scholarly journals Towards harmonizing subtyping methods for neuroimaging studies in Alzheimer’s disease

2020 ◽  
Author(s):  
Rosaleena Mohanty ◽  
Gustav Mårtensson ◽  
Konstantinos Poulakis ◽  
J-Sebastian Muehlboeck ◽  
Elena Rodriguez-Vieitez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reference Group ◽  
Group Level ◽  
Individual Level ◽  
Dementia Patients ◽  
Positron Emission ◽  
Tau Pet ◽  
The Individual

ABSTRACTBackgroundBiological subtypes in Alzheimer’s disease (AD), originally identified on neuropathological data, have been translated to in vivo biomarkers such as structural magnetic resonance imaging (sMRI) and positron emission tomography (PET), to disentangle the heterogeneity within AD. Although there is methodological variability across studies, comparable characteristics of subtypes are reported at the group level. In this study, we investigated whether group-level similarities translate to individual-level agreement across subtyping methods, in a head-to-head context.MethodsWe compared five previously published subtyping methods. Firstly, we validated the subtyping methods in 89 amyloid-beta positive (Aβ+) AD dementia patients (reference group: 70 Aβ-healthy individuals; HC) using sMRI. Secondly, we extended and applied the subtyping methods to 53 Aβ+ prodromal AD and 30 Aβ+ AD dementia patients (reference group: 200 Aβ-HC) using both sMRI and tau PET. Subtyping methods were implemented as outlined in each original study. Group-level and individual-level comparisons across methods were performed.ResultsEach individual method was replicated and the proof-of-concept was established. All methods captured subtypes with similar patterns of demographic and clinical characteristics, and with similar maps of cortical thinning and tau PET uptake, at the group level. However, large disagreements were found at the individual level.ConclusionsAlthough characteristics of subtypes may be comparable at the group level, there is a large disagreement at the individual level across subtyping methods. Therefore, there is an urgent need for consensus and harmonization across subtyping methods. We call for establishment of an open benchmarking framework to overcome this problem.

scholarly journals Comparison of subtyping methods for neuroimaging studies in Alzheimer’s disease: a call for harmonization

2020 ◽  
Author(s):  
Rosaleena Mohanty ◽  
Gustav Mårtensson ◽  
Konstantinos Poulakis ◽  
J-Sebastian Muehlboeck ◽  
Elena Rodriguez-Vieitez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Reference Group ◽  
Group Level ◽  
Healthy Individuals ◽  
Individual Level ◽  
Dementia Patients ◽  
Tau Pet ◽  
The Individual

Abstract Biological subtypes in Alzheimer’s disease, originally identified on neuropathological data, have been translated to in vivo biomarkers such as structural magnetic resonance imaging (sMRI) and positron emission tomography (PET), to disentangle the heterogeneity within Alzheimer’s disease. Although there is methodological variability across studies, comparable characteristics of subtypes are reported at the group level. In this study, we investigated whether group-level similarities translate to individual-level agreement across subtyping methods, in a head-to-head context. We compared five previously published subtyping methods. Firstly, we validated the subtyping methods in 89 amyloid-beta positive Alzheimer’s disease dementia patients (reference group: 70 amyloid-beta negative healthy individuals) using sMRI. Secondly, we extended and applied the subtyping methods to 53 amyloid-beta positive prodromal Alzheimer’s disease and 30 amyloid-beta positive Alzheimer’s disease dementia patients (reference group: 200 amyloid-beta negative healthy individuals) using sMRI and tau PET. Subtyping methods were implemented as outlined in each original study. Group-level and individual-level comparisons across methods were performed. Each individual subtyping method was replicated, and the proof-of-concept was established. At the group level, all methods captured subtypes with similar patterns of demographic and clinical characteristics, and with similar cortical thinning and tau PET uptake patterns. However, at the individual level large disagreements were found in subtype assignments. Although characteristics of subtypes are comparable at the group level, there is a large disagreement at the individual level across subtyping methods. Therefore, there is an urgent need for consensus and harmonization across subtyping methods. We call for establishment of an open benchmarking framework to overcome this problem.

