scholarly journals Biomarkers and the diagnosis of preclinical dementia

2018 ◽  
Vol 24 (6) ◽  
pp. 422-430 ◽  
Author(s):  
Philippa Lilford ◽  
Julian C. Hughes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Practice ◽  
Clinical Symptoms ◽  
Supporting Evidence ◽  
List Type ◽  
Ethical Implications ◽  
Drug Companies ◽  
University Of Bristol ◽  
Alzheimer’S Pathology

SUMMARYAlzheimer's disease pathology accumulates years before the onset of clinical symptoms and has been termed ‘preclinical dementia’. Biomarkers have been developed to detect this pathology – namely, brain amyloid deposition and markers of neurodegeneration. In this article we describe these biomarkers and review the evidence for their clinical use in predicting risk both in the cognitively ‘normal’ and in those who already have established cognitive decline. We also discuss the limitations and ethical considerations of these tests and consider whether we should start incorporating Alzheimer's disease biomarkers into clinical practice. We find that, because many cognitively healthy people will have Alzheimer's pathology, and it is not clear whether this does help predict future risk of Alzheimer's disease, diagnosing preclinical dementia carries numerous ethical implications and is currently not being advocated outside research settings.LEARNING OBJECTIVES•Understand the concepts of preclinical and prodromal Alzheimer's disease and the use of biomarkers in this context•Analyse the supporting evidence for the use of biomarkers in prodromal and preclinical dementia•Apply this information to everyday clinical practiceDECLARATION OF INTERESTJ. C. H. works in the Research Institute for the Care of Older People (RICE), which undertakes clinical drug trials for drug companies. He is a sub-investigator on a number of trials (some of which involve neuroimaging and biomarkers) and principal investigator and chief investigator on two trials (neither of which involves biomarkers). All of these trials concern Alzheimer's disease or dementia. He does not receive any direct personal payment from the trials: the payment goes to RICE, which does, however, fund almost half of his post. RICE is an independent charity and separate from the University of Bristol.

scholarly journals The Framing of “Alzheimer’s Disease”: Differences Between Scientific and Lay Literature and Their Ethical Implications

2020 ◽  
Author(s):  
Marthe Smedinga ◽  
Eline M Bunnik ◽  
Edo Richard ◽  
Maartje H N Schermer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Research Literature ◽  
Framing Analysis ◽  
Ethical Implications ◽  
Societal Needs ◽  
Diagnostic Certainty ◽  
Biomarker Testing ◽  
Design And Methods

Abstract Background and Objectives The meaning of Alzheimer’s disease (AD) is changing in research. It now refers to a pathophysiological process, regardless of whether clinical symptoms are present. In the lay literature, on the other hand, AD is understood as a form of dementia. This raises the question of whether researchers and the lay audience are still talking about the same thing. If not, how will these different understandings of AD shape perspectives on (societal) needs for people with AD? Research Design and Methods We use framing analysis to retrieve the understandings of the term AD that are upheld in the research literature and in national Dutch newspaper articles. We make explicit how the framings of AD steer our normative attitudes toward the disease. Results In the analyzed research articles, AD is framed as a pathological cascade, reflected by biomarkers, starting in cognitively healthy people and ending, inevitably, in dementia. In the lay literature, AD is used as a synonym for dementia, and an AD diagnosis is understood as an incentive to enjoy “the time that is left.” Discussion and Implications The two different uses of the term AD in research and in the lay literature may result in misunderstandings, especially those research framings that falsely imply that people with AD biomarkers will inevitably develop dementia. Adoption of the research understanding of AD in clinical practice will have normative implications for our view on priority setting in health care. For example, it legitimizes biomarker testing in people without dementia as improving “diagnostic” certainty.

scholarly journals BRIDGING THE GAP BETWEEN RESEARCH AND CLINICAL PRACTICE IN ASYMPTOMATIC ALZHEIMER’S DISEASE

2015 ◽  
pp. 1-13
Author(s):  
A.M. Downing ◽  
R. Yaari ◽  
D.E. Ball ◽  
K.J. Selzler
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Practice ◽  
Clinical Symptoms ◽  
Health Impact ◽  
Practice Environment ◽  
Specific Interest ◽  
Future State ◽  
Research Findings ◽  
Disease Modifying

Due to the growing global health impact of Alzheimer’s disease (AD), there is a greater need for interventions that prevent or delay the onset of clinical symptoms of this debilitating disease. Clinical trials for disease-modifying compounds in AD have shifted towards earlier stages in the spectrum of illness, including the stage prior to cognitive symptoms. A population of specific interest for clinical research includes individuals with evidence of Alzheimer’s disease pathology who are asymptomatic (ADPa). The challenges and barriers regarding medical treatment of ADPa must be identified and addressed prior to the completion of a positive clinical trial in order to accelerate the translation of research findings to clinical practice. This report applies an existing public health impact model from Spencer and colleagues (2013) to evaluate the readiness of the clinical practice environment to treat ADPa individuals if a disease-modifying agent achieves approval. We contrast the current clinical practice environment with a potential future state through investigating the effectiveness, reach, feasibility, sustainability, and transferability of the practice of treating ADPa individuals.

