L. Saint-Aubert

Cortical florbetapir-PET amyloid load in prodromal Alzheimer’s disease patients

BackgroundFlorbetapir (AV-45) has been shown to be a reliable tool to assess amyloid load in patients with Alzheimers disease (AD) at demential stages. Longitudinal studies also suggest that AV-45 has the ability to bind amyloid in the early stages of AD. In this study, we investigated AV-45 binding and its relation with cognitive performance in a group of patients at the prodromal stage of Alzheimers disease, recruited according to strict inclusion criteria.MethodsWe recruited patients at the prodromal stage of AD and matched control subjects. AV-45 binding was assessed using an innovative extraction method allowing quantifying uptake in the cortex only. AV-45 uptake was compared between groups in the precuneus, posterior cingulate, anterior cingulate, and orbito-frontal regions. Correlations between AV-45 uptake and cognitive performance were assessed.ResultsTwenty-two patients and 17 matched control subjects were included in the study. We report a significant increase of cortical AV-45 uptake in the patients compared to the control subjects in all regions of interest. Specific correlations were found within the patient group between mean global amyloid cortical load and cognitive performance in three different memory tests.ConclusionsThese findings suggest that at the prodromal stage of AD, memory decline is linked to an increase of cortical β-amyloid load.

Object recognition in congruent and incongruent natural scenes: A life-span study

Efficient processing of our complex visual environment is essential and many daily visual tasks rely on accurate and fast object recognition. It is therefore important to evaluate how object recognition performance evolves during the course of adulthood. Surprisingly, this ability has not yet been investigated in the aged population, although several neuroimaging studies have reported altered activity in high-level visual ventral regions when elderly subjects process natural stimuli. In the present study, color photographs of various objects embedded in contextual scenes were used to assess object categorization performance in 97 participants aged from 20 to 91. Objects were either animals or pieces of furniture, embedded in either congruent or incongruent contexts. In every age group, subjects showed reduced categorization performance, both in terms of accuracy and speed, when objects were seen in incongruent vs. congruent contexts. In subjects over 60 years old, object categorization was greatly slowed down when compared to young and middle-aged subjects. Moreover, subjects over 75 years old evidenced a significant decrease in categorization accuracy when objects were seen in incongruent contexts. This indicates that incongruence of the scene may be particularly disturbing in late adulthood, therefore impairing object recognition. Our results suggest that daily visual processing of complex natural environments may be less efficient with age, which might impact performance in everyday visual tasks.

Insight on AV-45 binding in white and grey matter from histogram analysis: a study on early Alzheimer’s disease patients and healthy subjects

PurposeAV-45 amyloid biomarker is known to show uptake in white matter in patients with Alzheimer’s disease (AD), but also in the healthy population. This binding, thought to be of a non-specific lipophilic nature, has not yet been investigated. The aim of this study was to determine the differential pattern of AV-45 binding in white matter in healthy and pathological populations.MethodsWe recruited 24 patients presenting with AD at an early stage and 17 matched, healthy subjects. We used an optimized positron emission tomography-magnetic resonance imaging (PET-MRI) registration method and an approach based on an intensity histogram using several indices. We compared the results of the intensity histogram analyses with a more canonical approach based on target-to-cerebellum Standard Uptake Value (SUVr) in white and grey matter using MANOVA and discriminant analyses. A cluster analysis on white and grey matter histograms was also performed.ResultsWhite matter histogram analysis revealed significant differences between AD and healthy subjects, which were not revealed by SUVr analysis. However, white matter histograms were not decisive to discriminate groups, and indices based on grey matter only showed better discriminative power than SUVr. The cluster analysis divided our sample into two clusters, showing different uptakes in grey, but also in white matter.ConclusionThese results demonstrate that AV-45 binding in white matter conveys subtle information not detectable using the SUVr approach. Although it is not more efficient than standard SUVr in discriminating AD patients from healthy subjects, this information could reveal white matter modifications.

A Case of Logopenic Primary Progressive Aphasia with C9ORF72 Expansion and Cortical Florbetapir Binding

We report the case of a 65-year-old woman, clinically diagnosed with the logopenic variant of primary progressive aphasia (PPA), and carrier of C9ORF72 expansion, despite cerebrospinal fluid biomarkers suggesting Alzheimers disease (AD). She underwent structural MRI, metabolic PET, and amyloid PET imaging using florbetapir. Comparison with healthy controls revealed widespread hypometabolism, left sided cortical atrophy, and an increased cortical amyloid load. No difference in amyloid binding was found between the patient and predemential AD patients. This case provides evidence of amyloidopathy in a carrier of C9ORF72 expansion exhibiting a clinical profile of the logopenic variant of PPA.

Amyloid Imaging with AV45 ( 18F-florbetapir) in a Cognitively Normal AβPP Duplication Carrier

We report the case of a 62-year-old asymptomatic carrier of AβPP gene duplication. He was investigated by MRI and the amyloid ligand (18)F-AV45, and compared to Alzheimers disease patients (n = 11) and healthy controls (n = 11). The neuropsychological examination was normal. Cortical thickness and AV45 retention were comparable to Alzheimers disease patients. AβPP duplication was diagnosed because cerebral amyloid angiopathy and Alzheimers disease pathology were found on the neuropathological examination of his youngest brother, who died at 42 from intracerebral hemorrhage. This is the first description of a pre-symptomatic AβPP duplication carrier over 60, despite widespread cerebral amyloid angiopathy, Alzheimers like atrophy, and amyloid deposition.

Diagnostic précoce de la maladie d’Alzheimer

INTRODUCTIONnDiagnosis of Alzheimers disease (AD) remains difficult to establish, and can only be considered as certain thanks to anatomopathological evidence, or genetic mutations. Current diagnostic criteria rely on innovative imaging and biological tools, in order to detect pathological cues from very early stages, and with best sensibility and sensitivity.nnnSTATE OF ARTnAdvances in neuro-imaging enabled the development of different tools to help establishing the diagnosis, such as cerebral atrophy assessment on magnetic resonance imaging (MRI), and cerebral metabolism study on positron emission tomography (PET). Besides, the increasing use of in vivo biological markers, combined to clinical criteria, enables to discriminate patients from healthy controls at even earlier stages. This includes studies on tau and beta-amyloid proteins concentrations in the cerebrosinal fluid, and amyloid-specific radioligands uptake. Familial forms of Alzheimer represent a great model for studying early or even pre-symptomatic AD, as genetic analyses constitute a diagnosis of certainty, even though they usually evolve earlier and faster.nnnPERSPECTIVES, CONCLUSIONnDiagnostic tools are more and more numerous and performant. According to patients clinical heterogeneity, it appears essential to associate different method to investigate, in order to make a diagnosis as early and as reliable as possible.