Open versus laparoscopic gastrectomy for advanced gastric cancer: a propensity score matching analysis of survival in a western population-on behalf of the Italian Research Group for Gastric Cancer.

BACKGROUND: Oncologic outcomes after laparoscopic gastrectomy for advanced gastric cancer in the West have been poorly investigated. The aim of the present study was to compare survival outcomes in patients undergoing curative-intent laparoscopic and open gastrectomy for advanced gastric cancer in several centres belonging to the Italian Research Group for Gastric Cancer. METHODS: Data of patients operated between 2015 and 2018 were retrospectively analysed. Propensity Score Matching was performed to balance baseline characteristics of patients undergoing laparoscopic and open gastrectomy. The primary endpoint was 3-year overall survival. Secondary endpoints were 3-year disease-free survival and short-term outcomes. Multivariable regression analyses for survival were conducted. RESULTS: Data were retrieved from 20 centres. Of the 717 patients included, 438 patients were correctly matched, 219 per group. The 3-year overall survival was 73.6% and 68.7% in the laparoscopic and open group, respectively (p = 0.40). When compared with open gastrectomy, laparoscopic gastrectomy showed comparable 3-year disease-free survival (62.8%, vs 58.9%, p = 0.40), higher rate of return to intended oncologic treatment (56.9% vs 40.2%, p = 0.001), similar 30-day morbidity/mortality. Prognostic factors for survival were ASA Score ≥ 3, age-adjusted Charlson Comorbidity Index ≥ 5, lymph node ratio ≥ 0.15, p/ypTNM Stage III and return to intended oncologic treatment. CONCLUSIONS: Laparoscopic gastrectomy for advanced gastric cancer offers similar rates of survival when compared to open gastrectomy, with higher rates of return to intended oncologic treatment. ASA score, age-adjusted Charlson Comorbidity Index, lymph node ratio, return to intended oncologic treatment and p/ypTNM Stage, but not surgical approach, are prognostic factors for survival.

Cigarette-smoking characteristics and interest in cessation in patients with head-and-neck cancer.

Purpose: Many patients diagnosed with head-and-neck cancer are current or former smokers. Despite the well-known adverse effects of smoking, continuation of smoking during cancer treatment is associated with reduced efficacy of that treatment and with cancer recurrence. In the present study, we examined smoking characteristics in patients with head-and-neck cancer near the time of cancer treatment. Methods: A prospective cohort of patients with head-and-neck cancer who attended a dental oncology clinic before receiving cancer treatment at a regional cancer centre were invited to participate in a study that involved completing an interviewer-administered questionnaire to assess smoking characteristics, intention to quit, motivation to quit, and strategies perceived to potentially aid in successful cessation. Results: The study enrolled 493 ever-smokers, with a response rate of 96.1% and a self-reported current smoker rate of 37.1% (n = 183). Most of the current smokers reported high nicotine dependence, with 84.7% (n = 155) indicating a time to first cigarette of 30 minutes or less. Most had previously attempted to quit smoking (77.0%), and many had prior unsuccessful quit attempts before resuming smoking again. Most were interested in quitting smoking (85.8%), and many (70.5%) were seriously considering quitting smoking within the subsequent 30 days. Conclusions: Patients with head-and-neck cancer reported high nicotine dependence and high interest in cessation opportunities near the time of treatment for cancer. Those results might provide support for provision of smoking cessation opportunities.

Comparison of a purely endoscopic three-layer technique versus pericranial flap for reconstruction of anterior skull base defects after sino-nasal tumor resection: assessment of postoperative frontal lobe sagging and frontal lobe falling.

BACKGROUND: The evolution of endoscopic skull base approaches has enabled surgeons to manage selected skull base tumors through a transnasal endoscope-assisted approach. On the other side, more extensive lesions may require a combined cranioendoscopic approach. In this paper, we analysed and compared the incidence of frontal lobe sagging after endoscopic multilayer (EM) reconstruction versus pericranial flap (PF) reconstruction. METHODOLOGY: Subjects were selected retrospectively according to specific inclusion and exclusion criteria. The degree of frontal lobe sagging after surgery was calculated based on the most inferior position of the frontal lobe relative to the nasion-sellar line defined on preoperative and postoperative imaging. A positive value signified upward displacement, and a negative value represented frontal lobe sagging. RESULTS: Twenty subjects were enrolled in our study. In the EM technique group the average frontal lobe displacement was -2,34 ± 1,55 mm. The average postoperative frontal lobe sagging was -0,45 ± 8,92 mm in subjects reconstructed with the PF. The skull base defect size correlated with the degree of frontal lobe sagging in subjects reconstructed with the PF, but not in the other group and when merging the two groups. CONCLUSIONS: In conclusion, the EM technique and the PF reconstruction showed a good reliability for the closure of anterior skull base defects. Moreover the PF seemed to prevent frontal lobe sagging but, for larger skull base defects, it could be useful to be combined with other autologous or heterologous materials to avoid the frontal lobe falling.

