Search

INTRODUCTION: Overlooking the heterogeneity in Alzheimer's disease (AD) may lead to diagnostic delays and failures. Neuroanatomical normative modeling captures individual brain variation and may inform our understanding of individual differences in AD‐related atrophy. METHODS: We applied neuroanatomical normative modeling to magnetic resonance imaging from a real‐world clinical cohort with confirmed AD (n = 86). Regional cortical thickness was compared to a healthy reference cohort (n = 33,072) and the number of outlying regions was summed (total outlier count) and mapped at individual‐ and group‐levels. RESULTS: The superior temporal sulcus contained the highest proportion of outliers (60%). Elsewhere, overlap between patient atrophy patterns was low. Mean total outlier count was higher in patients who were non‐amnestic, at more advanced disease stages, and without depressive symptoms. Amyloid burden was negatively associated with outlier count. DISCUSSION: Brain atrophy in AD is highly heterogeneous and neuroanatomical normative modeling can be used to explore anatomo‐clinical correlations in individual patients. [ABSTRACT FROM AUTHOR]

Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [18F]fluoromethyl-[1,2-2H4]choline ([18F]D4-FCH). [18F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a 1H/2D isotope effect, together with fluorine substitution. Due to the promising mechanistic and safety profiles of [18F]D4-FCH in vitro and preclinically, the radiotracer has transitioned to clinical development. [18F]D4-FCH is a safe positron emission tomography (PET) tracer, with a favourable radiation dosimetry profile for clinical imaging. [18F]D4-FCH PET/CT in lung and prostate cancers has shown highly heterogeneous intratumoral distribution and large lesion variability. Treatment with abiraterone or enzalutamide in metastatic castrate-resistant prostate cancer patients elicited mixed responses on PET at 12–16 weeks despite predominantly stable radiological appearances. The sum of the weighted tumour-to-background ratios (TBRs-wsum) was associated with the duration of survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Thymidylate synthase (TS) inhibitors have remained among the most effective chemotherapies used in the treatment of various cancer types. Imaging of tumour proliferative activity while on antifolates has been studied with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography (18F-FLT PET) imaging. The aim of this study was to use 18F-FLT PET/CT imaging to understand the basis of early drug action with the antifolate drug pemetrexed on TS inhibition. While every patient showed a global change in the plasma marker of TS inhibition after drug administration, tumour TS inhibition was selective and patients who showed a tumour change in the imaging biomarker had a greater therapy response and longer overall survival following a combination treatment including pemetrexed. The study findings implicate the potential use of 18F-FLT PET/CT to understand the basis of drug action in other studies involving TS inhibitors. Thymidylate synthase (TS) remains a major target for cancer therapy. TS inhibition elicits increases in DNA salvage pathway activity, detected as a transient compensatory "flare" in 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography (18F-FLT PET). We determined the magnitude of the 18F-FLT flare in non-small cell lung cancer (NSCLC) patients treated with the antifolate pemetrexed in relation to clinical outcome. Method: Twenty-one patients with advanced/metastatic non-small cell lung cancer (NSCLC) scheduled to receive palliative pemetrexed ± platinum-based chemotherapy underwent 18F-FLT PET at baseline and 4 h after initiating single-agent pemetrexed. Plasma deoxyuridine (dUrd) levels and thymidine kinase 1 (TK1) activity were measured before each scan. Patients were then treated with the combination therapy. The 18F-FLT PET variables were compared to RECIST 1.1 and overall survival (OS). Results: Nineteen patients had evaluable PET scans at both time points. A total of 32% (6/19) of patients showed 18F-FLT flares (>20% change in SUVmax-wsum). At the lesion level, only one patient had an FLT flare in all the lesions above (test–retest borders). The remaining had varied uptake. An 18F-FLT flare occurred in all lesions in 1 patient, while another patient had an 18F-FLT reduction in all lesions; 17 patients showed varied lesion uptake. All patients showed global TS inhibition reflected in plasma dUrd levels (p < 0.001) and 18F-FLT flares of TS-responsive normal tissues including small bowel and bone marrow (p = 0.004 each). Notably, 83% (5/6) of patients who exhibited 18F-FLT flares were also RECIST responders with a median OS of 31 m, unlike patients who did not exhibit 18F-FLT flares (15 m). Baseline plasma TK1 was prognostic of survival but its activity remained unchanged following treatment. Conclusions: The better radiological response and longer survival observed in patients with an 18F-FLT flare suggest the efficacy of the tracer as an indicator of the early therapeutic response to pemetrexed in NSCLC. [ABSTRACT FROM AUTHOR]

