Alzheimer’s Dementia: The Emerging Role of Positron Emission Tomography

Tripathi, Shailendra Mohan; Murray, Alison

doi:10.1177/1073858421997035

Cited by 11 publications

(9 citation statements)

References 96 publications

(113 reference statements)

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“…The ability to identify and quantify in vivo the hallmark pathological markers amyloid and tau has transformed drug development for AD [ 22 , 23 ]. The potential for imaging biomarker modalities such as positron emission tomography (PET) as drug development tools is unique, as it allows for defining and quantifying brain region-specific changes that may correlate with functional outcomes.…”

Section: Biomarkersmentioning

confidence: 99%

Transforming Drug Development for Neurological Disorders: Proceedings from a Multidisease Area Workshop

Stephenson,

Belfiore-Oshan,

Karten

et al. 2023

Neurotherapeutics

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Neurological disorders represent some of the most challenging therapeutic areas for successful drug approvals. The escalating global burden of death and disability for such diseases represents a significant worldwide public health challenge, and the rate of failure of new therapies for chronic progressive disorders of the nervous system is higher relative to other non-neurological conditions. However, progress is emerging rapidly in advancing the drug development landscape in both rare and common neurodegenerative diseases. In October 2022, the Critical Path Institute (C-Path) and the US Food and Drug Administration (FDA) organized a Neuroscience Annual Workshop convening representatives from the drug development industry, academia, the patient community, government agencies, and regulatory agencies regarding the future development of tools and therapies for neurological disorders. This workshop focused on five chronic progressive diseases: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Duchenne muscular dystrophy, and inherited ataxias. This special conference report reviews the key points discussed during the three-day dynamic workshop, including shared learnings, and recommendations that promise to catalyze future advancement of novel therapies and drug development tools.

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Section: Biomarkersmentioning

confidence: 99%

Transforming Drug Development for Neurological Disorders: Proceedings from a Multidisease Area Workshop

Stephenson,

Belfiore-Oshan,

Karten

et al. 2023

Neurotherapeutics

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show abstract

“…Cerebral glucose hypometabolism has been consistently demonstrated in the posterior cingulate gyrus, MTL, frontal cortices, and/or parieto-temporal regions of typical AD patients. Similarly, moderate hypometabolism has been detected in the basal ganglia, cerebellum, visual cortices, and sensorimotor thalamus (Tripathi and Murray, 2022 ).…”

Section: Petmentioning

confidence: 94%

“…It has been reported that [ 18 F]florbetapir-positive scans were predictive for progressive deterioration of cognitive states in MCI and AD patients, compared with those with a negative scan (Doraiswamy et al ., 2014 ). Furthermore, [ 18 F]flutemetamol and [ 18 F]florbetaben have been approved by the U.S. Food and Drug Administration (Tripathi and Murray, 2022 ). [ 18 F]flutemetamol has shown the ability to discriminate patients with AD from elderly healthy (Hatashita et al ., 2019 ).…”

Section: Petmentioning

confidence: 99%

“…Amyloid PET has been used in clinical trials of novel drugs that help reduce the formation of Aβ but has not yet achieved favourable outcomes. Failure of antiamyloid therapies for AD leads to a paradigm shift towards tau as a therapeutic target (Tripathi and Murray, 2022 ). Tau PET may offer new insights and be of great help in the differential diagnosis and treatment selection of AD patients.…”

Section: Petmentioning

confidence: 99%

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Neuroimaging modalities in the detection of Alzheimer's disease-associated biomarkers

Dang

Wang

et al. 2023

Psychoradiology

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Alzheimer's disease (AD) is the most common cause of dementia. Neuropathological changes in AD patients occur up to 10–20 years before the emergence of clinical symptoms. Specific diagnosis and appropriate intervention strategies are crucial during the phase of mild cognitive impairment (MCI) and AD. The detection of biomarkers has emerged as a promising tool for tracking the efficacy of potential therapies, making an early disease diagnosis, and prejudging treatment prognosis. Specifically, multiple neuroimaging modalities, including magnetic resonance imaging (MRI), positron emission tomography, optical imaging, and single photon emission-computed tomography, have provided a few potential biomarkers for clinical application. The MRI modalities described in this review include structural MRI, functional MRI, diffusion tensor imaging, magnetic resonance spectroscopy, and arterial spin labelling. These techniques allow the detection of presymptomatic diagnostic biomarkers in the brains of cognitively normal elderly people and might also be used to monitor AD disease progression after the onset of clinical symptoms. This review highlights potential biomarkers, merits and demerits of different neuroimaging modalities and their clinical value in MCI and AD patients. Further studies are necessary to explore more biomarkers and overcome the limitations of multiple neuroimaging modalities for inclusion in diagnostic criteria for AD.

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“…Positron emission tomography (PET) measures in vivo molecular processes in the brain by using a wide range of radioactive tracers, making it a useful biomarker for identifying amyloid-β and pathological tau aggregations as well as neurodegeneration and neuroinflammation in the brain of the elderly ( Chandra et al 2019 ; Thientunyakit et al 2022 ; Tripathi and Murray 2022 ). Cortical amyloid-β plaque deposition is commonly assessed with Pittsburgh Compound B (PiB) or fluorinated tracers and has been the focus of PET research for the last 25 years.…”

Section: Episodic Memory Impairment As a Clinical Hallmark Of Admentioning

confidence: 99%

Co-twin design in brain imaging—review on biomarkers of Alzheimer's disease

2023

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Twin samples allow to conduct a quasi-experimental co-twin case–control approach that can control for genetic and environmental confounding in brain–cognition associations, being more informative on causality compared with studies in unrelated individuals. We conducted a review of studies that have utilized discordant co-twin design to investigate the associations of brain imaging markers of Alzheimer's disease and cognition. Inclusion criteria encompassed twin pairs discordant for cognition or Alzheimer's disease imaging markers and reporting of within-twin pair comparison on the association between cognition and brain measures. Our PubMed search (2022 April 23, updated 2023 March 9) resulted in 18 studies matching these criteria. Alzheimer's disease imaging markers have been addressed only by few studies, most with small sample size. Structural magnetic resonance imaging studies have indicated greater hippocampal volume and thicker cortex in co-twins with better cognitive performance compared with their co-twins with poorer cognitive performance. No studies have looked at cortical surface area. Positron emission tomography imaging studies have suggested that lower cortical glucose metabolism rate and higher cortical neuroinflammation, amyloid, and tau accumulations are related to poorer episodic memory in within-twin pair comparisons. Thus far, only cross-sectional within-twin pair associations of cortical amyloid and hippocampal volume with cognition have been replicated.

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Alzheimer’s Dementia: The Emerging Role of Positron Emission Tomography

Cited by 11 publications

References 96 publications

Transforming Drug Development for Neurological Disorders: Proceedings from a Multidisease Area Workshop

Transforming Drug Development for Neurological Disorders: Proceedings from a Multidisease Area Workshop

Neuroimaging modalities in the detection of Alzheimer's disease-associated biomarkers

Co-twin design in brain imaging—review on biomarkers of Alzheimer's disease

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