Nivolumab and ipilimumab are associated with distinct immune landscape changes and response-associated immunophenotypes.

BACKGROUNDThe reshaping of the immune landscape by nivolumab (NIVO) and ipilimumab (IPI) and its relation to patient outcomes is not well described.METHODSWe used high-parameter flow cytometry and a computational platform, CytoBrute, to define immunophenotypes of up to 15 markers to assess peripheral blood samples from metastatic melanoma patients receiving sequential NIVO > IPI or IPI > NIVO (Checkmate-064).RESULTSThe 2 treatments were associated with distinct immunophenotypic changes and had differing profiles associated with response. Only 2 immunophenotypes were shared but had opposing relationships to response/survival. To understand the impact of sequential treatment on response/survival, phenotypes that changed after the initial treatment and differentiated response in the other cohort were identified. Immunophenotypic changes occurring after NIVO were predominately associated with response to IPI > NIVO, but changes occurring after IPI were predominately associated with progression after NIVO > IPI. Among these changes, CD4+CD38+CD39+CD127-GARP- T cell subsets were increased after IPI treatment and were negatively associated with response/survival for the NIVO > IPI cohort.CONCLUSIONCollectively, these data suggest that the impact of IPI and NIVO on the immunophenotypic landscape of patients is distinct and that the impact of IPI may be associated with resistance to subsequent NIVO therapy, consistent with poor outcomes in the IPI > NIVO cohort of Checkmate-064.

Clinical and pathophysiological outcomes of the robotic-assisted Heller-Dor myotomy for achalasia: a single-center experience.

Laparoscopic Heller myotomy and Dor fundoplication is considered a safe and effective treatment for achalasia. Robotic-assisted Heller-Dor procedure (RAHD) has emerged as an alternative approach due to improved visualization and fine motor control. The aim of this prospective study was to evaluate clinical, and functional results of RAHD. We evaluated a group of 66 patients with achalasia that underwent robotic-assisted Heller-Dor operation. Before treatment all patients underwent a diagnostic work-up such as upper endoscopy, esophageal barium swallow and high resolution manometry. The presence of postoperative gastroesophageal reflux disease was diagnosed by impedance and pH monitoring (MII-pH). Dysphagia improved in 92.4% of patients after treatment. Barium swallow series showed esophageal emptying in 100% of patients and a significant reduction of the esophageal diameter (p = 0.00235). Forty-five of 66 patients (68.2%) underwent upper endoscopy and 35 of 66 (53%) underwent MII-pH. Esophageal erosions were found in 4/45 (8,8%) and MII-pH showed abnormal results in 3/35 patients (8.6%). RAHD ensures a meticulous esophageal and gastric myotomy, allowing to visualize and divide each muscle fibers with a low rate of intraoperative and postoperative complications. resulting in turn in good clinical outcomes, radiological findings and functional results even if robotic tecnique definitely increases the surgical cost in the treatment of these functional esophageal disorders.

Ecchordosis physaliphora: a cautionary tale.

BACKGROUND: Ecchordosis physaliphora is a congenital, benign lesion originating from notochordal remnants along the craniospinal axis, most frequently located at the level of the clivus and sacrum. Sometimes ecchordosis physaliphora is difficult to recognise and treat, with a total of twenty-six cases described in the literature. METHODS: This study reports on three cases of previously undiagnosed ecchordosis physaliphora presenting with cerebrospinal fluid rhinorrhoea and meningitis. CONCLUSION: Endoscopic transclival or transsphenoid surgery including three-layer (fat, fascia and nasoseptal flap) reconstruction was used in all cases with complete resolution of the symptoms.

