Classification of Mild Cognitive Impairment and Alzheimer's Disease Using Manual Motor Measures.

INTRODUCTION: Manual motor problems have been reported in mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the specific aspects that are affected, their neuropathology, and potential value for classification modeling is unknown. The current study examined if multiple measures of motor strength, dexterity, and speed are affected in MCI and AD, related to AD biomarkers, and are able to classify MCI or AD. METHODS: Fifty-three cognitively normal (CN), 33 amnestic MCI, and 28 AD subjects completed five manual motor measures: grip force, Trail Making Test A, spiral tracing, finger tapping, and a simulated feeding task. Analyses included: 1) group differences in manual performance; 2) associations between manual function and AD biomarkers (PET amyloid ß, hippocampal volume, and APOE ε4 alleles); and 3) group classification accuracy of manual motor function using machine learning. RESULTS: amnestic MCI and AD subjects exhibited slower psychomotor speed and AD subjects had weaker dominant hand grip strength than CN subjects. Performance on these measures was related to amyloid ß deposition (both) and hippocampal volume (psychomotor speed only). Support vector classification well-discriminated control and AD subjects (area under the curve of 0.73 and 0.77 respectively), but poorly discriminated MCI from controls or AD. CONCLUSION: Grip strength and spiral tracing appear preserved, while psychomotor speed is affected in amnestic MCI and AD. The association of motor performance with amyloid ß deposition and atrophy could indicate that this is due to amyloid deposition in- and atrophy of motor brain regions, which generally occurs later in the disease process. The promising discriminatory abilities of manual motor measures for AD emphasize their value alongside other cognitive and motor assessment outcomes in classification and prediction models, as well as potential enrichment of outcome variables in AD clinical trials.

Prospective Pilot Study of 18F-Fluoroestradiol PET/CT in Patients With Invasive Lobular Carcinomas.

BACKGROUND. PET/CT with 18F-fluoroestradiol (FES) (FDA-approved in 2020) depicts tissues expressing estrogen receptor (ER). Invasive lobular carcinoma (ILC) is commonly ER positive. OBJECTIVE. The primary aim of this study was to assess the frequency with which sites of histologically proven ILC have abnormal uptake on FES PET/CT. METHODS. This prospective single-center pilot study, conducted from December 2020 to August 2021, enrolled patients with histologically confirmed ILC to undergo FES PET/CT; patients optionally underwent FDG PET/CT. Two nuclear radiologists assessed FES PET/CT and FDG PET/CT studies for abnormal uptake corresponding to known ILC sites at enrollment and for additional sites of abnormal uptake, resolving differences by consensus. The primary endpoint was percentage of known ILC sites showing abnormal FES uptake. The alternative to the null hypothesis was that more than 60% of sites would have abnormal FES uptake, exceeding the percentage of ILC with abnormal FDG uptake described in prior literature. A sample size of 24 biopsied lesions was preselected to provide 81% power for the alternative hypothesis (one-sided α = .10). Findings on FES PET/CT and FDG PET/CT were summarized for additional secondary endpoints. RESULTS. The final analysis included 17 patients (mean age, 59.1 ± 13.2 years) with 25 sites of histologically confirmed ILC at enrollment (22 breast lesions, two axillary lymph nodes, one distant metastasis). FES PET/CT showed abnormal uptake in 22 of 25 (88%) lesions, sufficient to reject the null hypothesis (p = .002). Thirteen patients underwent FDG PET/CT. Four of 23 (17%) sites of histologically confirmed ILC, including additional sites detected and confirmed after enrollment, were identified with FES PET/CT only, and 1 of 23 (4%) was identified only with FDG PET/CT (p = .18). FES PET/CT depicted additional lesions not detected with standard-of-care evaluation in 4 of 17 (24%) patients (two contralateral breast cancers and two metastatic axillary lymph nodes, all with subsequent histologic confirmation). Use of FES PET/CT resulted in changes in clinical stage with respect to standard-of-care evaluation in 3 of 17 (18%) patients. CONCLUSION. The primary endpoint of the trial was met. The frequency of abnormal FES uptake among sites of histologically known ILC was found to be to be significantly greater than 60%. CLINICAL IMPACT. This pilot study shows a potential role of FES PET/CT in evaluation of patients with ILC. TRIAL REGISTRATION. ClinicalTrials.gov NCT04252859.

