Comparison of patients with benzodiazepine receptor agonist-related psychiatric disorders and over-the-counter drug-related psychiatric disorders before and after the COVID-19 pandemic: Changes in psychosocial characteristics and types of abused drugs.

AIM: To investigate changes in the clinical characteristics of patients who abused benzodiazepine receptor agonists (BZRA) or over-the-counter (OTC) drugs before and after COVID-19 based on the 2018 and 2022 data of the "Nationwide Psychiatric Hospital (NPH) Survey on Drug-related Psychiatric Disorders." METHOD: A total of 446 and 155 cases, and 435 and 273 cases, who mainly abused BZRAs or OTC drugs, respectively, were extracted from the database of the two NPH Surveys. Demographic variables, education, employment, criminal record, drug use during the previous year, psychiatric diagnosis, and types of abused drugs were compared between 2018 and 2022. RESULT: A comparison of BZRA abusers revealed a decreased number of users during the previous year and an increase in the comorbidity rate of other disorders (F3 and F4 in ICD-10) in 2022. Etizolam, flunitrazepam, triazolam, and zolpidem were used most in both years, with an increase in zolpidem and a decrease in triazolam in 2022. A comparison of OTC drug abusers revealed a higher proportion of women and young patients in 2022. An increase in the comorbidity rate of F3 and F9 and a significant increase in the use of dextromethorphan products were observed in 2022, although codeine products were in the majority in both years. CONCLUSION: By comparing NPH Surveys before and after the COVID-19 pandemic, both BZRA abusers and OTC drug abusers present complex pathologies, requiring tailor-made treatment. The younger OTC drug abusers were particularly evident among women, and the abuse of dextromethorphan-containing OTC drugs has increased alarmingly.

Development of software for measuring brain amyloid accumulation using 18 F-florbetapir PET and calculating global Centiloid scale and regional Z-score values.

BACKGROUND AND PURPOSE: Quantitative measures have been proposed to aid the visual interpretation of amyloid PET. Our objective was to develop and validate quantitative software that enables calculation of the Centiloid (CL) scale and Z-score for amyloid PET with 18 F-florbetapir. METHODS: This software was developed as a toolbox in statistical parametric mapping 12 running on MATLAB Runtime. For each participant's amyloid PET, this software calculates the CL scale using the standard MRI-guided pipeline proposed by the Global Alzheimer's Association Interactive Network (GAAIN) and generates a Z-score map for comparison with a new amyloid-negative database constructed from 20 healthy controls. In 23 cognitively impaired patients with suspected Alzheimer's disease, Z-score values for a target cortical area from the new database were compared with those from the GAAIN database constructed from 13 healthy controls. The CL values obtained using low-dose CT of PET/CT equipment were then compared with those obtained using MRI. RESULTS: The CL calculation was validated with the 18 F-florbetapir dataset in the GAAIN repository. Z-score values obtained from the new database were significantly higher (mean ± standard deviation, 1.05 ± 0.77; p < .0001) than those obtained from the GAAIN database. The use of low-dose CT provided CL scales that were highly correlated with those obtained with MRI (R2  = .992) but showed a slight yet significant underestimation (-2.1 ± 4.2; p = .013). CONCLUSIONS: Our quantification software provides the CL scale and Z-score for measuring overall and local amyloid accumulation with the use of MRI or low-dose CT.

Age and Sex-Related Effects on Single-Subject Gray Matter Networks in Healthy Participants.

Recent developments in image analysis have enabled an individual's brain network to be evaluated and brain age to be predicted from gray matter images. Our study aimed to investigate the effects of age and sex on single-subject gray matter networks using a large sample of healthy participants. We recruited 812 healthy individuals (59.3 ± 14.0 years, 407 females, and 405 males) who underwent three-dimensional T1-weighted magnetic resonance imaging. Similarity-based gray matter networks were constructed, and the following network properties were calculated: normalized clustering, normalized path length, and small-world coefficients. The predicted brain age was computed using a support-vector regression model. We evaluated the network alterations related to age and sex. Additionally, we examined the correlations between the network properties and predicted brain age and compared them with the correlations between the network properties and chronological age. The brain network retained efficient small-world properties regardless of age; however, reduced small-world properties were observed with advancing age. Although women exhibited higher network properties than men and similar age-related network declines as men in the subjects aged < 70 years, faster age-related network declines were observed in women, leading to no differences in sex among the participants aged ≥ 70 years. Brain age correlated well with network properties compared to chronological age in participants aged ≥ 70 years. Although the brain network retained small-world properties, it moved towards randomized networks with aging. Faster age-related network disruptions in women were observed than in men among the elderly. Our findings provide new insights into network alterations underlying aging.

