scholarly journals Changes in retinal multilayer thickness and vascular network of patients with Alzheimer’s disease

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xi Mei ◽  
Conglong Qiu ◽  
Qi Zhou ◽  
Zhongming Chen ◽  
Yang Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Performance ◽  
Retinal Thickness ◽  
Vascular Density ◽  
Fiber Layer ◽  
Mean Values ◽  
Registration Number ◽  
Clinical Trail ◽  
The Difference

Abstract Background Retinal biomarkers of Alzheimer’s disease (AD) have been extensively investigated in recent decades. Retinal nervous and vascular parameters can reflect brain conditions, and they can facilitate early diagnosis of AD. Objective Our study aimed to evaluate the difference in retinal neuro-layer thickness and vascular parameters of patients with AD and healthy controls (HCs). Methods Non-invasive optical coherence tomography angiography (OCTA) was used to determine the combined thickness of the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), as well as the full retinal thickness (FRT). The vascular branching (VB), vascular curvature (VC), and vascular density (VD) for AD and HC groups were also obtained. The Mini-Mental State Examination (MMSE) was used to evaluate the cognitive performance of all the participants. After obtaining all the parameters, two-way analysis of variance (ANOVA) was used to compare the mean values of all the retinal parameters of the patients with AD and the HCs. Pearson's correlation was used to test the association between retinal parameters, MMSE scores, and vascular parameters. Results Seventy-eight eyes from 39 participants (19 AD and 20 HC; male, 52.6% in AD and 45.0% in HC; mean [standard deviation] age of 73.79 [7.22] years in AD and 74.35 [6.07] years in HC) were included for the analysis. The average RNFL + GCL thickness (106.32 ± 7.34 μm), FRTs of the four quadrants (290.35 ± 13.05 μm of inferior quadrant, 294.68 ± 9.37 μm of superior quadrant, 302.97 ± 6.52 μm of nasal quadrant, 286.02 ± 13.74 μm of temporal quadrant), and retinal VD (0.0148 ± 0.003) of patients with AD, compared with the HCs, were significantly reduced (p < 0.05). Retinal thickness was significantly correlated with the MMSE scores (p < 0.05). Meanwhile, retinal VD was significantly correlated with the average RNFL + GCL thickness (r2 = 0.2146, p < 0.01). When the vascular parameters were considered, the sensitivity of the AD diagnosis was increased from 0.874 to 0.892. Conclusion Our study suggested that the patients with AD, compared with age-matched HCs, had significantly reduced RNFL + GCL thickness and vascular density. These reductions correlated with the cognitive performance of the participants. By combining nerve and vessel parameters, the diagnosis of AD can be improved using OCTA technology. Trail registration Name of the registry: Chinese Clinical Trail Registry, Trial registration number: ChiCTR2000035243, Date of registration: Aug. 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx

scholarly journals Changes in Retinal Multilayer Thickness and Vascular Network of Patients With Alzheimer’s Disease

2021 ◽  
Author(s):  
Xi Mei ◽  
Chenjun Zou ◽  
Conglong Qiu ◽  
Zhongming Chen ◽  
Yang Chen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Retinal Thickness ◽  
Vascular Density ◽  
Fiber Layer ◽  
Mean Values ◽  
Non Invasive ◽  
Registration Number ◽  
Temporal Quadrant ◽  
The Difference

