Video-oculography (VOG) provides a fast, noninvasive way to quantify eye-movement and pupil responses linked to how the brain samples and interprets visual information. We propose a task-free, emotionally valenced viewing paradigm for automatic screening of neurodegenerative disorders. Participants freely viewed a curated set of IAPS (International Affective Picture System) images spanning positive/negative/neutral valence and face/object content while gaze and pupil signals were recorded. From these recordings, we derived compact oculomotor and pupillary descriptors that capture spatial viewing allocation, eye movements, pupil dynamics, and frequency dynamics, and used them to discriminate healthy controls from amnestic mild cognitive impairment (aMCI), behavioral-variant frontotemporal dementia (bvFTD), and posterior cortical atrophy (PCA). Best configurations achieved mean subject-level accuracies of $0.871 \pm 0.085$ for healthy controls (CTR) versus aMCI, 0.817±0.060 for CTR versus bvFTD, and $0.786 \pm 0.060$ for CTR versus PCA, supporting affect-sensitive free-viewing VOG as a low-burden complementary screening signal.

Background Although Alzheimer's disease (AD) is biologically well characterized, early and precise phenotypic diagnosis remains challenging, especially for atypical variants. Posterior cortical atrophy (PCA) is a rare form of AD with progressive neurovisual impairment related to degeneration in visual processing areas. Objective To investigate how alterations in eye movement metrics, measured through video-oculography (VOG), reflect dysfunction across distinct brain networks in various AD phenotypes, with particular emphasis on PCA. Methods This study compared oculomotor parameters derived from VOG saccade analysis in early AD patients exhibiting two clinical phenotypes, PCA-AD (n = 21) and amnestic mild cognitive impairment (aMCI-AD, n = 11), along with 27 age-matched controls. Parameters analyzed included saccade latency, gain, velocity, intrusions and antisaccade error rates. All patients exhibited cerebrospinal fluid biomarkers consistent with AD pathology. Results As expected, neuropsychological testing revealed more severe neurovisual and executive deficits in PCA-AD versus aMCI-AD, and greater memory storage impairment in aMCI. Oculomotor data showed that PCA-AD patients exhibited prolonged saccade latencies, reduced gain, slower vertical saccades, and increased antisaccade errors compared to controls and aMCI-AD. Receiver operating characteristic analysis combining key saccadic metrics demonstrated up to 90% sensitivity and specificity in distinguishing PCA from controls and aMCI. Conclusions These findings support the use of VOG oculomotor metrics as phenotypic biomarkers in differentiating AD clinical forms. In PCA, they reflect the dysfunction of visuo-spatial attentional networks and their interaction with subcortical eye movement control circuits.

Abnormal brain accumulation of amyloid-β peptides, represents one of the earliest biological indicators of Alzheimer’s disease (AD) risk. Estimation on amyloid positivity (A+) prevalence among older adults without dementia are needed to assess the epidemiological impact of AD diagnosis solely through biological markers. We combined data from the French MEMENTO clinical cohort, where amyloid status was assessed through reference procedures, with the nationally representative SHARE-HCAP survey. Using stabilized inverse odds of selection weights, we adjusted the MEMENTO sample to estimate the prevalence of A+ in the French population aged 65–85 without dementia and their five-year risk of developing AD dementia. A+ prevalence was 21.4% (95% CI: 18.4–24.7) in French adults aged 65–85 without dementia i.e. approximately 2.5 million individuals, reaching 27.5% in the 80–85 age group. Over five years of follow-up, the cumulative incidence of AD dementia was 22.7% among A+ individuals, 8.0% among cognitively normal A+ adults and 62.3% among those with mild cognitive impairment. While A+ is common in older adults without dementia, most do not develop dementia within five years. Defining AD by A+ could substantially increase diagnoses, raising major public health, ethical, and health system challenges, especially as new anti-amyloid therapies emerge.