The Effects of Citalopram and Thalamic Dopamine D2/3 Receptor Availability on Decision-Making and Loss Aversion in Alcohol Dependence.

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for patients who misuse alcohol, especially in the context of comorbid depressive symptoms. Deficits in impulse control and decision-making are linked to routine alcohol consumption and alcohol dependence. The goal of this study was to determine the effects of a single dose of citalopram on measures of impulsivity, decision-making, and/or brain dopamine receptor availability in alcohol-dependent individuals. A double-blind, placebo-controlled, within-subject, outpatient study was conducted with active alcohol-dependent (DSM-IV-TR criteria) participants (n = 12) and matched healthy controls (n = 13). Serial doses of both citalopram (40 mg) and saline were administered intravenously before laboratory tests of decision-making (Balloon Analogue Risk Task, delay discounting task, and Loss Aversion Gambling Task) and positron emission tomography with [18F]-fallypride to measure dopamine D2/3 receptor availability, separated by at least one week. Alcohol-dependent participants demonstrated greater loss aversion than healthy controls, but there were no group differences in risk taking on the Balloon Analogue Risk Task. Citalopram increased delay discounting across groups, with no group difference in the effect. There were no effects of citalopram on risk taking on the Balloon Analogue Risk Task. PET showed a negative correlation between thalamic dopamine D2/3 receptor availability and loss aversion across groups. The effect of citalopram to decrease the valuation of monetary reward as a function of delay raises the possibility that SSRIs can influence risky decision-making in clinical populations. In addition, these results suggest that altered thalamic dopamine signaling may play an important role in disproportionately valuing losses in patients with Alcohol Use Disorder. This trial is registered under ClinicalTrials.gov registration NCT01657760.

Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer's disease: a multicenter study.

OBJECTIVE: Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of amyloid PET imaging is still under investigation. The aim of this study was to evaluate the diagnostic impact and clinical utility in patient management of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also aimed to determine the cutoffs for amyloid positivity for quantitative measures by investigating the agreement between quantitative and visual assessments. METHODS: Ninety-nine patients suspected of having AD underwent 18F-florbetapir PET at five institutions. Site-specialized physicians provided a diagnosis of AD or non-AD with a percentage estimate of their confidence and their plan for patient management in terms of medication, prescription dosage, additional diagnostic tests, and care planning both before and after receiving the amyloid imaging results. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by four board-certified nuclear medicine physicians. The PET images were also quantitatively analyzed using the standardized uptake value ratio (SUVR) and Centiloid (CL) scale. RESULTS: Visual interpretation obtained 48 positive and 51 negative PET scans. The amyloid PET results changed the AD and non-AD diagnosis in 39 of 99 patients (39.3%). The change rates of 26 of the 54 patients (48.1%) with a pre-scan AD diagnosis were significantly higher than those of 13 of the 45 patients with a pre-scan non-AD diagnosis (χ2 = 5.334, p = 0.0209). Amyloid PET results also resulted in at least one change to the patient management plan in 42 patients (42%), mainly medication (20 patients, 20%) and care planning (25 patients, 25%). Receiver-operating characteristic analysis determined the best agreement of the quantitative assessments and visual interpretation of PET scans to have an area under the curve of 0.993 at an SUVR of 1.19 and CL of 25.9. CONCLUSION: Amyloid PET using 18F-florbetapir PET had a substantial clinical impact on AD and non-AD diagnosis and on patient management by enhancing diagnostic confidence. In addition, the quantitative measures may improve the visual interpretation of amyloid positivity.

Free water derived by multi-shell diffusion MRI reflects tau/neuroinflammatory pathology in Alzheimer's disease.

