Skip to main content

Marie Sarazin

Followers

40

Following

24

Co-authors

23

Public Views

Phone: +00 1 45 65 65 73
Address: Neurology of Memory and language, centre Hospitalier Sainte Anne, 1 rue Cabanis, 75014 Paris, France

less

Philippe Millet

Denis Guilloteau

Georgios Dervenoulas

Kings College London

Stanford University

Bart Van Berckel

Kamen Tsvetanov

Interests

Uploads

Papers by Marie Sarazin

Distinct dynamic profiles of microglial activation are associated with progression of Alzheimer's disease

Brain : a journal of neurology, 2018

Although brain neuroinflammation may play an instrumental role in the pathophysiology of Alzheime... more Although brain neuroinflammation may play an instrumental role in the pathophysiology of Alzheimer's disease, its actual impact on disease progression remains controversial, being reported as either detrimental or protective. This work aimed at investigating the temporal relationship between microglial activation and clinical progression of Alzheimer's disease. First, in a large cohort of patients with Alzheimer's disease we analysed the predictive value of microglial activation assessed by 18F-DPA-714 PET imaging on functional, cognitive and MRI biomarkers outcomes after a 2-year follow-up. Second, we analysed the longitudinal progression of 18F-DPA-714 binding in patients with Alzheimer's disease by comparison with controls, and assessed its influence on clinical progression. At baseline, all participants underwent a clinical assessment, brain MRI, 11C-PiB, 18F-DPA-714 PET imaging and TSPO genotyping. Participants were followed-up annually for 2 years. At the end o...

Distinct amyloid and tau PET signatures are associated with diverging clinical and imaging trajectories in patients with amnestic syndrome of the hippocampal type

Translational Psychiatry, 2021

We aimed to investigate the amyloid and tau PET imaging signatures of patients with amnestic synd... more We aimed to investigate the amyloid and tau PET imaging signatures of patients with amnestic syndrome of the hippocampal type (ASHT) and study their clinical and imaging progression according to their initial PET imaging status. Thirty-six patients with a progressive ASHT and 30 controls underwent a complete neuropsychological assessment, 3 T brain MRI, [11C]-PiB and [18F]-Flortaucipir PET imaging. Subjects were clinically followed-up annually over 2 years, with a second 3 T MRI (n = 27 ASHT patients, n = 28 controls) and tau-PET (n = 20 ASHT patients) at the last visit. At baseline, in accordance with the recent biological definition of Alzheimer’s disease (AD), the AD PET signature was defined as the combination of (i) positive cortical amyloid load, and (ii) increased tau tracer binding in the entorhinal cortices and at least one of the following regions: amygdala, parahippocampal gyri, fusiform gyri. Patients who did not meet these criteria were considered to have a non-AD patho...

P2-8 Déclineurs rapides et déclineurs lents : intérêt de l’étude en VBM dans la maladie d’alzheimer

Revue Neurologique, 2005

Identification of Atrophy Patterns in Alzheimer’s Disease Based on SVM Feature Selection and Anatomical Parcellation

Lecture Notes in Computer Science, 2008

In this paper, we propose a fully automated method to individually classify patients with Alzheim... more In this paper, we propose a fully automated method to individually classify patients with Alzheimer's disease (AD) and elderly control subjects based on anatomical magnetic resonance imaging (MRI). Our approach relies on the identification of gray matter (GM) atrophy patterns using whole-brain parcellation into anatomical regions and the extraction of GM characteristics in these regions. Discriminative features are identified using different feature selection (FS) methods and used in a Support Vector Machine (SVM) for individual classification. We compare two different types of parcellations corresponding to two different levels of anatomical details. We validate our approach with two distinct groups of subjects: an initial cohort of 16 AD patients and 15 elderly controls and a second cohort of 17 AD patients and 13 controls. We used the first cohort for training and region selection and the second cohort for testing and obtained high classification accuracy (90%).