Objectives: Visual rating scales (VRS) are the quantification method closest to the approach used in routine clinical practice to assess brain atrophy. Previous studies have suggested that the medial temporal atrophy (MTA) rating scale is a reliable diagnostic marker for AD, equivalent to volumetric quantification, while others propose a higher diagnostic utility for the Posterior Atrophy (PA) scale in early‐onset AD. Methods: Here, we reviewed 14 studies that assessed the diagnostic accuracy of PA and MTA, we explored the issue of cut‐off heterogeneity, and assessed 9 rating scales in a group of patients with biomarker‐confirmed diagnosis. A neuroradiologist blinded to all clinical information rated the MR images of 39 amyloid‐positive and 38 amyloid‐negative patients using 9 validated VRS assessing multiple brain regions. Automated volumetric analyses were performed on a subset of patients (n = 48) and on a group of cognitively normal individuals (n = 28). Results: No single VRS could differentiate amyloid‐positive from amyloid‐negative patients with other neurodegenerative conditions. 44% of amyloid‐positive patients were deemed to have age‐appropriate levels of MTA. In the amyloid‐positive group, 18% had no abnormal MTA or PA scores. These findings were substantially affected by cut‐off selection. Amyloid‐positive and amyloid‐negative patients had comparable hippocampal and parietal volumes, and MTA but not PA scores correlated with the respective volumetric measures. Interpretation: Consensus guidelines are needed before VRS can be recommended for use in the diagnostic workup of AD. Our data are suggestive of high intragroup variability and non‐superiority of volumetric quantification of atrophy over visual assessment. [ABSTRACT FROM AUTHOR]

Background: Depression has been suggested to be a cause of reversible cognitive impairment but also a risk factor for neurodegenerative disease. Studies suggest that depression prevalence may be high in early onset dementia, particularly Alzheimer's disease, but this has not been systematically assessed in a biomarker-validated clinical dementia cohort to date.Objective: To examine the prevalence, features, and association with amyloid pathology of lifetime depressive symptoms in a memory clinic cohort meeting appropriate use criteria for amyloid PET imaging.Methods: We included 300 patients from a single-center memory clinic cohort that received diagnostic biomarker evaluation with amyloid PET imaging according to appropriate use criteria. History of lifetime depressive symptoms was retrospectively assessed through structured review of clinical correspondence.Results: One hundred forty-two (47%) patients had a history of significant depressive symptoms ('D+'). Of these, 89% had ongoing symptoms and 60% were on antidepressants at the time of presentation to our Clinic. Depressive symptoms were equally highly prevalent in the amyloid-positive and the heterogeneous group of amyloid-negative patients.Conclusion: Approximately half of patients who meet appropriate use criteria for amyloid PET have a history of depressive symptoms. We suggest that depression is an important feature of both neurodegenerative and non-neurodegenerative cognitive impairment and may contribute to the diagnostic uncertainty behind referral to amyloid PET. [ABSTRACT FROM AUTHOR]

Systems vaccinology has been applied to detect signatures of human vaccine induced immunity but its ability, together with high definition in vivo clinical imaging is not established to predict vaccine reactogenicity. Within two European Commission funded high impact programs, BIOVACSAFE and ADITEC, we applied high resolution positron emission tomography/computed tomography (PET/CT) scanning using tissue-specific and non-specific radioligands together with transcriptomic analysis of muscle biopsies in a clinical model systematically and prospectively comparing vaccine-induced immune/inflammatory responses. 109 male participants received a single immunization with licensed preparations of either AS04-adjuvanted hepatitis B virus vaccine (AHBVV); MF59C-adjuvanted (ATIV) or unadjuvanted seasonal trivalent influenza vaccine (STIV); or alum-OMV-meningococcal B protein vaccine (4CMenB), followed by a PET/CT scan (n = 54) or an injection site muscle biopsy (n = 45). Characteristic kinetics was observed with a localized intramuscular focus associated with increased tissue glycolysis at the site of immunization detected by 18F-fluorodeoxyglucose (FDG) PET/CT, peaking after 1–3 days and strongest and most prolonged after 4CMenB, which correlated with clinical experience. Draining lymph node activation peaked between days 3–5 and was most prominent after ATIV. Well defined uptake of the immune cell-binding radioligand 11C-PBR28 was observed in muscle lesions and draining lymph nodes. Kinetics of muscle gene expression module upregulation reflected those seen previously in preclinical models with a very early (~6hrs) upregulation of monocyte-, TLR- and cytokine/chemokine-associated modules after AHBVV, in contrast to a response on day 3 after ATIV, which was bracketed by whole blood responses on day 1 as antigen presenting, inflammatory and innate immune cells trafficked to the site of immunization, and on day 5 associated with activated CD4+ T cells. These observations confirm the use of PET/CT, including potentially tissue-, cell-, or cytokine/chemokine-specific radioligands, is a safe and ethical quantitative technique to compare candidate vaccine formulations and could be safely combined with biopsy to guide efficient collection of samples for integrated whole blood and tissue systems vaccinology in small-scale but intensive human clinical models of immunization and to accelerate clinical development and optimisation of vaccine candidates, adjuvants, and formulations. [ABSTRACT FROM AUTHOR]