Introduction: Free-water (FW) imaging, a new analysis method for diffusion magnetic resonance imaging (MRI), can indicate neuroinflammation and degeneration. We evaluated FW in Alzheimer's disease (AD) using tau/inflammatory and amyloid positron emission tomography (PET). Methods: Seventy-one participants underwent multi-shell diffusion MRI, 18F-THK5351 PET, 11C-Pittsburgh compound B PET, and neuropsychological assessments. They were categorized into two groups: healthy controls (HCs) (n = 40) and AD-spectrum group (AD-S) (n = 31) using the Centiloid scale with amyloid PET and cognitive function. We analyzed group comparisons in FW and PET, correlations between FW and PET, and correlation analysis with neuropsychological scores. Results: In AD-S group, there was a significant positive correlation between FW and 18F-THK5351 in the temporal lobes. In addition, there were negative correlations between FW and cognitive function in the temporal lobe and cingulate gyrus, and negative correlations between 18F-THK5351 and cognitive function in the same regions. Discussion: FW imaging could be a biomarker for tau in AD alongside clinical correlations.

Dopamine dysfunction in depression: application of texture analysis to dopamine transporter single-photon emission computed tomography imaging.

Dopamine dysfunction has been associated with depression. However, results of recent neuroimaging studies on dopamine transporter (DAT), which reflect the function of the dopaminergic system, are inconclusive. The aim of this study was to apply texture analysis, a novel method to extract information about the textural properties of images (e.g., coarseness), to single-photon emission computed tomography (SPECT) imaging in depression. We performed SPECT using 123I-ioflupane to measure DAT binding in 150 patients with major depressive disorder (N = 112) and bipolar disorder (N = 38). The texture features of DAT binding in subregions of the striatum were calculated. We evaluated the relationship between the texture feature values (coarseness, contrast, and busyness) and severity of depression, and then examined the effects of medication and diagnosis on such relationship. Furthermore, using the data from 40 healthy subjects, we examined the effects of age and sex on the texture feature values. The degree of busyness of the limbic region in the left striatum linked to the severity of depression (p = 0.0025). The post-hoc analysis revealed that this texture feature value was significantly higher in both the severe and non-severe depression groups than in the remission group (p = 0.001 and p = 0.028, respectively). This finding remained consistent after considering the effect of medication. The effects of age and sex in healthy individuals were not evident in this texture feature value. Our findings imply that the application of texture analysis to DAT-SPECT may provide a state-marker of depression.

Potential Treat-to-Target Approach for Methamphetamine Use Disorder: A Pilot Study of Adenosine 2A Receptor Antagonist With Positron Emission Tomography.

Introduction: The misuse of stimulant drugs such as methamphetamine is a global public health issue. One important neurochemical mechanism of methamphetamine use disorder may be altered dopaminergic neurotransmission. For instance, previous studies using positron emission tomography (PET) have consistently shown that striatal dopamine D2-type receptor availability (quantified as binding potential; BPND) is lower in methamphetamine use disorder. Further, methamphetamine use is known to induce chronic neuroinflammation through multiple physiological pathways. Upregulation of D2-type receptor and/or attenuation of neuroinflammation may therefore provide a therapeutic effect for this disorder. In vitro studies have shown that blockage of adenosine 2A (A2A) receptors may prevent D2-receptor downregulation and neuroinflammation-related brain damage. However, no study has examined this hypothesis yet. Methods and Analysis: Using a within-subject design, this trial will assess the effect of the selective A2A receptor antagonist, istradefylline, primarily on D2-type BPND in the striatum, and secondarily on neuroinflammation in the whole brain in individuals with methamphetamine use disorder. The research hypotheses are that istradefylline will increase striatal D2-type BPND and attenuate neuroinflammation. Twenty participants with methamphetamine use disorder, aged 20-65, will be recruited to undergo [11C]raclopride PET (for every participant) and [11C]DAA1106 PET (if applicable) once before and once after administration of 40 mg/day istradefylline for 2 weeks. Neuropsychological measurements will be performed on the same days of the PET scans.

Amyloid PET quantification using low-dose CT-guided anatomic standardization.