Purpose: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD). Methods: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients. We built a framework for risk variant interpretation and risk gradation and assessed the detection rates among early-onset AD (EOAD, age of onset (AOO) <= 65 years, n = 608) depending on AOO and pedigree structure and late-onset AD (66 < AOO < 75, n = 92). Results: Twenty-one patients carried a LP/P variant in a Mendelian gene (all with EOAD, 3.4%), 20 of 21 affected APP, PSEN1, or PSEN2. LP/P variant detection rates in EOAD ranged from 1.7% to 11.6% based on AOO and pedigree structure. Risk factors were found in 69.5% of the remaining 679 patients, including 83 (12.2%) being heterozygotes for rare risk variants, in decreasing order of frequency, in TREM2, ABCA7, ATP8B4, SORL1, and ABCA1, including 5 heterozygotes for multiple rare risk variants, suggesting non-monogenic inheritance, even in some autosomal-dominant-like pedigrees. Conclusion: We suggest that genetic screening should be proposed to all EOAD patients and should no longer be prioritized based on pedigree structure. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

La paralisi sopranucleare progressiva (PSP) è una rara malattia neurodegenerativa di causa sconosciuta. È legata all’aggregazione e alla propagazione anomala della proteina Tau a quattro ripetizioni (tauopatia 4R) all’interno dei neuroni e delle cellule gliali, all’origine di una morte cellulare. All’esame istopatologico, si osservano aggregati neurofibrillari e astrociti a ciuffo. Clinicamente, oltre alla forma classica descritta inizialmente, la PSP può manifestarsi con fenotipi diversi, spesso rendendo la diagnosi precoce difficile da stabilire. Tra le forme più comuni si possono citare la sindrome di Richardson (PSP-RS), la PSP-parkinsonismo (PSP-P), la PSP con disturbi progressivi della deambulazione e freezing (PSP-PGF), la PSP con presentazione frontale (PSP-F), la PSP-disturbi della parola e/o del linguaggio (PSP-SL) e la PSP-sindrome corticobasale (PSP-SCB). Ciò solleva il problema della diagnosi differenziale con altre patologie neurodegenerative a rivelazione motoria e/o cognitiva, come la malattia di Parkinson (MPI), la degenerazione lobare frontotemporale (DLFT) o la malattia di Alzheimer (MA). Benché nessun esame paraclinico consenta di stabilire una diagnosi di certezza, gli argomenti forniti dalla RM cerebrale (atrofia del mesencefalo), dalla tomografia a emissione di positroni (PET) cerebrale con 18F-fluorodesossiglucosio (18F-FDG) (ipometabolismo frontomesiale e striatale) o ancora mediante esame oculografico (riduzione della velocità delle saccadi) costituiscono un valido aiuto alla diagnosi. Ancora oggi non esiste alcun trattamento curativo della PSP. Le terapie proposte (fisioterapia, ortofonia, ortesi, iniezione di tossina botulinica…) mirano così a gestire i sintomi motori e non motori e a prevenire le complicanze della malattia.

Abstract Objectives Define the cutoff thresholds of the Kappa (K) and Lambda (L) free light chains (FLC) indices for the detection of intrathecal immunoglobulin synthesis (IIS) using the new K and L FLC ELISA from SEBIA. The reference technique, which is not readily standardized between laboratories, is based on the demonstration of oligoclonal banding (OCB) in cerebrospinal fluid (CSF) which is absent in serum. For the past 6 years, we have also routinely calculated the K FLC index using The Binding Site (TBS) reagents on an Optilite instrument, an approach increasingly used as an alternative and/or a complement to electrophoretic analysis. Methods We analyzed 391 serum/CSF pairs divided into three groups. The first group were cases without OCB and with normal albumin CSF/serum ratio (n=174). The second group were cases with specific OCB (n=73). The last group included patients with increased albumin CSF/sera ratio without OCB (n=142). Results Analysis of the first group determined that the cutoffs for detection of IIS are respectively 2.55 and 1.02 for the K FLC and L FLC indices. Of the 73 cases with IIS, only 2 had a K FLC index below this threshold (sensitivity of 97.26%), while 16 out of 73 cases (78.08%) and 13 out of 72 cases (81.94%) had an IgG and L FLC index below the cutoffs, respectively. Additionally, we illustrate equivalent performances for prediction of the presence of OCB between SEBIA and TBS methods. Conclusions Sebia K FLC and L FLC assays are adequate alternative methods for the diagnosis of IIS.