The Quick Dementia Rating System and Its Relationship to Biomarkers of Alzheimer's Disease and Neuropsychological Performance.

INTRODUCTION: The Quick Dementia Rating System (QDRS) is a brief, patient-reported dementia staging tool that has approximated scores on the Clinical Dementia Rating Scale in patients with Alzheimer's disease (AD). However, no studies have examined its relationship with AD-related biomarkers. METHODS: One-hundred twenty-one older adults (intact, amnestic mild cognitive impairment, mild AD) completed the QDRS, and three biomarkers (amyloid deposition via positron emission tomography, hippocampal volume via magnetic resonance imaging, and apolipoprotein [APOE] ε4 status). RESULTS: The Total score on the QDRS was statistically significantly related to all three biomarkers (after controlling for age, education, sex, and race), with greater levels of dementia severity being associated with greater amyloid deposition, smaller hippocampi, and having copies of APOE ε4 allele. DISCUSSION: In participants across the cognitive spectrum, the QDRS showed modest relationships with amyloid deposition, hippocampal volumes, and APOE status. Therefore, the QDRS may offer a cost-effective screening method for clinical trials in AD.

Radium-223 plus Enzalutamide Versus Enzalutamide in Metastatic Castration-Refractory Prostate Cancer: Final Safety and Efficacy Results.

LESSONS LEARNED: Long-term safety of radium-223 with enzalutamide was confirmed in this clinical trial. PSA-PFS2 was prolonged with the combination compared with enzalutamide alone. BACKGROUND: Previously, we showed the combination of radium-223 and enzalutamide to be safe and associated with improved efficacy based on a concomitant decline in serum bone metabolism markers compared with enzalutamide alone in a phase II trial of men with metastatic castration-resistant prostate cancer (mCRPC) [1]. METHODS: Secondary endpoints were not included in our initial report, and we include them herein, after a median follow-up of 22 months. These objectives included long-term safety, prostate-specific antigen (PSA)-progression-free survival (PFS), and radiographic progression-free survival; PSA-PFS2 (time from start of protocol therapy to PSA progression on subsequent therapy); time to next therapy (TTNT); and overall survival (OS). Survival analysis and log-rank tests were performed using the R statistical package v.4.0.2 (https://www.r-project.org). Statistical significance was defined as p < .05. RESULTS: Of 47 patients (median age, 68 years), 35 received the combination and 12 enzalutamide alone. After a median follow-up of 22 months, final safety results did not show any increase in fractures or other adverse events in the combination arm. PSA-PFS2 was significantly improved, and other efficacy parameters were numerically improved in the combination over the enzalutamide arm. CONCLUSION: The combination of enzalutamide and radium-223 was found to be safe and associated with promising efficacy in men with mCRPC. These hypothesis-generating results portend well for the ongoing phase III PEACE III trial in this setting.

Analysis of retention of gadolinium by brain, bone, and blood following linear gadolinium-based contrast agent administration in rats with experimental sepsis.

PURPOSE: It is important to identify populations that may be vulnerable to the brain deposition of gadolinium (Gd) from MRI contrast agents. At intervals from 24 hours to 6 weeks following injection of a linear Gd contrast agent, the brain, blood and bone content of Gd were compared between control rats and those with experimental endotoxin-induced sepsis that results in neuroinflammation and blood-brain barrier disruption. METHODS: Male rats were injected intraperitoneally with 10 mg/kg lipopolysaccharide. Control animals received no injection. Twenty-four hours later, 0.2 mmol/kg of gadobenate dimeglumine was injected intravenously. Brain, blood, and bone Gd levels were measured at 24 hours, 1 week, 3 weeks, and 6 weeks by inductively coupled plasma mass spectroscopy. RESULTS: Blood Gd decreased rapidly between 24 hours and 1 week, and thereafter was undetectable, with no significant difference between lipopolysaccharide and control rats. Brain levels of Gd were significantly higher (4.29-2.36-fold) and bone levels slightly higher (1.35-1.11-fold) in lipopolysaccharide than control rats at all time points with significant retention at 6 weeks. CONCLUSION: Experimental sepsis results in significantly higher deposition of Gd in the brain and bone in rats. While blood Gd clears rapidly, brain and bone retained substantial Gd even at 6 weeks following contrast injection.

