Beyond the AJR: Tau PET, Amyloid PET, and MRI, as Prognostic Markers in Early Alzheimer Disease

2021 ◽  
Author(s):  
Phil Kuo ◽  
Katherine Zukotynski
Keyword(s):  
Alzheimer Disease ◽  
Prognostic Markers ◽  
Amyloid Pet ◽  
Tau Pet ◽  
Pet Amyloid

scholarly journals Topographic Distribution of Amyloid-β, Tau, and Atrophy in Patients With Behavioral/Dysexecutive Alzheimer Disease

Neurology ◽  
2020 ◽  
Vol 96 (1) ◽  
pp. e81-e92
Author(s):  
Joseph Therriault ◽  
Tharick A. Pascoal ◽  
Melissa Savard ◽  
Andrea L. Benedet ◽  
Mira Chamoun ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Clinical Symptoms ◽  
Characteristic Curve ◽  
Tertiary Care ◽  
Amyloid Β ◽  
Executive Dysfunction ◽  
Anterior Cingulate ◽  
Amyloid Pet ◽  
Clinical Criteria ◽  
Tau Pet

ObjectiveTo determine the associations between amyloid-PET, tau-PET, and atrophy with the behavioral/dysexecutive presentation of Alzheimer disease (AD), how these differ from amnestic AD, and how they correlate to clinical symptoms.MethodsWe assessed 15 patients with behavioral/dysexecutive AD recruited from a tertiary care memory clinic, all of whom had biologically defined AD. They were compared with 25 patients with disease severity– and age-matched amnestic AD and a group of 131 cognitively unimpaired (CU) elderly individuals. All participants were evaluated with amyloid-PET with [18F]AZD4694, tau-PET with [18F]MK6240, MRI, and neuropsychological testing.ResultsVoxelwise contrasts identified patterns of frontal cortical tau aggregation in behavioral/dysexecutive AD, with peaks in medial prefrontal, anterior cingulate, and frontal insular cortices in contrast to amnestic AD. No differences were observed in the distribution of amyloid-PET or atrophy as determined by voxel-based morphometry. Voxelwise area under the receiver operating characteristic curve analyses revealed that tau-PET uptake in the medial prefrontal, anterior cingulate, and frontal insular cortices were best able to differentiate between behavioral/dysexecutive and amnestic AD (area under the curve 0.87). Voxelwise regressions demonstrated relationships between frontal cortical tau load and degree of executive dysfunction.ConclusionsOur results provide evidence of frontal cortical involvement of tau pathology in behavioral/dysexecutive AD and highlight the need for consensus clinical criteria in this syndrome.

scholarly journals Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease

Neurology ◽  
2018 ◽  
Vol 91 (9) ◽  
pp. e859-e866 ◽  
Author(s):  
Andrew J. Aschenbrenner ◽  
Brian A. Gordon ◽  
Tammie L.S. Benzinger ◽  
John C. Morris ◽  
Jason J. Hassenstab
Keyword(s):  
Alzheimer Disease ◽  
Executive Functioning ◽  
Episodic Memory ◽  
Cognitive Decline ◽  
Hippocampal Volume ◽  
Cognitive Change ◽  
Pet Scan ◽  
Cognitive Domain ◽  
Amyloid Pet ◽  
Tau Pet

ObjectiveTo examine the independent and interactive influences of neuroimaging biomarkers on retrospective cognitive decline.MethodsA total of 152 middle-aged and older adult participants with at least 2 clinical and cognitive assessments, a Clinical Dementia Rating score of 0 or 0.5, and a flortaucipir (18F-AV-1451) tau PET scan, a florbetapir (18F-AV-45) amyloid PET scan, and a structural MRI scan were recruited from the Knight Alzheimer Disease Research Center at Washington University in St. Louis. Cognition was assessed with standard measures reflecting episodic memory, executive functioning, semantic fluency, and processing speed.ResultsResults from retrospective longitudinal analyses showed that each biomarker had a univariate association with the global cognitive composite; however, when each marker was analyzed in a single statistical model, only tau was a significant predictor of global cognitive decline. There was an interaction between tau and amyloid such that tau-related cognitive decline was worse in individuals with high amyloid. There was also an interaction with hippocampal volume indicating that individuals with high levels of all 3 pathologies exhibited the greatest declines in cognition. Additional analyses within each cognitive domain indicated that tau had the largest negative influence on tests of episodic memory and executive functioning.ConclusionsTogether, these results suggest that increasing levels of tau most consistently relate to declines in cognition preceding biomarker collection. These findings support models of Alzheimer disease (AD) staging that suggest that elevated β-amyloid alone may be insufficient to produce cognitive change in individuals at risk for AD and support the use of multiple biomarkers to stage AD progression.

scholarly journals Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Davina Biel ◽  
Matthias Brendel ◽  
Anna Rubinski ◽  
Katharina Buerger ◽  
Daniel Janowitz ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Prognostic Markers ◽  
Patient Specific ◽  
Amyloid Pet ◽  
Braak Stage ◽  
Cognitively Normal ◽  
Braak Staging ◽  
Pet Tracer ◽  
Tau Pet

