Neuroimaging in Alzheimer’s Disease

2013 ◽  
pp. 427-431 ◽  
Author(s):  
Hidenao Fukuyama
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Posterior Part ◽  
Lewy Body Disease ◽  
New Drugs ◽  
Amyloid Protein ◽  
Dementia Patients ◽  
Positron Emission ◽  
Occipital Lobes ◽  
The Brain

The diagnosis of Alzheimer’s disease (AD) is often based on clinical and pathological data. Positron emission tomography (PET) using the tracer 18F-FDG revealed findings specific to AD-mainly the posterior part of the brain and the association cortices of the parietal and occipital lobes were affected by a reduction in glucose metabolism. Recent advances in the development of tracers for amyloid protein, which is the key protein in the pathogenesis of AD, enables the pattern of deposition of amyloid protein in the brain to be visualized. Various tracers have been introduced to visualize other aspects of AD pathology. Recent clinical interests on dementia have focused on the early detection of AD and variation of Parkinson’s disease, namely dementia with Lewy body disease (DLB), because the earlier the diagnosis, the better the prognosis. The differential diagnosis of mild AD or mild cognitive impairment (MCI) as well as DLB has been studied using PET and MRI as part of the NIH’s Alzheimer disease Neuroimaging initiative (ADNI). At present, many countries are participating in the ADNI, which is yielding promising results. This chapter’s study will improve the development of new drugs for the treatment of dementia patients by enabling the evaluation of the effect and efficacy of those drugs.

Neuroimaging in Alzheimer’s Disease

2011 ◽  
pp. 231-235
Author(s):  
Hidenao Fukuyama
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Posterior Part ◽  
Lewy Body Disease ◽  
New Drugs ◽  
Amyloid Protein ◽  
Dementia Patients ◽  
Positron Emission ◽  
Occipital Lobes ◽  
The Brain

The diagnosis of Alzheimer’s disease (AD) is often based on clinical and pathological data. Positron emission tomography (PET) using the tracer 18F-FDG revealed findings specific to AD-mainly the posterior part of the brain and the association cortices of the parietal and occipital lobes were affected by a reduction in glucose metabolism. Recent advances in the development of tracers for amyloid protein, which is the key protein in the pathogenesis of AD, enables the pattern of deposition of amyloid protein in the brain to be visualized. Various tracers have been introduced to visualize other aspects of AD pathology. Recent clinical interests on dementia have focused on the early detection of AD and variation of Parkinson’s disease, namely dementia with Lewy body disease (DLB), because the earlier the diagnosis, the better the prognosis. The differential diagnosis of mild AD or mild cognitive impairment (MCI) as well as DLB has been studied using PET and MRI as part of the NIH’s Alzheimer disease Neuroimaging initiative (ADNI). At present, many countries are participating in the ADNI, which is yielding promising results. This chapter’s study will improve the development of new drugs for the treatment of dementia patients by enabling the evaluation of the effect and efficacy of those drugs.

The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer’s Disease Continuum: A Longitudinal Study

2021 ◽  
pp. 1-12
Author(s):  
Heng Zhang ◽  
Diyang Lyu ◽  
Jianping Jia ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Dementia Patients ◽  
Positron Emission ◽  
Potential Biomarker ◽  
Synaptic Degeneration ◽  
Over Time

Background: Synaptic degeneration has been suggested as an early pathological event that strongly correlates with severity of dementia in Alzheimer’s disease (AD). However, changes in longitudinal cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) as a synaptic biomarker in the AD continuum remain unclear. Objective: To assess the trajectory of CSF GAP-43 with AD progression and its association with other AD hallmarks. Methods: CSF GAP-43 was analyzed in 788 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including 246 cognitively normal (CN) individuals, 415 individuals with mild cognitive impairment (MCI), and 127 with AD dementia based on cognitive assessments. The associations between a multimodal classification scheme with amyloid-β (Aβ), tau, and neurodegeneration, and changes in CSF GAP-43 over time were also analyzed. Results: CSF GAP-43 levels were increased at baseline in MCI and dementia patients, and increased significantly over time in the preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stages of AD. Higher levels of CSF GAP-43 were also associated with higher CSF phosphorylated tau (p-tau) and total tau (t-tau), cerebral amyloid deposition and hypometabolism on positron emission tomography, the hippocampus and middle temporal atrophy, and cognitive performance deterioration at baseline and follow-up. Furthermore, CSF GAP-43 may assist in effectively predicting the probability of dementia onset at 2- or 4-year follow-up. Conclusion: CSF GAP-43 can be used as a potential biomarker associated with synaptic degeneration in subjects with AD; it may also be useful for tracking the disease progression and for monitoring the effects of clinical trials.