BACKGROUND: Centiloid (CL) scaling has become a standardized quantitative measure in amyloid PET because it facilitates the direct comparison of results across institutions, even when different analytical methods or tracers are used. Standard volumes of interest must be used to calculate the CL scale after the anatomic standardization of amyloid PET images using coregistered MRI; if the MRI is unavailable, the CL scale cannot be accurately calculated. This study sought to determine the substitutability of low-dose CT, which is used to correct PET attenuation in PET/CT equipment, by evaluating the measurement accuracy when low-dose CT is used as an alternative to MRI in the calculation of the CL scale. Amyloid PET images obtained using 18F-flutemetamol from 24 patients with possible or probable Alzheimer's disease were processed to calculate the CL scale using 3D T1-weighted MRI and low-dose CT of PET/CT. CLMRI and CLCT were, respectively, defined as the use of MRI and CT for anatomic standardization and compared. Regional differences in the CT-based and MRI-based standardized anatomic images were also investigated. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031180321 (registered 18 March 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031180321 ). RESULTS: A Bland-Altman plot showed that CLCT was slightly but significantly underestimated (mean ± standard deviation, - 1.7 ± 2.4; p < 0.002) compared with CLMRI. The 95% limits of agreement ranged from - 2.8 to - 0.7. Pearson correlation analysis showed a highly significant correlation of r = 0.998 between CLCT and CLMRI (p < 0.001). The linear regression equation was CLMRI = 1.027 × CLCT + 0.762. In a Bland-Altman plot, Spearman correlation analysis did not identify a significant association between the difference in CLMRI versus CLCT and CL load (ρ = - 0.389, p = 0.060). This slight underestimation of CLCT may derive from slightly higher uptake when the cerebellum is used as a reference area in CT-based anatomically standardized PET images versus MRI-based images. CONCLUSIONS: Low-dose CT of PET/CT can substitute for MRI in the anatomic standardization used to calculate the CL scale from amyloid PET, although a slight underestimation occurs.

Effects of an Adenosine A2A Receptor Antagonist on Striatal Dopamine D2-Type Receptor Availability: A Randomized Control Study Using Positron Emission Tomography.

Introduction: Altered dopaminergic neurotransmission, especially in the functioning of dopamine D2-type receptors, is considered central to the etiology of a variety of neuropsychiatric disorders. In particular, individuals with substance use disorders have been consistently observed to exhibit lower D2-type receptor availability (quantified as binding potential; BPND) using positron emission tomography (PET). Upregulation of D2-type receptor density thus may therefore provide a therapeutic effect for substance use disorders. Importantly, in vitro studies reveal that D2 receptors coexist with adenosine 2A (A2A) receptors to form the highest density of heteromers in the whole striatum, and there is a functional interaction between these two receptors. As such, blockade of A2A receptor's function may prevent D2 receptor downregulation, yet no study has currently examined this hypothesis in humans. Methods and Analysis: This double-blind, randomized controlled trial aims to evaluate the effect of the A2A receptor antagonist istradefylline (compared to placebo) on both dopamine D2-type receptor availability in the human brain and on neuropsychological measurements of impulsivity. It is hypothesized that istradefylline will both increase striatal D2-type BPND and improve control of impulsivity more than placebo. Forty healthy participants, aged 20-65 with no history of psychiatric or neurological disorders, will be recruited and randomized into two groups and will undergo [11C]raclopride PET, once before and once after administration of either 40 mg/day istradefylline or placebo for 2 weeks. Neuropsychological measurements will be administered on the same days of the PET scans. Ethics and Dissemination: The study protocol was approved by the Certified Review Boards (CRB) of National Center of Neurology and Psychiatry (CR18-011) and prospectively registered with the Japan Registry of Clinical Trials (jRCTs031180131; https://jrct.niph.go.jp/latest-detail/jRCTs031180131). The findings of this study will be disseminated through peer reviewed scientific journals and conferences. Clinical Trial Registration:www.ClinicalTrials.gov, identifier jRCTs031180131.

Striatal dopamine D2-type receptor availability and peripheral 17ß-estradiol.