Amyloid positron emission tomography (PET) imaging enables in vivo detection of brain Aβ deposition, one of the neuropathological hallmarks of Alzheimer's disease. There is increasing evidence to support its clinical utility, with major studies showing that amyloid PET imaging improves diagnostic accuracy, increases diagnostic certainty and results in therapeutic changes. The Amyloid Imaging Taskforce has developed appropriate use criteria to guide clinicians by predefining certain scenarios where amyloid PET would be justified. This review provides a practical guide on how and when to use amyloid PET, based on the available research and our own experience. We discuss its three main appropriate indications and illustrate these with clinical cases. We stress the importance of a multidisciplinary approach when deciding who might benefit from amyloid PET imaging. Finally, we highlight some practical points and common pitfalls in its interpretation. [ABSTRACT FROM AUTHOR]

Background: Patterns of atrophy in the brain highly differ between individual Alzheimer's Disease (AD) patients, however, most clinical research focuses on group‐level differences (Verdi et al., 2021). Here we used a novel technique, neuroanatomical normative modelling, to reveal individual patterns of cortical thickness by quantifying deviations from the normative range. We applied a hierarchical Bayesian regression (HBR) normative model (Kia et al., 2021), to amyloid‐positive AD patients who had clinical amyloid PET imaging at the Imperial Memory Clinic (IMC). Patients had either AD dementia or mild cognitive impairment due to AD. We hypothesised that there would be individual differences in patterns of cortical atrophy in these patients. Method: Cortical thickness across 148 regions of interest (ROIs) was generated using FreeSurfer from n=130 (102 AD patients and 28 healthy controls) T1‐weighted MRIs acquired from the IMC. A reference HBR normative model was trained on a separate dataset of n=34,490 healthy individuals to index population variability, which predicted cortical thickness at each ROI using age and sex. This generated cortical thickness z‐scores for each ROI, per patient (z‐score < ‐1.96 = outlier). Result: The patterns of cortical atrophy outliers were highly varied in amyloid‐positive AD patients. For instance, the largest proportion of outliers in a region was 60% within the superior temporal sulci, if atrophy were homogenous we would expect 100% of outliers to be here (Fig.1). This heterogeneity was also seen when comparing how similar outlier patterns were between patients (Fig.2). We also found that the proportions of outliers differ according to disease severity, e.g. the highest percentage of outliers was 70% within superior temporal sulci within the AD dementia subgroup, and 50% in superior temporal sulci in the mild cognitive impairment due to AD subgroup (Fig.3). Conclusion: Amyloid‐positivity results in heterogenous patterns of cortical atrophy. This is more pronounced in AD dementia, though still present in people with mild cognitive impairment due to AD. Neuroanatomical normative maps have the potential to be individualised markers of disease, and with application to longitudinal data could track individual disease progression. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether lesions in human TB are hypoxic or whether this influences disease pathology. Human TB is characterised by extensive lung destruction driven by host matrix metalloproteinases (MMPs), particularly collagenases such as matrix metalloproteinase-1 (MMP-1).Methods: We investigated tissue hypoxia in five patients with PET imaging using the tracer [18F]-fluoromisonidazole ([18F]FMISO) and by immunohistochemistry. We studied the regulation of MMP secretion in primary human cell culture model systems in normoxia, hypoxia, chemical hypoxia and by small interfering RNA (siRNA) inhibition.Results: [18F]FMISO accumulated in regions of TB consolidation and around pulmonary cavities, demonstrating for the first time severe tissue hypoxia in man. Patlak analysis of dynamic PET data showed heterogeneous levels of hypoxia within and between patients. In Mycobacterium tuberculosis (M.tb)-infected human macrophages, hypoxia (1% pO2) upregulated MMP-1 gene expression 170-fold, driving secretion and caseinolytic activity. Dimethyloxalyl glycine (DMOG), a small molecule inhibitor which stabilises the transcription factor hypoxia-inducible factor (HIF)-1α, similarly upregulated MMP-1. Hypoxia did not affect mycobacterial replication. Hypoxia increased MMP-1 expression in primary respiratory epithelial cells via intercellular networks regulated by TB. HIF-1α and NF-κB regulated increased MMP-1 activity in hypoxia. Furthermore, M.tb infection drove HIF-1α accumulation even in normoxia. In human TB lung biopsies, epithelioid macrophages and multinucleate giant cells express HIF-1α. HIF-1α blockade, including by targeted siRNA, inhibited TB-driven MMP-1 gene expression and secretion.Conclusions: Human TB lesions are severely hypoxic and M.tb drives HIF-1α accumulation, synergistically increasing collagenase activity which will lead to lung destruction and cavitation. [ABSTRACT FROM AUTHOR]

