scholarly journals Deep and Frequent Phenotyping study protocol: an observational study in prodromal Alzheimer’s disease

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e024498 ◽  
Author(s):  
Ivan Koychev ◽  
Jennifer Lawson ◽  
Tharani Chessell ◽  
Clare Mackay ◽  
Roger Gunn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Observational Study ◽  
Outcome Measures ◽  
Pet Imaging ◽  
Repeated Measures ◽  
Disease Process ◽  
Csf Biomarkers ◽  
Prodromal Phase ◽  
South Central

IntroductionRecent failures of potential novel therapeutics for Alzheimer’s disease (AD) have prompted a drive towards clinical studies in prodromal or preclinical states. However, carrying out clinical trials in early disease stages is extremely challenging—a key reason being the unfeasibility of using classical outcome measures of dementia trials (eg, conversion to dementia) and the lack of validated surrogate measures so early in the disease process. The Deep and Frequent Phenotyping (DFP) study aims to resolve this issue by identifying a set of markers acting as indicators of disease progression in the prodromal phase of disease that could be used as indicative outcome measures in proof-of-concept trials.Methods and analysisThe DFP study is a repeated measures observational study where participants will be recruited through existing parent cohorts, research interested lists/databases, advertisements and memory clinics. Repeated measures of both established (cognition, positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) markers of pathology, structural MRI markers of neurodegeneration) and experimental modalities (functional MRI, magnetoencephalography and/or electroencephalography, gait measurement, ophthalmological and continuous smartphone-based cognitive and other assessments together with experimental CSF, blood, tear and saliva biomarkers) will be performed. We will be recruiting male and female participants aged >60 years with prodromal AD, defined as absence of dementia but with evidence of cognitive impairment together with AD pathology as assessed using PET imaging or CSF biomarkers. Control participants without evidence of AD pathology will be included at a 1:4 ratio.Ethics and disseminationThe study gained favourable ethical opinion from the South Central—Oxford B NHS Research Ethics Committee (REC reference 17/SC/0315; approved on 18 August 2017; amendment 13 February 2018). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.

Usefulness of CSF Biomarkers in Predicting the Progression of Amnesic and Nonamnesic Mild Cognitive Impairment to Alzheimer’s Disease

2019 ◽  
Vol 12 (1) ◽  
pp. 35-42
Author(s):  
Ricard L. Ortega ◽  
Farida Dakterzada ◽  
Alfonso Arias ◽  
Ester Blasco ◽  
Alba Naudí ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Csf Biomarkers ◽  
Prodromal Phase ◽  
Diagnosis And Prognosis ◽  
Amnestic Mci ◽  
Atypical Presentations ◽  
T Tau

Objective: The aim of this study was to investigate the usefulness of Alzheimer’s disease Cerebrospinal Fluid (CSF) biomarkers in predicting the progression to dementia in patients with Mild Cognitive Impairment (MCI). Methods: One hundred and thirteen patients were consecutively recruited from April 2012 to April 2014. Measurement of CSF biomarkers (amyloid-β42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau)) and a neuropsychological evaluation were performed for all patients. We categorized patients with MCI as A+A- and N+N- based on the presence/absence of amyloid pathology and neurodegeneration, respectively. Results: Of 72 patients with MCI, 26 (36%) progressed to dementia. These patients had lower CSF Aβ42 levels and higher p-tau and t-tau levels at baseline. The proportion that progressed to dementia was 14.3% (2/14), 36.8% (7/19), 66.7% (4/6) and 75% (12/16) in the A-N-, A+N-, A-N+ (SNAP), and A+N+ patients, respectively (p < 0.05). There were significant differences in the probability of progression from amnestic MCI (aMCI) to AD between the A+N+ and A-N- patients (OR = 8.1, 95% CI 1.5-42.3, p = 0.001) but not between SNAP (OR = 7.3, 95% CI 0.9-61, p = 0.02) or A+N- (OR = 2.1, 95% CI 0.4 to 10.4, p = 0.15) patients compared to the A-N- subgroup. None of the biomarker profiles of the subgroups predicted the time until the progression to AD. Conclusion: The use of CSF AD biomarkers in clinical practice improves the certainty of diagnosis and prognosis of patients, especially in patients in the prodromal phase or in patients with atypical presentations.