Research using rodent models has established a relationship between the steroid hormone estrogen and dopamine function, by revealing changes throughout the estrous cycle and by directly manipulating neuroendocrine signaling through ovariectomy and administration of estrogen. However, a direct link between estrogen levels and dopamine signaling had not been established in humans. The goal of this study, therefore, was to assess the relationship between circulating 17ß-estradiol and dopamine signaling in the human brain by testing for a relationship between two proxies for these variables: peripheral 17ß-estradiol and striatal dopamine D2-type receptor availability, measured with [18F]fallypride and positron emission tomography (PET). Sixteen (23-45 years of age) women were tested on 2 days of the menstrual cycle estimated prospectively to occur during (a) the early follicular phase, when estrogen levels are near their nadir, and (b) the periovulatory phase, when estrogen levels peak. PET scans with [18F]fallypride were performed on these 2 days, and serum 17ß-estradiol was measured using radioimmunoassay. Dopamine D2-type receptor availability did not differ significantly in the whole striatum or the caudate, putamen, or accumbens subregions during the high-estrogen vs. the low-estrogen phases of the menstrual cycle. We conclude that circulating estrogen levels do not affect dopamine D2-type receptor availability in the human striatum although other indices of dopaminergic function may be affected.

Gray matter structural networks related to 18F-THK5351 retention in cognitively normal older adults and Alzheimer's disease patients.

OBJECTIVE: This study aimed to examine the alterations in gray matter networks related to tau retention in Alzheimer's disease (AD) patients and cognitively normal (CN) older individuals. METHODS: Eighteen amyloid-positive AD patients and 30 age- and sex-matched amyloid-negative CN controls were enrolled. All underwent 3D T1-weighted MRI, amyloid positron-emission tomography imaging (PET) with 11C-Pittsburgh Compound B (PiB), and tau PET with 18F-THK5351. The structural networks extracted from the T1-weighted MRI data based on cortical similarities within single subjects were analyzed. Based on graph theoretical approach, global and local network properties across the whole brain were computed. Group comparisons of global and local network properties were evaluated between the groups. Then, we correlated the global and local network measures with total cerebral 18F-THK5351 retention. RESULTS: AD patients moved toward more randomized global network compared to controls and regional differences were observed in the default mode network (DMN) area. No significant correlations existed between global network properties and tau retention. On a local level, AD and controls showed opposite relationships between network properties and tau retention mainly in the DMN areas; CN controls showed positive correlations, whereas AD showed negative correlations. CONCLUSION: We found opposite relationships between local network properties and tau retention between amyloid-positive AD patients and amyloid-negative controls. Our findings suggest that the presence of amyloid and induced exacerbated tau retention alter the relationship of local network properties and tau retention.

Association between neurite metrics and tau/inflammatory pathology in Alzheimer's disease.

INTRODUCTION: The molecular mechanism of neurodegeneration, including tau and neurite complexity, is an important topic in Alzheimer's disease (AD) research. METHODS: We recruited 27 amyloid-positive individuals identified through 11C-Pittsburgh compound B (PiB) positron emission tomography (PET) and 31 amyloid-negative individuals with normal cognition. All participants underwent 11C-PiB and 18F-THK5351 PET and magnetic resonance imaging (MRI) with neurite orientation dispersion and density imaging (NODDI) protocol. The neurite density index (NDI), orientation dispersion index (ODI), and PET images were analyzed to calculate voxel-wise correlations among the imaging modalities and correlations with cognitions. RESULTS: In the amyloid-positive participants, there were significant negative correlations between 18F-THK5351 and NDI and between 18F-THK5351 and ODI. The bilateral mesial and lateral temporal lobes were mainly involved. Regarding cognition, 18F-THK5351 showed more marked associations with all cognitive domains than the other modalities. DISCUSSION: Tau and neuroinflammation in AD may reduce the neurite density and orientation dispersion, particularly in the mesial and lateral temporal lobes.

Risk factors for the onset of dependence and chronic psychosis due to cannabis use: Survey of patients with cannabis-related psychiatric disorders.

AIM: The objective of the current study was to identify risk factors that affect the onset of dependence and chronic psychosis due to cannabis use. METHODS: We examined clinical genetic factors, psychiatric disorders prior to cannabis use, starting age of cannabis use, duration and frequency of cannabis use, types of cannabis products used, combined use of other psychoactive substances, and the psychiatric diagnosis of 71 patients with cannabis-related psychiatric disorders who underwent treatment at nine mental health hospitals in Japan. Information was collected from cross-sectional interview surveys conducted by each patient's attending psychiatrist. RESULTS: For the diagnosis of dependence syndrome due to the use of cannabis, we found associations with the number of years of cannabis use and the use of cannabis products with a high Δ9-tetrahydrocannabinol (THC) content. However, we found no association between diagnosis of residual and late-onset psychotic disorders and clinical genetic factors, presence of preceding psychiatric disorders, duration and frequency of cannabis use, starting age of cannabis use, or combined use of other psychoactive substances; an association was found only for the absence of use of cannabis products other than dried cannabis. CONCLUSION: The onset of cannabis dependence was related to long-term cannabis use and the use of cannabis products with a high THC content. However, chronic psychosis was not associated with total THC intake or psychiatric vulnerability. Thus, unknown factors appear to be involved in the onset of chronic psychosis.

