Alpha-peak power modulation with transcranial alternate current stimulation for Alzheimer’s Disease – A pilot study in healthy controls(tACS)

The lack of sensitive and specific biomarkers for the early detection of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is a major hurdle to improving patient management. A targeted, quantitative metabolomics approach using both 1H NMR and mass spectrometry was employed to investigate the performance of urine metabolites as potential biomarkers for MCI and AD. Correlation-based feature selection (CFS) and least absolute shrinkage and selection operator (LASSO) methods were used to develop biomarker panels tested using support vector machine (SVM) and logistic regression models for diagnosis of each disease state. Metabolic changes were investigated to identify which biochemical pathways were perturbed as a direct result of MCI and AD in urine. Using SVM, we developed a model with 94% sensitivity, 78% specificity, and 78% AUC to distinguish healthy controls from AD sufferers. Using logistic regression, we developed a model with 85% sensitivity, 86% specificity, and an AUC of 82% for AD diagnosis as compared to cognitively healthy controls. Further, we identified 11 urinary metabolites that were significantly altered to include glucose, guanidinoacetate, urocanate, hippuric acid, cytosine, 2- and 3-hydroxyisovalerate, 2-ketoisovalerate, tryptophan, trimethylamine N oxide, and malonate in AD patients, which are also capable of diagnosing MCI, with a sensitivity value of 76%, specificity of 75%, and accuracy of 81% as compared to healthy controls. This pilot study suggests that urine metabolomics may be useful for developing a test capable of diagnosing and distinguishing MCI and AD from cognitively healthy controls.

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A Non-Interventional Pilot Study to Explore the Role of Gut Flora in Alzheimer's Disease

Case Medical Research ◽

10.31525/ct1-nct04100889 ◽

2019 ◽

Author(s):

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Pilot Study ◽

Gut Flora

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Different Morphology of Neuritic Plaques in the Archicortex of Alzheimer’s Disease with Comorbid Synucleinopathy: A Pilot Study

Current Alzheimer Research ◽

10.2174/1875692117999201215162043 ◽

2020 ◽

Vol 17 ◽

Author(s):

Nikol Jankovska ◽

Tomas Olejar ◽

Jaromir Kukal ◽

Radoslav Matej

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Pilot Study ◽

Time Course ◽

Clinical Course ◽

Lewy Bodies ◽

Dystrophic Neurites ◽

Neuritic Plaques ◽

Structural Differences ◽

Lewy Body Variant

Background: Bulbous neuritic changes in neuritic plaques have already been described, and their possible effect on the clinical course of the disease has been discussed. OBJECTIVE: In our study, we focused on the location and density of these structures in patients with only Alzheimer’s disease (AD) and patients with AD in comorbidity with synucleinopathies. Methods: Utilizing immunohistochemistry and confocal microscopy, we evaluated differences of neocortical and archicortical neuritic plaques and the frequency of bulbous changes in the archicortex of 14 subjects with Alzheimer’s disease (AD), 10 subjects with the Lewy body variant of Alzheimer's disease (AD/DLB), and 4 subjects with Alzheimer's disease with amygdala Lewy bodies (AD/ALB). Also, the progression and density of neuritic changes over the time course of the disease were evaluated. Results: We found structural differences in bulbous dystrophic neurites more often in AD/DLB and AD/ALB than in pure AD cases. The bulbous neuritic changes were more prominent in the initial and progressive phases and were reduced in cases with a long clinical course. Conclusion: Our results indicate that there is a prominent difference in the shape and composition of neocortical and archicortical neuritic plaques and, moreover, that bulbous neuritic changes can be observed at a higher rate in AD/DLB and AD/ALB subjects compared to pure AD subjects. This observation probably reflects that these subacute changes are more easily seen in the faster clinical course of AD patients with comorbidities.

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

10.2196/preprints.14905 ◽

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

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Handwriting in Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-210279 ◽

2021 ◽

pp. 1-9

Author(s):

Margarete Delazer ◽

Laura Zamarian ◽

Atbin Djamshidian

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Course ◽

Typical Feature ◽

Healthy Controls ◽

Spearman Correlation ◽

Writing Difficulties ◽

Motor Programs ◽

Processing Level ◽

Diagnostic Values

Background: Agraphia is a typical feature in the clinical course of Alzheimer’s disease (AD). Objective: Assess the differences between AD and normal aging as regards kinematographic features of handwriting and elucidate writing deficits in AD. Methods: The study included 23 patients with AD (78.09 years/SD = 7.12; MMSE 21.39/SD = 3.61) and 34 healthy controls (75.56 years/SD = 5.85; MMSE 29.06/SD = 0.78). Both groups performed alphabetical and non-alphabetical writing tasks. The kinematographic assessment included the average number of inversions per stroke (NIV; number of peaks in the velocity profile in a single up or down stroke), percentage of automated segments, frequency (average number of strokes per second), writing pressure, and writing velocity on paper. Results: A total of 14 patients showed overt writing difficulties reflected by omissions or substitutions of letters. AD patients showed less automated movements (as measured by NIV), lower writing velocity, and lower frequency of up-and-down strokes in non-alphabetical as well as in alphabetical writing. In the patient group, Spearman correlation analysis between overt writing performance and NIV was significant. That means patients who had less errors in writing a sentence showed a higher automaticity in handwriting. The correctness of alphabetical writing and some kinematographic measures in writing non-alphabetical material reached excellent diagnostic values in ROC analyses. There was no difference in the application of pressure on the pen between patients and controls. Conclusion: Writing disorders are multi-componential in AD and not strictly limited to one processing level. The slow and poorly automated execution of motor programs is not bound to alphabetical material.

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Assessing visuo-constructive functions in patients with subjective cognitive decline, mild cognitive impairment and Alzheimer’s disease with the Vienna Visuo-Constructional Test 3.0 (VVT 3.0)

Neuropsychiatrie ◽

10.1007/s40211-021-00385-x ◽

2021 ◽

Author(s):

Noel Valencia ◽

Johann Lehrner

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Multinomial Logistic Regression ◽

Subjective Cognitive Decline ◽

Healthy Controls ◽

Considerable Potential ◽

Multinomial Logistic Regression Analysis

Summary Background Visuo-Constructive functions have considerable potential for the early diagnosis and monitoring of disease progression in Alzheimer’s disease. Objectives Using the Vienna Visuo-Constructional Test 3.0 (VVT 3.0), we measured visuo-constructive functions in subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and healthy controls to determine whether VVT performance can be used to distinguish these groups. Materials and methods Data of 671 participants was analyzed comparing scores across diagnostic groups and exploring associations with relevant clinical variables. Predictive validity was assessed using Receiver Operator Characteristic curves and multinomial logistic regression analysis. Results We found significant differences between AD and the other groups. Identification of cases suffering from visuo-constructive impairment was possible using VVT scores, but these did not permit classification into diagnostic subgroups. Conclusions In summary, VVT scores are useful indicators for visuo-constructive impairment but face challenges when attempting to discriminate between several diagnostic groups.

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