Relationship of Hippocampal Volume to Amyloid Burden across Diagnostic Stages of Alzheimer's Disease

2015 ◽  
Vol 41 (1-2) ◽  
pp. 68-79 ◽  
Author(s):  
Paula T. Trzepacz ◽  
Helen Hochstetler ◽  
Peng Yu ◽  
Peter Castelluccio ◽  
Michael M. Witte ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Logistic Regression ◽  
Area Under The Curve ◽  
Hippocampal Volume ◽  
Elastic Net ◽  
Amyloid Pet ◽  
Or Education ◽  
Positron Emission ◽  
Relationship Of

Aims: To assess how hippocampal volume (HV) from volumetric magnetic resonance imaging (vMRI) is related to the amyloid status at different stages of Alzheimer's disease (AD) and its relevance to patient care. Methods: We evaluated the ability of HV to predict the florbetapir positron emission tomography (PET) amyloid positive/negative status by group in healthy controls (HC, n = 170) and early/late mild cognitive impairment (EMCI, n = 252; LMCI, n = 136), and AD dementia (n = 75) subjects from the Alzheimer's Disease Neuroimaging Initiative Grand Opportunity (ADNI-GO) and ADNI2. Logistic regression analyses, including elastic net classification modeling with 10-fold cross-validation, were used with age and education as covariates. Results: HV predicted amyloid status only in LMCI using either logistic regression [area under the curve (AUC) = 0.71, p < 0.001] or elastic net classification modeling [positive predictive value (PPV) = 72.7%]. In EMCI, age (AUC = 0.70, p < 0.0001) and age and/or education (PPV = 63.1%), but not HV, predicted amyloid status. Conclusion: Using clinical neuroimaging, HV predicted amyloid status only in LMCI, suggesting that HV is not a biomarker surrogate for amyloid PET in clinical applications across the full diagnostic spectrum.

scholarly journals The Who, When, Why, and How of PET Amyloid Imaging in Management of Alzheimer’s Disease—Review of Literature and Interesting Images

Diagnostics ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 65 ◽  
Author(s):  
Subapriya Suppiah ◽  
Mellanie-Anne Didier ◽  
Sobhan Vinjamuri
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Area Under The Curve ◽  
Standard Uptake Value ◽  
Amyloid Imaging ◽  
Carrier Status ◽  
Amyloid Pet ◽  
Positron Emission ◽  
Cutoff Points ◽  
Pet Amyloid

Amyloid imaging using positron emission tomography (PET) has an emerging role in the management of Alzheimer’s disease (AD). The basis of this imaging is grounded on the fact that the hallmark of AD is the histological detection of beta amyloid plaques (Aβ) at post mortem autopsy. Currently, there are three FDA approved amyloid radiotracers used in clinical practice. This review aims to take the readers through the array of various indications for performing amyloid PET imaging in the management of AD, particularly using 18F-labelled radiopharmaceuticals. We elaborate on PET amyloid scan interpretation techniques, their limitations and potential improved specificity provided by interpretation done in tandem with genetic data such as apolipiprotein E (APO) 4 carrier status in sporadic cases and molecular information (e.g., cerebral spinal fluid (CSF) amyloid levels). We also describe the quantification methods such as the standard uptake value ratio (SUVr) method that utilizes various cutoff points for improved accuracy of diagnosing AD, such as a threshold of 1.122 (area under the curve 0.894), which has a sensitivity of 92.3% and specificity of 90.5%, whereas the cutoff points may be higher in APOE ε4 carriers (1.489) compared to non-carriers (1.313). Additionally, recommendations for future developments in this field are also provided.

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.