Abstract Background: Retinal biomarkers of Alzheimer’s disease (AD) were largely investigated during last decades. Brain conditions could be reflected by retinal nervous and vascular parameters. It can be used to enhance the accuracy of early diagnosis of AD.Objective: Our study aimed to evaluate the difference of retinal neuro-layer thickness and vascular parameters between AD patients and health control (HC) subjects.Methods: Non-invasive technology of optical coherence tomography angiography (OCTA) were adopted to acquire the combination thickness of retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), as well as the full retinal thickness (FRT). Vascular branch (VB), vascular curvature (VC), and vascular density (VD) were also collected in AD and HC groups. Mini-mental state examination (MMSE) was adopted to evaluate the cognitive levels of all subjects. After obtaining all the parameters, we used Mann-Whitney U test to compare the mean values of all retinal regions parameters between ADs and HCs. Pearson's correlation was used to test the association between retinal parameters and MMSE score, and vascular parameters.Results: Compared with HCs, the RNFL+GCL thickness of inferior quadrant, FRT of inferior and temporal quadrant, and retinal VD of patients with AD were significantly reduced (p < 0.05). The retinal thickness had significant correlations with MMSE scores (p < 0.05). Meanwhile, the retinal VD was significantly correlated with the average RNFL+GCL thickness (p < 0.05, r = 0.5956).Conclusion: In conclusion, our study suggested that AD patients had significant reduced RNFL+GCL thickness and vascular density compared with the age-matched HCs. Meanwhile, these reductions correlated with the cognitive level of the subjects. Trial registration number: ChiCTR2000035243Date of registration: Aug., 5, 2020URL of trial registry record: http://www.chictr.org.cn/index.aspx

Evaluating Thrombin Inhibition in Alzheimer’s Disease (The BEACON Trial): Protocol for a Pilot Study (Preprint)

2019 ◽  
Author(s):  
Cláudia Yang Santos ◽  
Christine Getter ◽  
John Stoukides ◽  
Brian Ott ◽  
Stephen Salloway ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Cognitive Performance ◽  
Thrombin Inhibitor ◽  
Placebo Control ◽  
Open Label ◽  
Double Blind ◽  
Thrombin Inhibition ◽  
Approved Drugs

BACKGROUND The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzheimer’s disease (AD) have not been delineated. We reported that microvessels isolated from AD brains overexpress a diverse array of neurotoxic and inflammatory proteins, which is consistent with the process of vascular activation. In pre-clinical studies using AD animal models we showed that a vascular activation inhibitor reduced vascular-derived neuroinflammation and improved cognitive performance. Thrombin is a key mediator of cerebrovascular activation in AD. OBJECTIVE This study aims to investigate the safety and potential efficacy of the direct thrombin inhibitor dabigatran, in patients with mild cognitive impairment (MCI) or mild AD to decrease vascular-derived neuroinflammation and improve cognitive performance. METHODS Participants will be enrolled then evaluated quarterly throughout the 24-month study. This is a 24-month randomized-control, double-blind, placebo-controlled, multicenter, delayed-start, pilot study evaluating thrombin inhibition in people with biomarker-confirmed MCI probably due to AD or mild AD. 40 - 60 participants will be recruited between 50 - 85 years old. In the initial 9-months of study, either dabigatran or placebo will be orally administered to patients at a dose of 150 mg per day. After 9 months of the placebo-control (Phase I), the placebo arm will cross-over to an active, open-label (Phase II) where all patients will be treated with a 150 mg daily dose of dabigatran orally for an additional 12 months. A 3-month non-treatment follow-up period will assess duration of effects. RESULTS Beginning in July 2019, and concluding in August 2022, this study is expected to publish final results in January 2023. CONCLUSIONS BEACON is a first-in-kind randomized clinical trial targeting thrombin activation in AD therapeutics. This trial will stimulate translational investigations of an FDA-approved drugs in a newly defined therapeutic areas. CLINICALTRIAL Clinicaltrials.gov NCT03752294

scholarly journals Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer’s Disease: Results from the Gothenburg H70 Birth Cohort Studies

2021 ◽  
Vol 79 (1) ◽  
pp. 225-235
Author(s):  
Maya Arvidsson Rådestig ◽  
Johan Skoog ◽  
Henrik Zetterberg ◽  
Jürgen Kern ◽  
Anna Zettergren ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cohort Studies ◽  
Cognitive Performance ◽  
Birth Cohort ◽  
Population Based ◽  
Tau Pathology ◽  
Preclinical Alzheimer’S Disease ◽  
Preclinical Ad