Long-term Changes in 18F-Flutemetamol Uptake in Nondemented Older Adults.

PURPOSE: Longitudinal studies into the variability of F-Flutemetamol uptake are lacking. METHODS/PATIENTS: Therefore, the current study examined change in F-Flutemetamol uptake in 19 nondemented older adults (65 to 82 y old) who were either cognitively intact or had Mild Cognitive Impairment (MCI) who were scanned twice across 3.6 years. RESULTS: Baseline and follow-up composite SUVRs were significantly correlated (0.96, P<0.001). Significant increases in the composite SUVR from baseline to follow-up were observed (P=0.002). For the total sample, the average difference over this time period when using the composite SUVR was 6.8%. Similar results were seen in subsets of the total sample (MCI vs. cognitively intact, amyloid positive vs. negative). Finally, a Reliable Change Index that exceeded ±0.046 SUVR units would indicate a significant change of F-Flutemetamol. CONCLUSIONS: The current results extend the limited literature on longitudinal variability of F-Flutemetamol uptake across 3.6 years, which should give clinicians and researchers more confidence in the stability of this amyloid imaging agent in longer therapeutic and prevention trials in cognitive decline in MCI and Alzheimer disease.

Stimuli-responsive reagent system for enabling microfluidic immunoassays with biomarker purification and enrichment.

Immunoassays have been translated into microfluidic device formats, but significant challenges relating to upstream sample processing still limit their applications. Here, stimuli-responsive polymer-antibody conjugates are utilized in a microfluidic immunoassay to enable rapid biomarker purification and enrichment as well as sensitive detection. The conjugates were constructed by covalently grafting poly(N-isopropylacrylamide) (PNIPAAm), a thermally responsive polymer, to the lysine residues of anti-prostate specific antigen (PSA) Immunoglobulin G (IgG) using carbodiimide chemistry via the polymer end-carboxylate. The antibody-PNIPAAm (capture) conjugates and antibody-alkaline phosphatase (detection) conjugates formed sandwich immunocomplexes via PSA binding in 50% human plasma. The complexes were loaded into a recirculating poly(dimethylsiloxane) microreactor, equipped with micropumps and transverse flow features, for subsequent separation, enrichment, and quantification. The immunocomplexes were captured by heating the solution to 39 °C, mixed over the transverse features for 2 min, and washed with warm buffer. In one approach, the assay utilized immunocomplex solution that was contained in an 80 nL microreactor, which was loaded with solution at room temperature and subsequently heated to 39 °C. The assay took 25 min and resulted in 37 pM PSA limit of detection (LOD), which is comparable to a plate ELISA employing the same antibody pair. In another approach, the microreactor was preheated to 39 °C, and immunocomplex solution was flowed through the reactor, mixed, and washed. When the specimen volume was increased to 7.5 µL by repeating the capture process three times, the higher specimen volume led to immunocomplex enrichment within the microreactor. The resulting assay LOD was 0.5 pM, which is 2 orders of magnitude lower than the plate ELISA. Both approaches generate antigen specific signal over a clinically significant range. The sample processing capabilities and subsequent utility in a biomarker assay demonstrate the opportunity for stimuli-responsive polymer-protein conjugates in novel diagnostic technologies.

Practice effects and amyloid deposition: preliminary data on a method for enriching samples in clinical trials.

