First nationwide study on driving under the influence of drugs in Switzerland.

In Switzerland, a two-tier system based on impairment by any psychoactive substances which affect the capacity to drive safely and zero tolerance for certain illicit drugs came into force on 1 January 2005. According to the new legislation, the offender is sanctioned if Delta(9)-tetrahydrocannabinol THC is >or=1.5ng/ml or amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), cocaine, free morphine are >or=15ng/ml in whole blood (confidence interval+/-30%). For all other psychoactive substances, impairment must be proven in applying the so-called "three pillars expertise". At the same time the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.80 to 0.50g/kg. The purpose of this study was to analyze the prevalence of drugs in the first year after the introduction of the revision of the Swiss Traffic Law in the population of drivers suspected of driving under the influence of drugs (DUID). A database was developed to collect the data from all DUID cases submitted by the police or the Justice to the eight Swiss authorized laboratories between January and December 2005. Data collected were anonymous and included the age, gender, date and time of the event, the type of vehicle, the circumstances, the sampling time and the results of all the performed toxicological analyses. The focus was explicitly on DUID; cases of drivers who were suspected to be under the influence of ethanol only were not considered. The final study population included 4794 DUID offenders (4243 males, 543 females). The mean age of all drivers was 31+/-12 years (range 14-92 years). One or more psychoactive drugs were detected in 89% of all analyzed blood samples. In 11% (N=530) of the samples, neither alcohol nor drugs were present. The most frequently encountered drugs in whole blood were cannabinoids (48% of total number of cases), ethanol (35%), cocaine (25%), opiates (10%), amphetamines (7%), benzodiazepines (6%) and methadone (5%). Other medicinal drugs such as antidepressants and benzodiazepine-like were detected less frequently. Poly-drug use was prevalent but it may be underestimated because the laboratories do not always analyze all drugs in a blood sample. This first Swiss study points out that DUID is a serious problem on the roads in Switzerland. Further investigations will show if this situation has changed in the following years.

On The Spot Damage Detection Methodology for Highway Bridges, July 2010

Vibration-based damage identification (VBDI) techniques have been developed in part to address the problems associated with an aging civil infrastructure. To assess the potential of VBDI as it applies to highway bridges in Iowa, three applications of VBDI techniques were considered in this study: numerical simulation, laboratory structures, and field structures. VBDI techniques were found to be highly capable of locating and quantifying damage in numerical simulations. These same techniques were found to be accurate in locating various types of damage in a laboratory setting with actual structures. Although there is the potential for these techniques to quantify damage in a laboratory setting, the ability of the methods to quantify low-level damage in the laboratory is not robust. When applying these techniques to an actual bridge, it was found that some traditional applications of VBDI methods are capable of describing the global behavior of the structure but are most likely not suited for the identification of typical damage scenarios found in civil infrastructure. Measurement noise, boundary conditions, complications due to substructures and multiple material types, and transducer sensitivity make it very difficult for present VBDI techniques to identify, much less quantify, highly localized damage (such as small cracks and minor changes in thickness). However, while investigating VBDI techniques in the field, it was found that if the frequency-domain response of the structure can be generated from operating traffic load, the structural response can be animated and used to develop a holistic view of the bridge’s response to various automobile loadings. By animating the response of a field bridge, concrete cracking (in the abutment and deck) was correlated with structural motion and problem frequencies (i.e., those that cause significant torsion or tension-compression at beam ends) were identified. Furthermore, a frequency-domain study of operational traffic was used to identify both common and extreme frequencies for a given structure and loading. Common traffic frequencies can be compared to problem frequencies so that cost-effective, preventative solutions (either structural or usage-based) can be developed for a wide range of IDOT bridges. Further work should (1) perfect the process of collecting high-quality operational frequency response data; (2) expand and simplify the process of correlating frequency response animations with damage; and (3) develop efficient, economical, preemptive solutions to common damage types.