Objective. The objective was to assess body surface area (BSA) for scaling extracellular fluid volume (ECV) in comparison with estimated lean body mass (LBM) and total body water (TBW) across a range of body mass indices (BMI). Methods. This was a multi-centre study from 15 centres that submitted raw data from routine measurement of GFR in potential kidney transplant donors. There were 819 men and 1059 women in total. ECV was calculated from slope-intercept and slope-only measurements of GFR. ECV was scaled using two methods: Firstly, division of ECV by the scaling variable (ratio method), and secondly the regression method of Turner and Reilly. Subjects were placed into five BMI groups: < 20, 20-24.9, 25-29.9, 30-34.9, and 35 + kg/m2. LBM and TBW were estimated from previously published, gender-specific prediction equations. Results. Ratio and regression scaling gave almost identical results. ECV scaled to BSA by either method was higher in men in all BMI groups but ECV scaled to LBM and TBW was higher in women. There was, however, little difference between men and women in respect to ECV per unit weight in any BMI group, even though women have 10% more adipose tissue. The relations between TBW and BSA and between LBM and BSA, but not between LBM and TBW, were different between men and women. Conclusion. Lean tissue in women contains more extracellular water than in men, a difference that is obscured by scaling to BSA. The likely problem with BSA is its insensitivity to body composition. [ABSTRACT FROM AUTHOR]

Background: The early cognitive profile of Alzheimer's Disease (AD) is typically characterised by predominant impairment in episodic memory, reflecting medial temporal lobe dysfunction. However, little is known about the cognitive profile associated with AD pathology in those patients who meet Appropriate Use Criteria (AUC, Johnson et al., 2013) for Amyloid PET Imaging (API). In this group, AD pathology is frequently associated with an atypical clinical course or presentation. Here, we systematically evaluate the cognitive profiles of AUC‐meeting patients in a real‐world clinical setting, combining the information provided by the neuropsychological assessment with the results of Amyloid PET Imaging. Method: From a larger sample of 396 patients who underwent Amyloid PET at the Imperial Memory Centre between December 2013 and June 2019, we included those individuals who also had at least one formal neuropsychological assessment (minimum of 4 tests) within 18 months of API (n=124). Both these were solely conducted for clinical purposes, and API was requested after multidisciplinary team discussion. Cognitive measures in amyloid positive (Aβ+) and negative (Aβ‐) patients were compared using non‐parametric tests. Results: Neuropsychological assessment preceded Amyloid PET Imaging in most cases, for both amyloid‐positive (n=51, mean age 67.24±9.32 years, 58.8% female) and amyloid‐negative (n=73, mean age 67.9±9.64 years, 41.1% female) groups. Cognitive performance in the amyloid‐positive group was significantly worse in 6 of the 14 cognitive measures taken into account: visuo‐spatial functioning, executive functioning, working memory, verbal learning, verbal delayed recall, and confrontation naming (Figure 1). Verbal learning, verbal delayed recall and confrontation naming were the most frequently impaired measures in the amyloid‐positive group, with around 50% of patients performing below 2 standard deviations. Notably, self‐reported symptoms of depression were significantly higher in the amyloid‐negative (7.3±4.38) than in the amyloid‐positive group (4.68±3.7) (p=.002) (Figure 2). Conclusions: In a sample of patients attending a tertiary Behavioural Neurology clinic, neuropsychological evaluation revealed worse performance in positive API across a range of domains, particularly verbal memory and confrontation naming, with higher rates of symptoms of depression being reported more frequently in the amyloid negative group. [ABSTRACT FROM AUTHOR]