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 Efficacy and Limitations of rCBF-SPECT in the Diagnosis of Alzheimer’s Disease With Amyloid-PET

2019 ◽  
Vol 34 (5) ◽  
pp. 314-321
Author(s):  
Miwako Takahashi ◽  
Tomoko Tada ◽  
Tomomi Nakamura ◽  
Keitaro Koyama ◽  
Toshimitsu Momose
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Amyloid Pet ◽  
Clinical Dementia Rating ◽  
Positron Emission ◽  
Rcbf Spect

This study aimed to assess efficacy and limitations of regional cerebral blood flow imaging using single-photon emission computed tomography (rCBF-SPECT) in the diagnosis of Alzheimer’s disease (AD) with amyloid-positron emission tomography (amyloid-PET). Thirteen patients, who underwent both rCBF-SPECT and amyloid-PET after clinical diagnosis of AD or mild cognitive impairment, were retrospectively identified. The rCBF-SPECTs were classified into 4 grades, from typical AD pattern to no AD pattern of hypoperfusion; amyloid-beta (Aβ) positivity was assessed by amyloid-PET. Four patients were categorized into a typical AD pattern on rCBF-SPECT, and all were Aβ+. The other 9 patients did not exhibit a typical AD pattern; however, 4 were Aβ+. The Mini-Mental State Examination score and Clinical Dementia Rating scale were not significantly different between Aβ+ and Aβ– patients. A typical AD pattern on rCBF-SPECT can reflect Aβ+; however, if not, rCBF-SPECT has a limitation to predict amyloid pathology.

Amyloid imaging in Alzheimer’s disease: a potential new era of personalized medicine?

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Antoine Leuzy ◽  
Eduardo Zimmer ◽  
Serge Gauthier ◽  
Pedro Rosa-Neto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Personalized Medicine ◽  
Amyloid Imaging ◽  
Phase Iii ◽  
Diagnostic Process ◽  
European Medicines Agency ◽  
Amyloid Pet ◽  
Positron Emission

AbstractRecent advances along clinical and neuropathological lines, as well as in our ability to detect the deposition of β-amyloid (Aβ) in vivo using positron emission tomography (PET), have helped redefine Alzheimer’s disease (AD) as a dynamic clinicobiological entity. On the basis of these advances, AD is now conceptualized as a continuum comprising asymptomatic, minimally symptomatic, and dementia phases, with detection of brain Aβ — in particular, via PET amyloid imaging — central to the diagnostic process. In this respect, [18F]florbetapir (Amyvid™) and [18F]flutemetamol (Vizamyl™) have recently received approval for clinical use from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), with additional radiofluorinated tracers for detection of Aβ in phase III trials. Recent initiatives such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) suggest that Aβ production, oligomerization and aggregation begins many years, possibly decades, before detectable cognitive impairment, with Aβ shown to associate with cognitive decline and conversion to dementia. While personalized medicine has now emerged as a prospect for the field, the recent decision by the Centers for Medicare & Medicaid Services (CMS) — who declined to cover the cost of amyloid PET imaging citing insufficient evidence to support its clinical utility — highlights that such a move may be premature.

scholarly journals Association of Carotid and Intracranial Stenosis with Alzheimer’s Disease Biomarkers

2020 ◽  
Author(s):  
Koung Mi Kang ◽  
Min Soo Byun ◽  
Jun Ho Lee ◽  
Dahyun Yi ◽  
Hye Jeong Choi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Volume ◽  
Artery Stenosis ◽  
Intracranial Artery ◽  
Positron Emission ◽  
Intracranial Artery Stenosis ◽  
Intracranial Arteries ◽  
Demographic Covariates

Abstract Background To clarify whether atherosclerosis of the carotid and intracranial arteries is related to Alzheimer’s disease (AD) pathology in vivo, we investigated the associations of carotid and intracranial artery stenosis with cerebral beta-amyloid (Aβ) deposition and neurodegeneration in middle- and old-aged individuals. Given the differential progression of Aβ deposition and neurodegeneration across clinical stages of AD, we focused separately on cognitively normal (CN) and cognitively impaired (CI) groups.Methods A total of 281 CN and 199 CI (mild cognitive impairment and AD dementia) subjects underwent comprehensive clinical assessment, [11C] Pittsburgh Compound B positron emission tomography, and magnetic resonance (MR) imaging including MR angiography. We evaluated extracranial carotid and intracranial arteries for the overall presence, severity (i.e. number and degree of narrowing) and location of stenosis.Results We found no associations between carotid and intracranial artery stenosis and cerebral Aβ burden in either CN or CI group. In terms of AD-related neurodegeneration, exploratory univariate analyses showed associations between the presence and severity of stenosis and neurodegeneration biomarkers of AD (i.e. reduced hippocampal volume [HV] and cortical thickness in the AD-signature regions) in both CN and CI groups. In confirmatory multivariate analyses controlling for demographic covariates and diagnosis, the association between number of stenotic intracranial arteries ≥ 2 and reduced HV in the CI group remained significant.Conclusions Neither carotid nor intracranial artery stenosis appears to be associated with brain Aβ burden, while intracranial artery stenosis is related to amyloid-independent neurodegeneration, particularly hippocampal atrophy. These observations support the importance of proper management of intracranial artery stenosis for delaying the progression of AD neurodegeneration and related cognitive decline.

