scholarly journals Matching Clinical Diagnosis and Amyloid Biomarkers in Alzheimer’s Disease and Frontotemporal Dementia

2021 ◽  
Vol 11 (1) ◽  
pp. 47
Author(s):  
Giulia Giacomucci ◽  
Salvatore Mazzeo ◽  
Silvia Bagnoli ◽  
Matteo Casini ◽  
Sonia Padiglioni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diagnostic Accuracy ◽  
Frontotemporal Dementia ◽  
Clinical Diagnosis ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Predictive Values ◽  
Csf Analysis ◽  
Positron Emission

Background: The aims of this study were to compare the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of different cerebrospinal fluid (CSF) amyloid biomarkers and amyloid-Positron Emission Tomography (PET) in patients with a clinical diagnosis of Alzheimer’s disease (AD) and Frontotemporal Dementia (FTD); to compare concordance between biomarkers; and to provide an indication of their use and interpretation. Methods: We included 148 patients (95 AD and 53 FTD), who underwent clinical evaluation, neuropsychological assessment, and at least one amyloid biomarker (CSF analysis or amyloid-PET). Thirty-six patients underwent both analyses. One-hundred-thirteen patients underwent Apolipoprotein E (ApoE) genotyping. Results: Amyloid-PET presented higher diagnostic accuracy, sensitivity, and NPV than CSF Aβ1–42 but not Aβ42/40 ratio. Concordance between CSF biomarkers and amyloid-PET was higher in FTD patients compared to AD cases. None of the AD patients presented both negative Aβ biomarkers. Conclusions: CSF Aβ42/40 ratio significantly increased the diagnostic accuracy of CSF biomarkers. On the basis of our current and previous data, we suggest a flowchart to guide the use of biomarkers according to clinical suspicion: due to the high PPV of both amyloid-PET and CSF analysis including Aβ42/40, in cases of concordance between at least one biomarker and clinical diagnosis, performance of the other analysis could be avoided. A combination of both biomarkers should be performed to better characterize unclear cases. If the two amyloid biomarkers are both negative, an underlying AD pathology can most probably be excluded.

scholarly journals Behavioral variant of frontotemporal dementia or frontal variant of Alzheimer's disease? A case study

2019 ◽  
Vol 13 (3) ◽  
pp. 356-360
Author(s):  
Leonardo Cruz de Souza ◽  
Luciano Inácio Mariano ◽  
Renata Freire de Moraes ◽  
Paulo Caramelli
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Dementia ◽  
Csf Biomarkers ◽  
Positron Emission ◽  
Personality Changes ◽  
Clinical Presentations ◽  
History Of ◽  
Executive Deficits

ABSTRACT Alzheimer's disease (AD) has heterogeneous clinical presentations. Amnestic progressive disorder leading to dementia is the most typical, but non-amnestic presentations are also recognized. Here we report a case of frontal variant of AD. A right-handed woman, aged 68 years, was referred for progressive behavioral disorders and personality changes. She had a corroborated history of dietary changes, hyperorality, impulsivity, affective indifference and apathy, with functional impairment. Cognitive assessment yielded severe executive deficits. Positron emission tomography with fluorodeoxyglucose showed marked hypometabolism in frontotemporal regions, with relative preservation of parietal regions. CSF AD biomarkers showed low Aβ42, high Tau and high P-Tau. The patient fulfilled criteria for probable behavioral variant frontotemporal dementia. However, considering the AD pathophysiological signature on CSF biomarkers, a diagnosis of frontal variant of AD was established. In the perspective of disease-modifying therapies, it is important to identify atypical Alzheimer presentations, as these patients may be candidates for specific treatments.

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.

Unravelling the Association Between Amyloid-PET and Cerebrospinal Fluid Biomarkers in the Alzheimer’s Disease Spectrum: Who Really Deserves an A+?

2021 ◽  
pp. 1-12
Author(s):  
Luca Sacchi ◽  
Tiziana Carandini ◽  
Giorgio Giulio Fumagalli ◽  
Anna Margherita Pietroboni ◽  
Valeria Elisa Contarino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Linear Regression Models ◽  
Csf Analysis ◽  
Disease Spectrum

