scholarly journals Assessment of Tau Pathology as Measured by 18F-THK5317 and 18F-Flortaucipir PET and Their Relation to Brain Atrophy and Cognition in Alzheimer’s Disease

2021 ◽  
pp. 1-15
Author(s):  
Elisa Colato ◽  
Konstantinos Chiotis ◽  
Daniel Ferreira ◽  
Mariam S. Mazrina ◽  
Laetitia Lemoine ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Volume Index ◽  
Discriminative Ability ◽  
Therapeutic Trials ◽  
Prodromal Ad ◽  
Global Brain

Background: In Alzheimer’s disease (AD), the abnormal aggregation of hyperphosphorylated tau leads to synaptic dysfunction and neurodegeneration. Recently developed tau PET imaging tracers are candidate biomarkers for diagnosis and staging of AD. Objective: We aimed to investigate the discriminative ability of 18F-THK5317 and 18F-flortaucipir tracers and brain atrophy at different stages of AD, and their respective associations with cognition. Methods: Two cohorts, each including 29 participants (healthy controls [HC], prodromal AD, and AD dementia patients), underwent 18F-THK5317 or 18F-flortaucipir PET, T1-weighted MRI, and neuropsychological assessment. For each subject, we quantified regional 18F-THK5317 and 18F-flortaucipir uptake within six bilateral and two composite regions of interest. We assessed global brain atrophy for each individual by quantifying the brain volume index, a measure of brain volume-to-cerebrospinal fluid ratio. We then quantified the discriminative ability of regional 18F-THK5317, 18F-flortaucipir, and brain volume index between diagnostic groups, and their associations with cognition in patients. Results: Both 18F-THK5317 and 18F-flortaucipir outperformed global brain atrophy in discriminating between HC and both prodromal AD and AD dementia groups. 18F-THK5317 provided the highest discriminative ability between HC and prodromal AD groups. 18F-flortaucipir performed best at discriminating between prodromal and dementia stages of AD. Across all patients, both tau tracers were predictive of RAVL learning, but only 18F-flortaucipir predicted MMSE. Conclusion: Our results warrant further in vivo head-to-head and antemortem-postmortem evaluations. These validation studies are needed to select tracers with high clinical validity as biomarkers for early diagnosis, prognosis, and disease staging, which will facilitate their incorporation in clinical practice and therapeutic trials.

scholarly journals Atrophy of Basal Forebrain Initiates with Tau Pathology in Individuals at Risk for Alzheimer’s Disease

2019 ◽  
Vol 30 (4) ◽  
pp. 2083-2098
Author(s):  
Jose L Cantero ◽  
Mercedes Atienza ◽  
Carmen Lage ◽  
Laszlo Zaborszky ◽  
Eduard Vilaplana ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Nucleus Basalis ◽  
Tau Pathology ◽  
Projection System ◽  
Prodromal Ad

Abstract Evidence suggests that the basal forebrain (BF) cholinergic system degenerates early in the course of Alzheimer’s disease (AD), likely due to the vulnerability of BF cholinergic neurons to tau pathology. However, it remains unclear whether the presence of tauopathy is the only requirement for initiating the BF degeneration in asymptomatic subjects at risk for AD (AR-AD), and how BF structural deficits evolve from normal aging to preclinical and prodromal AD. Here, we provide human in vivo magnetic resonance imaging evidence supporting that abnormal cerebrospinal fluid levels of phosphorylated tau (T+) are selectively associated with bilateral volume loss of the nucleus basalis of Meynert (nbM, Ch4) in AR-AD individuals. Spreading of atrophy to medial septum and vertical limb of diagonal band Broca (Ch1–Ch2) occurred in both preclinical and prodromal AD. With the exception of A+, all groups revealed significant correlations between volume reduction of BF cholinergic compartments and atrophy of their innervated regions. Overall, these results support the central role played by tauopathy in instigating the nbM degeneration in AR-AD individuals and the necessary coexistence of both AD proteinopathies for spreading damage to larger BF territories, thus affecting the core of the BF cholinergic projection system.

scholarly journals Automated Brain Volumetric Program Measuring Regional Brain Atrophy in Diagnosis of Mild Cognitive Impairment and Alzheimer’s Disease Dementia

2021 ◽  
Author(s):  
Dong-Woo Ryu ◽  
Yun Jeong Hong ◽  
Jung Hee Cho ◽  
Kichang Kwak ◽  
Jong-Min Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Diagnostic Accuracy ◽  
Predictive Model ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Volume Ratio ◽  
Rater Reliability