New experimental apparatus for the study of the Bénard-Rayleigh problem

A new experimental system to measure the equivalent thermal conductivity of a liquid with regard to the Bénard-Rayleigh problem was constructed. The liquid is enclosed within walls of polymethylmethacrylate between two copper plates in which there are thermocouples to measure the difference in temperature between the lower and upper surfaces of the layer of liquid. Heat flux is measured by means of a linear heat fluxmeter consisting of 204 thermocouples in series. The fluxmeter was calibrated and the linear relationship that exists between the heat flux and the emf generated was verified. The thermal conductivity of the polymethylmethacrylate employed was measured and measurements of the equivalent conductivity in cylindrical boundaries of two silicone oils were made. The critical value of the temperature difference and the contribution of the convective process to the transmission of heat were determined.

Radiological detection of dissolved cocaine

Introduction: Smuggling dissolved drugs, especially cocaine, in bottled liquids is a problem at borders nowadays. Common fluoroscopy of packages at the border cannot detect contaminated liquids. To find a dissolved drug, an immunological test using a drug-test panel has to be performed. This means that a control sample of the cargo must be opened to perform the test. As it is not possible to open all boxes, and as smugglers hide the drugcontaining boxes between regularly filled boxes, contaminated cargos can be overlooked. Investigators sometimes cannot perform the drug-test panel because they try not to arouse the smugglers' suspicion in order to follow the cargo and to find the recipient. Aims: The objective of our studies was to define non-invasive examination techniques to investigate cargos that are suspicions to contain dissolved cocaine without leaving traces on the samples. We examined vessels containing cocaine by radiological cross-section techniques such as multidetector computed tomography (MDCT) and magnetic resonance spectroscopy (MRS). Methods: In a previous study, we examined bottles of wine containing dissolved cocaine in different quantities using an MDCT unit. To distinguish between bottles containing red wine and those where cocaine was solved in the wine, cross sectional 2D-images have been reconstructed and the absorption of X-rays was quantified by measuring the mean density of the liquid inside the bottles. In our new study, we investigated phantoms containing cocaine dissolved in water with or without ethanol as well as cocaine dissolved in different sorts of commercially available wine by the use of a clinical magnetic resonance unit (3 tesla). To find out if dissolved cocaine could be detected, magnetic resonance spectroscopy (1H MRS) was performed. Results: By using a MDCT-unit and measuring the mean attenuation of X-rays, it is possible to distinguish weather substances are dissolved in a liquid or not, if a comparative liquid without any solutions is available. The increase of the mean density indicates the presence of dissolved substances without the possibility to identify the substance. By using magnetic resonance spectroscopy, dissolved cocaine can be clearly identified because it produces distinctive resonances in the spectrum. In contrast to MDCT, this technique shows a high sensitivity (detection of 1 mM cocaine in wine). Conclusions: Cross-sectional imaging techniques such as MDCT and MRS appropriated to examine cargos that are suspicious to contain dissolved cocaine. They allow to perform non-invasive investigations without leaving any trace on the cargo. While an MDCT scan can detect dissolved substances in liquids, identification of cocaine can be obtained by MR-spectroscopy. Acknowledgment: This work was supported by the Centre d'Imagerie BioMédicale (CIBM) of the University of Lausanne (UNIL), the Swiss Federal Institute of Technology Lausanne (EPFL), the University of Geneva (UniGe), the Centre Hospitalier Universitaire Vaudois (CHUV), the Hôpitaux Universitaire de Genève (HUG) and the Leenaards and the Jeantet Foundations.

Seizure detection with automated EEG analysis: a validation study focusing on periodic patterns.

