AD Resemblance Atrophy Index as a Diagnostic Biomarker for Alzheimer’s Disease: A Retrospective Clinical and Biological Validation

2021 ◽  
Vol 79 (3) ◽  
pp. 1023-1032
Author(s):  
Yingren Mai ◽  
Qun Yu ◽  
Feiqi Zhu ◽  
Yishan Luo ◽  
Wang Liao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Structure ◽  
Imaging Biomarker ◽  
Imaging Biomarkers ◽  
Clinical Scenario ◽  
Clinical Criteria ◽  
Positron Emission ◽  
And Gender ◽  
Sensitivity Specificity

Background: Magnetic resonance imaging (MRI) provides objective information about brain structural atrophy in patients with Alzheimer’s disease (AD). This multi-structural atrophic information, when integrated as a single differential index, has the potential to further elevate the accuracy of AD identification from normal control (NC) compared to the conventional structure volumetric index. Objective: We herein investigated the performance of such an MRI-derived AD index, AD-Resemblance Atrophy Index (AD-RAI), as a neuroimaging biomarker in clinical scenario. Method: Fifty AD patients (19 with the Amyloid, Tau, Neurodegeneration (ATN) results assessed in cerebrospinal fluid) and 50 age- and gender-matched NC (19 with ATN results assessed using positron emission tomography) were recruited in this study. MRI-based imaging biomarkers, i.e., AD-RAI, were quantified using AccuBrain®. The accuracy, sensitivity, specificity, and area under the ROC curve (AUC) of these MRI-based imaging biomarkers were evaluated with the diagnosis result according to clinical criteria for all subjects and ATN biological markers for the subgroup. Results: In the whole groups of AD and NC subjects, the accuracy of AD-RAI was 91%, sensitivity and specificity were 88% and 96%, respectively, and the AUC was 92%. In the subgroup of 19 AD and 19 NC with ATN results, AD-RAI results matched completely with ATN classification. AD-RAI outperforms the volume of any single brain structure measured. Conclusion: The finding supports the hypothesis that MRI-derived composite AD-RAI is a more accurate imaging biomarker than individual brain structure volumetry in the identification of AD from NC in the clinical scenario.

Molecular Imaging in Alzheimer’s Disease

2011 ◽  
Vol 6 (1) ◽  
pp. 16
Author(s):  
Karl Herholz ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Imaging ◽  
Clinical Symptoms ◽  
Accurate Method ◽  
Imaging Biomarker ◽  
Pet Tracer ◽  
Specificity And Sensitivity ◽  
Positron Emission ◽  
Dementia Research

The most sensitive and accurate method for molecular imaging in human Alzheimer’s disease (AD) is positron emission tomography (PET). The most widely available PET tracer, which is also used in clinical oncology, is 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG is an imaging biomarker for early and differential diagnosis of AD. Even higher molecular specificity and sensitivity for detection of AD before dementia onset is provided by high-affinity ligands for fibrillary amyloid. 11C-Pittsburgh Compound B is widely being used in research laboratories, while new 18F-labelled ligands are currently undergoing formal clinical trials as amyloid imaging agents and are expected to become commercially available for clinical use in the near future. A large variety of tracers is being developed and used in dementia research for activated microglia and multiple neurotransmitter systems to study disease pathophysiology, biological correlates of clinical symptoms and new possibilities for treatment. Current studies in humans are investigating cholinergic, serotonergic and dopaminergic neurotransmission.

scholarly journals Imaging biomarkers for amyloid: a new generation of probes and what lies ahead

2014 ◽  
Vol 26 (5) ◽  
pp. 703-707 ◽  
Author(s):  
Antoine Leuzy ◽  
Eduardo Rigon Zimmer ◽  
Venkat Bhat ◽  
Pedro Rosa-Neto ◽  
Serge Gauthier
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Work Group ◽  
Imaging Biomarkers ◽  
Amyloid A ◽  
Positron Emission ◽  
Communicative Disorders ◽  
Physiologic Parameters ◽  
New Generation

Since the original 1984 criteria for Alzheimer's disease (AD), put forth by a work group jointly established by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA) (McKhann et al., 1984), important advances have occurred in our ability to detect AD pathophysiology, with the incorporation of biomarkers – defined as anatomic, biochemical, or physiologic parameters that provide in vivo evidence of AD neuropathology (Cummings, 2011) – that can improve the certainty of AD diagnosis. Use of imaging biomarkers such as positron emission tomography (PET) with amyloid ligands, particularly in asymptomatic and pre-dementia stages of AD, however, has been the subject of debate (Dubois et al., 2013), with arguments both for and against the biomarker driven diagnosis of AD.

