scholarly journals Associations Between Perceived Fatigability and Amyloid Status in the Baltimore Longitudinal Study of Aging

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 208-209
Author(s):  
Ryan Dougherty ◽  
Amal Wanigatunga ◽  
Murat Bilgel ◽  
Yang An ◽  
Eleanor Simonsick ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Perceived Exertion ◽  
Volume Ratio ◽  
Rating Of Perceived Exertion ◽  
Pittsburgh Compound B ◽  
Brain Volumes ◽  
Positron Emission ◽  
Baltimore Longitudinal Study ◽  
Distribution Volume Ratio ◽  
Cortical Distribution

Abstract Higher level of and greater longitudinal increase in perceived fatigability are linked to cognitive decline and lower brain volumes in older adults. However, it remains unclear whether perceived fatigability is associated with Alzheimer’s disease-related brain pathology. In the BLSA, 163 participants without neurological disease or cognitive impairment (aged 74.7+/-8.4 years, 45% men) were assessed for perceived fatigability using rating of perceived exertion after a 5-minute (0.67 m/s) treadmill walk and Aß burden using 11C-Pittsburgh compound B (PiB) positron emission tomography. Forty-four participants were PiB+ based on a mean cortical distribution volume ratio (DVR) cut point of 1.066. After adjusting for demographics, body composition, comorbidities and ApoE-e4, higher perceived fatigability was not associated with PiB+ status (OR=0.84; 95% CI: 0.69, 1.05). Results suggest perceived fatigability may contribute to cognitive decline through pathways other than Aß pathology. Future studies should target other mechanisms linking perceived fatigability and cognitive decline.

scholarly journals Longitudinal Association Between Perceived Fatigability and Cognitive Function in Older Adults: Results from the Baltimore Longitudinal Study of Aging

2019 ◽  
Vol 75 (9) ◽  
pp. e67-e73
Author(s):  
Elizabeth A Salerno ◽  
Amal A Wanigatunga ◽  
Yang An ◽  
Jacek K Urbanek ◽  
Eleanor M Simonsick ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Cognitive Function ◽  
Executive Functions ◽  
Cognitive Decline ◽  
Perceived Exertion ◽  
Rating Of Perceived Exertion ◽  
Future Research ◽  
Mixed Effect ◽  
Age Related ◽  
Baltimore Longitudinal Study

Abstract Background Cognitive decline is consistently associated with diminished life satisfaction and inability to live independently. Identifying early, novel markers of cognitive decline is imperative for improving clinical detection and promoting long-term quality of life. Fatigability, one’s perceived exertion after a standardized walking task, has been associated with declines in physical function; however, it remains unclear as to whether these effects may also extend to cognitive function. Methods We examined whether perceived fatigability, assessed as the rating of perceived exertion (RPE) after a 5 min slow-paced treadmill walk (0.67 m/s, 0% grade), is longitudinally associated with cognitive performance in the domains of memory, executive functions, language, and attention among 934 cognitively intact individuals aged at least 50 years participating in the Baltimore Longitudinal Study of Aging (BLSA); Mage = 69.6 ± 10.1, 51.9% female participants. Continuous associations between RPE and each domain (individual test and composite scores) were assessed using linear mixed-effect models adjusted for demographics and comorbid conditions. Results In fully adjusted models, higher fatigability at baseline was associated with declines in all cognitive domains over an average 2.2 years of follow-up (p < .04 for all). Longitudinally, increased fatigability over time was associated with worsened executive functions (β= −0.01, p = .002). Conclusions These findings suggest that perceived fatigability after a standardized walking task may aid in identification of individuals at a higher risk of future cognitive decline. Future research should examine underlying biological mechanisms contributing to this relationship as well as whether future interventions may target fatigability in midlife to attenuate age-related cognitive decline.