PET TAU AND AMYLOID-BETA DIFFER IN THEIR RELATIONSHIP TO AGE, COGNITION AND CSF BIOMARKERS IN MILD ALZHEIMER’S DISEASE: AN OBSERVATIONAL STUDY

2017 ◽  
Vol 13 (7) ◽  
pp. P243
Author(s):  
Ivan G. Koychev ◽  
Roger N. Gunn ◽  
Azadeh Firouzian ◽  
Jennifer Lawson ◽  
Giovanna Zamboni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Observational Study ◽  
Amyloid Beta ◽  
Csf Biomarkers

Biomarkers for Alzheimer’s disease

2020 ◽  
pp. 99-116
Author(s):  
Andrea Vergallo ◽  
Harald Hampel ◽  
René S. Bun ◽  
Simone Lista
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Dynamic Range ◽  
Emission Tomography ◽  
Csf Biomarkers ◽  
Serum Proteomics ◽  
Positron Emission ◽  
T Tau ◽  
Technological Platforms

Reflecting the neuropathological hallmarks of Alzheimer’s disease (AD), cerebrospinal fluid (CSF) concentrations of Aβ‎1-42, t-tau, and p-tau and positive amyloid positron emission tomography (PET) imaging are considered core biomarkers for AD. Unfortunately, their use for screening is limited by their invasive nature (CSF biomarkers) or high cost (PET imaging). Among the biologic specimens that may be scrutinized for identifying novel AD biomarkers, circulating blood is a convenient source for sampling. The dynamic range of high-throughput technological platforms, coupled with advances in bioinformatics, holds the promise that proteomics will be a significant contributor to the field of blood-based AD biomarkers. Here, the chapter summarizes the blood-based biomarker platforms applied to the investigation of AD and reviews recent achievements in plasma/serum proteomics related to AD. These findings set the stage for the implementation of systems biology in the context of the evolving precision medicine paradigm for AD.

[P1-448]: PET TAU AND AMYLOID-BETA DIFFER IN THEIR RELATIONSHIP TO AGE, COGNITION AND CSF BIOMARKERS IN MILD ALZHEIMER's DISEASE: AN OBSERVATIONAL STUDY

2017 ◽  
Vol 13 (7S_Part_9) ◽  
pp. P456-P457
Author(s):  
Ivan G. Koychev ◽  
Roger N. Gunn ◽  
Azadeh Firouzian ◽  
Jennifer Lawson ◽  
Giovanna Zamboni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Observational Study ◽  
Amyloid Beta ◽  
Csf Biomarkers

Auditory Dysfunction in Alzheimer's Disease

2010 ◽  
Vol 15 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Sridhar Krishnamurti
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Health Care ◽  
Care Setting ◽  
Neurodegenerative Disorder ◽  
Disease Process ◽  
Clinical Protocols ◽  
Speech Language Pathologist ◽  
Auditory Dysfunction

Alzheimer's disease is neurodegenerative disorder which affects a growing number of older adults every year. With an understanding of auditory dysfunction in Alzheimer's disease, the speech-language pathologist working in the health care setting can provide better service to these individuals. The pathophysiology of the disease process in Alzheimer's disease increases the likelihood of specific types of auditory deficits as opposed to others. This article will discuss the auditory deficits in Alzheimer's disease, their implications, and the value of clinical protocols for individuals with this disease.

Crossed Cerebellar Diaschisis in Alzheimer’s Disease

2018 ◽  
Vol 15 (13) ◽  
pp. 1267-1275 ◽  
Author(s):  
F.E. Reesink ◽  
D. Vállez García ◽  
C.A. Sánchez-Catasús ◽  
D.E. Peretti ◽  
A.T. Willemsen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Left Hemisphere ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Pathophysiological Mechanism ◽  
Crossed Cerebellar Diaschisis ◽  
Amyloid Accumulation ◽  
Cerebellar Diaschisis ◽  
18F Fdg

Background: We describe the phenomenon of crossed cerebellar diaschisis (CCD) in four subjects diagnosed with Alzheimer’s disease (AD) according to the National Institute on Aging - Alzheimer Association (NIA-AA) criteria, in combination with 18F-FDG PET and 11C-PiB PET imaging. Methods: 18F-FDG PET showed a pattern of cerebral metabolism with relative decrease most prominent in the frontal-parietal cortex of the left hemisphere and crossed hypometabolism of the right cerebellum. 11C-PiB PET showed symmetrical amyloid accumulation, but a lower relative tracer delivery (a surrogate of relative cerebral blood flow) in the left hemisphere. CCD is the phenomenon of unilateral cerebellar hypometabolism as a remote effect of supratentorial dysfunction of the brain in the contralateral hemisphere. The mechanism implies the involvement of the cortico-ponto-cerebellar fibers. The pathophysiology is thought to have a functional or reversible basis but can also reflect in secondary morphologic change. CCD is a well-recognized phenomenon, since the development of new imaging techniques, although scarcely described in neurodegenerative dementias. Results: To our knowledge this is the first report describing CCD in AD subjects with documentation of both 18F-FDG PET and 11C-PiB PET imaging. CCD in our subjects was explained on a functional basis due to neurodegenerative pathology in the left hemisphere. There was no structural lesion and the symmetric amyloid accumulation did not correspond with the unilateral metabolic impairment. Conclusion: This suggests that CCD might be caused by non-amyloid neurodegeneration. The pathophysiological mechanism, clinical relevance and therapeutic implications of CCD and the role of the cerebellum in AD need further investigation.