scholarly journals Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tatsuhiro Terada ◽  
Joseph Therriault ◽  
Min Su Peter Kang ◽  
Melissa Savard ◽  
Tharick Ali Pascoal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Clinical Symptoms ◽  
Mitochondrial Complex I ◽  
Braak Stage ◽  
Mitochondrial Complex ◽  
Temporal Area

Abstract Background Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF. Methods Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. Results The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR. Conclusions Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.

scholarly journals Induced Pluripotent Stem Cell-Derived Neural Precursors Improve Memory, Synaptic and Pathological Abnormalities in a Mouse Model of Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1802
Author(s):  
Enrique Armijo ◽  
George Edwards ◽  
Andrea Flores ◽  
Jorge Vera ◽  
Mohammad Shahnawaz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Memory Loss ◽  
Amyloid Β ◽  
Cerebral Atrophy ◽  
Brain Inflammation ◽  
Neural Precursors ◽  
Model Of Alzheimer’S Disease ◽  
Induced Pluripotent

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

scholarly journals The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 371
Author(s):  
Patrycja Pawlik ◽  
Katarzyna Błochowiak
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Early Diagnosis ◽  
Neurodegenerative Diseases ◽  
Diagnostic Tool ◽  
Clinical Symptoms ◽  
Early Screening ◽  
Salivary Biomarkers

Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms.

scholarly journals Diet, nutrients and metabolism: cogs in the wheel driving Alzheimer's disease pathology?

2015 ◽  
Vol 113 (10) ◽  
pp. 1499-1517 ◽  
Author(s):  
Rhona Creegan ◽  
Wendy Hunt ◽  
Alexandra McManus ◽  
Stephanie R. Rainey-Smith
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Aged Care ◽  
Ageing Population ◽  
People With Dementia ◽  
Stage Disease ◽  
Custodial Care ◽  
Global Statistics ◽  
End Stage

Alzheimer's disease (AD), the most common form of dementia, is a chronic, progressive neurodegenerative disease that manifests clinically as a slow global decline in cognitive function, including deterioration of memory, reasoning, abstraction, language and emotional stability, culminating in a patient with end-stage disease, totally dependent on custodial care. With a global ageing population, it is predicted that there will be a marked increase in the number of people diagnosed with AD in the coming decades, making this a significant challenge to socio-economic policy and aged care. Global estimates put a direct cost for treating and caring for people with dementia at $US604 billion, an estimate that is expected to increase markedly. According to recent global statistics, there are 35·6 million dementia sufferers, the number of which is predicted to double every 20 years, unless strategies are implemented to reduce this burden. Currently, there is no cure for AD; while current therapies may temporarily ameliorate symptoms, death usually occurs approximately 8 years after diagnosis. A greater understanding of AD pathophysiology is paramount, and attention is now being directed to the discovery of biomarkers that may not only facilitate pre-symptomatic diagnosis, but also provide an insight into aberrant biochemical pathways that may reveal potential therapeutic targets, including nutritional ones. AD pathogenesis develops over many years before clinical symptoms appear, providing the opportunity to develop therapy that could slow or stop disease progression well before any clinical manifestation develops.

scholarly journals Motor-Skill Learning in Alzheimer’s Disease: A Review with an Eye to the Clinical Practice

2007 ◽  
Vol 17 (3) ◽  
pp. 203-212 ◽  
Author(s):  
Ilse A. D. A. van Halteren-van Tilborg ◽  
Erik J. A. Scherder ◽  
Wouter Hulstijn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Practice ◽  
Motor Skill ◽  
Skill Learning ◽  
Motor Skill Learning

Is Olfactory Epithelium Biopsy Useful for Confirming Alzheimer’s Disease?

2018 ◽  
Vol 128 (3) ◽  
pp. 184-192 ◽  
Author(s):  
Maria Dantas Costa Lima Godoy ◽  
Marco Aurélio Fornazieri ◽  
Richard L. Doty ◽  
Fábio de Rezende Pinna ◽  
José Marcelo Farfel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Olfactory Epithelium ◽  
Clinical Symptoms ◽  
Middle Turbinate ◽  
Superior Turbinate ◽  
Significant Difference ◽  
Amyloid Beta Proteins

Objectives: The clinical symptoms of Alzheimer’s disease (AD) are preceded by a long asymptomatic period associated with “silent” deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. Methods: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. Results: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate ( r = .58, P = .002). Conclusion: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD.

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