Background New diagnostic criteria of Progressive Supranuclear Palsy (PSP) have highlighted the interest of Eye Movement Records (EMR) at the early stage of the disease. Objectives To investigate the metabolic brain correlates of ocular motor dysfunction using [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in early PSP. Methods Retrospective observational descriptive study on longitudinal data with patients who underwent EMR and FDG-PET at the stage of suggestive and possible PSP according to Movement Disorders Society criteria. Longitudinal follow-up enables to confirm diagnosis of probable PSP. Using the Statistical Parametric Mapping software, we performed whole-brain voxel-based correlations between oculomotor variables and FDG-PET metabolism. Results Thirty-seven patients with early PSP who fulfilled criteria of probable PSP during the follow-up were included. Decrease in the gain of vertical saccades correlated with reduced metabolism in Superior Colliculi (SC). We also found a positive correlation between mean velocity of horizontal saccades and SC metabolism as well as dorsal nuclei in the pons. Finally, increase in horizontal saccades latencies correlated with decrease of posterior parietal metabolism. Conclusions These findings suggest the early involvement of SC in saccadic dysfunction in the course of PSP.

Inherited neuropathies are a genetically and phenotypically heterogenous group of disorders leading to sensory and motor dysfunction. For years, these neuropathies have been considered as non-treatable diseases, as no drug is able to induce nerve regrowth. Progress in molecular tools has changed this view and several neuropathies can now be efficiently treated. Some more will be treatable in the upcoming years. Basically, these new treatments can be divided into four categories, depending on the target: gene therapy; gene expression therapy; protein modification or replacement (enzyme replacement therapy, ERT); downstream therapies. In this short review, we will provide a few examples for each of them in the field of peripheral neuropathies.

Corticobasal syndrome (CBS) is a neuropathologically heterogeneous entity. The use of cerebrospinal fluid and amyloid biomarkers enables detection of underlying Alzheimer's disease (AD) pathology. We thus compared clinical, eye movement, and 18FDG-PET imaging characteristics in CBS in two groups of patients divided according to their amyloid biomarkers profile. Fourteen patients presenting with CBS and amyloidosis (CBS-A+) were compared with 16 CBS patients without amyloidosis (CBS-A-). The two groups showed similar motor abnormalities (parkinsonism, dystonia) and global cognitive functions. Unlike CBS-A+ patients who displayed more posterior cortical abnormalities, CBS-A- patients demonstrated more anterior cortical and brain stem dysfunctions on the basis of neuropsychological testing, study of saccade velocities and brain hypometabolism areas on 18FDG-PET. Interestingly, Dopamine Transporter SPECT imaging showed similar levels of dopaminergic degeneration in both groups. These findings confirm common and distinct brain abnormalities between the different neurodegenerative diseases that result in CBS. We demonstrate the importance of a multidisciplinary approach to improve diagnosis in vivo in particular on oculomotor examination.

An adaptive collocation-based surrogate model is developed for the solution of equations with random coefficients, referred to as stochastic equations. The surrogate model is defined on a Voronoi tessellation of the samples of the random parameters with centers chosen to be statistically representative of these samples. We investigate various interpolants over Voronoi cells in order to formulate surrogates and analyze their convergence properties. Unlike Monte Carlo solutions, relatively small numbers of deterministic calculations are needed to implement surrogate models. These models can be used to generate large sets of solution samples with a minimum computational effort. In this work, we propose a framework for an adaptive construction of the surrogate such that by refining the Voronoi cells, the mapping between the random parameters and the solution is incorporated. A rigorous refinement measure which is quantitatively indicative of the performance of the surrogate is used to drive adaptivity. We present numerical examples that compare this surrogate with other collocation-based surrogates and demonstrate the theoretical aspects of the adaptive method.