No significant elevation of translocator protein binding in the brains of recently abstinent methamphetamine users.

BACKGROUND: Radioligands for the translocator protein (TSPO) 18 kDa have been used with positron emission tomography (PET) to assess neuroinflammation and microglial activation in psychiatric disorders. One study using this approach showed substantial TSPO elevation throughout the brain in chronic methamphetamine users following long-term abstinence (0.5-4 years), but clients typically present for treatment earlier in abstinence. METHODS: We used PET with [11C]DAA1106 to compare standardized uptake values (SUVs) as an index of TSPO binding in the brains of methamphetamine-dependent participants who were abstinent for < 6 months (n = 11) and healthy controls (n = 12). We also assayed other typical correlates of Methamphetamine Dependence (e.g., striatal D2-type dopamine receptor deficits, depressed mood, anxiety and impaired emotion regulation). RESULTS: Methamphetamine users exhibited depression (p < 0.0001), anxiety (p = 0.002), difficulties in emotional regulation (p = 0.01), and lower striatal dopamine D2-type receptor availability vs. controls (p = 0.02). SUVs for [11C]DAA1106 were larger in all brain regions of methamphetamine-dependent participants vs. controls, but the effect size was small to medium and not statistically significant. CONCLUSIONS: The discrepancy between the lack of significant difference in TSPO binding in early-abstinent methamphetamine users vs. controls in this study and a previous report of elevated binding in longer-abstinent methamphetamine users may reflect methodological differences or limitations of TSPO binding as an index of neuroinflammation. It also seems possible that gliosis increases over time during the first 6 months of abstinence; longitudinal studies could clarify this possibility.

Quantitative Evaluation of 18F-Flutemetamol PET in Patients With Cognitive Impairment and Suspected Alzheimer's Disease: A Multicenter Study.

Background: In clinical practice, equivocal findings are inevitable in visual interpretation of whether amyloid positron emission tomography (PET) is positive or negative. It is therefore necessary to establish a more objective quantitative evaluation method for determining the indication for disease-modifying drugs currently under development. Aims: We aimed to determine cutoffs for positivity in quantitative analysis of 18F-flutemetamol PET in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also evaluated the clinical efficacy of amyloid PET in the diagnosis of AD. This study was registered in the Japan Registry of Clinical Trials (jRCTs, 031180321). Methods: Ninety-three patients suspected of having AD underwent 18F-flutemetamol PET in seven institutions. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by two board-certified nuclear medicine physicians. If the two readers obtained different interpretations, the visual rating was rerun until they reached consensus. The PET images were quantitatively analyzed using the standardized uptake value ratio (SUVR) and standardized Centiloid (CL) scale with the whole cerebellum as a reference area. Results: Visual interpretation obtained 61 positive and 32 negative PET scans. Receiver operating characteristic analysis determined the best agreement of quantitative assessments and visual interpretation of PET scans to have an area under curve of 0.982 at an SUVR of 1.13 and a CL of 16. Using these cutoff values, there was high agreement between the two approaches (kappa = 0.88). Five discordant cases had SUVR and CL values ranging from 1.00 to 1.22 and from 1 to 26, respectively. In these discordant cases, either diffuse or mildly focal elevation of cortical activity confused visual interpretation. The amyloid PET outcome significantly altered the diagnosis of AD (χ2 = 51.3, p < 0.0001). PET imaging elevated the proportions of the very high likelihood category from 20.4 to 46.2% and the very low likelihood category from 0 to 22.6%. Conclusion: Quantitative analysis of amyloid PET using 18F-flutemetamol can objectively evaluate amyloid positivity using the determined cutoffs for SUVR and CL. Moreover, amyloid PET may have added value over the standard diagnostic workup in dementia patients with cognitive impairment and suspected AD.