Standardization of hippocampus volumetry using automated brain structure volumetry tool for an initial Alzheimer’s disease imaging biomarker

2018 ◽  
Vol 60 (6) ◽  
pp. 769-776 ◽  
Author(s):  
Jill Abrigo ◽  
Lin Shi ◽  
Yishan Luo ◽  
Qianyun Chen ◽  
Winnie Chiu Wing Chu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Intraclass Correlation ◽  
Area Under The Curve ◽  
Imaging Biomarker ◽  
Imaging Biomarkers ◽  
Dice Similarity Coefficient ◽  
Reference Dataset ◽  
Magnetic Resonance Imaging Mri ◽  
Hippocampus Segmentation

Background One significant barrier to incorporate Alzheimer’s disease (AD) imaging biomarkers into diagnostic criteria is the lack of standardized methods for biomarker quantification. The European Alzheimer’s Disease Consortium-Alzheimer’s Disease Neuroimaging Initiative (EADC-ADNI) Harmonization Protocol project provides the most authoritative guideline for hippocampal definition and has produced a manually segmented reference dataset for validation of automated methods. Purpose To validate automated hippocampal volumetry using AccuBrain™, against the EADC-ADNI dataset, and assess its diagnostic performance for differentiating AD and normal aging in an independent cohort. Material and Methods The EADC-ADNI reference dataset comprise of manually segmented hippocampal labels from 135 volumetric T1-weighted scans from various scanners. Dice similarity coefficient (DSC), intraclass correlation coefficient (ICC), and Pearson’s r were obtained for AccuBrain™ and FreeSurfer. The magnetic resonance imaging (MRI) of a separate cohort of 299 individuals (150 normal controls, 149 with AD) were obtained from the ADNI database and processed with AccuBrain™ to assess its diagnostic accuracy. Area under the curve (AUC) for total hippocampal volumes (HV) and hippocampal fraction (HF) were determined. Results Compared with EADC-ADNI dataset ground truths, AccuBrain™ had a mean DSC of 0.89/0.89/0.89, ICC of 0.94/0.96/0.95, and r of 0.95/0.96/0.95 for right/left/total HV. AccuBrain™ HV and HF had AUC of 0.76 and 0.80, respectively. Thresholds of ≤ 5.71 mL and ≤ 0.38% afforded 80% sensitivity for AD detection. Conclusion AccuBrain™ provides accurate automated hippocampus segmentation in accordance with the EADC-ADNI standard, with great potential value in assisting clinical diagnosis of AD.

Molecular Imaging in Alzheimer’s Disease

US Neurology ◽  
2010 ◽  
Vol 06 (02) ◽  
pp. 28
Author(s):  
Karl Herholz ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Imaging ◽  
Clinical Symptoms ◽  
Accurate Method ◽  
Imaging Biomarker ◽  
Pet Tracer ◽  
Specificity And Sensitivity ◽  
Positron Emission ◽  
Dementia Research

The most sensitive and accurate method for molecular imaging in human Alzheimer’s disease (AD) is positron emission tomography (PET). The most widely available PET tracer, which is also used in clinical oncology, is 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG is an imaging biomarker for early and differential diagnosis of AD. Even higher molecular specificity and sensitivity for detection of AD before dementia onset is provided by high-affinity ligands for fibrillary amyloid. 11C-Pittsburgh Compound B is widely being used in research laboratories, while new 18F-labeled ligands are currently undergoing formal clinical trials as amyloid imaging agents and are expected to become commercially available for clinical use in the near future. A large variety of tracers is being developed and used in dementia research for activated microglia and multiple neurotransmitter systems to study disease pathophysiology, biological correlates of clinical symptoms, and new possibilities for treatment. Current studies in humans are investigating cholinergic, serotonergic, and dopaminergic neurotransmission.

Comorbidity of Cerebrovascular and Alzheimer’s Disease in Aging

2020 ◽  
Vol 78 (1) ◽  
pp. 321-334
Author(s):  
Ying Xia ◽  
Nawaf Yassi ◽  
Parnesh Raniga ◽  
Pierrick Bourgeat ◽  
Patricia Desmond ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrovascular Disease ◽  
Amyloid Β ◽  
Later Life ◽  
Imaging Biomarkers ◽  
Comorbid Condition ◽  
Cross Sectional ◽  
Positron Emission