Partner bereavement and brain pathologies: a propensity score matching study

2021 ◽  
Author(s):  
Jee Wook Kim ◽  
Min Soo Byun ◽  
Jun Ho Lee ◽  
Dahyun Yi ◽  
Min Jung Kim ◽  
...  
Keyword(s):  
Propensity Score ◽  
Cognitive Decline ◽  
Propensity Score Matching ◽  
Cerebral White Matter ◽  
Older Individuals ◽  
Pittsburgh Compound B ◽  
Cerebrovascular Injury ◽  
Positron Emission ◽  
Lifetime Partner

Abstract Background: Partner bereavement is one of life’s greatest stresses and has been suggested to trigger or accelerate cognitive decline and dementia. However, little information is available about potential brain pathologies underlying the association between partner bereavement and cognitive decline. Aims: We aimed to test the hypothesis that lifetime partner bereavement is associated with in vivo human brain pathologies underlying cognitive decline. Method: A total of 319 ever-married older adults between 61 and 90 years of age underwent comprehensive clinical assessments and multimodal brain imaging including [11C] Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, [18F] fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Results: Participants were classified as experiencing no partner bereavement or partner bereavement, and comparisons using propensity score matching (59 cases and 59 controls) were performed. Partner bereavement was significantly associated with higher cerebral white matter hyperintensities (WMH) volume compared to no partner bereavement. Interactions and subsequent subgroup analyses showed that partner bereavement was significantly associated with higher WMH in the older (>75 years) subgroup and among those with no- or low-skill occupations. In addition, partner bereavement at 60 years or over affect WMH volume compared to no partner bereavement, whereas partner bereavement at 60 years did not. No group differences were observed in other brain pathologies between partner bereavement categories. Conclusions: The findings suggest that the partner bereavement may contribute to dementia or cognitive decline by increasing cerebrovascular injury, particularly in older individuals and those with no- or low-skill occupations.

scholarly journals Abnormal neuroinflammation in fibromyalgia and CRPS using [11C]-(R)-PK11195 PET

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246152
Author(s):  
Seongho Seo ◽  
Ye-Ha Jung ◽  
Dasom Lee ◽  
Won Joon Lee ◽  
Joon Hwan Jang ◽  
...  
Keyword(s):  
Primary Motor Cortex ◽  
Volume Ratio ◽  
Pain Syndrome ◽  
Superior Temporal Gyrus ◽  
Emission Tomography ◽  
Healthy Controls ◽  
Positron Emission ◽  
Postcentral Gyrus ◽  
Distribution Volume Ratio ◽  
Critical Regions

Purpose Fibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain and neuroinflammation, which may contribute to the multifactorial pathological mechanisms in both FM and CRPS. The aim of this study was to assess neuroinflammation in FM patients compared with that in patients with CRPS and healthy controls. Methods Neuroinflammation was measured as the distribution volume ratio (DVR) of [11C]-(R)-PK11195 positron emission tomography (PET) in 12 FM patients, 11 patients with CRPS and 15 healthy controls. Results Neuroinflammation in FM patients was significantly higher in the left pre (primary motor cortex) and post (primary somatosensory cortex) central gyri (p < 0.001), right postcentral gyrus (p < 0.005), left superior parietal and superior frontal gyri (p < 0.005), left precuneus (p < 0.01), and left medial frontal gyrus (p = 0.036) compared with healthy controls. Furthermore, the DVR of [11C]-(R)-PK11195 in FM patients demonstrated decreased neuroinflammation in the medulla (p < 0.005), left superior temporal gyrus (p < 0.005), and left amygdala (p = 0.020) compared with healthy controls. Conclusions To the authors’ knowledge, this report is the first to describe abnormal neuroinflammation levels in the brains of FM patients compared with that in patients with CRPS using [11C]-(R)-PK11195 PET. The results suggested that abnormal neuroinflammation can be an important pathological factor in FM. In addition, the identification of common and different critical regions related to abnormal neuroinflammation in FM, compared with patients with CRPS and healthy controls, may contribute to improved diagnosis and the development of effective medical treatment for patients with FM.

scholarly journals Longitudinal Association Between Perceived Fatigability and Brain Volumes in Community-Dwelling Older Adults

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 209-209
Author(s):  
Fangyu Liu ◽  
Yang An ◽  
Amal Wanigatunga ◽  
Alden Gross ◽  
Eleanor Simonsick ◽  
...  
Keyword(s):  
Older Adults ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Perceived Exertion ◽  
Community Dwelling ◽  
Rating Of Perceived Exertion ◽  
Intracranial Volume ◽  
Brain Volumes ◽  
Potential Marker ◽  
Longitudinal Association