Background: The link between late‐life depression and Alzheimer's disease (AD) has long been investigated, however it is still unclear whether depression acts as a risk factor, a prodromal feature or a comorbid condition in AD. Clarifying the nature of this link has important implications in the early intervention and diagnosis of AD. The relatively recent introduction of in‐vivo brain biomarkers for AD pathology offers the chance to explore the relationship between depression and pathologically‐confirmed neurodegeneration. Here, we examined the association among objective cognitive functioning, self‐reported cognitive failures and AD pathology in patients with late‐life depression. Method: Sixty‐three older adults with no formal diagnosis of cognitive impairment underwent a comprehensive cognitive assessment and Amyloid‐PET Imaging at the Imperial Memory Unit. Participants were classified into two groups, according to the presence (n=33, mean age=71.82 ±4.98) or absence (n=30, mean age=71.30 ±5.80) of late‐life depression. Late‐life depression was confirmed through validated questionnaires (GDS ≥ 6 and/or HDRS ≥ 12) and medical history review. Amyloid‐PET images were qualitatively read as amyloid positive or amyloid negative by two experienced nuclear medicine radiologists (NMRs). Equivocal scans (6%) were read by a third independent NMR. Cognitive data in the two groups were compared using non‐parametric tests. Results: Amyloid status did not differ significantly between the two groups (p=.367), with 3 (9%) depressed and 5 (17%) non‐depressed participants reported as amyloid‐positive. Despite higher levels of self‐reported cognitive failures (p<.001), the depressed group did not differ from the non‐depressed group in a global measure of cognition (MMSE depressed: 28.09±1.69; non‐depressed: 28.93±4.66) and showed worse performance in 4 (Word List short‐delay recall, Digit Span backward and forward, Coding) of the 17 cognitive measures administered. Follow up data, currently being collected at our Unit, will add information about the long‐term trajectory of cognition in late life depression. Conclusions: In our sample, depressive symptoms were associated with a limited number of cognitive measures but not with AD pathology. This suggests that depression seems to have a limited role in the early diagnosis of AD. Future studies should examine the role of specific features of depression and of other widespread neuropsychiatric symptoms (e.g., anxiety) in AD. [ABSTRACT FROM AUTHOR]

Background: The clinical use of amyloid‐PET imaging (API) is guided by a set of published appropriate use criteria (Johnson et al., 2013). Patients meeting these criteria have suspected Alzheimer's Disease (AD) accompanied by an atypical clinical presentation leading to substantial diagnostic uncertainty. Previous large‐cohort studies have investigated this clinical population from a diagnostic standpoint, looking at the impact of using amyloid‐PET to elucidate the aetiology of impairment. However, data concerning their clinical phenotypes is lacking. In this study, we investigated the prevalence of depression and its association with Alzheimer's pathology in Memory Clinic patients who received clinical API. Method: We reviewed the clinical records of 185 older adults (mean age 67.09±9.35, 49% females) who were assessed in our Clinic between January 2017 and June 2019 and received API. Referral to amyloid‐PET followed a multidisciplinary meeting and was in line with appropriate use criteria. Patients were categorised as 'D+', with history of depression, if they had received a previous depression diagnosis and/or if they had a history of depressive symptoms. Overall depression prevalence was compared with published cohort data. Amyloid‐PET results (positive versus negative) were compared between the D+ and the D‐ (without history of depression) groups. In D+ patients, we determined the onset and status of depressive symptoms. Result: Of 185 patients, 98 (53%) had a history of depression. Of these, 89 individuals had ongoing symptoms at the time of referral to our Clinic and 59 of them were on antidepressants. The mean age of depression onset was 58.25(±12.25) years. Depression prevalence in this cohort was considerably higher than that generally seen in memory clinics (20%; Knapskog et al., 2014) and in healthy older adults (19%; McDougall et al.,2017). Depression history was not associated with amyloid‐PET results (%positive: D+ 39.8%, D‐ 50.6%, χ2(1)=2.16 p=.14), age (mean±SD: D+ 66.47±9.03 years, D‐ 67.79±9.71 years, t(183)=‐.95 p=.342), or sex (%female: D+ 44.9%, D‐ 52.9%, χ2(1)=.1.17 p=.304). Conclusion: Depression prevalence is high in patients referred for clinical amyloid‐PET imaging and is independent of the presence or absence of Alzheimer's pathology. Depression may be one of the key contributors to diagnostic uncertainty in this group. [ABSTRACT FROM AUTHOR]

