scholarly journals Recent Progress in the Identification of Non-Invasive Biomarkers to Support the Diagnosis of Alzheimer’s Disease in Clinical Practice and to Assist Human Clinical Trials

10.5772/60008 ◽  
2015 ◽  
Author(s):  
Francois Bernier ◽  
Pavan Kumar ◽  
Yoshiaki Sato ◽  
Yoshiya Oda
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Recent Progress ◽  
Non Invasive

scholarly journals Photobiomodulation for Alzheimer’s Disease: Has the Light Dawned?

Photonics ◽  
2019 ◽  
Vol 6 (3) ◽  
pp. 77 ◽  
Author(s):  
Michael Hamblin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Near Infrared ◽  
Infrared Light ◽  
Western World ◽  
Diverse Range ◽  
Non Invasive ◽  
Dementia Patients ◽  
Relieve Pain

Next to cancer, Alzheimer’s disease (AD) and dementia is probably the most worrying health problem facing the Western world today. A large number of clinical trials have failed to show any benefit of the tested drugs in stabilizing or reversing the steady decline in cognitive function that is suffered by dementia patients. Although the pathological features of AD consisting of beta-amyloid plaques and tau tangles are well established, considerable debate exists concerning the genetic or lifestyle factors that predispose individuals to developing dementia. Photobiomodulation (PBM) describes the therapeutic use of red or near-infrared light to stimulate healing, relieve pain and inflammation, and prevent tissue from dying. In recent years PBM has been applied for a diverse range of brain disorders, frequently applied in a non-invasive manner by shining light on the head (transcranial PBM). The present review discusses the mechanisms of action of tPBM in the brain, and summarizes studies that have used tPBM to treat animal models of AD. The results of a limited number of clinical trials that have used tPBM to treat patients with AD and dementia are discussed.

Simulating the Effects of Common Comedications and Genotypes on Alzheimer’s Cognitive Trajectory Using a Quantitative Systems Pharmacology Approach

2020 ◽  
Vol 78 (1) ◽  
pp. 413-424
Author(s):  
Hugo Geerts ◽  
Athan Spiros
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Second Generation ◽  
Standard Of Care ◽  
Systems Pharmacology ◽  
Quantitative Systems Pharmacology ◽  
Pharmacodynamic Interactions ◽  
Cognitive Trajectory

Background: Many Alzheimer’s disease patients in clinical practice are on polypharmacy for treatment of comorbidities. Objective: While pharmacokinetic interactions between drugs have been relatively well established with corresponding treatment guidelines, many medications and common genotype variants also affect central brain circuits involved in cognitive trajectory, leading to complex pharmacodynamic interactions and a large variability in clinical trials. Methods: We applied a mechanism-based and ADAS-Cog calibrated Quantitative Systems Pharmacology biophysical model of neuronal circuits relevant for cognition in Alzheimer’s disease, to standard-of-care cholinergic therapy with COMTVal158Met, 5-HTTLPR rs25531, and APOE genotypes and with benzodiazepines, antidepressants, and antipsychotics, all together 9,585 combinations. Results: The model predicts a variability of up to 14 points on ADAS-Cog at baseline (COMTVV 5-HTTLPRss APOE 4/4 combination is worst) and a four-fold range for the rate of progression. The progression rate is inversely proportional to baseline ADAS-Cog. Antidepressants, benzodiazepines, first-generation more than second generation, and most antipsychotics with the exception of aripiprazole worsen the outcome when added to standard-of-care in mild cases. Low dose second-generation benzodiazepines revert the negative effects of risperidone and olanzapine, but only in mild stages. Non APOE4 carriers with a COMTMM and 5HTTLPRLL are predicted to have the best cognitive performance at baseline but deteriorate somewhat faster over time. However, this effect is significantly modulated by comedications. Conclusion: Once these simulations are validated, the platform can in principle provide optimal treatment guidance in clinical practice at an individual patient level, identify negative pharmacodynamic interactions with novel targets and address protocol amendments in clinical trials.

scholarly journals Biomarkers in Mild Stages of Alzheimer’s disease: Utility in clinical practice and their relation with nutritional and lifestyle factors

2016 ◽  
Vol 6 (10) ◽  
pp. 627
Author(s):  
Carol Dillon ◽  
Patricio Pérez Leguizamon ◽  
Silvina Heisecke ◽  
Diego M. Castro ◽  
Jorge Lopez Camelo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Clinical Research ◽  
Lifestyle Factors ◽  
Clinical Settings ◽  
Treatment Methods ◽  
Primary Endpoints ◽  
Alzheimer’S Disease Dementia

