scholarly journals Impact of age and sex correction on the diagnostic performance of dopamine transporter SPECT

2020 ◽  
Author(s):  
Helen Schmitz-Steinkrüger ◽  
Catharina Lange ◽  
Ivayla Apostolova ◽  
Franziska L. Mathies ◽  
Lars Frings ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Diagnostic Performance ◽  
Specific Binding ◽  
Clinical Sample ◽  
Performance Measure ◽  
Specific Binding Ratio ◽  
Parkinsonian Syndromes ◽  
Age Related ◽  
The Impact ◽  
Age And Sex

Abstract Purpose The specific binding ratio (SBR) of 123I-FP-CIT (FP-CIT) in the putamen decreases with age by about 5% per decade and most likely is about 10% higher in females. However, the clinical utility of age and sex correction of the SBR is still a matter of debate. This study tested the impact of age and sex correction on the diagnostic performance of the putamen SBR in three independent patient samples. Methods Research sample: 207 healthy controls (HC) and 438 Parkinson’s disease (PD) patients. Clinical sample A: 183 patients with neurodegenerative parkinsonian syndrome (PS) and 183 patients with non-neurodegenerative PS from one site. Clinical sample B: 84 patients with neurodegenerative PS and 38 patients with non-neurodegenerative PS from another site. Correction for age and sex of the putamen SBR was based on linear regression in the HC or non-neurodegenerative PS, separately in each sample. The area under the ROC curve (AUC) was used as performance measure. Results The putamen SBR was higher in females compared to males (PPMI: 14%, p < 0.0005; clinical sample A: 7%, p < 0.0005; clinical sample B: 6%, p = 0.361). Age-related decline of the putamen SBR ranged between 3.3 and 10.4% (p ≤ 0.019). In subjects ≥ 50 years, age and sex explained < 10% of SBR between-subjects variance. Correction of the putamen SBR for age and sex resulted in slightly decreased AUC in the PPMI sample (0.9955 versus 0.9969, p = 0.025) and in clinical sample A (0.9448 versus 0.9519, p = 0.057). There was a small, non-significant AUC increase in clinical sample B (0.9828 versus 0.9743, p = 0.232). Conclusion These findings do not support age and sex correction of the putaminal FP-CIT SBR in the diagnostic workup of parkinsonian syndromes. This most likely is explained by the fact that the proportion of between-subjects variance caused by age and sex is considerably below the symptom threshold of about 50% reduction in neurodegenerative PS.

Enhanced chronotropic and inotropic responses of rat myocardium to cholinergic stimulus with aging

1992 ◽  
Vol 70 (12) ◽  
pp. 1618-1624 ◽  
Author(s):  
Na Su ◽  
Njanoor Narayanan
Keyword(s):  
Muscarinic Receptor ◽  
Heart Function ◽  
Specific Binding ◽  
Adrenergic Stimulation ◽  
Chronotropic Response ◽  
Related Difference ◽  
Age Related ◽  
Rat Hearts ◽  
Inotropic Responses ◽  
The Impact

The ability of the heart to respond to adrenergic stimulation diminishes with aging, and this may be one of the factors contributing to the age-associated decline in cardiac stress responsiveness. On the other hand, little is known about the impact of aging on the responsiveness of the heart to cholinergic stimulation. In this study, we determined the chronotropic and inotropic responses of the isolated, Langendorff-perfused hearts from adult (6–8 months) and aged (28–30 months) rats to cholinergic agonists so as to assess age-related alterations in postsynaptic cholinergic control of heart function. The results showed the following. (i) In isolated perfused spontaneously beating rat hearts, the negative chronotropic response to acetylcholine (10−9–10−5 M) was up to 4-fold greater in the aged compared with adult hearts; this age-related difference was less marked (2-fold) but not abolished in the presence of a maximally effective concentration (5 μM) of the cholinesterase inhibitor eserine. (ii) The cholinesterase-resistant agonist carbachol (10−9–2.5 × 10−6 M) elicited a 2- to 3-fold greater negative chronotropic response in the aged compared with adult hearts. (iii) In isolated perfused, electrically paced (4 Hz) rat hearts, carbachol (10−9–10−3 M) elicited a concentration-dependent negative inotropic response, which was 2-fold greater in the aged compared with adult heart at all carbachol concentrations, (iv) Acetylcholinesterase activities (micromoles per gram per hour) were 50–60% lower in the aged atria (83 ± 21) and ventricles (24 ± 6) than in adult atria (210 ± 20) and ventricles (47 ± 7). (v) No significant age-related difference was observed in the specific binding of (–)-[3H]quinuclidinyl benzilate to muscarinic receptor sites in atria or ventricles. These findings demonstrate a striking enhancement in the responses of the heart to cholinergic stimulus with aging, which can be attributed in part, but not solely to age-associated decline in cholinesterase activity. Age-associated alterations in muscarinic receptor linked events may also underlie the cholinergic hypersensitivity of the aging heart.Key words: aging, muscarinic receptor, cardiac performance in vitro, cholineresterase activity.