Clinical trials in Alzheimer disease are moving toward prevention studies in prodromal individuals with amyloid burden. However, methods are needed to identify individuals expected to be amyloid positive for these studies to be feasible and cost-effective. The current study sought to determine whether short-term practice effects on cognitive tests can identify those with notable uptake on amyloid imaging. Twenty-five, nondemented older adults (15 cognitively intact, 10 with mild cognitive impairment) underwent amyloid imaging through F-flutemetamol and 2 cognitive testing sessions across 1 week to determine practice effects on a visual memory test. Results indicated that, whereas F-flutemetamol uptake showed little association with baseline performance on a visual memory test (r=-0.04, P=0.85), it was significantly correlated with practice effects across 1 week on that same memory measure (r=-0.45, P=0.02), with greater uptake being associated with lower practice effects. The odds ratio of notable F-flutemetamol uptake was 5 times higher in individuals with low practice effects compared with high practice effects. Although these preliminary results need to be replicated in larger samples, short-term practice effects on cognitive tests may provide an affordable screening method to identify individuals who are amyloid positive, which could enrich samples for preventative clinical trials in Alzheimer disease.

Short-Term Practice Effects on Cognitive Tests Across the Late Life Cognitive Spectrum and How They Compare to Biomarkers of Alzheimer's Disease.

Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.

Assessing variability in non-contrast CT for the evaluation of stroke: The effect of CT image reconstruction conditions on AI-based CAD measurements of ASPECTS value and hypodense volume.

Purpose: To rule out hemorrhage, non-contrast CT (NCCT) scans are used for early evaluation of patients with suspected stroke. Recently, artificial intelligence tools have been developed to assist with determining eligibility for reperfusion therapies by automating measurement of the Alberta Stroke Program Early CT Score (ASPECTS), a 10-point scale with > 7 or ≤ 7 being a threshold for change in functional outcome prediction and higher chance of symptomatic hemorrhage, and hypodense volume. The purpose of this work was to investigate the effects of CT reconstruction kernel and slice thickness on ASPECTS and hypodense volume. Methods: The NCCT series image data of 87 patients imaged with a CT stroke protocol at our institution were reconstructed with 3 kernels (H10s-smooth, H40s-medium, H70h-sharp) and 2 slice thicknesses (1.5mm and 5mm) to create a reference condition (H40s/5mm) and 5 non-reference conditions. Each reconstruction for each patient was analyzed with the Brainomix e-Stroke software (Brainomix, Oxford, England) which yields an ASPECTS value and measure of total hypodense volume (mL). Results: An ASPECTS value was returned for 74 of 87 cases in the reference condition (13 failures). ASPECTS in non-reference conditions changed from that measured in the reference condition for 59 cases, 7 of which changed above or below the clinical threshold of 7 for 3 non-reference conditions. ANOVA tests were performed to compare the differences in protocols, Dunnett's post-hoc tests were performed after ANOVA, and a significance level of p < 0.05 was defined. There was no significant effect of kernel (p = 0.91), a significant effect of slice thickness (p < 0.01) and no significant interaction between these factors (p = 0.91). Post-hoc tests indicated no significant difference between ASPECTS estimated in the reference and any non-reference conditions. There was a significant effect of kernel (p < 0.01) and slice thickness (p < 0.01) on hypodense volume, however there was no significant interaction between these factors (p = 0.79). Post-hoc tests indicated significantly different hypodense volume measurements for H10s/1.5mm (p = 0.03), H40s/1.5mm (p < 0.01), H70h/5mm (p < 0.01). No significant difference was found in hypodense volume measured in the H10s/5mm condition (p = 0.96). Conclusion: Automated ASPECTS and hypodense volume measurements can be significantly impacted by reconstruction kernel and slice thickness.

A photoinduced nanoparticle separation in microchannels via pH-sensitive surface traps.