Background: We have previously shown that older adults with preclinical Alzheimer’s disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology. Objective: We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology. Methods: The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n = 316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories. Results: Among participants with CDR 0 (n = 259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p = 0.003), object Delayed (p = 0.042) and Immediate recall (p = 0.033)). Among participants with CDR 0.5 (n = 57), those with amyloid pathology (A+) scored worse in category fluency (p = 0.003). Conclusion: Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.

scholarly journals A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shifu Xiao ◽  
Piu Chan ◽  
Tao Wang ◽  
Zhen Hong ◽  
Shuzhen Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Controlled Trial ◽  
Drug Effects ◽  
Disease Assessment ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
The Difference

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

Lower cerebral oxygen utilization is associated with Alzheimer’s disease-related neurodegeneration and poorer cognitive performance among apolipoprotein E ε4 carriers

2021 ◽  
pp. 0271678X2110563
Author(s):  
W Hudson Robb ◽  
Omair A Khan ◽  
Humza A Ahmed ◽  
Judy Li ◽  
Elizabeth E Moore ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Episodic Memory ◽  
Apolipoprotein E ◽  
Cognitive Performance ◽  
Lateral Ventricle ◽  
Oxygen Metabolism ◽  
Cerebral Oxygen ◽  
P Values ◽  
Apoe Ε4

Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) are markers of cerebral oxygen homeostasis and metabolism that may offer insights into abnormal changes in brain aging. The present study cross-sectionally related OEF and CMRO2 to cognitive performance and structural neuroimaging variables among older adults (n = 246, 74 ± 7 years, 37% female) and tested whether apolipoprotein E ( APOE)-ε4 status modified these associations. Main effects of OEF and CMRO2 were null (p-values >0.06), and OEF interactions with APOE-ε4 status on cognitive and structural imaging outcomes were null (p-values >0.06). However, CMRO2 interacted with APOE-ε4 status on language (p = 0.002), executive function (p = 0.03), visuospatial (p = 0.005), and episodic memory performances (p = 0.03), and on hippocampal (p = 0.006) and inferior lateral ventricle volumes (p = 0.02). In stratified analyses, lower oxygen metabolism related to worse language (p = 0.02) and episodic memory performance (p = 0.03) among APOE-ε4 carriers only. Associations between CMRO2 and cognitive performance were primarily driven by APOE-ε4 carriers with existing cognitive impairment. Congruence across language and episodic memory results as well as hippocampal and inferior lateral ventricle volume findings suggest that APOE-ε4 may interact with cerebral oxygen metabolism in the pathogenesis of Alzheimer’s disease and related neurodegeneration.

scholarly journals Prevalência, desempenho cognitivo e funcionalidade de idosos com Doença de Alzheimer em instituições de longa permanência de Bento Gonçalves

2017 ◽  
Vol 5 (1) ◽  
pp. 23 ◽  
Author(s):  
Daniela Fernandes Tonholi ◽  
Gisele Oltramari
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Performance ◽  
Junior High School ◽  
Functional Independence Measure ◽  
The Elderly ◽  
Functional Independence ◽  
Cross Sectional Study ◽  
Functional Evaluation ◽  
Cross Sectional

Aims: To determine the prevalence, cognitive performance and functionality of elderly people with Alzheimer's disease in long-stay institutions for the elderlyin the city of Bento Gonçalves. Methods: Cross-sectional study including 24 elderly residents in long-stay institutions for the elderly, sociodemographic datawere obtained, and the elderly were subjected to functional evaluation by the Functional Independence Measure and evaluation of cognitive performancethrough the mental state the Mini (MMSE). Results: Most of the residents were female (83%), as 54.2% schooling had completed junior high school, mostof the elderly (70.8%) was admitted by the will of the family, 100% of the elderly showed cognitive performance bad, and the smaller the more dependentcognitive performance was the individual. Conclusion: institutionalized elderly with Alzheimer's disease had negative results on cognitive performance,as well as deficits in their ability to perform activities of daily living, thus altering their functionality.Keywords: aging; functionality; cognition; Alzheimer Disease; long-stay institutions.

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