Normal Values of Renal Function measured with 99mTechnetium Mercaptoacetyltriglycine SPECT in Mice with Respect to Age, Sex and Circadian Rhythm

2018 ◽  
Vol 57 (06) ◽  
pp. 224-233 ◽  
Author(s):  
Kai Huang ◽  
Mathias Lukas ◽  
Ingo Steffen ◽  
Catharina Lange ◽  
Eleonore Huang ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Normal Values ◽  
Pinhole Spect ◽  
Time Activity ◽  
Renal Uptake ◽  
Time To Peak ◽  
Age Related ◽  
The Impact ◽  
Old Mice ◽  
Age And Sex

Summary Aim: The aim of this study is to present normal values for 99mtechnetium mercaptoacetyltriglycine renal uptake kinetics as a function of age, sex and circadian rhythm in mice using multi-pinhole SPECT. Methods: Dynamic multi-pinhole SPECT semistationary acquisitions consisting of 10 20 s frames followed by 25 50 s frames began prior to intravenous injection of 50 MBq in 12 female (F) and 12 male (M) C57BL/6N mice. Each mouse had follow-up imaging at 1, 3, 6, 12 and 22 months of age. To assess physiological changes related to circadian rhythm, animals were imaged during light (sleeping phase, SP) and dark conditions (awake phase, AP). Renal excretion time activity curves were analysed to determine maximum time to peak uptake (Tmax). Results: There was an age-related effect on renal Tmax. In one-month-old mice median Tmax (1.8 min) occurred later than in 3-month-old mice (1.7 min; p = 0.035). Thereafter, mice showed continuously increasing time to renal Tmax up to an age of 22 months (2.3 min; p < 0.001). Female mice showed a significantly later renal Tmax than males (F 2.1 min, M 1.7 min; p < 0.001) from 3 months onwards. An effect of circadian rhythm on renal uptake was also observed with borderline relevance. Pooled results for all animals showed that renal Tmax appeared at a later timepoint after injection during SP (2.0 min) than during AP (1.8 min; p = 0.019), while in age and sex matched animal groups no significant differences were observed. Conclusion: This study showed that kidney function in mice is dependent on age and sex, whereas circadian rhythm does not cause a significant effect. Therefore, age and sex should be considered as important study design considerations for renal scintigraphy in mice, while the impact of circadian rhythm seems negligible.

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

A form of Autoimmune Diabetes in Adults Named LADA – An Update on Essential Features and Controversies

2019 ◽  
Vol 15 (3) ◽  
pp. 172-173 ◽  
Author(s):  
Valdemar Grill ◽  
Bjørn O. Åsvold
Keyword(s):  
Genetic Background ◽  
Clinical Utility ◽  
Autoimmune Diabetes ◽  
Classical Type ◽  
Phenotypic Characteristics ◽  
Latent Autoimmune Diabetes ◽  
The Impact

Latent Autoimmune Diabetes in the Adult, LADA has been investigated less than “classical” type 1 and type 2 diabetes and the criteria for and the relevance of a LADA diagnosis has been challenged. Despite the absence of a genetic background that is exclusive to LADA, this form of diabetes displays phenotypic characteristics that distinguish it from other forms of diabetes. LADA is heterogeneous in terms of the impact of autoimmunity and lifestyle factors, something that poses problems as to therapy and follow-up perhaps particularly in those with marginal positivity. Yet, there appears to be clear clinical utility in classifying individuals as LADA.