Background: The use of biomarkers in basic and clinical research as well as in clinical practice has become so common that their presence as primary endpoints in clinical trials is now accepted. A biomarker refers to a broad subcategory of medical signs. The aims of this article are to consider the of use biomarkers in Mild stages of Alzheimer’s disease (AD) in research and clinical settings, in addition to defining their utility in clinical practice relating this with nutritional and lifestyle factors as possible treatment. Methods: We searched MEDLINE, PubMed, and AgeLine databases using different keywords.Conclusions: A summary of the utility of biomarkers in AD and nutritional and lifestyle factors used as treatment in mild stages are described.Key words: Biomarkers, Alzheimer’s disease, Dementia, Utility, Clinical practice, Nutritional

scholarly journals A novel technology for objective, accurate and non-invasive early diagnosis and monitoring of Alzheimer’s disease in clinics and clinical trials

2019 ◽  
Author(s):  
Kaveh Vejdani ◽  
Thomas Liebmann ◽  
Nicolas Pannetier ◽  
Elham Khosravi ◽  
Mohsen Yousefnezhad ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Brain Mri ◽  
Controlled Environment ◽  
Fully Integrated ◽  
Non Invasive ◽  
Novel Technology ◽  
Diagnostic Certainty ◽  
Effect Monitoring

AbstractWe have developed a novel medical image processing technology for objective, accurate, and non-invasive diagnosis, prognosis, and monitoring of Alzheimer’s disease using standard clinical brain MRI (magnetic resonance imaging) and basic clinical cognitive assessment. The technology is a robust, highly accurate, fully automated, high-throughput, cloud-based platform, which operates in a fully integrated and controlled environment. In diagnosis mode, our technology performs with 91% balanced accuracy on blind testing to diagnose the current neurocognitive status, and in prognosis modeor early detection at mild cognitive impairment (MCI) stage with 88% balanced accuracy on blind testing to predict progression from MCI to Alzheimer’s dementia (AD) within 5 years. Such prognostic capability is currently non-existent, even in specialty clinics and hospitals, a major factor in Alzheimer’s clinical trial failures. The algorithm’s diagnostic certainty precisely mirrors the diagnostic confidence of an expert cognitive neurologist for both MCI (Spearman’s Rho = 1) and AD (Rho = 1). In addition to widespread clinical applications, this novel technology can enable correct patient selection and therapeutic effect monitoring in clinical trials of Alzheimer’s disease, the crucial elements to finding a cure.

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
Author(s):  
Nishant Verma ◽  
S. Natasha Beretvas ◽  
Belen Pascual ◽  
Joseph C. Masdeu ◽  
Mia K. Markey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Latent Variable ◽  
Brain Regions ◽  
Disease Assessment ◽  
Latent Variable Analysis ◽  
The Relationship ◽  
Selection Of

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

Recent Updates in the Alzheimer’s Disease Etiopathology and Possible Treatment Approaches: A Narrative Review of Current Clinical Trials

2020 ◽  
Vol 13 (4) ◽  
pp. 273-294 ◽  
Author(s):  
Elahe Zarini-Gakiye ◽  
Javad Amini ◽  
Nima Sanadgol ◽  
Gholamhassan Vaezi ◽  
Kazem Parivar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Small Molecules ◽  
Clinical Trial Design ◽  
Treatment Approaches ◽  
Drug Candidates ◽  
Novel Treatments ◽  
Approved Drugs ◽  
Tau Aggregation

Background: Alzheimer’s disease (AD) is the most frequent subtype of incurable neurodegenerative dementias and its etiopathology is still not clearly elucidated. Objective: Outline the ongoing clinical trials (CTs) in the field of AD, in order to find novel master regulators. Methods: We strictly reviewed all scientific reports from Clinicaltrials.gov and PubMed databases from January 2010 to January 2019. The search terms were “Alzheimer's disease” or “dementia” and “medicine” or “drug” or “treatment” and “clinical trials” and “interventions”. Manuscripts that met the objective of this study were included for further evaluations. Results: Drug candidates have been categorized into two main groups including antibodies, peptides or hormones (such as Ponezumab, Interferon β-1a, Solanezumab, Filgrastim, Levemir, Apidra, and Estrogen), and naturally-derived ingredients or small molecules (such as Paracetamol, Ginkgo, Escitalopram, Simvastatin, Cilostazo, and Ritalin-SR). The majority of natural candidates acted as anti-inflammatory or/and anti-oxidant and antibodies exert their actions via increasing amyloid-beta (Aβ) clearance or decreasing Tau aggregation. Among small molecules, most of them that are present in the last phases act as specific antagonists (Suvorexant, Idalopirdine, Intepirdine, Trazodone, Carvedilol, and Risperidone) or agonists (Dextromethorphan, Resveratrol, Brexpiprazole) and frequently ameliorate cognitive dysfunctions. Conclusion: The presences of a small number of candidates in the last phase suggest that a large number of candidates have had an undesirable side effect or were unable to pass essential eligibility for future phases. Among successful treatment approaches, clearance of Aβ, recovery of cognitive deficits, and control of acute neuroinflammation are widely chosen. It is predicted that some FDA-approved drugs, such as Paracetamol, Risperidone, Escitalopram, Simvastatin, Cilostazoand, and Ritalin-SR, could also be used in off-label ways for AD. This review improves our ability to recognize novel treatments for AD and suggests approaches for the clinical trial design for this devastating disease in the near future.

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