Effect of age, ethnicity, sex, cognitive status and APOE genotype on amyloid load and the threshold for amyloid positivity.

The threshold for amyloid positivity by visual assessment on PET has been validated by comparison to amyloid load measured histopathologically and biochemically at post mortem. As such, it is now feasible to use qualitative visual assessment of amyloid positivity as an in-vivo gold standard to determine those factors which can modify the quantitative threshold for amyloid positivity. We calculated quantitative amyloid load, measured as Standardized Uptake Value Ratios (SUVRs) using [18-F]florbetaben PET scans, for 159 Hispanic and non-Hispanic participants, who had been classified clinically as Cognitively Normal (CN), Mild Cognitive Impairment (MCI) or Dementia (DEM). PET scans were visually rated as amyloid positive (A+) or negative (A-), and these judgments were used as the gold standard with which to determine (using ROC analyses) the SUVR threshold for amyloid positivity considering factors such as age, ethnicity (Hispanic versus non-Hispanic), gender, cognitive status, and apolipoprotein E ε4 carrier status. Visually rated scans were A+ for 11% of CN, 39.0% of MCI and 70% of DEM participants. The optimal SUVR threshold for A+ among all participants was 1.42 (sensitivity = 94%; specificity = 92.5%), but this quantitative threshold was higher among E4 carriers (SUVR = 1.52) than non-carriers (SUVR = 1.31). While mean SUVRs did not differ between Hispanic and non-Hispanic participants;, a statistically significant interaction term indicated that the effect of E4 carrier status on amyloid load was greater among non-Hispanics than Hispanics. Visual assessment, as the gold standard for A+, facilitates determination of the effects of various factors on quantitative thresholds for amyloid positivity. A continuous relationship was found between amyloid load and global cognitive scores, suggesting that any calculated threshold for the whole group, or a subgroup, is artefactual and that the lowest calculated threshold may be optimal for the purposes of early diagnosis and intervention.

What Slows Down Phytoplasma Proliferation? Speculations on the Involvement of AtSEOR2 Protein in Plant Defence Signalling.

Considering the crude methods used to control phytoplasma diseases, a deeper knowledge on the defence mechanisms recruited by the plant to face phytoplasma invasion is required. Recently, we demonstrated that Arabidopsis mutants lacking AtSEOR1 gene showed a low phytoplasma titre. In wild type plants AtSEOR1 and AtSEOR2 are tied in filamentous proteins. Knockout of the AtSEOR1 gene may pave the way for an involvement of free AtSEOR2 proteins in defence mechanisms. Among the proteins conferring resistance against pathogenic bacteria, AtRPM1-interacting protein has been found to interact with AtSEOR2 in a high-quality, matrix-based yeast-two hybrid assay. For this reason, we investigated the expression levels of Arabidopsis AtRIN4, and the associated AtRPM1 and AtRPS2 genes in healthy and Chrysanthemum yellows-infected wild-type and Atseor1ko lines.

Glycogen Synthase Kinase-3ß Inhibition Links Mitochondrial Dysfunction, Extracellular Matrix Remodelling and Terminal Differentiation in Chondrocytes.

Following inflammatory stimuli, GSK3 inhibition functions as a hub with pleiotropic effects leading to cartilage degradation. However, little is known about the effects triggered by its direct inhibition as well as the effects on mitochondrial pathology, that contributes to osteoarthritis pathogenesis. To this aim we assessed the molecular mechanisms triggered by GSK3ß inactivating stimuli on 3-D (micromass) cultures of human articular chondrocytes. Stimuli were delivered either at micromass seeding (long term) or after maturation (short term) to explore "late" effects on terminal differentiation or "early" mitochondrial effects, respectively. GSK3ß inhibition significantly enhanced mitochondrial oxidative stress and damage and endochondral ossification based on increased nuclear translocation of Runx-2 and ß-catenin, calcium deposition, cell death and enhanced remodelling of the extracellular matrix as demonstrated by the increased collagenolytic activity of supernatants, despite unmodified (MMP-1) or even reduced (MMP-13) collagenase gene/protein expression. Molecular dissection of the underlying mechanisms showed that GSK3ß inhibition achieved with pharmacological/silencing strategies impacted on the control of collagenolytic activity, via both decreased inhibition (reduced TIMP-3) and increased activation (increased MMP-10 and MMP-14). To conclude, the inhibition of GSK3ß enhances terminal differentiation via concerted effects on ECM and therefore its activity represents a tool to keep articular cartilage homeostasis.