scholarly journals Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET

2020 ◽  
Vol 12 (524) ◽  
pp. eaau5732 ◽  
Author(s):  
Renaud La Joie ◽  
Adrienne V. Visani ◽  
Suzanne L. Baker ◽  
Jesse A. Brown ◽  
Viktoriya Bourakova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Pet ◽  
Specific Distribution ◽  
Positron Emission ◽  
Pet Radiotracers ◽  
Β Amyloid ◽  
Tau Pet ◽  
Prospective Longitudinal

β-Amyloid plaques and tau-containing neurofibrillary tangles are the two neuropathological hallmarks of Alzheimer’s disease (AD) and are thought to play crucial roles in a neurodegenerative cascade leading to dementia. Both lesions can now be visualized in vivo using positron emission tomography (PET) radiotracers, opening new opportunities to study disease mechanisms and improve patients’ diagnostic and prognostic evaluation. In a group of 32 patients at early symptomatic AD stages, we tested whether β-amyloid and tau-PET could predict subsequent brain atrophy measured using longitudinal magnetic resonance imaging acquired at the time of PET and 15 months later. Quantitative analyses showed that the global intensity of tau-PET, but not β-amyloid–PET, signal predicted the rate of subsequent atrophy, independent of baseline cortical thickness. Additional investigations demonstrated that the specific distribution of tau-PET signal was a strong indicator of the topography of future atrophy at the single patient level and that the relationship between baseline tau-PET and subsequent atrophy was particularly strong in younger patients. These data support disease models in which tau pathology is a major driver of local neurodegeneration and highlight the relevance of tau-PET as a precision medicine tool to help predict individual patient’s progression and design future clinical trials.

scholarly journals Functional Abnormality Associated With Tau Deposition in Alzheimer’s Disease – A Hybrid Positron Emission Tomography/MRI Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Liping Fu ◽  
Zhi Zhou ◽  
Linwen Liu ◽  
Jinming Zhang ◽  
Hengge Xie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Standardized Uptake Value ◽  
Occipital Lobe ◽  
Posterior Cingulate Cortex ◽  
Functional Abnormality ◽  
Individual Level ◽  
Positron Emission ◽  
Mri Scans ◽  
The Individual

Objective: To investigate the characteristics of tau deposition and its impact on functional connectivity (FC) in Alzheimer’s disease (AD).Methods: Hybrid PET/MRI scans with [18F]-THK5317 and neuropsychological assessments were undertaken in 26 participants with AD and 19 healthy controls (HC). The standardized uptake value ratio (SUVR) of [18F]-THK5317 PET imaging was compared between the AD and HC groups. Significant clusters that revealed higher tau deposition in the AD group compared to the HC group were selected as regions of interest (ROI) for FC analysis. We evaluated the difference in the FC between the two groups for each ROI pair. The clinical and radiological characteristics were compared between the AD patients with negative FC and AD patients with positive FC for exploratory analysis.Results: The bilateral inferior lateral temporal lobe, dorsal prefrontal cortex, precuneus, posterior cingulate cortex, hippocampus, and occipital lobe showed significantly higher [18F]-THK5317 accumulation in AD patients. Decreased FC in regions with higher SUVR was observed in AD patients, and the FC strength was negatively correlated with regional SUVR. Patients with a positive FC exhibited older ages, better cognitive performances, and a lower SUVR than patients with a negative FC.Conclusions: An impact of tau deposition was observed on FC at the individual level in AD patients. Our findings suggested that the combination of tau-PET and rs-fMRI might help predict AD progression.

scholarly journals Detecting Alzheimer’s disease biomarkers with a brief tablet-based cognitive battery: sensitivity to Aβ and tau PET

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Elena Tsoy ◽  
Amelia Strom ◽  
Leonardo Iaccarino ◽  
Sabrina J. Erlhoff ◽  
Collette A. Goode ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Health Assessment ◽  
Area Under The Curve ◽  
Cognitive Measures ◽  
Regional Patterns ◽  
Logistic Regression Models ◽  
Positron Emission ◽  
Tau Pet

