memory problems are also paramount.

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Systems Pharmacological Approach to Investigate the Mechanism of Acori Tatarinowii Rhizoma for Alzheimer’s Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/5194016 ◽

2018 ◽

Vol 2018 ◽

pp. 1-20 ◽

Cited By ~ 5

Author(s):

Zhenyan Song ◽

Fang Yin ◽

Biao Xiang ◽

Bin Lan ◽

Shaowu Cheng

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Therapeutic Effects ◽

Biological Processes ◽

Pathway Enrichment ◽

Study Results ◽

Target Network ◽

Anti Inflammatory

In traditional Chinese medicine (TCM), Acori Tatarinowii Rhizoma (ATR) is widely used to treat memory and cognition dysfunction. This study aimed to confirm evidence regarding the potential therapeutic effect of ATR on Alzheimer’s disease (AD) using a system network level based in silico approach. Study results showed that the compounds in ATR are highly connected to AD-related signaling pathways, biological processes, and organs. These findings were confirmed by compound-target network, target-organ location network, gene ontology analysis, and KEGG pathway enrichment analysis. Most compounds in ATR have been reported to have antifibrillar amyloid plaques, anti-tau phosphorylation, and anti-inflammatory effects. Our results indicated that compounds in ATR interact with multiple targets in a synergetic way. Furthermore, the mRNA expressions of genes targeted by ATR are elevated significantly in heart, brain, and liver. Our results suggest that the anti-inflammatory and immune system enhancing effects of ATR might contribute to its major therapeutic effects on Alzheimer’s disease.

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EEG-Based Emotion Classification for Alzheimer’s Disease Patients Using Conventional Machine Learning and Recurrent Neural Network Models

Sensors ◽

10.3390/s20247212 ◽

2020 ◽

Vol 20 (24) ◽

pp. 7212

Author(s):

Jungryul Seo ◽

Teemu H. Laine ◽

Gyuhwan Oh ◽

Kyung-Ah Sohn

Keyword(s):

Neural Network ◽

Machine Learning ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Recurrent Neural Network ◽

Classification Model ◽

Support Vector ◽

Number Of Patients ◽

Study Results ◽

Conventional Machine

As the number of patients with Alzheimer’s disease (AD) increases, the effort needed to care for these patients increases as well. At the same time, advances in information and sensor technologies have reduced caring costs, providing a potential pathway for developing healthcare services for AD patients. For instance, if a virtual reality (VR) system can provide emotion-adaptive content, the time that AD patients spend interacting with VR content is expected to be extended, allowing caregivers to focus on other tasks. As the first step towards this goal, in this study, we develop a classification model that detects AD patients’ emotions (e.g., happy, peaceful, or bored). We first collected electroencephalography (EEG) data from 30 Korean female AD patients who watched emotion-evoking videos at a medical rehabilitation center. We applied conventional machine learning algorithms, such as a multilayer perceptron (MLP) and support vector machine, along with deep learning models of recurrent neural network (RNN) architectures. The best performance was obtained from MLP, which achieved an average accuracy of 70.97%; the RNN model’s accuracy reached only 48.18%. Our study results open a new stream of research in the field of EEG-based emotion detection for patients with neurological disorders.

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Secondary Metabolites from Plants Possessing Inhibitory Properties against Beta-Amyloid Aggregation as Revealed by Thioflavin-T Assay and Correlations with Investigations on Transgenic Mouse Models of Alzheimer’s Disease

Biomolecules ◽

10.3390/biom10060870 ◽

2020 ◽

Vol 10 (6) ◽

pp. 870 ◽

Cited By ~ 4

Author(s):

Raluca Stefanescu ◽

Gabriela Dumitriṭa Stanciu ◽

Andrei Luca ◽

Luminita Paduraru ◽

Bogdan-Ionel Tamba

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Secondary Metabolites ◽

Transgenic Mouse ◽

Mouse Models ◽

Beta Amyloid ◽

Thioflavin T ◽

Amyloid Angiopathy ◽

Transgenic Mouse Models ◽

Study Results

Alzheimer’s disease is a neurodegenerative disorder for which there is a continuous search of drugs able to reduce or stop the cognitive decline. Beta-amyloid peptides are composed of 40 and 42 amino acids and are considered a major cause of neuronal toxicity. They are prone to aggregation, yielding oligomers and fibrils through the inter-molecular binding between the amino acid sequences (17–42) of multiple amyloid-beta molecules. Additionally, amyloid deposition causes cerebral amyloid angiopathy. The present study aims to identify, in the existing literature, natural plant derived products possessing inhibitory properties against aggregation. The studies searched proved the anti-aggregating effects by the thioflavin T assay and through behavioral, biochemical, and histological analysis carried out upon administration of natural chemical compounds to transgenic mouse models of Alzheimer’s disease. According to our present study results, fifteen secondary metabolites from plants were identified which presented both evidence coming from the thioflavin T assay and transgenic mouse models developing Alzheimer’s disease and six additional metabolites were mentioned due to their inhibitory effects against fibrillogenesis. Among them, epigallocatechin-3-gallate, luteolin, myricetin, and silibinin were proven to lower the aggregation to less than 40%.