Abstract Perceived fatigability is linked to declining physical and cognitive performance, yet whether fatigability reflects early subclinical change in brain structure is unknown. Using mixed effects models, we assessed the longitudinal association of 3T MRI-derived brain volumes with perceived fatigability after a 5-min treadmill walk (0.67 m/s, 0% grade) using the Borg Rating of Perceived Exertion scale (range 6-20) in 802 BLSA participants (age 68.2+/-12.4 years, 45% men 66% White). In models adjusted for intracranial volume, demographics, chronic conditions, and CESD score, declining gray matter volumes in the frontal (β=-0.01) and temporal (β=-0.02) lobes, as well as the hippocampus (β=-0.25), precuneus (β=-0.10) and thalamus (β=-0.19) were associated with higher fatigability. Larger ventricular volumes were also associated with higher fatigability (β=0.02). Brain atrophy, particularly in gray matter and the hippocampal region, is longitudinally associated with increased fatigability in cognitively normal older adults, making it a potential marker of brain atrophy.

scholarly journals Quantification of [18F]florbetapir: A test–retest tracer kinetic modelling study

2018 ◽  
Vol 39 (11) ◽  
pp. 2172-2180 ◽  
Author(s):  
Sandeep SV Golla ◽  
Sander CJ Verfaillie ◽  
Ronald Boellaard ◽  
Sofie M Adriaanse ◽  
Marissa D Zwan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Volume Ratio ◽  
Distribution Volume ◽  
Emission Tomography ◽  
Retest Reliability ◽  
Positron Emission ◽  
Distribution Volume Ratio ◽  
Test Retest Reliability

Accumulation of amyloid beta can be visualized using [18F]florbetapir positron emission tomography. The aim of this study was to identify the optimal model for quantifying [18F]florbetapir uptake and to assess test–retest reliability of corresponding outcome measures. Eight Alzheimer’s disease patients (age: 67 ± 6 years, Mini-Mental State Examination (MMSE): 23 ± 3) and eight controls (age: 63 ± 4 years, MMSE: 30 ± 0) were included. Ninety-minute dynamic positron emission tomography scans, together with arterial blood sampling, were acquired immediately following a bolus injection of 294 ± 32 MBq [18F]florbetapir. Several plasma input models and the simplified reference tissue model (SRTM) were evaluated. The Akaike information criterion was used to identify the preferred kinetic model. Compared to controls, Alzheimer’s disease patients had lower MMSE scores and evidence for cortical Aβ pathology. A reversible two-tissue compartment model with fitted blood volume fraction (2T4k_VB) was the preferred model for describing [18F]florbetapir kinetics. SRTM-derived non-displaceable binding potential (BPND) correlated well (r2 = 0.83, slope = 0.86) with plasma input-derived distribution volume ratio. Test–retest reliability for plasma input-derived distribution volume ratio, SRTM-derived BPND and SUVr(50–70) were r = 0.88, r = 0.91 and r = 0.86, respectively. In vivo kinetics of [18F]florbetapir could best be described by a reversible two-tissue compartmental model and [18F]florbetapir BPND can be reliably estimated using an SRTM.

scholarly journals In-vivo Measurement of LDOPA Uptake, Dopamine Reserve and Turnover in the Rat Brain Using [18F]FDOPA PET

2012 ◽  
Vol 33 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Matthew D Walker ◽  
Katherine Dinelle ◽  
Rick Kornelsen ◽  
Siobhan McCormick ◽  
Chenoa Mah ◽  
...  
Keyword(s):  
Volume Ratio ◽  
Distribution Volume ◽  
Binding Potential ◽  
In Vivo Measurement ◽  
Longitudinal Measurements ◽  
Positron Emission ◽  
Distribution Volume Ratio ◽  
6 Hydroxydopamine ◽  
Effective Distribution