Background: Cerebrovascular disease often coexists with Alzheimer’s disease (AD). While both diseases share common risk factors, their interrelationship remains unclear. Increasing the understanding of how cerebrovascular changes interact with AD is essential to develop therapeutic strategies and refine biomarkers for early diagnosis. Objective: We investigate the prevalence and risk factors for the comorbidity of amyloid-β (Aβ) and cerebrovascular disease in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing, and further examine their cross-sectional association. Methods: A total of 598 participants (422 cognitively normal, 89 with mild cognitive impairment, 87 with AD) underwent positron emission tomography and structural magnetic resonance imaging for assessment of Aβ deposition and cerebrovascular disease. Individuals were categorized based on the comorbidity status of Aβ and cerebrovascular disease (V) as Aβ–V–, Aβ–V+, Aβ+V–, or Aβ+V+. Results: Advancing age was associated with greater likelihood of cerebrovascular disease, high Aβ load and their comorbidity. Apolipoprotein E ɛ4 carriage was only associated with Aβ positivity. Greater total and regional WMH burden were observed in participants with AD. However, no association were observed between Aβ and WMH measures after stratification by clinical classification, suggesting that the observed association between AD and cerebrovascular disease was driven by the common risk factor of age. Conclusion: Our observations demonstrate common comorbid condition of Aβ and cerebrovascular disease in later life. While our study did not demonstrate a convincing cross-sectional association between Aβ and WMH burden, future longitudinal studies are required to further confirm this.

Commentary

2012 ◽  
Vol 25 (2) ◽  
pp. 181-184 ◽  
Author(s):  
John T. O'Brien
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Body ◽  
Diagnostic System ◽  
Improve Patient Care ◽  
Imaging Biomarkers ◽  
Current Phase ◽  
Biological Entity ◽  
Clinical Criteria ◽  
The Many

Dubois, Gauthier, and Cummings argue strongly and coherently for the need for revision of the Alzheimer's diagnostic accuracy and the many benefits to moving to a new diagnostic system. What they propose represents a fundamental paradigm shift in our field, moving Alzheimer's disease from a clinic-pathological to a clinic-biological entity, and separating the diagnosis of Alzheimer's disease from Alzheimer's dementia. In other words, recognising that people can have Alzheimer's disease for many years before they develop the global cognitive decline needed to fulfil current clinical criteria for dementia. The new diagnostic criteria are strongly supported by a very large body of research over the last 25 years and seek to advance the previous McKhann et al. (1984) criteria by, in particular, enhancing diagnostic specificity since, for the first time, CSF and imaging biomarkers are needed to “rule in” rather than simply rule out other disorders. The authors emphasise that these are research criteria and that they require validation and further investigation of clinical utility, whilst also pointing out that they have already been implemented in current Phase 2 clinical studies. Such a parallel introduction of criteria to our field whilst validation is ongoing is nothing new for psychiatry, or indeed dementia, and the same happened for the original Alzheimer's disease criteria as well. Dubois, Gauthier, and Cummings end with a stated aspiration to move the criteria from research to clinical settings, and by doing so hopefully increase the accuracy of the clinical diagnosis of Alzheimer's disease and ultimately improve patient care.

scholarly journals Fifteen Years of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study: Progress and Observations from 2,359 Older Adults Spanning the Spectrum from Cognitive Normality to Alzheimer’s Disease

2021 ◽  
pp. 1-26
Author(s):  
Christopher Fowler ◽  
Stephanie R. Rainey-Smith ◽  
Sabine Bird ◽  
Julia Bomke ◽  
Pierrick Bourgeat ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Age At Onset ◽  
Cognitive Testing ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Investigation Methods ◽  
Aβ Amyloid ◽  
Magnetic Resonance Imaging Mri ◽  
A Prospective Study

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer’s disease dementia (AD)) as an ‘Inception cohort’ who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an ‘Enrichment cohort’ (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.

scholarly journals Recent Developments in Positron Emission Tomography Tracers for Proteinopathies Imaging in Dementia

2022 ◽  
Vol 13 ◽  
Author(s):  
Ruiqing Ni ◽  
Roger M. Nitsch
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Parkinson's Disease ◽  
Amyloid Β ◽  
Emission Tomography ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Imaging Probes

An early detection and intervention for dementia represent tremendous unmet clinical needs and priorities in society. A shared feature of neurodegenerative diseases causing dementia is the abnormal accumulation and spreading of pathological protein aggregates, which affect the selective vulnerable circuit in a disease-specific pattern. The advancement in positron emission tomography (PET) biomarkers has accelerated the understanding of the disease mechanism and development of therapeutics for Alzheimer’s disease and Parkinson’s disease. The clinical utility of amyloid-β PET and the clinical validity of tau PET as diagnostic biomarker for Alzheimer’s disease continuum have been demonstrated. The inclusion of biomarkers in the diagnostic criteria has introduced a paradigm shift that facilitated the early and differential disease diagnosis and impacted on the clinical management. Application of disease-modifying therapy likely requires screening of patients with molecular evidence of pathological accumulation and monitoring of treatment effect assisted with biomarkers. There is currently still a gap in specific 4-repeat tau imaging probes for 4-repeat tauopathies and α-synuclein imaging probes for Parkinson’s disease and dementia with Lewy body. In this review, we focused on recent development in molecular imaging biomarkers for assisting the early diagnosis of proteinopathies (i.e., amyloid-β, tau, and α-synuclein) in dementia and discussed future perspectives.