Abstract Background To systematically examine the clinical utility of tau-PET and Braak-staging as prognostic markers of future cognitive decline in older adults with and without cognitive impairment. Methods In this longitudinal study, we included 396 cognitively normal to dementia subjects with 18F-Florbetapir/18F-Florbetaben-amyloid-PET, 18F-Flortaucipir-tau-PET and ~ 2-year cognitive follow-up. Annual change rates in global cognition (i.e., MMSE, ADAS13) and episodic memory were calculated via linear-mixed models. We determined global amyloid-PET (Centiloid) plus global and Braak-stage-specific tau-PET SUVRs, which were stratified as positive(+)/negative(−) at pre-established cut-offs, classifying subjects as Braak0/BraakI+/BraakI–IV+/BraakI–VI+/Braakatypical+. In bootstrapped linear regression, we assessed the predictive accuracy of global tau-PET SUVRs vs. Centiloid on subsequent cognitive decline. To test for independent tau vs. amyloid effects, analyses were further controlled for the contrary PET-tracer. Using ANCOVAs, we tested whether more advanced Braak-stage predicted accelerated future cognitive decline. All models were controlled for age, sex, education, diagnosis, and baseline cognition. Lastly, we determined Braak-stage-specific conversion risk to mild cognitive impairment (MCI) or dementia. Results Baseline global tau-PET SUVRs explained more variance (partial R2) in future cognitive decline than Centiloid across all cognitive tests (Cohen’s d ~ 2, all tests p < 0.001) and diagnostic groups. Associations between tau-PET and cognitive decline remained consistent when controlling for Centiloid, while associations between amyloid-PET and cognitive decline were non-significant when controlling for tau-PET. More advanced Braak-stage was associated with gradually worsening future cognitive decline, independent of Centiloid or diagnostic group (p < 0.001), and elevated conversion risk to MCI/dementia. Conclusion Tau-PET and Braak-staging are highly predictive markers of future cognitive decline and may be promising single-modality estimates for prognostication of patient-specific progression risk in clinical settings.

scholarly journals The implications of different approaches to define AT(N) in Alzheimer disease

Neurology ◽  
2020 ◽  
Vol 94 (21) ◽  
pp. e2233-e2244 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Antoine Leuzy ◽  
Shorena Janelidze ◽  
Sebastian Palmqvist ◽  
Erik Stomrud ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Cognitive Decline ◽  
Clinical Stage ◽  
Hippocampal Volume ◽  
Cognitively Impaired ◽  
Amyloid Pet ◽  
Prognostic Information ◽  
Neurofilament Light ◽  
Amyloid Aβ ◽  
Tau Pet

ObjectiveTo compare different β-amyloid (Aβ), tau, and neurodegeneration (AT[N]) variants within the Swedish BioFINDER studies.MethodsA total of 490 participants were classified into AT(N) groups. These include 53 cognitively unimpaired (CU) and 48 cognitively impaired (CI) participants (14 mild cognitive impairment [MCI] and 34 Alzheimer disease [AD] dementia) from BioFINDER-1 and 389 participants from BioFINDER-2 (245 CU and 144 CI [138 MCI and 6 AD dementia]). Biomarkers for A were CSF Aβ42 and amyloid-PET ([18F]flutemetamol); for T, CSF phosphorylated tau (p-tau) and tau PET ([18F]flortaucipir); and for (N), hippocampal volume, temporal cortical thickness, and CSF neurofilament light (NfL). Binarization of biomarkers was achieved using cutoffs defined in other cohorts. The relationship between different AT(N) combinations and cognitive trajectories (longitudinal Mini-Mental State Examination scores) was examined using linear mixed modeling and coefficient of variation.ResultsAmong CU participants, A−T−(N)− or A+T−(N)− variants were most common. However, more T+ cases were seen using p-tau than tau PET. Among CI participants, A+T+(N)+ was more common; however, more (N)+ cases were seen for MRI measures relative to CSF NfL. Tau PET best predicted longitudinal cognitive decline in CI and p-tau in CU participants. Among CI participants, continuous T (especially tau PET) and (N) measures improved the prediction of cognitive decline compared to binary measures.ConclusionsOur findings show that different AT(N) variants are not interchangeable, and that optimal variants differ by clinical stage. In some cases, dichotomizing biomarkers may result in loss of important prognostic information.

PET Amyloid and Tau Status Are Differently Affected by Patient Features

2020 ◽  
Vol 78 (3) ◽  
pp. 1129-1136
Author(s):  
Meng-Shan Tan ◽  
Yu-Xiang Yang ◽  
Hui-Fu Wang ◽  
Wei Xu ◽  
Chen-Chen Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Clinical Genetic ◽  
Multivariable Logistic Regression Model ◽  
Tau Pet ◽  
Pet Amyloid