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Advancing Alzheimer’s Disease Care and Services Among Racial and Ethnic Minorities

Innovation in Aging ◽

10.1093/geroni/igaa057.2682 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 745-745

Author(s):

Lenora Smith ◽

Roland Thorpe

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

African American ◽

Ethnic Minorities ◽

Health Care Expenditures ◽

Racial And Ethnic Minorities ◽

Care Services ◽

Study Results ◽

Using Data ◽

The Impact

Abstract Research shows consistent and adverse disparities among racial and ethnic minorities compared to non-Hispanic Whites in the prevalence and incidence of Alzheimer’s disease, mortality, participation in clinical trials, use of medications and other interventions, health care expenditures, and quality-of-life outcomes. The literature suggests numerous underlying causes, including factors related to measurement of the disease, genetics, socioeconomic factors, cultural differences, lack of culturally competent interventions, and discrimination in services and care. Although these disparities are well known, little is known about the effectiveness of various strategies to address these differences within the context of Alzheimer’s disease services and care. This symposium aims to contribute to this knowledge. The first presentation examines the role of race with marital status and risk for dementia using data from the Health and Retirement Study. Results suggest differences for unmarried White and unmarried older adults of color, which can inform dementia care services. The second presentation highlights the opportunities and challenges of facilitating cognitive impairment screenings among African American congregations. The third presentation introduces attitudes about brain donation among African American research participants and suggestions to increase involvement. The symposium concludes with a presentation on hearing care disparities in dementia with practical recommendations on how to close this gap in hearing care. The findings from these papers contribute significantly to the impact of ethnoracial differences in dementia and the need to include more diverse populations in ADRD research to promote equity. Alzheimer’s Disease Research Interest Group Sponsored Symposium.

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The Potential of Rhythmic Sensory Stimulation Treatments for Persons with Alzheimer’s Disease

Music and Medicine ◽

10.47513/mmd.v9i3.536 ◽

2017 ◽

Vol 9 (3) ◽

pp. 167

Author(s):

Amy Clements-Cortes ◽

Lee Bartel ◽

Heidi Ahonen ◽

Morris Freedman

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Visual Stimulation ◽

Somatosensory System ◽

Sensory Stimulation ◽

Case Vignette ◽

Music Listening ◽

Study Results ◽

Study Support ◽

Study Participants

Background: Rhythmic Sensory Stimulation (RSS) is a treatment being implemented for persons diagnosed with a variety of disorders such as fibromyalgia and Alzheimer’s disease (AD). This paper provides qualitative results of observations and interactions of AD study participants who received both RSS and visual stimulation sessions for six weeks. A case vignette is also provided. Objective: The study proposed that RSS could stimulate the auditory and somatosensory system at 40Hz with the potential for improvements in cognition for persons with AD. Method: 18 participants at three stages of AD participated: mild, moderate and severe. Participants received a total of 13 sessions in this AB cross-over design study. Results: Qualitative findings from the study support RSS as a potential treatment for persons with AD to increased alertness, stimulate discussion, and increase interaction and awareness of surroundings. Conclusion: Further research needs to explore the effect of the frequency of sessions provided, the duration of effects, and whether AD severity interacts with the RSS treatment. Further investigations could also study the effect of auditory 40Hz stimulation alone, as well as the inclusion of music listening during the RSS sessions.

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P-072: Incidence of Alzheimer's disease in 2854 elderly patients with spontaneous memory complaints: GuidAge study. Results at year 1

Alzheimer s & Dementia ◽

10.1016/j.jalz.2007.04.325 ◽

2007 ◽

Vol 3 (3S_Part_1) ◽

pp. S121-S122

Author(s):

Sandrine Andrieu ◽

Jacques Touchon ◽

Florence Pasquier ◽

Mehemed Ouzid ◽

Hélène Mathiex- Fortunet ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Elderly Patients ◽

Memory Complaints ◽

Study Results

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Differential blood miRNA expression in brain amyloid imaging defined Alzheimer's disease and controls.

10.21203/rs.2.17624/v1 ◽

2019 ◽

Author(s):

Helen Zong Ying Wu ◽

Anbupalam Thalamuthu ◽

Lesley Cheng ◽

Christopher Fowler ◽

Colin L Masters ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mirna Expression ◽