To compare commercially available image analysis tools Hermes BRASS and Siemens Syngo.VIA with clinical assessment in 18F-Florbetapir PET scans 225 scans were reported by clinicians and quantified using two software packages. Scans were classified into Type A (typical features) or non-Type A (atypical features) for both positive and negative scans. For BRASS, scans with z-score ≥ 2 in 2 ≥ region of interest were classed positive. For Syngo.VIA a positive scan was indicated when mean cortical standardized uptake value ratio (mcSUVR) ≥ 1.17. 81% scans were Type A, and 19% scans were non-Type A. The sensitivity of BRASS and Syngo.VIA for Type A scans was 98.8 and 96.3%, specificity was 73 and 92%, respectively. Sensitivity for non-Type A scans was 95.8 and 79.2%, specificity was 36.8 and 57.9%, respectively. A third threshold of identifiable levels of plaque (1.08 ≤ mcSUVR ≤ 1.17) was recommended for Syngo.VIA to increase detection of false negative scans. The false positive rate of BRASS significantly decreased when an alternative positive threshold value of mcSUVR ≥ 1.18. Introduction of alternative criteria did not improve prediction outcome for non-Type A scans. More complex solutions are recommended. Hermes criteria for a positive scan leads to a high sensitivity but a low specificity. Siemens Syngo.VIA criteria gives a high sensitivity and specificity and agrees better with the clinical report. Alternative thresholds and classifications may help to improve agreement with the clinical report. Software packages may assist with clinical reporting of more difficult to interpret cases that require a more experienced read. [ABSTRACT FROM AUTHOR]

This study investigates the usefulness of quantitative SUVR thresholds on sub types of typical (type A) and atypical (non-type A) positive (Aβ+) and negative (Aβ-) 18F-florbetapir scans and aims to optimise the thresholds. Clinical 18F-florbetapir scans (n = 100) were categorised by sub type and visual reads were performed independently by three trained readers. Inter-reader agreement and reader-to-reference agreement were measured. Optimal SUVR thresholds were derived by ROC analysis and were compared with thresholds derived from a healthy control group and values from published literature. Sub type division of 18F-florbetapir PET scans improves accuracy and agreement of visual reads for type A: accuracy 90%, 96% and 70% and agreement κ > 0.7, κ ≥ 0.85 and −0.1 < κ < 0.9 for all data, type A and non-type A respectively. Sub type division also improves quantitative classification accuracy of type A: optimum mcSUVR thresholds were found to be 1.32, 1.18 and 1.48 with accuracy 86%, 92% and 76% for all data, type A and non-type A respectively. Aβ+/Aβ- mcSUVR threshold of 1.18 is suitable for classification of type A studies (sensitivity = 97%, specificity = 88%). Region-wise SUVR thresholds may improve classification accuracy in non-type A studies. Amyloid PET scans should be divided by sub type before quantification. We have derived and validated mcSUVR thresholds for Aβ+/Aβ- 18F-florbetapir studies. This work demonstrates that division into sub types improves reader accuracy and agreement and quantification accuracy in scans with typical presentation and highlights the atypical presentations not suited to global SUVR quantification. [ABSTRACT FROM AUTHOR]

The number of people living with dementia is increasing, but as yet there remains no cure or disease-modifying treatment. This review aims to help readers understand the role of 18F-FDG PET/CT imaging in the investigation of cognitive impairment and how the advent of amyloid PET/CT imaging may hold the key to radically changing management of the most common form of dementia - Alzheimer's disease. The indications for 18F-FDG PET/CT and amyloid PET/CT imaging in cognitive impairment are outlined. Additionally, the mechanisms of action, technique, patient preparation and acquisition parameters for both are detailed. We conclude by providing a framework for interpreting 18F-FDG PET/CT and amyloid PET/CT imaging in the more common conditions that lead to cognitive impairment conditions with tips on avoiding pitfalls in interpretation. [ABSTRACT FROM AUTHOR]