scholarly journals The differential diagnostic value of the callosal angle and Evans index in mild cognitive impairment and Alzheimer's disease

2020 ◽  
Vol 16 ◽  
Author(s):  
Mengqi Liu ◽  
Jing Zhang ◽  
Linxiong Zong ◽  
Wenping Fan ◽  
Botao Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Diagnostic Value ◽  
Imaging Biomarker ◽  
Imaging Biomarkers ◽  
P Value ◽  
Significant Difference ◽  
Evans Index

Background: Callosal angle (CA) and Evans index (EI) had been considered as imaging biomarkers to diagnosis normal-pressure hydrocephalus as traditional MR measurement methods. Objective: The current study was aimed to evaluate the differential diagnostic value of CA and EI in the mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods: Five-hundred and two subjects were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, which included 168 normal controls (NC), 233 MCI and 101 AD patients. The structural MR images were interactively applied with multiplanar reconstruction to measure the CA and EI. Results: CA presented no significant difference among NC, MCI and AD groups (H value = 3.848, P value = 0.146), and EI was demonstrated the higher in MCI and AD groups than that in NC groups (P = 0.000 and 0.001, respectively). MCI group had significant larger EI (0.29±0.04) than that (0.27±0.03) in NC group in 70-75 years old sub-groups. ROC showed that the area under the curve was 0.704±0.045 for NC-MCI in 70-75 years old groups. The correlation analysis indicated that EI was significantly negatively related with MMSE scores of MCI patients (r = -0.131, P = 0.046). Conclusion: EI might serve as a screening imaging biomarker for MCI in 70-75 years old, and show limited differential value for the diagnosis of AD. CA could present no diagnostic value for MCI and AD in the current study.

scholarly journals Patterns of Cortical and Subcortical Amyloid Burden across Stages of Preclinical Alzheimer’s Disease

2016 ◽  
Vol 22 (10) ◽  
pp. 978-990 ◽  
Author(s):  
Emily C. Edmonds ◽  
Katherine J. Bangen ◽  
Lisa Delano-Wood ◽  
Daniel A. Nation ◽  
Ansgar J. Furst ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Standardized Uptake Value ◽  
Imaging Biomarkers ◽  
Preclinical Alzheimer’S Disease ◽  
Preclinical Ad ◽  
Novel Approach ◽  
Positron Emission ◽  
Subcortical Regions ◽  
Cortical Regions

AbstractObjectives: We examined florbetapir positron emission tomography (PET) amyloid scans across stages of preclinical Alzheimer’s disease (AD) in cortical, allocortical, and subcortical regions. Stages were characterized using empirically defined methods. Methods: A total of 312 cognitively normal Alzheimer’s Disease Neuroimaging Initiative participants completed a neuropsychological assessment and florbetapir PET scan. Participants were classified into stages of preclinical AD using (1) a novel approach based on the number of abnormal biomarkers/cognitive markers each individual possessed, and (2) National Institute on Aging and the Alzheimer’s Association (NIA-AA) criteria. Preclinical AD groups were compared to one another and to a mild cognitive impairment (MCI) sample on florbetapir standardized uptake value ratios (SUVRs) in cortical and allocortical/subcortical regions of interest (ROIs). Results: Amyloid deposition increased across stages of preclinical AD in all cortical ROIs, with SUVRs in the later stages reaching levels seen in MCI. Several subcortical areas showed a pattern of results similar to the cortical regions; however, SUVRs in the hippocampus, pallidum, and thalamus largely did not differ across stages of preclinical AD. Conclusions: Substantial amyloid accumulation in cortical areas has already occurred before one meets criteria for a clinical diagnosis. Potential explanations for the unexpected pattern of results in some allocortical/subcortical ROIs include lack of correspondence between (1) cerebrospinal fluid and florbetapir PET measures of amyloid, or between (2) subcortical florbetapir PET SUVRs and underlying neuropathology. Findings support the utility of our novel method for staging preclinical AD. By combining imaging biomarkers with detailed cognitive assessment to better characterize preclinical AD, we can advance our understanding of who is at risk for future progression. (JINS, 2016, 22, 978–990)

Sign in / Sign up

Export Citation Format

Share Document