TGF-ß1 differentially modulates the collagen VI α5 and α6 chains in human tendon cultures.

Collagen VI is a microfibrillar collagen with a potential regulatory role in tendon repair mechanism. We studied the expression of collagen VI α5 and α6 chains in normal human tendon fibroblast cultures, both under basal condition and in response to TGF-ß1, a potent regulator of tendon healing. Under basal condition, we found that the α5 chain was expressed, although to a lesser extent with respect to the α3 chain; in contrast, the α6 chain was absent. The treatment with TGFß1 induced an opposite effect on the expression of the α5 and α6 chains; in fact, while the α5 chain was dramatically reduced, the α6 chain was induced and released in the culture medium. These data indicate that collagen VI α5 and α6 chains are differentially involved in tendon matrix homeostasis. The α6 chain may represent a new potential biomarker for monitoring TGFß1-related events in tendon, as healing and fibrotic scar formation.

Combined microscopy and molecular analyses show phloem occlusions and cell wall modifications in tomato leaves in response to 'Candidatus Phytoplasma solani'.

Callose deposition, phloem-protein conformational changes and cell wall thickening are calcium-mediated occlusions occurring in the plant sieve elements in response to different biotic and abiotic stresses. However, the significance of these structures in plant-phytoplasma interactions requires in-depth investigations. We adopted a novel integrated approach, based on the combined use of microscopic and molecular analyses, to investigate the structural modifications induced in tomato leaf tissues in presence of phytoplasmas, focusing on vascular bundles and on the occlusion structures. Phloem hyperplasia and string-like arrangement of xylem vessels were found in infected vascular tissue. The diverse occlusion structures were differentially modulated in the phloem in response to phytoplasma infection. Callose amount was higher in midribs from infected plants than in healthy ones. Callose was observed at sieve plates but not at pore-plasmodesma units. A putative callose synthase gene encoding a protein with high similarity to Arabidopsis CalS7, responsible for callose deposition at sieve plates, was upregulated in symptomatic leaves, indicating a modulation in the response to stolbur infection. P-proteins showed configuration changes in infected sieve elements, exhibiting condensation of the filaments. The transcripts for a putative P-protein 2 and a sieve element occlusion-related protein were localized in the phloem but only the first one was modulated in the infected tissues.

Defective collagen VI α6 chain expression in the skeletal muscle of patients with collagen VI-related myopathies.

Collagen VI is a non-fibrillar collagen present in the extracellular matrix (ECM) as a complex polymer; the mainly expressed form is composed of α1, α2 and α3 chains; mutations in genes encoding these chains cause myopathies known as Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and myosclerosis myopathy (MM). The collagen VI α6 chain is a recently identified component of the ECM of the human skeletal muscle. Here we report that the α6 chain was dramatically reduced in skeletal muscle and muscle cell cultures of genetically characterized UCMD, BM and MM patients, independently of the clinical phenotype, the gene involved and the effect of the mutation on the expression of the "classical" α1α2α3 heterotrimer. By contrast, the collagen VI α6 chain was normally expressed or increased in the muscle of patients affected by other forms of muscular dystrophy, the overexpression matching with areas of increased fibrosis. In vitro treatment with TGF-ß1, a potent collagen inducer, promoted the collagen VI α6 chain deposition in the ECM of normal muscle cells, whereas, in cultures derived from collagen VI-related myopathy patients, the collagen VI α6 chain failed to develop a network outside the cells and accumulated in the endoplasmic reticulum. The defect of the α6 chain points to a contribution to the pathogenesis of collagen VI-related disorders.

Three-dimensional cellular distribution in polymeric scaffolds for bone regeneration: a microCT analysis compared to SEM, CLSM and DNA content.

