Extension and refinement of the predictive value of different classes of markers in ADNI: Four-year follow-up data

BackgroundThis study examined the predictive value of different classes of markers in the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) over an extended 4-year follow-up in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.MethodsMCI patients were assessed for clinical, cognitive, magnetic resonance imaging (MRI), positron emission tomography–fluorodeoxyglucose (PET-FDG), and cerebrospinal fluid (CSF) markers at baseline and were followed on a yearly basis for 4 years to ascertain progression to AD. Logistic regression models were fitted in clusters, including demographics, APOE genotype, cognitive markers, and biomarkers (morphometric, PET-FDG, CSF, amyloid-β, and tau).ResultsThe predictive model at 4 years revealed that two cognitive measures, an episodic memory measure and a Clock Drawing screening test, were the best predictors of conversion (area under the curve = 0.78).ConclusionsThis model of prediction is consistent with the previous model at 2 years, thus highlighting the importance of cognitive measures in progression from MCI to AD. Cognitive markers were more robust predictors than biomarkers.     

APOE-by-sex interactions on brain structure and metabolism in healthy elderly controls

Background

The APOE effect on Alzheimer Disease (AD) risk is stronger in women than in men but its mechanisms have not been established. We assessed the APOE-by-sex interaction on core CSF biomarkers, brain metabolism and structure in healthy elderly control individuals (HC).

Methods

Cross-sectional study. HC from the Alzheimer’s Disease Neuroimaging Initiative with available CSF (n = 274) and/or 3T-MRI (n = 168) and/or a FDG-PET analyses (n = 328) were selected. CSF amyloid-β_1–42 (Aβ_1–42), total-tau (t-tau) and phospho-tau (p-tau_181p) levels were measured by Luminex assays. We analyzed the APOE-by-sex interaction on the CSF biomarkers in an analysis of covariance (ANCOVA). FDG uptake was analyzed by SPM8 and cortical thickness (CTh) was measured by FreeSurfer. FDG and CTh difference maps were derived from interaction and group analyses.

Results

APOE4 carriers had lower CSF Aβ_1–42 and higher CSF p-tau_181p values than non-carriers, but there was no APOE-by-sex interaction on CSF biomarkers. The APOE-by-sex interaction on brain metabolism and brain structure was significant. Sex stratification showed that female APOE4 carriers presented widespread brain hypometabolism and cortical thinning compared to female non-carriers whereas male APOE4 carriers showed only a small cluster of hypometabolism and regions of cortical thickening compared to male non-carriers.

Conclusions

The impact of APOE4 on brain metabolism and structure is modified by sex. Female APOE4 carriers show greater hypometabolism and atrophy than male carriers. This APOE-by-sex interaction should be considered in clinical trials in preclinical AD where APOE4 status is a selection criterion.     

Usefulness of positron emission tomography-computed tomography in respiratory medicine

The introduction of positron emission tomography (PET) into the management of neoplastic disease in respiratory patients signified an important change from classic algorithms based exclusively on anatomic information obtained through computed tomography (CT). Non-small cell lung cancer and solitary pulmonary nodule were the 2 diseases in which metabolic PET imaging offered the highest diagnostic yield, as has been evident since the inclusion of this technology among the services available within the Spanish national health service. However, a number of limitations were encountered in relation to the lack of anatomic definition in PET imaging, as had been described in the literature. The appearance in 2001 of hybrid PET-CT devices has not only helped remedy those defects, but has also made it possible to combine anatomic and metabolic information in a single image, making this hybrid technology the most valuable tool in the current diagnostic arsenal.     

Energetic cost of brain functional connectivity

The brain''s functional connectivity is complex, has high energetic cost, and requires efficient use of glucose, the brain''s main energy source. It has been proposed that regions with a high degree of functional connectivity are energy efficient and can minimize consumption of glucose. However, the relationship between functional connectivity and energy consumption in the brain is poorly understood. To address this neglect, here we propose a simple model for the energy demands of brain functional connectivity, which we tested with positron emission tomography and MRI in 54 healthy volunteers at rest. Higher glucose metabolism was associated with proportionally larger MRI signal amplitudes, and a higher degree of connectivity was associated with nonlinear increases in metabolism, supporting our hypothesis for the energy efficiency of the connectivity hubs. Basal metabolism (in the absence of connectivity) accounted for 30% of brain glucose utilization, which suggests that the spontaneous brain activity accounts for 70% of the energy consumed by the brain. The energy efficiency of the connectivity hubs was higher for ventral precuneus, cerebellum, and subcortical hubs than for cortical hubs. The higher energy demands of brain communication that hinges upon higher connectivity could render brain hubs more vulnerable to deficits in energy delivery or utilization and help explain their sensitivity to neurodegenerative conditions, such as Alzheimer’s disease.     

Impact of PET-FDG in the diagnosis and therapeutic care of patients presenting with metastases of unknown primary

We carried out a study to evaluate the contribution of positron emission tomography with ¹⁸F-fluorodeoxyglucose (PET-FDG) in the diagnosis and therapeutic care of patients presenting with metastases of unknown primary. PET-FDG was prospectively performed in 51 patients. The PET-FDG data were confirmed histologically or by a follow-up on average at 13 months. PET-FDG identified the primary in 24 percent of cases, and detected the presence of additional metastases in 41 percent of cases. PET-FDG led to a therapeutic modification for 12 patients (24 percent). Furthermore, the therapeutic impact seems more marked in localized forms than in the multifocal. This broad exploratory study confirms the important role of PET-FDG in the diagnosis and therapeutic management of patients with metastases of unknown primary.