Messenger Rna ◽

Amyloid Imaging ◽

Imaging Biomarkers ◽

Small Rna Sequencing ◽

Amyloid Burden ◽

Imaging Results ◽

Study Results

Abstract Background: Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer’s disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this study is to establish candidate blood miRNA biomarkers for AD by comparing differences in miRNA expression between participants with brain amyloid imaging defined AD and normal cognition. Methods: Blood RNA was extracted from a subset of participants from the Australian Imaging Biomarkers Lifestyle Study of Ageing cohort (AIBL) with brain amyloid imaging results. MiRNA profiling was performed using small RNA sequencing on 71 participants, comprising 40 AD with high brain amyloid burden on imaging (amyloid positive) and 31 cognitively normal controls with low brain amyloid burden (amyloid negative). Cross-sectional comparisons were made between groups to examine differential miRNA expression levels using Fisher’s exact tests. Replication of results was undertaken using a publicly available dataset of blood miRNA data of AD and controls. In silico analysis of downstream messenger RNA targets of candidate miRNAs was performed to elucidate potential biological function. Results: After quality control, 816 miRNAs were available for analysis. There were 71 significantly differentially expressed miRNAs between the AD and control groups (p<0.05). Two of these miRNAs, miR-146b-5p and miR-15b-5p, were also significant in the replication cohort. Pathways analysis showed these miRNAs to be involved in innate immune system and regulation of the cell cycle respectively, both of which have relevance to AD pathogenesis. Conclusion: Blood miR-146b-5p and miR15b-5p showed consistent differential expression in AD compared to controls. Further replication and translational studies in strictly phenotyped cohorts are needed to establish their role as biomarkers for AD to have clinical utility.

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Genome Wide Meta-Analysis identifies common genetic signatures shared by heart function and Alzheimer’s disease

Scientific Reports ◽

10.1038/s41598-019-52724-2 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

M. E. Sáez ◽

A. González-Pérez ◽

B. Hernández-Olasagarre ◽

A. Beà ◽

S. Moreno-Grau ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cardiac Function ◽

Heart Development ◽

Heart Function ◽

Meta Analysis ◽

Genome Wide ◽

Study Results ◽

Apoptotic Genes ◽

The Impact

Abstract Echocardiography has become an indispensable tool for the study of heart performance, improving the monitoring of individuals with cardiac diseases. Diverse genetic factors associated with echocardiographic measures have been previously reported. The impact of several apoptotic genes in heart development identified in experimental models prompted us to assess their potential association with human cardiac function. This study aimed at investigating the possible association of variants of apoptotic genes with echocardiographic traits and to identify new genetic markers associated with cardiac function. Genome wide data from different studies were obtained from public repositories. After quality control and imputation, a meta-analysis of individual association study results was performed. Our results confirmed the role of caspases and other apoptosis related genes with cardiac phenotypes. Moreover, enrichment analysis showed an over-representation of genes, including some apoptotic regulators, associated with Alzheimer’s disease. We further explored this unexpected observation which was confirmed by genetic correlation analyses. Our findings show the association of apoptotic gene variants with echocardiographic indicators of heart function and reveal a novel potential genetic link between echocardiographic measures in healthy populations and cognitive decline later on in life. These findings may have important implications for preventative strategies combating Alzheimer’s disease.

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Repurposing bromocriptine for Aβ metabolism in Alzheimer’s disease (REBRAnD) study: randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer’s disease with presenilin 1 (PSEN1) mutations

BMJ Open ◽

10.1136/bmjopen-2021-051343 ◽

2021 ◽

Vol 11 (6) ◽

pp. e051343

Author(s):

Takayuki Kondo ◽

Haruhiko Banno ◽

Taro Okunomiya ◽

Yoko Amino ◽

Kayoko Endo ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Peer Review Process ◽

Presenilin 1 ◽

High Dose ◽

Maintenance Period ◽

Double Blind ◽

Safety And Efficacy ◽

Study Results ◽

Trial Drug

IntroductionAlzheimer’s disease (AD) is one of the most common causes of dementia. Pathogenic variants in the presenilin 1 (PSEN1) gene are the most frequent cause of early-onset AD. Medications for patients with AD bearing PSEN1 mutation (PSEN1-AD) are limited to symptomatic therapies and no established radical treatments are available. Induced pluripotent stem cell (iPSC)-based drug repurposing identified bromocriptine as a therapeutic candidate for PSEN1-AD. In this study, we used an enrichment strategy with iPSCs to select the study population, and we will investigate the safety and efficacy of an orally administered dose of bromocriptine in patients with PSEN1-AD.Methods and analysisThis is a multicentre, randomised, placebo-controlled trial. AD patients with PSEN1 mutations and a Mini Mental State Examination-Japanese score of ≤25 will be randomly assigned, at a 2:1 ratio, to the trial drug or placebo group (≥4 patients in TW-012R and ≥2 patients in placebo). This clinical trial consists of a screening period, double-blind phase (9 months) and extension phase (3 months). The double-blind phase for evaluating the efficacy and safety is composed of the low-dose maintenance period (10 mg/day), high-dose maintenance period (22.5 mg/day) and tapering period of the trial drug. Additionally, there is an open-labelled active drug extension period for evaluating long-term safety. Primary outcomes are safety and efficacy in cognitive and psychological function. Also, exploratory investigations for the efficacy of bromocriptine by neurological scores and biomarkers will be conducted.Ethics and disseminationThe proposed trial is conducted according to the Declaration of Helsinki, and was approved by the Institutional Review Board (K070). The study results are expected to be disseminated at international or national conferences and published in international journals following the peer-review process.Trial registration numberjRCT2041200008, NCT04413344.

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