In orthopaedic surgery the tissues damaged by injury or disease could be replaced using constructs based on biocompatible materials, cells and growth factors. Scaffold design, porosity and early colonization are key components for the implant success. From biological point of view, attention may be also given to the number, type and size of seeded cells, as well as the seeding technique and cell morphological and volumetric alterations. This paper describes the use of the microCT approach (to date used principally for mineralized matrix quantification) to observe construct colonization in terms of cell localization, and make a direct comparison of the microtomographic sections with scanning electron microscopy images and confocal laser scanning microscope analysis. Briefly, polycaprolactone scaffolds were seeded at different cell densities with MG63 osteoblastic-like cells. Two different endpoints, 1 and 2 weeks, were selected for the three-dimensional colonization and proliferation analysis of the cells. By observing all images obtained, in addition to a more extensive distribution of cells on scaffolds surfaces than in the deeper layers, cell volume increased at 2 weeks compared to 1 week after seeding. Combining the cell number quantification by deoxyribonucleic acid analysis and the single cell volume changes by confocal laser scanning microscope, we validated the microCT segmentation method by finding no statistical differences in the evaluation of the cell volume fraction of the scaffold. Furthermore, the morphological results of this study suggest that an effective scaffold colonization requires a precise balance between different factors, such as number, type and size of seeded cells in addition to scaffold porosity.

Identification of ZDHHC14 as a novel human tumour suppressor gene.

Genomic changes affecting tumour suppressor genes are fundamental to cancer. We applied SNP array analysis to a panel of testicular germ cell tumours to search for novel tumour suppressor genes and identified a frequent small deletion on 6q25.3 affecting just one gene, ZDHHC14. The expression of ZDHHC14, a putative protein palmitoyltransferase with unknown cellular function, was decreased at both RNA and protein levels in testicular germ cell tumours. ZDHHC14 expression was also significantly decreased in a panel of prostate cancer samples and cell lines. In addition to our findings of genetic and protein expression changes in clinical samples, inducible overexpression of ZDHHC14 led to reduced cell viability and increased apoptosis through the classic caspase-dependent apoptotic pathway and heterozygous knockout of ZDHHC14 increased [CORRECTED] cell colony formation ability. Finally, we confirmed our in vitro findings of the tumour suppressor role of ZDHHC14 in a mouse xenograft model, showing that overexpression of ZDHHC14 inhibits tumourigenesis. Thus, we have identified a novel tumour suppressor gene that is commonly down-regulated in testicular germ cell tumours and prostate cancer, as well as given insight into the cellular functional role of ZDHHC14, a potential protein palmitoyltransferase that may play a key protective role in cancer.

Carbodiimide inactivation of MMPs and effect on dentin bonding.

The use of protein cross-linking agents during bonding procedures has been recently proposed to improve bond durability. This study aimed to use zymography and in situ zymography techniques to evaluate the ability of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) cross-linker to inhibit matrix metalloproteinase (MMP) activity. The hypotheses tested were that: (1) bonding procedures increase dentin gelatinolytic activity and (2) EDC pre-treatment prevents this enzymatic activity. The zymographic assay was performed on protein extracts obtained from dentin powder treated with Optibond FL or Scotchbond 1XT with or without 0.3M EDC pre-treatment. For in situ zymography, adhesive/dentin interfaces were created with the same adhesives applied to acid-etched dentin slabs pre-treated or not with EDC conditioner. Zymograms revealed increased expression of dentin endogenous MMP-2 and -9 after adhesive application, while the use of EDC as a primer inactivated dentin gelatinases. Results of in situ zymograpy showed that hybrid layers of tested adhesives exhibited intense collagenolytic activity, while almost no fluorescence signal was detected when specimens were pre-treated with EDC. The correlative analysis used in this study demonstrated that EDC could contribute to inactivate endogenous dentin MMPs within the hybrid layer created by etch-and-rinse adhesives.

Mesenchymal stem cells as delivery vehicle of porphyrin loaded nanoparticles: effective photoinduced in vitro killing of osteosarcoma.

Mesenchymal stem cells (MSC) have the unique ability to home and engraft in tumor stroma. These features render them potentially a very useful tool as targeted delivery vehicles which can deliver therapeutic drugs to the tumor stroma. In the present study, we investigate whether fluorescent core-shell PMMA nanoparticles (FNPs) post-loaded with a photosensitizer, namely meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) and uploaded by MSC could trigger osteosarcoma (OS) cell death in vitro upon specific photoactivation. In co-culture studies we demonstrate using laser confocal microscopy and time lapse imaging, that only after laser irradiation MSC loaded with photosensitizer-coated fluorescent NPs (TPPS@FNPs) undergo cell death and release reactive oxygen species (ROS) which are sufficient to trigger cell death of all OS cells in the culture. These results encourage further studies aimed at proving the efficacy of this novel tri-component system for PDT applications.