A microfluidic surface trap was developed for capturing pH-sensitive nanoparticles via a photoinitiated proton-releasing reaction of o-nitrobenzaldehyde (o-NBA) that reduces the solution pH in microchannels. The surface trap and nanoparticles were both modified with a pH-responsive polymer-poly(N-isorpopylacylamide-co-propylacrylic acid), P(NIPAAm-co-PAA). The o-NBA-coated microchannel walls demonstrated rapid proton release upon UV light irradiation, allowing the buffered solution pH in the microchannel to decrease from 7.4 to 4.5 in 60 s. The low solution pH switched the polymer-modified surfaces to be more hydrophobic, which enabled the capture of the pH-sensitive nanobeads onto the trap. When a photomask was utilized to limit the UV irradiation to a specific channel region, we were able to restrict the particle separation to only the exposed region. Via control of the UV irradiation, this technique enables not only prompt pH changes within the channel but also the capture of target molecules at specific channel locations.

Change in the Quick Dementia Rating System Across Time in Older Adults with and without Cognitive Impairment.

BACKGROUND: The Quick Dementia Rating System (QDRS) is a brief, informant-reported dementia staging tool that approximates scores on the Clinical Dementia Rating Scale in patients with Alzheimer's disease (AD). OBJECTIVE: The current study sought to examine change in the QDRS across time, which is necessary for clinical and research efforts. METHODS: One-hundred ten older adults (intact, mild cognitive impairment [MCI], mild AD, classified with Alzheimer's Disease Neuroimaging Initiative criteria) were rated on the QDRS by an informant and had an amyloid positron emission tomography scan at baseline. The informant re-rated each participant on the QDRS after one year. Dependent t-tests compared the entire sample and various subgroups (e.g., cognitive status, amyloid status) on baseline and follow-up QDRS scores. RESULTS: In the entire sample, the Total score on the QDRS significantly increased (i.e., worsened) on follow-up (p < 0.001). When subgroups were analyzed, the MCI and mild AD subjects showed increasing (i.e., worsening) QDRS Total scores (both p < 0.001), but the intact subjects remained stable over time (p = 0.28). Additionally, those classified as being amyloid positive at baseline showed significantly increased QDRS Total scores at follow-up (p < 0.001) compared to those who were amyloid negative at baseline, whose QDRS Total scores remained stable over time (p = 0.63). CONCLUSION: The QDRS can potentially demonstrate worsening functioning status across one year, especially in those who have MCI or mild AD and those who are amyloid positive. Therefore, the current results preliminarily suggest that the QDRS may provide an efficient tool for tracking progression in clinical trials in AD.

Recall and recognition subtests of the repeatable battery for the assessment of neuropsychological status and their relationship to biomarkers of Alzheimer's disease.

Recently, two new recognition subtests for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were developed and initially validated in a cohort of older adults who were cognitively intact or classified as amnestic Mild Cognitive Impairment (MCI) or mild Alzheimer's disease (AD). The current paper extends that validation by comparing the recall and recognition subtests of the RBANS, including the existing and recently developed scores, to three commonly used biomarkers in AD in an expanded sample from the initial validation. One hundred fifty-four older adults (65 intact, 46 MCI, 43 AD) were administered the RBANS, which included the recently developed subtests for Story Recognition and Figure Recognition (hits, false positives, total correct), as part of a study on memory and biomarkers. Participants also completed magnetic resonance imaging to obtain hippocampal volumes, positron emission tomography to obtain amyloid plaque deposition, and a blood draw to obtain APOE ε4 status. Whereas correlations between recall scores and biomarkers tended to be moderate (average r = ±0.48), these correlations were comparable across the three recognition total scores (average r = ±0.42), but tended to be lower for recognition hits (average r = ±0.28) and false positives (average r = ±0.38). These results further validate the existing and recently developed recognition scores on the RBANS as providing useful information about brain and genetic pathology in older adults with intact and impaired cognitive functioning.

SNMMI Clinical Trial Network Research Series for Technologists: Application of Good Clinical Practice to Clinical Research in Medical Imaging.

This article is part of a series developed by the Clinical Trials Network of the Society of Nuclear Medicine and Molecular Imaging to offer training and information for molecular imaging technologists and researchers about various aspects of clinical research. This article covers the topic of good clinical practice and how that relates to those portions of the Code of Federal Regulations that govern clinical research in the United States, such as title 21, part 312, and the Common Rule. The purpose of this article is to inform technologists and researchers about standard roles, documents, guidance, and processes that are elemental to the conduct of clinical trials and to offer additional resources for learning about these processes.