OBJECTIVE: To evaluate an automated seizure detection (ASD) algorithm in EEGs with periodic and other challenging patterns. METHODS: Selected EEGs recorded in patients over 1year old were classified into four groups: A. Periodic lateralized epileptiform discharges (PLEDs) with intermixed electrical seizures. B. PLEDs without seizures. C. Electrical seizures and no PLEDs. D. No PLEDs or seizures. Recordings were analyzed by the Persyst P12 software, and compared to the raw EEG, interpreted by two experienced neurophysiologists; Positive percent agreement (PPA) and false-positive rates/hour (FPR) were calculated. RESULTS: We assessed 98 recordings (Group A=21 patients; B=29, C=17, D=31). Total duration was 82.7h (median: 1h); containing 268 seizures. The software detected 204 (=76.1%) seizures; all ictal events were captured in 29/38 (76.3%) patients; in only in 3 (7.7%) no seizures were detected. Median PPA was 100% (range 0-100; interquartile range 50-100), and the median FPR 0/h (range 0-75.8; interquartile range 0-4.5); however, lower performances were seen in the groups containing periodic discharges. CONCLUSION: This analysis provides data regarding the yield of the ASD in a particularly difficult subset of EEG recordings, showing that periodic discharges may bias the results. SIGNIFICANCE: Ongoing refinements in this technique might enhance its utility and lead to a more extensive application.

Feasibility Study for Detection and Quantification of Corrosion in Bridge Barrier Rails, RB11-012, 2013

"Technical challenges exist with infrastructure that can be addressed by nondestructive evaluation (NDE) methods, such as detecting corrosion damage to reinforcing steel that anchor concrete bridge railings to bridge road decks. Moisture and chloride ions reach the anchors along the cold joint between the rails and deck, causing corrosion that weakens the anchors and ultimately the barriers. The Center for Nondestructive Evaluation at Iowa State University has experience in development of measurement techniques and new sensors using a variety of interrogating energies. This research evaluated feasibility of three technologies — x-ray radiation, ground-penetrating radar (GPR), and magnetic flux leakage (MFL) — for detection and quantification of corrosion of embedded reinforcing steel. Controlled samples containing pristine reinforcing steel with and without epoxy and reinforcing steel with 25 percent and 50 percent section reduction were embedded in concrete at 2.5 in. deep for laboratory evaluation. Two of the techniques, GPR and MFL, were used in a limited field test on the Iowa Highway 210 Bridge over Interstate 35 in Story County. The methods provide useful and complementary information. GPR provides a rapid approach to identify reinforcing steel that has anomalous responses. MFL provides similar detection responses but could be optimized to provide more quantitative correlation to actual condition. Full implementation could use either GPR or MFL methods to identify areas of concern, followed by radiography to give a visual image of the actual condition, providing the final guidance for maintenance actions." The full 103 page report and the 2 page Tech Transfer Summary are included in this link.

Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study.

OBJECTIVE(S): To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death. DESIGN: Virological failure was defined as experiencing two consecutive viral loads of more than 400 copies/ml in the time window between 0.5 and 2 years from starting antiretroviral therapy (baseline). Patients were grouped according to evidence of virological failure and whether there was detection of the International AIDS Society resistance mutations to one, two or three drug classes in the time window. METHODS: Standard survival analysis using Kaplan-Meier curves and Cox proportional hazards regression model with time-fixed covariates defined at baseline was employed. RESULTS: We studied 8229 patients in EuroSIDA who started antiretroviral therapy and who had at least 2 years of clinical follow-up. We observed 829 AIDS events and 571 deaths during 38,814 person-years of follow-up resulting in an overall incidence of new AIDS and death of 3.6 per 100 person-years of follow-up [95% confidence interval (CI):3.4-3.8]. By 96 months from baseline, the proportion of patients with a new AIDS diagnosis or death was 20.3% (95% CI:17.7-22.9) in patients with no evidence of virological failure and 53% (39.3-66.7) in those with virological failure and mutations to three drug classes (P = 0.0001). An almost two-fold difference in risk was confirmed in the multivariable analysis (adjusted relative hazard = 1.8, 95% CI:1.2-2.7, P = 0.005). CONCLUSION: Although this study shows an association between the detection of resistance at failure and risk of clinical progression, further research is needed to clarify whether resistance reflects poor adherence or directly increases the risk of clinical events via exhaustion of drug options.

Multicenter study of a new fully automated HBsAg screening assay with enhanced sensitivity for the detection of HBV mutants.