Background: Amyloid-β (Aβ) plaques and tau neurofibrillary tangles are two neuropathological hallmarks of Alzheimer’s disease (AD), which both can be visualized in vivo using PET radiotracers, opening new opportunities to study disease mechanisms. Objective: Our study investigated 11 non-PET factors in 5 categories (including demographic, clinical, genetic, MRI, and cerebrospinal fluid (CSF) features) possibly affecting PET amyloid and tau status to explore the relationships between amyloid and tau pathology, and whether these features had a different association with amyloid and tau status. Methods: We included 372 nondemented elderly from the Alzheimer’s Disease Neuroimaging Initiative cohort. All underwent PET amyloid and tau analysis simultaneously, and were grouped into amyloid/tau quadrants based on previously established abnormality cut points. We examined the associations of above selected features with PET amyloid and tau status using a multivariable logistic regression model, then explored whether there was an obvious correlation between the significant features and PET amyloid or tau levels. Results: Our results demonstrated that PET amyloid and tau status were differently affected by patient features, and CSF biomarker features provided most significant values associating PET findings. CSF Aβ42/40 was the most important factor affecting amyloid PET status, and negatively correlated with amyloid PET levels. CSF pTau could significantly influence both amyloid and tau PET status. Besides CSF pTau and Aβ42, APOE ɛ4 allele status and Mini-Mental State Examination scores also could influence tau PET status, and significantly correlated with tau PET levels. Conclusion: Our results support that tau pathology possibly affected by Aβ-independent factors, implicating the importance of tau pathology in AD pathogenesis.

SUBJECT-LEVEL ASSESSMENT OF REGIONAL CORRELATIONS BETWEEN TAU-PET, AMYLOID-PET, MRI AND FDG-PET ACROSS THE CLINICAL SPECTRUM OF ALZHEIMER’S DISEASE

2017 ◽  
Vol 13 (7) ◽  
pp. P203
Author(s):  
Jennifer L. Whitwell ◽  
Nirubol Tosakulwong ◽  
Stephen D. Weigand ◽  
Jonathan Graff-Radford ◽  
Prashanthi Vemuri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fdg Pet ◽  
Clinical Spectrum ◽  
Amyloid Pet ◽  
Tau Pet ◽  
Pet Amyloid

SUBJECT-LEVEL ASSESSMENT OF REGIONAL CORRELATIONS BETWEEN TAU-PET, AMYLOID-PET, MRI AND FDG-PET ACROSS THE CLINICAL SPECTRUM OF ALZHEIMER’S DISEASE

2017 ◽  
Vol 13 (7) ◽  
pp. P149
Author(s):  
Jennifer L. Whitwell ◽  
Nirubol Tosakulwong ◽  
Stephen D. Weigand ◽  
Jonathan Graff-Radford ◽  
Prashanthi Vemuri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fdg Pet ◽  
Clinical Spectrum ◽  
Amyloid Pet ◽  
Tau Pet ◽  
Pet Amyloid

scholarly journals Is comprehensiveness critical? Comparing short and long format cognitive assessments in preclinical Alzheimer disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jason Hassenstab ◽  
Jessica Nicosia ◽  
Megan LaRose ◽  
Andrew J. Aschenbrenner ◽  
Brian A. Gordon ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Multiple Regression ◽  
Cortical Thickness ◽  
Symptom Onset ◽  
Alternative Assessment ◽  
Amyloid Pet ◽  
Cognitively Normal ◽  
Long Form ◽  
Neuroimaging Biomarkers ◽  
Tau Pet

Abstract Background Comprehensive testing of cognitive functioning is standard practice in studies of Alzheimer disease (AD). Short-form tests like the Montreal Cognitive Assessment (MoCA) use a “sampling” of measures, administering key items in a shortened format to efficiently assess cognition while reducing time requirements, participant burden, and administrative costs. We compared the MoCA to a commonly used long-form cognitive battery in predicting AD symptom onset and sensitivity to AD neuroimaging biomarkers. Methods Survival, area under the receiver operating characteristic (ROC) curve (AUC), and multiple regression analyses compared the MoCA and long-form measures in predicting time to symptom onset in cognitively normal older adults (n = 6230) from the National Alzheimer’s Coordinating Center (NACC) cohort who had, on average, 2.3 ± 1.2 annual assessments. Multiple regression models in a separate sample (n = 416) from the Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) compared the sensitivity of the MoCA and long-form measures to neuroimaging biomarkers including amyloid PET, tau PET, and cortical thickness. Results Hazard ratios suggested that both the MoCA and the long-form measures are similarly and modestly efficacious in predicting symptomatic conversion, although model comparison analyses indicated that the long-form measures slightly outperformed the MoCA (HRs > 1.57). AUC analyses indicated no difference between the measures in predicting conversion (DeLong’s test, Z = 1.48, p = 0.13). Sensitivity to AD neuroimaging biomarkers was similar for the two measures though there were only modest associations with tau PET (rs = − 0.13, ps < 0.02) and cortical thickness in cognitively normal participants (rs = 0.15–0.16, ps < 0.007). Conclusions Both test formats showed weak associations with symptom onset, AUC analyses indicated low diagnostic accuracy, and biomarker correlations were modest in cognitively normal participants. Alternative assessment approaches are needed to improve how clinicians and researchers monitor cognitive changes and disease progression prior to symptom onset.

Sign in / Sign up

Export Citation Format

Share Document