Change on the Repeatable Battery for the Assessment of Neuropsychological Status and its relationship to brain amyloid.

BACKGROUND: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been associated with commonly used biomarkers of Alzheimer's disease (AD), including brain amyloid plaque density. However, less is known about if changes in the RBANS across time are also related to brain amyloid deposition. The current study sought to expand on prior work by examining the relationship between changes over time on the RBANS and amyloid deposition via positron emission tomography (PET). METHOD: One-hundred twenty-six older adults with intact or impaired cognition and daily functioning underwent repeat assessment with the RBANS across nearly 16 months, as well as had a baseline amyloid PET scan. RESULTS: In the entire sample, amyloid deposition was significantly related to change on all five Indexes and the Total Scale score of the RBANS, with greater amyloid being associated with worsening cognition. This pattern was also observed in 11 of 12 subtests. CONCLUSIONS: Whereas prior studies have identified a relationship between baseline RBANS and amyloid status, the current findings support that changes in the RBANS are also indicative of AD brain pathology, even if these findings are mediated by cognitive status. Although replication in a more diverse sample is needed, these results continue to support the use of the RBANS in AD clinical trials.

Repeatable battery for the assessment of neuropsychological status and its relationship to biomarkers of Alzheimer's disease.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been associated with commonly used biomarkers of Alzheimer's disease (AD). However, prior studies have typically utilized small and poorly characterized samples, and they have not analyzed the subtests of the RBANS. The current study sought to expand on prior work by examining the relationship between the Indexes and subtest scores of the RBANS and three AD biomarkers: amyloid deposition via positron emission tomography, hippocampal volume via magnetic resonance imaging, and APOE ε4 status.One-hundred twenty-one older adults across the AD continuum (intact, amnestic Mild Cognitive Impairment, mild AD), who were mostly Caucasian and well-educated, underwent assessment with the RBANS and collection of the three biomarkers.Greater amyloid deposition was significantly related to lower scores on all five Indexes and the Total Scale score of the RBANS, as well as 11 of 12 subtests. For bilateral hippocampal volume, significant correlations were observed for 4 of the 5 Indexes, Total Scale score, and 9 of 12 subtests, with smaller hippocampi being related to lower RBANS scores. Participants with at least one APOE ε4 allele had significantly lower scores on 3 of the 5 Indexes, Total Scale score, and 8 of the 12 subtests.In this sample of participants across the dementia spectrum, most RBANS Indexes and subtests showed relationships with the amyloid deposition, hippocampal volumes, and APOE status, with poorer performance on the RBANS being associated with biomarker positivity. Although memory scores on the RBANS have traditionally been linked to biomarkers in AD, other Index and subtest scores also hold promise as indicators of AD. Replication in a more diverse sample is needed.

Delayed and More Variable Unimanual and Bimanual Finger Tapping in Alzheimer's Disease: Associations with Biomarkers and Applications for Classification.

BACKGROUND: Despite reports of gross motor problems in mild cognitive impairment (MCI) and Alzheimer's disease (AD), fine motor function has been relatively understudied. OBJECTIVE: We examined if finger tapping is affected in AD, related to AD biomarkers, and able to classify MCI or AD. METHODS: Forty-seven cognitively normal, 27 amnestic MCI, and 26 AD subjects completed unimanual and bimanual computerized tapping tests. We tested 1) group differences in tapping with permutation models; 2) associations between tapping and biomarkers (PET amyloid-ß, hippocampal volume, and APOEɛ4 alleles) with linear regression; and 3) the predictive value of tapping for group classification using machine learning. RESULTS: AD subjects had slower reaction time and larger speed variability than controls during all tapping conditions, except for dual tapping. MCI subjects performed worse than controls on reaction time and speed variability for dual and non-dominant hand tapping. Tapping speed and variability were related to hippocampal volume, but not to amyloid-ß deposition or APOEɛ4 alleles. Random forest classification (overall accuracy = 70%) discriminated control and AD subjects, but poorly discriminated MCI from controls or AD. CONCLUSIONS: MCI and AD are linked to more variable finger tapping with slower reaction time. Associations between finger tapping and hippocampal volume, but not amyloidosis, suggest that tapping deficits are related to neuropathology that presents later during the disease. Considering that tapping performance is able to differentiate between control and AD subjects, it can offer a cost-efficient tool for augmenting existing AD biomarkers.