Abstract A quantitative analysis of brain volume can assist in diagnosis of Alzheimer’s disease (AD) ususally accompannied by brain atrophy. With an automated analysis program Quick Brain Volumetry (QBraVo) developed for volumetric measurements, we measured regional volumes and ratios to evaluate their performance in discriminating AD dementia (ADD) and mild cognitive impairment (MCI) patients from normal controls (NC). Validation of QBraVo was based on intra-rater and inter-rater reliability with a manual measurement. The regional volumes and ratios to total intracranial volume (TIV) and to total brain volume (TBV) or total cerebrospinal fluid volume (TCV) were compared among subjects. The regional volume to total cerebellar volume ratio named Standardized Atrophy Volume Ratio (SAVR) was calculated to compare brain atrophy. Diagnostic performances to distinguish among NC, MCI, and ADD were compared between MMSE, SAVR, and the predictive model. In total, 56 NCs, 44 MCI, and 45 ADD patients were enrolled. The average run time of QBraVo was 5 minutes 36 seconds. Intra-rater reliability was 0.999. Inter-rater reliability were high for TBV, TCV, and TIV (R = 0.97, 0.89 and 0.93, respectively). The medial temporal SAVR showed the highest performance for discriminating ADD from NC (AUC = 0.808, diagnostic accuracy = 80.2%). The predictive model using both MMSE and medial temporal SAVR improved the diagnostic performance for MCI in NC (AUC = 0.844, diagnostic accuracy = 79%). Our results demonstrated QBraVo as a fast and accurate method to measure brain volume. The regional volume calculated as SAVR could help to diagnose ADD and MCI and increase diagnostic accuracy for MCI.

Measurement of global brain atrophy in alzheimer's disease with unsupervised segmentation of spin-echo MRI studies

2000 ◽  
Vol 11 (3) ◽  
pp. 260-266 ◽  
Author(s):  
Arturo Brunetti ◽  
Alfredo Postiglione ◽  
Enrico Tedeschi ◽  
Andrea Ciarmiello ◽  
Mario Quarantelli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Atrophy ◽  
Spin Echo ◽  
Unsupervised Segmentation ◽  
Mri Studies ◽  
Global Brain

scholarly journals Differential effects of ischemic vascular disease and Alzheimer’s disease on brain atrophy and cognition

2015 ◽  
Vol 36 (1) ◽  
pp. 204-215 ◽  
Author(s):  
Ling Zheng ◽  
Harry V Vinters ◽  
Wendy J Mack ◽  
Michael W Weiner ◽  
Helena C Chui ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Infarction ◽  
Vascular Disease ◽  
Brain Atrophy ◽  
Cortical Atrophy ◽  
Elderly Persons ◽  
Indirect Pathway ◽  
Global Cognition

We previously reported that pathologic measures of arteriosclerosis (AS), cerebral infarction, and Alzheimer’s disease (AD) are independently correlated with cortical gray matter (CGM) atrophy measured by in vivo magnetic resonance imaging (MRI). Here, we use path analyses to model the associations between these three pathology measures and cognitive impairment, as mediated by CGM atrophy, after controlling for age and education. In this sample of 116 elderly persons followed longitudinally to autopsy (ischemic vascular disease (IVD) program project), differential patterns were observed between AS and atrophy/cognition versus AD and atrophy/cognition. The total effect of AD pathology on global cognition ( β = −0.61, s.e. = 0.06) was four times stronger than that of AS ( β = −0.15, s.e. = 0.08). The effect of AS on cognition appears to occur through cerebral infarction and CGM atrophy ( β = −0.13, s.e. = 0.04). In contrast, the effects of AD pathology on global cognition ( β = −0.50, s.e. = 0.07) occur through a direct pathway that is five times stronger than the indirect pathway acting through CGM atrophy ( β = −0.09, s.e. = 0.03). The strength of this direct AD pathway was not significantly mitigated by adding hippocampal volume to the model. AD pathology affects cognition not only through brain atrophy, but also via an unmeasured pathway that could be related to synaptic dysfunction before the development of cortical atrophy.

scholarly journals Longitudinal analysis of brain atrophy in Alzheimer’s disease and frontotemporal dementia

2019 ◽  
Vol 47 (10) ◽  
pp. 5019-5027 ◽  
Author(s):  
Silvia Marino ◽  
Lilla Bonanno ◽  
Viviana Lo Buono ◽  
Rosella Ciurleo ◽  
Francesco Corallo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Dementia ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Lower Percentage ◽  
Moderate Increase ◽  
Mri Findings ◽  
Cross Sectional ◽  
Early Onset Dementia

Objectives Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are among the leading causes of early-onset dementia. This study aimed to assess the rate of whole brain atrophy by comparing bvFTD and AD. Methods Two patients (one man with AD, and one woman with bvFTD) had neuropsychological and neuroimaging assessment by using automated techniques for cross-sectional and longitudinal atrophy measurements. Results In the patient with AD, magnetic resonance imaging (MRI) showed decreased bilateral hippocampal and mesial-temporal volume. However, conventional images showed no difference between baseline (T0) and after 1 year (T1). In the patient with bvFTD, MRI showed bilateral frontotemporal lobe atrophy and a moderate increase in atrophy between T0 and T1, particularly in the temporal lobes. A cross-sectional cerebral volume examination showed a considerable reduction in brain volume in the patient with bvFDT and a moderate reduction in the patient with AD. A longitudinal cerebral volume examination showed a lower percentage brain volume change in the patient with bvFTS compared with the patient with AD. Conclusions Our results suggest that bvFTD has more neurodegenerative progression. MRI findings should be considered as a reliable marker of disease progression in the brain. Our findings offer potential for monitoring treatment outcomes.

Sign in / Sign up

Export Citation Format

Share Document