scholarly journals Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shorena Janelidze ◽  
Erik Stomrud ◽  
Ruben Smith ◽  
Sebastian Palmqvist ◽  
Niklas Mattsson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Pet Tracer ◽  
Positron Emission ◽  
Diagnostic Work ◽  
Work Up ◽  
The Brain ◽  
Better Than

AbstractCerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort (n = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.

scholarly journals The potential role for sphingolipids in neuropathogenesis of Alzheimer’s disease

2013 ◽  
Vol 59 (1) ◽  
pp. 25-50 ◽  
Author(s):  
A.V. Alessenko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Role ◽  
Potential Role ◽  
Early Stage ◽  
New Drugs ◽  
Neuronal Function ◽  
Sphingosine 1 Phosphate ◽  
The Brain

The review discusses the functional role of sphingolipids in the pathogenesis of Alzheimer's disease. Certain evidence exist that the imbalance of sphingolipids such as sphingomyelin, ceramide, sphingosine, sphingosine-1-phosphate and galactosylceramide in the brain of animals and humans, in the cerebrospinal fluid and blood plasma of patients with Alzheimer's disease play a crucial role in neuronal function by regulating growth, differentiation and cell death in CNS. Activation of sphingomyelinase, which leads to the accumulation of the proapoptotic agent, ceramide, can be considered as a new mechanism for AD and may be a prerequisite for the treatment of this disease by using drugs that inhibit sphingomyelinase activity. The role of sphingolipids as biomarkers for the diagnosis of the early stage of Alzheimer's disease and monitoring the effectiveness of treatment with new drugs is discussed.

scholarly journals The Challenges of Diagnosis in Alzheimer’s Disease

US Neurology ◽  
2018 ◽  
Vol 14 (1) ◽  
pp. 15 ◽  
Author(s):  
Nenad Bogdanovic
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Amyloid Pet ◽  
Positive Finding ◽  
Positron Emission ◽  
University Of Oslo ◽  
The University ◽  
Study Participants ◽  
The Brain

Current neuropathologic examination of the brain is still the gold standard for diagnosis of Alzheimer’s disease (AD). Postmortem studies, however, have indicated that current methods for the clinical diagnosis of AD are suboptimal.1Recent research has demonstrated the clinical utility of amyloid-beta positron emission tomography (PET) scans, which detect the presence of amyloid-beta plaques in the brain. In a study presented at the Alzheimer’s Association International Conference (AAIC) in London, UK, July 2017, by Nenad Bogdanovic, MD, PhD, of the University of Oslo in Norway, amyloid PET imaging was found to be a fundamental diagnostic tool for AD, establishing a definite diagnosis or excluding AD in all 50 study participants.2 The use of cerebrospinal fluid (CSF) amyloid testing with a higher amyloid-beta plaque threshold than that traditionally used to establish a positive finding also resulted in high diagnostic accuracy, resulting in diagnosis or exclusion in 44 of 50 participants (88%) compared with only 21 individuals (42%) using traditional cutoffs.2

scholarly journals Alzheimer’s Disease-Related Metabolic Pattern in Diverse Forms of Neurodegenerative Diseases

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2023
Author(s):  
Angus Lau ◽  
Iman Beheshti ◽  
Mandana Modirrousta ◽  
Tiffany A. Kolesar ◽  
Andrew L. Goertzen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Bodies ◽  
Future Research ◽  
Metabolic Pattern ◽  
Dementia Patients ◽  
Positron Emission ◽  
Psychological Dysfunction ◽  
Underlying Causes ◽  
Neuroimaging Biomarkers

Dementia is broadly characterized by cognitive and psychological dysfunction that significantly impairs daily functioning. Dementia has many causes including Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). Detection and differential diagnosis in the early stages of dementia remains challenging. Fueled by AD Neuroimaging Initiatives (ADNI) (Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. As such, the investigators within ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report.), a number of neuroimaging biomarkers for AD have been proposed, yet it remains to be seen whether these markers are also sensitive to other types of dementia. We assessed AD-related metabolic patterns in 27 patients with diverse forms of dementia (five had probable/possible AD while others had atypical cases) and 20 non-demented individuals. All participants had positron emission tomography (PET) scans on file. We used a pre-trained machine learning-based AD designation (MAD) framework to investigate the AD-related metabolic pattern among the participants under study. The MAD algorithm showed a sensitivity of 0.67 and specificity of 0.90 for distinguishing dementia patients from non-dementia participants. A total of 18/27 dementia patients and 2/20 non-dementia patients were identified as having AD-like patterns of metabolism. These results highlight that many underlying causes of dementia have similar hypometabolic pattern as AD and this similarity is an interesting avenue for future research.