In a multicenter study a new, fully automated Roche Diagnostics Elecsys HBsAg II screening assay with improved sensitivity to HBsAg mutant detection was compared to well-established HBsAg tests: AxSYM HBsAg V2 (Abbott), Architect HBsAg (Abbott), Advia Centaur HBsAg (Bayer) Enzygnost HBsAg 5.0 (Dade-Behring), and Vitros Eci HBsAg (Ortho). A total of 16 seroconversion panels, samples of 60 HBsAg native mutants, and 31 HBsAg recombinant mutants, dilution series of NIBSC and PEI standards, 156 HBV positive samples comprising genotypes A to G, 686 preselected HBsAg positive samples from different stages of infection, 3,593 samples from daily routine, and 6,360 unselected blood donations were tested to evaluate the analytical and clinical sensitivity, the detection of mutants, and the specificity of the new assay. Elecsys HBsAg II showed a statistically significant better sensitivity in seroconversion panels to the compared tests. Fifty-seven out of 60 native mutants and all recombinant mutants were found positive. Among 156 HBV samples with different genotypes and 696 preselected HBsAg positive samples Elecsys HBsAg II achieved a sensitivity of 100%. The lower detection limit for NIBSC standard was calculated to be 0.025 IU/ml and for the PEI standards ad and ay it was <0.001 and <0.005 U/ml, respectively. Within 2,724 daily routine specimens and 6.360 unselected blood donations Elecsys HBsAg II showed a specificity of 99.97 and 99.88%, respectively. In conclusion the new Elecsys HBsAg II shows a high sensitivity for the detection of all stages of HBV infection and HBsAg mutants paired together with a high specificity in blood donors, daily routine samples, and potentially interfering sera.

Detection of smuggled cocaine in cargo using MDCT.

OBJECTIVE: Smuggling dissolved drugs, especially cocaine, in bottled liquids is an ongoing problem at borders. Common fluoroscopy of packages at the border cannot detect contaminated liquids. The objective of our study was to develop an MDCT screening method to detect cocaine-containing vessels that are hidden between uncontaminated ones in a shipment. MATERIALS AND METHODS: Studies were performed on three wine bottles containing cocaine solutions that were confiscated at the Swiss border. Reference values were obtained by scans of different sorts of commercially available wine and aqueous solutions of dissolved sugar. All bottles were scanned using MDCT, and data evaluation was performed by measuring the mean peak of Hounsfield units. To verify the method, simulated testing was performed. RESULTS: Using measurements of the mean peak of Hounsfield units enables the detection of dissolved cocaine in wine bottles in a noninvasive and rapid fashion. Increasing opacity corresponds well with the concentration of dissolved cocaine. Simulated testing showed that it is possible to distinguish between cocaine-contaminated and uncontaminated wine bottles. CONCLUSION: The described method is an efficacious screening method to detect cocaine-contaminated bottles that are hidden between untreated bottles in cargo. The noninvasive examination of cargo allows a questionable delivery to be tracked without arousing the suspicion of the smugglers.