SNMMI Clinical Trials Network Research Series for Technologists: Clinical Research Primer-Regulatory Process, Part I: How and When Radiopharmaceuticals Can Be Used.

CE credit: For CE credit, you can access the test for this article, as well as additional JNMT CE tests, online at https://www.snmmilearningcenter.org Complete the test online no later than March 2025. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 75% of the questions correctly to receive Continuing Education Hour (CEH) credit. Credit amounts can be found in the SNMMI Learning Center Activity. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test.The radiopharmaceutical development and approval process in the United States has changed dramatically over the past decade with the emergence of several new and exciting diagnostic and therapeutic drugs. This impressive expansion is a direct result of the symbiotic relationship that exists between drug development, clinical research, and improved regulatory guidance. The correlative increase in clinical research has introduced diverse opportunities for newcomers in medical and scientific professions. Knowing how to successfully navigate the clinical research process can be challenging for a novice. The pathway is highly regulated and, with the addition of radiopharmaceuticals, may be confusing and daunting. Moreover, very little clinical research education and training is provided in the typical collegiate curricula for these new initiates. This article will familiarize the reader with the U.S. regulatory process by providing basic definitions and understanding of how and when radiopharmaceuticals can be used in clinical research, including those involving investigational new drug applications and radioactive drug research committees. A later article will expand the reader's clinical research knowledge by focusing on the identity and role of the institutional review board.

Improving Prediction of Amyloid Deposition in Mild Cognitive Impairment With a Timed Motor Task.

Cortical amyloid deposition is one of the hallmark biomarkers of Alzheimer's disease (AD). However, given how cost- and time-intensive amyloid imaging can be, there is a continued need for a low-cost, non-invasive, and accessible enrichment strategy to pre-screen individuals for their likelihood of amyloid prior to imaging. Previous work supports the use of coordinated limb movement as a potential screening tool, even after controlling for cognitive and daily function. Thirty-six patients diagnosed with amnestic mild cognitive impairment over the age of 65 underwent 18F-Flutemetamol amyloid-positron emission tomography (PET) imaging and then completed a timed motor task involving upper limb coordination. This task takes ∼5 minutes to administer and score. Multivariate linear regression and receiver operator characteristic analyses showed that including motor task performance improved model prediction of amyloid burden. Results support the rationale for including functional upper extremity motor assessment as a cost- and time-effective means to screen participants for amyloid deposition.

SNMMI Clinical Trials Network Research Series for Technologists: Clinical Research Primer- Use of Imaging Agents in Therapeutic Drug Development and Approval.

The process of bringing a new drug to market is complex and has recently necessitated a new drug discovery paradigm for the pharmaceutical industry that is both more efficient and more economical. Key to this has been the increasing use of nuclear medicine and molecular imaging to support drug discovery efforts by answering critical questions on the pathway for development and approval of a new therapeutic drug. Some of these questions include: (i) Does the new drug reach its intended target in the body at sufficient levels to effectively treat or diagnose disease without unacceptable toxicity? (ii) How is the drug absorbed, metabolized, and excreted? (iii) What is the effective dose in humans? To conduct the appropriate imaging studies to answer such questions, pharmaceutical companies are increasingly partnering with molecular imaging departments. Nuclear medicine technologists are critical to this process as they perform scans to collect the qualitative and quantitative imaging data used to measure study endpoints. This article describes preclinical and clinical research trials and provides an overview of the different ways that radiopharmaceuticals are used to answer critical questions during therapeutic drug development.