scholarly journals Biomarkers for Alzheimer’s Disease Early Diagnosis

2020 ◽  
Vol 10 (3) ◽  
pp. 114 ◽  
Author(s):  
Eva Ausó ◽  
Violeta Gómez-Vicente ◽  
Gema Esquiva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Loss ◽  
Diagnostic Tools ◽  
Csf Biomarkers ◽  
Diagnosis And Prognosis ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Alzheimer’s disease (AD) is the most common cause of dementia, affecting the central nervous system (CNS) through the accumulation of intraneuronal neurofibrillary tau tangles (NFTs) and β-amyloid plaques. By the time AD is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions. Therefore, the availability of early and reliable diagnosis markers of the disease would allow its detection and taking preventive measures to avoid neuronal loss. Current diagnostic tools in the brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aβ and tau) detection are invasive and expensive. Brain-secreted extracellular vesicles (BEVs) isolated from peripheral blood have emerged as novel strategies in the study of AD, with enormous potential as a diagnostic evaluation of therapeutics and treatment tools. In addition; similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Since the eyes are more accessible than the brain, several eye tests that detect cellular and vascular changes in the retina have also been proposed as potential screening biomarkers. The aim of this study is to summarize and discuss several potential markers in the brain, eye, blood, and other accessible biofluids like saliva and urine, and correlate them with earlier diagnosis and prognosis to identify individuals with mild symptoms prior to dementia.

scholarly journals VBM-Based Alzheimer’s Disease Detection from the Region of Interest of T1 MRI with Supportive Gaussian Smoothing and a Bayesian Regularized Neural Network

2021 ◽  
Vol 11 (13) ◽  
pp. 6175
Author(s):  
Bijen Khagi ◽  
Kun Ho Lee ◽  
Kyu Yeong Choi ◽  
Jang Jae Lee ◽  
Goo-Rak Kwon ◽  
...  
Keyword(s):  
Neural Network ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Statistical Parametric Mapping ◽  
Region Of Interest ◽  
Extraction Process ◽  
Dementia Patients ◽  
Mri Features ◽  
Mri Scans ◽  
The Brain

This paper presents an efficient computer-aided diagnosis (CAD) approach for the automatic detection of Alzheimer’s disease in patients’ T1 MRI scans using the voxel-based morphometry (VBM) analysis of the region of interest (ROI) in the brain. The idea is to generate a normal distribution of feature vectors from ROIs then later use for classification via Bayesian regularized neural network (BR-NN). The first dataset consists of the magnetic resonance imaging (MRI) of 74 Alzheimer’s disease (AD), 42 mild cognitive impairment (MCI), and 74 control normal (CN) from the ADNI1 dataset. The other dataset consists of the MRI of 42 Alzheimer’s disease dementia (ADD), 42 normal controls (NCs), and 39 MCI due to AD (mAD) from our GARD2 database. We aim to create a generalized network to distinguish normal individuals (CN/NC) from dementia patients AD/ADD and MCI/mAD. Our performance relies on our feature extraction process and data smoothing process. Here the key process is to generate a Statistical Parametric Mapping (SPM) t-map image from VBM analysis and obtain the region of interest (ROI) that shows the optimistic result after two-sample t-tests for a smaller value of p < 0.001(AD vs. CN). The result was overwhelming for the distinction between AD/ADD and CN/NC, thus validating our idea for discriminative MRI features. Further, we compared our performance with other recent state-of-the-art methods, and it is comparatively better in many cases. We have experimented with two datasets to validate the process. To validate the network generalization, BR-NN is trained from 70% of the ADNI dataset and tested on 30% of the ADNI, 100% of the GARD dataset, and vice versa. Additionally, we identified the brain anatomical ROIs that may be relatively responsible for brain atrophy during the AD diagnosis.

scholarly journals Tau-first subtype of Alzheimer's disease consistently identified across in vivo and post mortem studies

2020 ◽  
Author(s):  
Leon M Aksman ◽  
Neil P Oxtoby ◽  
Marzia A Scelsi ◽  
Peter A Wijeratne ◽  
Alexandra L Young ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Tau Proteins ◽  
Post Mortem ◽  
Positron Emission ◽  
Soluble Trem2 ◽  
The Brain ◽  
Insight Into

Alzheimer's disease (AD) is marked by the spread of misfolded amyloid-β and tau proteins throughout the brain. While it is commonly believed that amyloid-β abnormality drives the cascade of AD pathogenesis, several in vivo and post mortem studies indicate that in some subjects localized tau-based neurofibrillary tangles precede amyloid-β pathology. This suggests that there may be multiple distinct subtypes of protein aggregation pathways within AD, with potentially different demographic, cognitive and comorbidity profiles. We investigated this hypothesis, applying data-driven disease progression subtyping models to post mortem immunohistochemistry and in vivo positron emission tomography (PET) and cerebrospinal fluid (CSF) based measures of protein pathologies in two large observational cohorts. We consistently identified both amyloid-first and tau-first AD subtypes, where tau-first subjects had higher levels of soluble TREM2 compared to amyloid-first subjects. Our work provides insight into AD progression that may be valuable for interventional trials targeting amyloid-β and tau.

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