Pharmacogenetic Study on Antidementia Drugs

Differences in efficacy and safety of drugs among patients are a recognized problem in pharmacotherapy. The reasons are multifactorial and, therefore, the choice of a drug and its dosage for a particular patient based on different clinical and genetic factors is suggested to improve the clinical outcome. Four drugs are currently used for the treatment of Alzheimer's disease: three acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and the N-methyl-D-aspartate-antagonist memantine. For these drugs, a high interindividual variability in plasma levels was observed, which might influence the response to treatment. The main objective of this thesis was to provide a better understanding of clinical and genetic factors affecting the plasma levels of antidementia drugs. Furthermore, the relationship between plasma levels, genetic variations and side effects was assessed. For this purpose, a pharmacogenetic study was conducted including 300 patients from a naturalistic clinical setting. Analytical methods for the simultaneous measurement of antidementia drugs in plasma have been developed and validated using liquid chromatography methods coupled with mass spectrometry detection. Presently, these methods are used in the therapeutic drug monitoring service of our laboratory. The routine use of therapeutic drug monitoring for antidementia drugs cannot yet be recommended with the available data, but it may be beneficial for some patients in special clinical cases such as insufficient treatment response, side effects or drug interactions. Donepezil and galantamine are extensively metabolized by the liver enzymes cytochromes P450 (CYP) 2D6 and 3A and are substrates of the drug transporter P-glycoprotein. The relationship of variations in genes affecting the activity of these metabolic enzymes and drug transporter (CYP2D6, CYP3A, POR, NR1I2, ABCB1) with donepezil and galantamine plasma levels was investigated. The CYP2D6 genotype appeared to be the major genetic factor involved in the pharmacokinetics of these two drugs. Thus, CYP2D6 poor metabolizers demonstrated significantly higher drug plasma levels than extensive metabolizers. Additionally, in the donepezil study population, the frequency of side effects was significantly increased in poor metabolizers. Lower donepezil plasma levels were observed in ultra rapid metabolizers, which might expose those patients to the risk of non-response. Memantine is mainly eliminated unchanged by the kidney, with implication of tubular secretion by renal transporters. A population pharmacokinetic model was developed to quantify the effects of clinical factors and genetic variations in renal cation transporters (SLC22A1/2/5, SLC47A1, ABCB1), and nuclear receptors (NR1I2, NR1I3, PPARG) involved in transporter expression, on memantine plasma levels. In addition to the renal function and gender, a genetic variation in the nuclear receptor Pregnane-X-Receptor (NR1I2) significantly affected memantine elimination. These findings suggest that an individualized therapy approach for antidementia drugs, taking into account clinical characteristics and genetic background of a patient, might increase efficacy and safety of the treatment. - Les différences interindividuelles dans l'efficacité et la tolérance des médicaments sont un problème connu en pharmacothérapie. Les raisons sont multiples, et le choix du médicament et de la dose, basé sur des facteurs cliniques et génétiques spécifiques au patient, peut contribuer à améliorer la réponse clinique. Quatre médicaments sont couramment utilisés dans le traitement de la maladie d'Alzheimer : trois inhibiteurs de l'acétylcholinestérase (donépézil, galantamine, rivastigmine) et un antagoniste du récepteur N-méthyl-D-aspartate, la mémantine. Une forte variabilité interindividuelle dans les taux plasmatiques de ces quatre composés a été observée, ce qui pourrait influencer la réponse au traitement. L'objectif principal de ce travail de thèse est de mieux comprendre les facteurs cliniques et génétiques influençant les taux des médicaments pro-cognitifs. En outre, des associations entre les taux, la variabilité génétique et les effets secondaires ont été recherchées. Dans ce but, 300 patients sous traitement avec un médicament pro-cognitif ont été recrutés pour une étude pharmacogénétique. Des méthodes de dosage simultané de médicaments pro-cognitifs par chromatographie liquide couplée à la spectrométrie de masse ont été développées et validées. Ces méthodes sont actuellement utilisées dans le service de suivi thérapeutique de notre unité. Malgré le fait qu'un suivi des taux sanguins des pro-cognitifs ne puisse pas encore être recommandé en routine, un dosage peut être utile dans des cas cliniques spécifiques, comme une réponse insuffisante, une intolérance ou une interaction médicamenteuse. Le donépézil et la galantamine sont fortement métabolisés par les cytochromes P450 (CYP) 2D6 et 3A, et sont également substrats du transporteur P-glycoprotéine. Les associations entre les polymorphismes génétiques de ces enzymes, cofacteur, récepteur nucléaire et transporteur (CYP2D6, CYP3A, POR, NR1I2, ABCB1) et les taux de donépézil et de galantamine ont été étudiées. Le génotype du CYP2D6 a été montré comme le facteur génétique majeur impliqué dans la pharmacocinétique de ces deux médicaments. Ainsi, les métaboliseurs déficients du CYP2D6 ont démontré des taux plasmatiques significativement plus élevés comparé aux bons métaboliseurs. De plus, dans la population traitée avec le donépézil, la fréquence des effets secondaires était plus élevée chez les métaboliseurs déficients. Des taux plasmatiques bas ont été mesurés chez les métaboliseurs ultra-rapides traités avec le donépézil, ce qui pourrait être un facteur de risque à une non-réponse au traitement. La mémantine est principalement éliminée sous forme inchangée par les reins, et partiellement par sécrétion tubulaire grâce à des transporteurs rénaux. Un modèle de cinétique de population a été développé pour quantifier les effets des différents facteurs cliniques et de la variabilité génétique des transporteurs rénaux (SLC22A1/2/5, SLC47A1, ABCB1) et des récepteurs nucléaires (NR1I2, NR1I3, PPARG, impliqués dans l'expression des transporteurs) sur les taux plasmatiques de mémantine. En plus de la fonction rénale et du genre, une variation génétique dans le récepteur nucléaire Pregnane-X-Receptor (NR1I2) a montré une influence significative sur l'élimination de la mémantine. Ces résultats suggèrent qu'une approche thérapeutique individualisée, prenant en compte des facteurs cliniques et génétiques du patient, pourrait améliorer l'efficacité et la sécurité du traitement pro-cognitif.

MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.

Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p < 0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients.

Bioreporters and biosensors for arsenic detection. Biotechnological solutions for a world-wide pollution problem.

A wide variety of whole cell bioreporter and biosensor assays for arsenic detection has been developed over the past decade. The assays permit flexible detection instrumentation while maintaining excellent method of detection limits in the environmentally relevant range of 10-50 μg arsenite per L and below. New emerging trends focus on genetic rewiring of reporter cells and/or integration into microdevices for more optimal detection. A number of case studies have shown realistic field applicability of bioreporter assays.

Mild Cognitive Impairment and Early Detection of Alzheimer`s Disease. A Positron Emission Tomography Study

Alzheimer`s disease (AD) is characterised neuropathologically by the presence of extracellular amyloid plaques, intraneuronal neurofibrillary tangles, and cerebral neuronal loss. The pathological changes in AD are believed to start even decades before clinical symptoms are detectable. AD gradually affects episodic memory, cognition, behaviour and the ability to perform everyday activities. Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia disorders, especially AD. The predictive accuracy of the current and commonly used MCI criteria devide this disorder into amnestic (aMCI) and non-amnestic (naMCI) MCI. It seems that many individuals with aMCI tend to convert to AD. However many MCI individuals will remain stable and some may even recover. At present, the principal drugs for the treatment of AD provide only symptomatic and palliative benefits. Safe and effective mechanism-based therapies are needed for this devastating neurodegenerative disease of later life. In conjunction with the development of new therapeutic drugs, tools for early detection of AD would be important. In future one of the challenges will be to detect at an early stage these MCI individuals who will convert to AD. Methods which can predict which MCI subjects will convert to AD will be much more important if the new drug candidates prove to have disease-arresting or even disease–slowing effects. These types of drugs are likely to have the best efficacy if administered in the early or even in the presymptomatic phase of the disease when the synaptic and neuronal loss has not become too widespread. There is no clinical method to determine with certainly which MCI individuals will progress to AD. However there are several methods which have been suggested as predictors of conversion to AD, e.g. increased [11C] PIB uptake, hippocampal atrophy in MRI, low CSF A beta 42 level, high CSF tau-protein level, apolipoprotein E (APOE) ε4 allele and impairment in episodic memory and executive functions. In the present study subjects with MCI appear to have significantly higher [¹¹C] PIB uptake vs healthy elderly in several brain areas including frontal cortex, the posterior cingulate, the parietal and lateral temporal cortices, putamen and caudate. Also results from this PET study indicate that over time, MCI subjects who display increased [¹¹C] PIB uptake appear to be significantly more likely to convert to AD than MCI subjects with negative [¹¹C] PIB retention. Also hippocampal atrophy seems to increase in MCI individuals clearly during the conversion to AD. In this study [¹¹C] PIB uptake increases early and changes relatively little during the AD process whereas there is progressive hippocampal atrophy during the disease. In addition to increased [¹¹C] PIB retention and hippocampal atrophy, the status of APOE ε4 allele might contribute to the conversion from MCI to AD.