Abstract Background β-amyloid (Aβ) and tau positron emission tomography (PET) detect the pathological changes that define Alzheimer’s disease (AD) in living people. Cognitive measures sensitive to Aβ and tau burden may help streamline identification of cases for confirmatory AD biomarker testing. Methods We examined the association of Brain Health Assessment (BHA) tablet-based cognitive measures with dichotomized Aβ -PET status using logistic regression models in individuals with mild cognitive impairment (MCI) or dementia (N = 140; 43 Aβ-, 97 Aβ+). We also investigated the relationship between the BHA tests and regional patterns of tau-PET signal using voxel-wise regression analyses in a subsample of 60 Aβ+ individuals with MCI or dementia. Results Favorites (associative memory), Match (executive functions and speed), and Everyday Cognition Scale scores were significantly associated with Aβ positivity (area under the curve [AUC] = 0.75 [95% CI 0.66–0.85]). We found significant associations with tau-PET signal in mesial temporal regions for Favorites, frontoparietal regions for Match, and occipitoparietal regions for Line Orientation (visuospatial skills) in a subsample of individuals with MCI and dementia. Conclusion The BHA measures are significantly associated with both Aβ and regional tau in vivo imaging markers and could be used for the identification of patients with suspected AD pathology in clinical practice.

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.

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.

Associations of Neprilysin Activity in CSF with Biomarkers for Alzheimer’s Disease

2019 ◽  
Vol 19 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Timo Grimmer ◽  
Oliver Goldhardt ◽  
Igor Yakushev ◽  
Marion Ortner ◽  
Christian Sorg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fdg Pet ◽  
Amyloid Β ◽  
Neuronal Injury ◽  
Pittsburgh Compound B ◽  
Positron Emission ◽  
Amyloid Load ◽  
Alzheimer’S Pathology

Background: Neprilysin (NEP) cleaves amyloid-β 1–42 (Aβ42) in the brain. Hence, we aimed to elucidate the effect of NEP on Aβ42 in cerebrospinal fluid (CSF) and on in vivo brain amyloid load using amyloid positron emission tomography (PET) with [11C]PiB (Pittsburgh compound B). In addition, associations with the biomarkers for neuronal injury, CSF-tau and FDG-PET, were investigated. Methods: Associations were calculated using global and voxel-based (SPM8) linear regression analyses in the same cohort of 23 highly characterized Alzheimer’s disease patients. Results: CSF-NEP was significantly inversely associated with CSF-Aβ42 and positively with the extent of neuronal injury as measured by CSF-tau and FDG-PET. Conclusions: Our results on CSF-NEP are compatible with the assumption that local degradation, amongst other mechanisms of amyloid clearance, plays a role in the development of Alzheimer’s pathology. In addition, CSF-NEP is associated with the extent and the rate of neurodegeneration.

scholarly journals In vivo imaging of synaptic loss in Alzheimer’s disease with [18F]UCB-H positron emission tomography

2019 ◽  
Vol 47 (2) ◽  
pp. 390-402 ◽  
Author(s):  
Christine Bastin ◽  
Mohamed Ali Bahri ◽  
François Meyer ◽  
Marine Manard ◽  
Emma Delhaye ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
In Vivo Imaging ◽  
Emission Tomography ◽  
Synaptic Loss ◽  
Positron Emission

scholarly journals Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer’s disease

2020 ◽  
Vol 6 (16) ◽  
pp. eaaz2387 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Emelie Andersson ◽  
Shorena Janelidze ◽  
Rik Ossenkoppele ◽  
Philip Insel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Pet ◽  
Phosphorylated Tau ◽  
Positron Emission ◽  
Aβ Aggregation ◽  
Tau Pet ◽  
5Xfad Mice ◽  
Tau Aggregation ◽  
T Tau

The links between β-amyloid (Aβ) and tau in Alzheimer’s disease are unclear. Cognitively unimpaired persons with signs of Aβ pathology had increased cerebrospinal fluid (CSF) phosphorylated tau (P-tau181 and P-tau217) and total-tau (T-tau), which increased over time, despite no detection of insoluble tau aggregates [normal Tau positron emission tomography (PET)]. CSF P-tau and T-tau started to increase before the threshold for Amyloid PET positivity, while Tau PET started to increase after Amyloid PET positivity. Effects of Amyloid PET on Tau PET were mediated by CSF P-tau, and high CSF P-tau predicted increased Tau PET rates. Individuals with MAPT mutations and signs of tau deposition (but without Aβ pathology) had normal CSF P-tau levels. In 5xFAD mice, CSF tau increased when Aβ aggregation started. These results show that Aβ pathology may induce changes in soluble tau release and phosphorylation, which is followed by tau aggregation several years later in humans.

Sign in / Sign up

Export Citation Format

Share Document