Background: Association between cerebrospinal fluid (CSF)-amyloid-β (Aβ)42 and amyloid-PET measures is inconstant across the Alzheimer’s disease (AD) spectrum. However, they are considered interchangeable, along with Aβ 42/40 ratio, for defining ‘Alzheimer’s Disease pathologic change’ (A+). Objective: Herein, we further characterized the association between amyloid-PET and CSF biomarkers and tested their agreement in a cohort of AD spectrum patients. Methods: We include ed 23 patients who underwent amyloid-PET, MRI, and CSF analysis showing reduced levels of Aβ 42 within a 365-days interval. Thresholds used for dichotomization were: Aβ 42 <  640 pg/mL (Aβ 42+); pTau >  61 pg/mL (pTau+); and Aβ 42/40 <  0.069 (ADratio+). Amyloid-PET scans were visually assessed and processed by four pipelines (SPMCL, SPMAAL, FSGM, FSWC). Results: Different pipelines gave highly inter-correlated standardized uptake value ratios (SUVRs) (rho = 0.93–0.99). The most significant findings were: pTau positive correlation with SPMCL SUVR (rho = 0.56, p = 0.0063) and Aβ 42/40 negative correlation with SPMCL and SPMAAL SUVRs (rho = –0.56, p = 0.0058; rho = –0.52, p = 0.0117 respectively). No correlations between CSF-Aβ 42 and global SUVRs were observed. In subregion analysis, both pTau and Aβ 42/40 values significantly correlated with cingulate SUVRs from any pipeline (R2 = 0.55–0.59, p <  0.0083), with the strongest associations observed for the posterior/isthmus cingulate areas. However, only associations observed for Aβ 42/40 ratio were still significant in linear regression models. Moreover, combining pTau with Aβ 42 or using Aβ 42/40, instead of Aβ 42 alone, increased concordance with amyloid-PET status from 74% to 91% based on visual reads and from 78% to 96% based on Centiloids. Conclusion: We confirmed that, in the AD spectrum, amyloid-PET measures show a stronger association and a better agreement with CSF-Aβ 42/40 and secondarily pTau rather than Aβ 42 levels.

Brazilian Version of Addenbrooke’s Cognitive Examination—Revised in the Differential Diagnosis of Alzheimer’S Disease and Behavioral Variant Frontotemporal Dementia

2021 ◽  
Author(s):  
Viviane Amaral-Carvalho ◽  
Thais Bento Lima-Silva ◽  
Luciano Inácio Mariano ◽  
Leonardo Cruz de Souza ◽  
Henrique Cerqueira Guimarães ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Diagnosis ◽  
Diagnostic Accuracy ◽  
Frontotemporal Dementia ◽  
Predictive Value ◽  
Univariate Analysis ◽  
Behavioral Variant Frontotemporal Dementia ◽  
Present Sample ◽  
Addenbrooke’S Cognitive Examination

Abstract Introduction Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are frequent causes of dementia and, therefore, instruments for differential diagnosis between these two conditions are of great relevance. Objective To investigate the diagnostic accuracy of Addenbrooke’s Cognitive Examination-Revised (ACE-R) for differentiating AD from bvFTD in a Brazilian sample. Methods The ACE-R was administered to 102 patients who had been diagnosed with mild dementia due to probable AD, 37 with mild bvFTD and 161 cognitively healthy controls, matched according to age and education. Additionally, all subjects were assessed using the Mattis Dementia Rating Scale and the Neuropsychiatric Inventory. The performance of patients and controls was compared by using univariate analysis, and ROC curves were calculated to investigate the accuracy of ACE-R for differentiating AD from bvFTD and for differentiating AD and bvFTD from controls. The verbal fluency plus language to orientation plus name and address delayed recall memory (VLOM) ratio was also calculated. Results The optimum cutoff scores for ACE-R were &lt;80 for AD, &lt;79 for bvFTD, and &lt;80 for dementia (AD + bvFTD), with area under the receiver operating characteristic curves (ROC) (AUC) &gt;0.85. For the differential diagnosis between AD and bvFTD, a VLOM ratio of 3.05 showed an AUC of 0.816 (Cohen’s d = 1.151; p &lt; .001), with 86.5% sensitivity, 71.4% specificity, 72.7% positive predictive value, and 85.7% negative predictive value. Conclusions The Brazilian ACE-R achieved a good diagnostic accuracy for differentiating AD from bvFTD patients and for differentiating AD and bvFTD from the controls in the present sample.

scholarly journals Agreement of amyloid PET and CSF biomarkers for Alzheimer's disease on Lumipulse

2019 ◽  
Vol 6 (9) ◽  
pp. 1815-1824 ◽  
Author(s):  
Daniel Alcolea ◽  
Jordi Pegueroles ◽  
Laia Muñoz ◽  
Valle Camacho ◽  
Diego López‐Mora ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Csf Biomarkers ◽  
Amyloid Pet

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.

scholarly journals Diagnostic accuracy of 18F amyloid PET tracers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis

2015 ◽  
Vol 43 (2) ◽  
pp. 374-385 ◽  
Author(s):  
Elizabeth Morris ◽  
Anastasia Chalkidou ◽  
Alexander Hammers ◽  
Janet Peacock ◽  
Jennifer Summers ◽  
...  
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diagnostic Accuracy ◽  
Meta Analysis ◽  
Amyloid Pet ◽  
Pet Tracers

P1-105: Behavioral variant of Alzheimer's disease in an old woman mimicking frontotemporal dementia: Diagnosis contribution of CSF biomarkers

2011 ◽  
Vol 7 ◽  
pp. S143-S144
Author(s):  
Pauline Lapalus ◽  
Claire Paquet ◽  
Jacques Hugon ◽  
Julien Dumurgier ◽  
Jean Pierre Guichard ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Dementia ◽  
Csf Biomarkers ◽  
Dementia Diagnosis
Sign in / Sign up

Export Citation Format

Share Document