Human Fibronectin Extra-Domain B (EDB)-Specific Aptide (APTEDB) Radiolabelling with Technetium-99m as a Potent Targeted Tumour-Imaging Agent

2018 ◽  
Vol 18 (2) ◽  
pp. 277-285 ◽  
Author(s):  
Mohsen Mohammadgholi ◽  
Nourollah Sadeghzadeh ◽  
Mostafa Erfani ◽  
Saeid Abediankenari ◽  
Seyed Mohammad Abedi ◽  
...  
Keyword(s):  
Radioligand Binding ◽  
Specific Binding ◽  
Specific Protein ◽  
Tumour Imaging ◽  
Specific Binding Ratio ◽  
Tumour Uptake ◽  
Technetium 99M ◽  
In Vivo Experiments ◽  
Human Fibronectin

Background: Human fibronectin extra-domain B (EDB) is particularly expressed during angiogenesis progression. It is, thus, a promising marker of tumour growth. Aptides are a novel class of peptides with high-affinity binding to specific protein targets. APTEDB is an antagonist-like ligand that especially interacts with human fibronectin EDB. Objective: This study was the first attempt in which the hydrazinonicotinamide (HYNIC)-conjugated APTEDB was labelled with technetium-99m (99mTc) as an appropriate radiotracer and tricine/EDDA exchange labeling. Methods: Radiochemical purity, normal saline, and serum stability were evaluated by HPLC and radio-isotope TLC scanner. Other examinations, such as protein-binding calculation, dissociation radioligand binding assay, and partition coefficient constant determination, were also carried out. The cellular-specific binding of 99mTc- HYNIC-conjugated APTEDB was assessed in two EDB-positive (U87MG) and EDB-negative (U373MG) cell lines. Bio-distribution was investigated in normal mice as well as in U87MG and U373MG tumour-bearing mice. Eventually, the radiolabelled APTEDB was used for tumour imaging using planar SPECT. Results: Radiolabelling was achieved with high purity (up to 97%) and accompanied by high solution (over 90% after overnight) and serum (80% after 2 hours) stability. The obtained cellular-specific binding ratio was greater than nine-fold. In-vivo experiments showed rapid blood clearance with mainly renal excretion and tumour uptake specificity (0.48±0.03% ID/g after 1h). The results of the imaging also confirmed considerable tumour uptake for EDB-positive cell line compared with the EDB-negative one. Conclusion: Aptides are considered to be a potent candidate for biopharmaceutical applications. They can be modified with imaging or therapeutic agents. This report shows the capability of 99mTc-HYNIC-APTEDB for human EDB-expressing tumours detection.

Asymmetric Dopaminergic Dysfunction in Brain-First versus Body-First Parkinson’s Disease Subtypes

2021 ◽  
pp. 1-11
Author(s):  
Karoline Knudsen ◽  
Tatyana D. Fedorova ◽  
Jacob Horsager ◽  
Katrine B. Andersen ◽  
Casper Skjærbæk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Specific Binding ◽  
Asymmetry Index ◽  
The Body ◽  
Specific Binding Ratio ◽  
Dat Spect ◽  
Vagal Innervation ◽  
Nigrostriatal Degeneration

Background: We have hypothesized that Parkinson’s disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type. Objective: To analyse striatal asymmetry in [18F]FDOPA PET and [123I]FP-CIT DaT SPECT data from iRBD patients, de novo PD patients with RBD (PD +RBD) and de novo PD patients without RBD (PD - RBD). These groups were defined as prodromal body-first, de novo body-first, and de novo brain-first, respectively. Methods: We included [18F]FDOPA PET scans from 21 iRBD patients, 11 de novo PD +RBD, 22 de novo PD - RBD, and 18 controls subjects. Also, [123I]FP-CIT DaT SPECT data from iRBD and de novo PD patients with unknown RBD status from the PPPMI dataset was analysed. Lowest putamen specific binding ratio and putamen asymmetry index (AI) was defined. Results: Nigrostriatal degeneration was significantly more symmetric in patients with RBD versus patients without RBD or with unknown RBD status in both FDOPA (p = 0.001) and DaT SPECT (p = 0.001) datasets. Conclusion: iRBD subjects and de novo PD +RBD patients present with significantly more symmetric nigrostriatal dopaminergic degeneration compared to de novo PD - RBD patients. The results support the hypothesis that body-first PD is characterized by more symmetric distribution most likely due to more symmetric propagation of pathogenic α-synuclein compared to brain-first PD.

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