Longitudinal measurements of dopamine (DA) uptake and turnover in transgenic rodents may be critical when developing disease-modifying therapies for Parkinson's disease (PD). We demonstrate methodology for such measurements using [18F]fluoro-3,4-dihydroxyphenyl- L-alanine ([18F]FDOPA) positron emission tomography (PET). The method was applied to 6-hydroxydopamine lesioned rats, providing the first PET-derived estimates of DA turnover for this species. Control ( n = 4) and unilaterally lesioned ( n = 11) rats were imaged multiple times. Kinetic modeling was performed using extended Patlak, incorporating a kloss term for metabolite washout, and modified Logan methods. Dopaminergic terminal loss was measured via [11C]-(+)-dihydrotetrabenazine (DTBZ) PET. Clear striatal [18F]FDOPA uptake was observed. In the lesioned striatum the effective DA turnover increased, shown by a reduced effective distribution volume ratio ( EDVR) for [18F]FDOPA. Effective distribution volume ratio correlated ( r > 0.9) with the [11C]DTBZ binding potential ( BPND). The uptake and trapping rate ( kref) decreased after lesioning, but relatively less so than [11C]DTBZ BPND. For normal controls, striatal estimates were kref = 0.037 ± 0.005 per minute, EDVR = 1.07 ± 0.22 and kloss = 0.024 ± 0.003 per minute (30 minutes turnover half-time), with repeatability (coefficient of variation) ≤11%. [18F]fluoro-3,4-dihydroxyphenyl- L-alanine PET enables measurements of DA turnover in the rat, which is useful for developing novel therapies for PD.

scholarly journals The Use of Alternative Forms of Graphical Analysis to Balance Bias and Precision in PET Images

2010 ◽  
Vol 31 (2) ◽  
pp. 535-546 ◽  
Author(s):  
Jean Logan ◽  
David Alexoff ◽  
Joanna S Fowler
Keyword(s):  
Volume Ratio ◽  
Image Data ◽  
Compartment Model ◽  
Graphical Analysis ◽  
Distribution Volume ◽  
Good Precision ◽  
Reference Tissue ◽  
Positron Emission ◽  
Distribution Volume Ratio ◽  
Uptake Data

Graphical analysis (GA) is an efficient method for estimating total tissue distribution volume ( VT) from positron emission tomography (PET) uptake data. The original GA produces a negative bias in VT in the presence of noise. Estimates of VT using other GA forms have less bias but less precision. Here, we show how the bias terms are related between the GA methods and how using an instrumental variable (IV) can also reduce bias. Results are based on simulations of a two-compartment model with VT's ranging from 10.5 to 64 mL/cm3 and from PET image data with the tracer [11C]DASB ([11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl) benzonitrile). Four estimates of VT (or distribution volume ratio (DVR) using a reference tissue) can be easily computed from different formulations of GA including the IV. As noise affects the estimates from all four differently, they generally do not provide the same estimates. By taking the median value of the four estimates, we can decrease the bias and reduce the effect of large values contributing to noisy images. The variance of the four estimates can serve as a guide to the reliability of the median estimate. This may provide a general method for the generation of parametric images with little bias and good precision.

scholarly journals Improving PET Receptor Binding Estimates from Logan Plots Using Principal Component Analysis

2007 ◽  
Vol 28 (4) ◽  
pp. 852-865 ◽  
Author(s):  
Aniket Joshi ◽  
Jeffrey A Fessler ◽  
Robert A Koeppe
Keyword(s):  
Principal Component Analysis ◽  
Intervention Studies ◽  
Simulated Data ◽  
Volume Ratio ◽  
Principal Component ◽  
Component Analysis ◽  
Correlated Errors ◽  
Post Intervention ◽  
Positron Emission ◽  
Distribution Volume Ratio

This work reports a principal component analysis (PCA)-based approach for reducing bias in distribution volume ratio ( DVR) estimates from Logan plots in positron emission tomography (PET). Comparison has been made of all existing bias-removal methods with the proposed PCA method, for both single-estimate PET studies and intervention studies where pre- and post-intervention estimates are made. Bias in Logan-based DVR estimates is because of the noise in the PET timeactivity curves (TACs) that propagates as correlated errors in dependent and independent variables of the Logan equation. Intervention studies show this same bias but also higher variance in DVR estimates. In this work, noise in the TACs was reduced by fitting the curves to a low-dimension PCA-based linear model, leading to reduced bias and variance in DVR. For validating the approach, TACs with realistic noise were simulated for a 11C-labeled tracer with carfentanil (CFN)-like kinetics for both single-measurement and intervention studies. Principal component analysis and existing methods were applied to the simulated data and their performance was compared by statistical analysis. The results indicated that existing methods either removed only part of the bias or reduced bias at the expense of precision. The proposed method removed ∼90% of the bias while also improving precision in both single- and dual-measurement simulations. After validation of the proposed method in simulations, PCA, along with the existing methods, was applied to human [11C]CFN data acquired for both single estimation of DVR and dual-estimation intervention studies. Similar results were observed in human scans as were seen in the simulation studies.