An automated radiosynthesis of (S)-[18F]28 for PET imaging of Alzheimer's disease

2021 ◽  
Vol 174 ◽  
pp. 109740
Author(s):  
Ji-Kui Xie ◽  
Xing-Xing Zhu ◽  
Kai-Xuan Wang ◽  
Shi-Cun Wang ◽  
Qiang Xie
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Automated Radiosynthesis

scholarly journals Potential Virus Involvement in Alzheimer’s Disease: Results from a Phase IIa Trial Evaluating Apovir, an Antiviral Drug Combination

2021 ◽  
pp. 1-19
Author(s):  
Nina Lindblom ◽  
Lars Lindquist ◽  
Jacob Westman ◽  
Mikael Åström ◽  
Roger Bullock ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Drug Combination ◽  
Antiviral Treatment ◽  
Antiviral Drug ◽  
Disease Process ◽  
Drop Out ◽  
Large Drop ◽  
Drop Out Rate

Background: Accumulating data suggest infectious agents are involved in Alzheimer’s disease (AD). The two primary aims of this trial were to assess safety and efficacy of an antiviral drug combination on AD progression. Objective: The trial evaluated whether Apovir, a combination of two antiviral agents, pleconaril (active on enteroviruses) and ribavirin (active on several viruses), could slow AD progression. Methods: Sixty-nine patients 60–85 years were treated with Apovir or placebo for 9 months and followed until 12 months after end of treatment. Cognitive tests, safety, biomarkers, drug plasma, and cerebrospinal fluid concentrations were assessed. Results: The tolerability of Apovir was compromised as demonstrated by the large drop-out rate and increased frequency and severity of adverse events. The primary endpoint, demonstrating a difference in change from baseline to 9 months between groups in ADAS-cog total score, was not met (p = 0.1809). However, there were observations indicating potential effects on both ADAS-cog and CDR-SB but these effects need to be verified. Also, there was a decrease in cerebrospinal fluid amyloid-β in Apovir at 9 months (p = 0.0330) but no change in placebo. Conclusion: This was the first randomized, placebo controlled clinical trial exploring antiviral treatment on AD progression. The trial is considered inconclusive due to the large drop-out rate. New trials are needed to verify if the indications of effect observed can be confirmed and which component(s) in Apovir contributed to such effects. Pleconaril alone may be studied to improve the tolerability and to verify if enterovirus is involved in the disease process.

scholarly journals Alignment of dietary patterns with the Dietary Guidelines for Americans 2015-2020 and risk of all-cause and cause-specific mortality in the Women’s Health Initiative Observational Study

2020 ◽  
Author(s):  
Stephanie M George ◽  
Jill Reedy ◽  
Elizabeth M Cespedes Feliciano ◽  
Aaron Aragaki ◽  
Bette J Caan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Observational Study ◽  
Women's Health ◽  
Diet Quality ◽  
Lower Risk ◽  
Dietary Guidelines ◽  
Women's Health Initiative ◽  
Health Initiative ◽  
The Women’S Health Initiative

Abstract Poor diet quality is a leading risk factor for death in the United States (U.S.). We examined the association between Healthy Eating Index-2015 (HEI-2015) scores and death from all-causes, cardiovascular disease (CVD), cancer, Alzheimer’s Disease and Dementia not otherwise specified (NOS) among postmenopausal women in the Women’s Health Initiative Observational Study (1993-2017). This analysis included 59,388 participants who completed a food frequency questionnaire and were free of cancer, CVD and diabetes at enrollment. Stratified Cox proportional hazards models were fit using person-years from enrollment as the underlying time metric. We estimated multivariable adjusted hazard ratios and 95% confidence intervals for risk of death associated with HEI-2015 quintiles, with higher scores reflecting more optimal diet quality. Over a median of 18.2 years, 9,679 total deaths 3,303 cancer deaths, 2,362 CVD deaths, and 488 deaths from Alzheimer’s Disease and Dementia NOS occurred. Compared to those with lower scores, women with higher HEI-2015 scores had an 18% lower risk of all-cause mortality and 21% lower risk of cancer mortality. HEI-2015 scores were not associated with mortality from CVD, Alzheimer’s Disease and dementia NOS. Consuming a diet aligned with 2015-2020 U.S. Dietary Guidelines may have beneficial impacts for preventing death from cancer and overall.

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