Endocytosis and intracellular localisation of type 1 ribosome-inactivating protein saporin-s6.

Saporin-S6 is a single-chain ribosome-inactivating protein (RIP) that has low toxicity in cells and animals. When the protein is bound to a carrier that facilitates cellular uptake, the protein becomes highly and selectively toxic to the cellular target of the carrier. Thus, saporin-S6 is one of the most widely used RIPs in the preparation of immunoconjugates for anti-cancer therapy. The endocytosis of saporin-S6 by the neoplastic HeLa cells and the subsequent intracellular trafficking were investigated by confocal microscopy that utilises indirect immunofluorescence analysis and transmission electron microscopy that utilises a direct assay with gold-conjugated saporin-S6 and an indirect immunoelectron microscopy assay. Our results indicate that saporin-S6 was taken up by cells mainly through receptor-independent endocytosis. Confocal microscopy analysis showed around 30% co-localisation of saporin-S6 with the endosomal compartment and less than 10% co-localisation with the Golgi apparatus. The pathway identified by the immunofluorescence assay and transmission electron microscopy displayed a progressive accumulation of saporin-S6 in perinuclear vesicular structures. The main findings of this work are the following: i) the nuclear localisation of saporin-S6 and ii) the presence of DNA gaps resulting from abasic sites in HeLa nuclei after intoxication with saporin-S6.

Errors in ADAS-cog administration and scoring may undermine clinical trials results.

BACKGROUND: The Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) is the most widely used cognitive outcome measure in AD trials. Although errors in administration and scoring have been suggested as factors masking accurate estimates and potential effects of treatments, there have been few formal examinations of errors with the ADAS-cog. METHODS: We provided ADAS-cog administration training using standard methods to raters who were designated as experienced, potential raters by sponsors or contract research organizations for two clinical trials. Training included 1 hour sessions on test administration, scoring, question periods, and required that raters individually view and score a model ADAS-cog administration. Raters scores were compared to the criterion scores established for the model administration. RESULTS: A total of 108 errors were made by 80.6% of the 72 raters; 37.5% made 1 error, 25.0% made 2 errors and 18.0% made 3 or more. Errors were made in all ADAS-cog subsections. The most common were in word finding difficulty (67% of the raters), word recognition (22%), and orientation (22%). For the raters who made 1, 2, or ≥ 3 errors the ADAS-cog score was 17.5 (95% CI, 17.3 - 17.8), 17.8 (17.0 - 18.5), and 18.8 (17.6 - 20.0), respectively, and compared to the criterion score, 18.3. ADAS-cog means differed significantly and the variances were more than twice as large between those who made errors on word finding and those who did not, 17.6 (SD=1.4) vs. 18.8 (SD=0.9), respectively (χ(2) = 37.2, P < .001). CONCLUSIONS: Most experienced raters made at least one error that may affect ADAS-cog scores and clinical trials outcomes. These errors may undermine detection of medication effects by contributing both to a biased point estimate and increased variance of the outcome.

Early detection of Alzheimer's disease with PET imaging.

Preclinical diagnosis of Alzheimer's disease (AD) is one of the major challenges for the prevention of AD. AD biomarkers are needed not only to reveal preclinical pathologic changes, but also to monitor progression and therapeutics. PET neuroimaging can reliably assess aspects of the molecular biology and neuropathology of AD. The aim of this article is to review the use of FDG-PET and amyloid PET imaging in the early detection of AD.

Evaluation of Early Dementia (Mild Cognitive Impairment).

Early diagnosis of Alzheimer disease (AD) is one of the major challenges for the prevention of this dementia. The pathologic lesions associated with AD develop many years before the clinical manifestations of the disease become evident, during a likely transitional period between normal aging and the appearance of first cognitive symptoms. AD biomarkers are needed not only to reveal these early pathologic changes but also to monitor progression in cognitive and behavioral decline and brain lesions. PET neuroimaging can reliably assess indirect and direct aspects of the molecular biology and neuropathology of AD. This article reviews the use of [18F] 2-fluoro-2-deoxy-D-glucose-PET and amyloid PET imaging in the early detection of AD.