Les événements stressants de vie pourraient contribuer aux plaintes et déficits au stade de déficit cognitif léger (mild cognitive impairment), et à une progression plus rapide vers la démence de type Alzheimer (MA). L'objectif de ce travail est de préciser l'impact du stress chez des patients non-déments consultant un centre mémoire et d'étudier son substrat en TEP cérébrale au 18FDG. Cette étude s'appuie sur la cohorte MEMENTO, une cohorte nationale clinique de 2323 participants. Nous avons identifié à l'inclusion 512 sujets présentant une plainte cognitive subjective ou un déficit cognitif léger, pour lesquels les variables suivantes étaient disponibles : âge, sexe, niveau éducatif, statut tabagique, statut TEP amyloïde, statut APO-E, CDR, MMSE, scores NPI, TEP au 18FDG et échelle de stress. Cette dernière était cotée entre 0 et 10 (stress maximal) par les patients en fonction de la gêne ressentie. Des analyses statistiques ont été conduites pour établir le lien entre ces variables. Une analyse SPM12 de corrélation TEP au 18FDG voxel-à-voxel sur cerveau entier a également été réalisée selon le niveau de stress rapporté (en tenant compte des co-variables suivantes : âge, sexe, niveau éducatif, statut amyloïde, CDR, MMSE). Le score moyen à l'échelle de stress sur les 512 sujets de l'échantillon analytique était de 3,5 (écart-type) 2,6 (min 0–max 10). Ce score n'était pas modifié selon les statuts APO-E ɛ4, TEP amyloïde ou tabagique (ANOVA p > 0,25). Les personnes dont les scores de stress étaient les plus élevés étaient plus fréquemment des femmes, jeunes, moins diplômées, avec une plus grande sévérité aux scores CDR, MMSE et NPI (ANOVA/Pearson, p < 0,04). Après prise en compte des facteurs de confusion, la sévérité du stress exprimé était associée à un hypermétabolisme de la région amygdalienne droite et à un hypométabolisme temporal inférieur/latéral droit (p < 0,001, k > 180). Le stress associé aux événements de vie chez des patients non-déments consultant en centre mémoire est associé à une plus grande sévérité clinique, indépendante du statut APO-E ɛ4 et amyloïde, avec une dysfonction métabolique du lobe temporal droit en TEP au 18FDG. Des analyses complémentaires seront nécessaires pour préciser si ce profil est associé à une réorganisation différentielle des réseaux cérébraux associés à la MA avec un possible impact sur la conversion vers une démence.

BACKGROUND/OBJECTIVE:Performances on spatial decision eye-tracking tasks are known to be impaired in patients with moderate Alzheimer's disease (AD), but the clinical relevance of this deficit during earlier stages of AD remains unclear.METHODS:This study recruited patients with amnestic mild cognitive impairment (aMCI, prodromal AD), patients with mild AD, and age-matched controls from three French memory clinics. Participants' ability to make spatial judgments and decisions was assessed with an eye-tracking system, and cognitive performance on conventional neuropsychological tests was evaluated.RESULTS:We enrolled 26 controls, 25 aMCI patients (median Mini-Mental State Exam [MMSE] 26), and 23 mild-AD patients (median MMSE 23). Patients with mild AD had higher error rates on the spatial decision task than aMCI patients and controls (32.4% versus 23.5%; p < 0.01 and 32.4% versus 22.2%; p < 0.05, respectively), but there were no differences among the groups in anticipation rate or the percentage of express saccades. Additionally, error rates on the spatial decision task were inversely correlated with performance on visual memory tests (immediate and delayed recall on the DMS- 48: r =-0.44, p = 0.0019 and r =-0.43, p = 0.0020, respectively), semantic fluency (r =-0.44, p = 0.0016), and global cognition (MMSE: r =-0.44, p = 0.0019). Performance on the spatial decision task was not correlated with anti-saccades, processing speed, or attentional performance.CONCLUSIONS:Patients with mild AD made more errors on a spatial decision task than aMCI patients and controls. We hypothesize that impaired visuospatial judgment may explain these results and distinguish aMCI patients from mild AD patients.