scholarly journals Feedback-Controlled Bolus plus Infusion (FC-B/I) Method for Quantitative Drug Assessment in Living Brain with PET

2012 ◽  
Vol 33 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Hiroyuki Ohba ◽  
Norihiro Harada ◽  
Shingo Nishiyama ◽  
Takeharu Kakiuchi ◽  
Yuichi Kimura ◽  
...  
Keyword(s):  
Bolus Injection ◽  
Direct Interaction ◽  
Volume Ratio ◽  
Emission Tomography ◽  
Dependent Manner ◽  
Drug Candidates ◽  
Positron Emission ◽  
Distribution Volume Ratio ◽  
Target Molecules ◽  
Dose Dependent

We have developed a feedback-controlled bolus plus infusion (FC-B/I) method for monitoring the interaction between positron emission tomography (PET) ligands and their specific target molecules with PET. The usefulness of the FC-B/I method was evaluated by the direct interaction between [11C]raclopride, a dopamine D2 receptor (D2R) ligand, and cold raclopride (10 and 100 μg/kg) in the brains of conscious monkeys. The present results demonstrated that the FC-B/I method could achieve the equilibrium state of [11C]raclopride in the striatum of monkey brain, and also that the cold raclopride-induced reduction of [11C]raclopride binding to D2R was observed in a dose-dependent manner. Good correlations of distribution volume ratio of the striatum to cerebellum between the conventional bolus plus infusion (B/I) method and the FC-B/I method as well as between the conventional bolus injection method and the FC-B/I method were observed. These results indicated that the system could be a useful tool for the evaluation of interaction between drug candidates and their target molecules like enzymes, receptors, and transporters by using of their specific PET ligands.

scholarly journals Head-to-head comparison of tau positron emission tomography tracers [18F]flortaucipir and [18F]RO948

2019 ◽  
Vol 47 (2) ◽  
pp. 342-354 ◽  
Author(s):  
Ruben Smith ◽  
Michael Schöll ◽  
Antoine Leuzy ◽  
Jonas Jögi ◽  
Tomas Ohlsson ◽  
...  
Keyword(s):  
Medial Temporal Lobe ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Volume Ratio ◽  
Brain Regions ◽  
Positron Emission ◽  
Binding Time ◽  
Distribution Volume Ratio ◽  
Target Binding

Abstract Purpose [18F]flortaucipir binds to paired helical filament tau and accurately identifies tau in Alzheimer’s disease (AD). However, “off-target” binding interferes with the quantification of [18F]flortaucipir in several brain regions. Recently, other tau PET tracers have been developed. Here, we compare [18F]flortaucipir with the novel tau tracer [18F]RO948 head-to-head in vivo. Methods We included 18 participants with AD, three with amyloid-β-positive amnestic mild cognitive impairment, and four healthy controls. All underwent [18F]flortaucipir (80–100 min) and [18F]RO948 (70–90) PET scans within approximately 1 month. Four study participants underwent 0–100-min dynamic scanning. Standardized uptake value ratios (SUVRs) were created using an inferior cerebellar reference region. Results Neocortical tracer retention was highly comparable using both SUVR and distribution volume ratio-1 values obtained from dynamic scans. However, [18F]RO948 retention was significantly higher in the entorhinal cortex and lower in the basal ganglia, thalamus, and choroid plexus compared with [18F]flortaucipir. Increased off-target binding was observed with age for both tracers. Several cases exhibited strong [18F]RO948 retention in the skull/meninges. This extra-cerebral signal, however, did not affect diagnostic accuracy and remained relatively unchanged when re-examining a subsample after 1 year. Kinetic modeling showed an increase in [18F]flortaucipir SUVR over the scanning interval, compared with a plateau for [18F]RO948. Conclusion [18F]RO948 and [18F]flortaucipir bound comparably in neocortical regions, but [18F]RO948 showed higher retention in the medial temporal lobe and lower intracerebral “off-target” binding. Time-dependent bias of SUVR estimates may prove less of a factor with [18F]RO948, compared with previous tau ligands.

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