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 Longitudinal Observation of Early-Onset Alzheimer’s Disease Dementia with Positive CSF Biomarkers/Negative Amyloid-β Positron-Emission Tomography

2021 ◽  
Vol 39 (3) ◽  
pp. 214-218
Author(s):  
Min Hye Kim ◽  
Joonho Lee ◽  
Hong Nam Kim ◽  
In Ja Shin ◽  
Keun Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Early Onset ◽  
Brain Magnetic Resonance Imaging ◽  
Amyloid Β ◽  
Emission Tomography ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Positron Emission

We report a 61-year-old woman with clinical course for Alzheimer’s disease (AD) dementia and discordant amyloid-β positron-emission tomography (PET) and cerebrospinal fluid biomarkers. Brain magnetic resonance imaging revealed remarkable atrophy in the hippocampus. However, repeated delayed <sup>18</sup>F-flutemetamol brain amyloid PET images with 1 year-interval revealed no amyloid deposition, whereas her CSF revealed low Aβ42, high total tau and p-tau181. This discordant amyloid-β PET and CSF biomarkers in this early-onset AD dementia might be associated with her low resilience or mixed pathology.

scholarly journals Predicting Brain Amyloid Using Multivariate Morphometry Statistics, Sparse Coding, and Correntropy: Validation in 1,125 Individuals from the ADNI and OASIS Databases

2020 ◽  
Author(s):  
Jianfeng Wu ◽  
Qunxi Dong ◽  
Jie Gui ◽  
Jie Zhang ◽  
Yi Su ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sparse Coding ◽  
Hippocampal Volume ◽  
Amyloid Pet ◽  
Individual Subject ◽  
Max Pooling ◽  
Preclinical Ad ◽  
The Individual ◽  
Low Dimensional

ABSTRACTBiomarker assisted preclinical/early detection and intervention in Alzheimer’s disease (AD) may be the key to therapeutic breakthroughs. One of the presymptomatic hallmarks of AD is the accumulation of beta-amyloid (Aβ) plaques in the human brain. However, current methods to detect Aβ pathology are either invasive (lumbar puncture) or quite costly and not widely available (amyloid PET). Our prior studies show that MRI-based hippocampal multivariate morphometry statistics (MMS) are an effective neurodegenerative biomarker for preclinical AD. Here we attempt to use MRI-MMS to make inferences regarding brain amyloid burden at the individual subject level. As MMS data has a larger dimension than the sample size, we propose a sparse coding algorithm, Patch Analysis-based Surface Correntropy-induced Sparse coding and max-pooling (PASCS-MP), to generate a low-dimensional representation of hippocampal morphometry for each individual subject. Then we apply these individual representations and a binary random forest classifier to predict brain Aβ positivity for each person. We test our method in two independent cohorts, 841 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and 260 subjects from the Open Access Series of Imaging Studies (OASIS). Experimental results suggest that our proposed PASCS-MP method and MMS can discriminate Aβ positivity in people with mild cognitive impairment (MCI) (Accuracy (ACC)=0.89 (ADNI)) and in cognitively unimpaired (CU) individuals (ACC=0.79 (ADNI) and ACC=0.82 (OASIS)). These results compare favorably relative to measures derived from traditional algorithms, including hippocampal volume and surface area, shape measures based on spherical harmonics (SPHARM) and our prior Patch Analysis-based Surface Sparse-coding and Max-Pooling (PASS-MP) methods.

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