ObjectiveTo estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants.MethodsWe conducted a meta‐analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid‐β pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) ε4 status was determined using generalized estimating equation models.ResultsAmyloid‐β positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p < 0.001). Prevalence of amyloid‐β positivity increased with age in nfvPPA (from 10% at age 50 years to 27% at age 80 years, p < 0.01) and svPPA (from 6% at age 50 years to 32% at age 80 years, p < 0.001), but not in lvPPA (p = 0.94). Across PPA variants, ApoE ε4 carriers were more often amyloid‐β positive (58.0%) than noncarriers (35.0%, p < 0.001). Autopsy data revealed Alzheimer disease pathology as the most common pathologic diagnosis in lvPPA (76%), frontotemporal lobar degeneration–TDP‐43 in svPPA (80%), and frontotemporal lobar degeneration–TDP‐43/tau in nfvPPA (64%).InterpretationThis study shows that the current PPA classification system helps to predict underlying pathology across different cohorts and clinical settings, and suggests that age and ApoE genotype should be considered when interpreting amyloid‐β biomarkers in PPA patients. Ann Neurol 2018;84:737–748

Saccade alterations are potential early signs of Alzheimer's disease. However, uncertainty persists in how early and reliably automated saccade recording systems detect impairments. This multicenter pathophysiological case-control transversal study explored saccade execution in carefully diagnosed amnestic mild cognitive impairment patients fulfilling research criteria for prodromal Alzheimer's disease (n = 29), as compared to both aged-matched mild Alzheimer's disease patients (n = 23) and controls (n = 27). Auto-coded saccades from horizontal (gap) vertical (step) stimulus elicited pro-saccades, and anti-saccade (gap) tasks were compared across the 3 groups. Mild cognitive impairment patients committed significantly more anti-saccade errors compared to controls (46.9 versus 24.3%, p < 0.001). Conventional analyses of the auto-coded stimulus elicited saccades parameters did not distinguish the amnestic mild cognitive impairment from controls or the mild Alzheimer's disease group. However, an offline analysis of manually coded saccade latencies, using resampling statistics did reveal subtle differences among the groups. Analysis of the manually coded data revealed that the mild Alzheimer's disease group had a reliably larger self-corrected error-rate than in amnestic mild cognitive impairment and controls (p = 0.003). Analysis of the manually coded saccade latencies, using more sensitive lognormal bootstrap analysis revealed a continuum, from amnestic mild cognitive impairment to mild Alzheimer's disease, of an increased severity of impaired inhibition of stimulus elicited saccades and correct voluntary saccade initiation. Anti-saccade error rates and psychometric measures of executive and several other cognitive functions were moderately and negatively correlated. Overall, inhibitory impairments in stimulus elicited saccades, characteristic of Alzheimer's disease, may be detected early in presumed prodromal patients using a simple, automated anti-saccade task.

Background:Neurodegeneration biomarkers are routinely used in the diagnosis of Alzheimer's disease (AD). Objective:To evaluate the respective contributions of two neuroimaging biomarkers, structural MRI and 18FDG-PET, in the assessment of neurodegeneration in AD dementia. Methods:Patients with mild AD dementia diagnosed based on clinical and cerebrospinal fluid criteria and cognitively healthy subjects, from the Marseille cohort ADAge with cognitive, structural MRI and 18FDG-PET assessments, were included. Extent of atrophy on MRI and of hypometabolism on 18FDG-PET were individually evaluated in each patient using a voxel-based analysis on whole-brain approach and compared to healthy subjects. Patients were divided in distinct groups according to their atrophy extent on the one hand and to their hypometabolism extent on the other, then, to their imaging profile combining the extent of the two biomarkers. Results:Fifty-two patients were included. The MMSE score was significantly lower in the "Extensive hypometabolism" group than in the "Limited hypometabolism" group (respectively 19.5/30 versus 23/30). A lower Innotest Amyloid Tau Index was associated with an extensive hypometabolism (p = 0.04). There were more patients with low educational level in the "Extensive atrophy" group, while a higher educational level was more found in the "Limited atrophy" group (p = 0.005). Conclusion:18FDG-PET hypometabolism extent is associated with the pathological processes and clinical severity of AD, while MRI atrophy seems to be influenced by the cognitive reserve. In the context of mild AD dementia, these two biomarkers of neurodegeneration are thus not interchangeable and require to be considered in combination rather than in isolation.

Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are two atypical parkinsonian syndromes first described half a century ago. The spectrum of these conditions as well as, more generally, the concept of tauopathy have dramatically changed over the past decade and especially in recent years. In particular, clinicopathological correlations have led to the description of several subtypes of these diseases and the features they share with other neurodegenerative diseases. The present paper is a review of how the concepts of PSP and CBD have evolved over time. In particular, it focuses on the different presentations of the disease and the overlapping syndromes that can complicate the differential diagnoses. Also discussed are some of the tools that may prove useful in making a diagnosis. Indeed, differential diagnosis issues are of particular importance in light of the likely emergence of pathology-specific disease-modifying therapies in the near future.

Introduction. - The diagnosis of Alzheimer's disease (AD) and its related disorders rely on clinical criteria. There is, however, a large clinical overlap between the different neurodegenerative diseases affecting cognition and, frequently, there ere diagnostic uncertainties with atypical clinical presentations. Current clinical practice's can now regularly use positron emission tomography (PET) and single-photon emission computed tomography (SPECT) molecular imaging to help resolve such uncertainties. The Neurology Group of the French Society of Nuclear Medicine and Federations of Memory, Resources and Research Centers have collaborated to establish clinical guidelines to determine which molecular imaging techniques to use when seeking a differential diagnosis between AD and other neurodegenerative disorders affecting cognition.State of knowledge. - According to the current medical literature, the potential usefulness of molecular imaging to address the typical clinical criteria in common forms of AD remains modest, as typical AD presentations rarely raise questions of differential diagnoses with other neurodegenerative disorders. However, molecular imaging could be of significant value in the diagnosis of atypical neurodegenerative disorders, including early onset, rapid cognitive decline, prominent non-amnestic presentations involving language, visuospatial, behavioral/executive and/or non-cognitive symptoms in AD, or prominent amnestic presentations in other non-AD dementias.Conclusion and perspective. - The clinical use of molecular imaging should be recommended for assessing cognitive disturbances particularly in patients with early clinical onset (before age 65) and atypical presentations. However, diagnostic tools should always be part of the global clinical approach, as an isolated positive result cannot adequately establish a diagnosis of any neurodegenerative disorder. (C) 2016 Elsevier Masson SAS. All rights reserved.

OBJECTIVE : To examine if patients with sporadic early-onset Alzheimer's disease (EOAD) and those with late-onset Alzheimer's disease (LOAD) exhibit distinct patterns of impairment across memory subdomains. METHOD : One group of EOAD patients (n=20, MMSE = 21, mean age: 60.6), one group of LOAD patients (n=20, MMSE = 22, mean age: 77.9) and two groups of matched younger and older controls (n=40) participated. All patients presented with mild dementia (CDR=1). The diagnosis of AD was supported by evidence of both amyloïdopathy and neuronal injury from CSF biomarkers (Innotest). All participants underwent a detailed neuropsychological assessment, a MRI scan and a FDG-PET scan. For each neuropsychological test, individual z-scores were calculated and then averaged into a global patient group z-score (EOAD/LOAD) for each cognitive domain. RESULTS : Both EOAD and LOAD groups were impaired in all the cognitive domains when compared to their respective control groups. Concerning memory domains both groups were similarly affected on measures of verbal episodic memory, short term memory and working memory. The EOAD group was not more affected than the LOAD group in any memory domain. By contrast LOAD patients showed significantly poorer performance than EOAD patients in semantic memory (p < 0.0001). VBM analysis with MRI and SPM with PET-FDG showed that impaired semantic performance in patients was associated with reduced gray matter volume in the anterior temporal lobe region bilaterally and greater hypometabolism in the left temporoparietal region, both areas being key regions of the semantic network. DISCUSSION : Contrary to previous studies, our results do not support the view that EOAD patients show a preservation of memory in the early stage of the disease. EOAD and LOAD patients present with distinct patterns of memory impairment, and LOAD patients show a prominent semantic memory impairment