Importance of lack of interest in patients with mild cognitive impairment

by Philippe Robert and Marie Sarazin

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2008

Apathy is one of the most common behavioral symptoms in mild cognitive impairment (MCI). The aim ... more Apathy is one of the most common behavioral symptoms in mild cognitive impairment (MCI). The aim of the authors' study was to examine the influence of the apathy dimensions, i.e., emotional blunting, lack of initiative, and lack of interest, on the risk of developing of Alzheimer disease (AD) in patients with MCI. Longitudinal study. Fourteen French memory clinics. Apathy was assessed in 214 MCI patients. The main endpoint considered was the development of AD during the 3-year follow-up. The neuropsychiatric evaluation included the Goldberg anxiety scale and the Montgomery and Asberg Depression Rating Scale; apathy was assessed with the Apathy Inventory. After 3 years, 59 patients (27.2%) had developed AD. The risk of conversion to AD was significantly higher for patients with lack of interest. Using Cox analyses, controlling for age, gender and education, the difference between survival curves was significant for lack of interest. Lack of interest, a mild behavioral sign, could...

P2-004: Brain perfusion SPECT profile in posterior cortical atrophy

Background: Diffraction enhanced imaging (DEI) is a new imaging modality that generates contrast ... more Background: Diffraction enhanced imaging (DEI) is a new imaging modality that generates contrast from the refraction of ϫ-rays. DEI's images show enhanced soft tissue contrast as compared to conventional radiography. Objective: We tested the hypothesis that amyloid deposits (A␤ plaques), one of the hallmarks of Alzheimer's disease (AD), can be visualized by DEI when applied in the micro-computed tomography (microCT) mode. Methods: Formalin-fixed brains excised from the skull of AD-model [B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J, male, 6 months] and age-matched wild-type mouse brains were imaged whole using 20 keV ϫ-rays on the DEI system at the National Synchrotron Light Source. Volumetric refraction microCT data sets of the mouse brains were generated with a voxel size of 9 m. Post-imaging, the brains were sectioned using a cryotome and immunostained to mark the A␤ plaques. Images from the refraction microCT data set were compared to the corresponding digitized histological sections using anatomical landmarks and processing software. Several anatomical structures within the brain, such as hippocampal subregions and white matter tracks, were visualized. Importantly, structures resembling small 'nodules' were seen in the refraction microCT images of the AD-model mouse brain but not in the wild-type brain. The size and physical density of the nodules were measured and compared to A␤ plaques on the histological sections. Results: Histological stained brain sections corresponding to the refraction microCT slice images demonstrated that the nodule-like structures in the cortex and hippocampus of the ADmodel mouse brain corresponded to locations of A␤ plaques. The size of the plaques, as determined from the refraction microCT data, was 44 Ϯ 13 m. The difference in density between the plaques and the surrounding brain tissue was 21 Ϯ 4 mg/cc. Conclusions: We have demonstrated that the DEI technique can be used both to visualize A␤ plaques and measure their density. As such, it provides novel physical information which is not currently available with other imaging tech-niques. This technique can be extended to in vivo imaging of mice allowing for tracking and characterizing A␤ plaques over time.

DIAGNOSIS VALUE OF HIPPOCAMPAL VOLUME IN BIOLOGICALLY CONFIRMED AD

Alzheimer's & Dementia, 2014

computed with the BMAS algorithm in a "leave-one out" fashion. Segmentation accuracy was assessed... more computed with the BMAS algorithm in a "leave-one out" fashion. Segmentation accuracy was assessed using Dice and relative volume error (RVE) with the provided hippocampal segmentations as reference. Pearson's correlation between computed and reference volumes was also calculated. Finally cohort separation power was measured with the area under the ROC curve (AUC). Results: As detailed in Tables 1 and 2, accuracy of the proposed BMAS segmentation was high (Dice¼ 86.59% 6 1.80) and total hippocampal volumes (right + left) were very close to the reference volumes (RVE¼3.96% 6 3.31). BMAS hippocampus segmentations were highly correlated to the reference hippocampus segmentations (r¼0.96 with p<0.001). Similar ability for subject cohort separation was observed for the reference and BMAS hippocampus segmentations (see ). Conclusions: The implementation of BMAS based on the new 100 atlases from the hippocampal protocol was straightforward and successful. BMAS results were highly correlated with those of the harmonized hippocampal protocol and its ability to separate subject cohorts was also very similar. The newly released library of atlases generated based on the hippocampal protocol can be used as the new gold standard for benchmarking various segmentation methods in terms of accuracy and reproducibility and as the reference library for processing MRI scans in prospective AD trials.

by Marie Sarazin and Sophie Auriacombe

[Procedural learning and Parkinson disease: implication of striato-frontal loops]

Revue Neurologique

To investigate procedural learning in non demented patients with idiopathic Parkinson's disea... more To investigate procedural learning in non demented patients with idiopathic Parkinson's disease (PD). Experimental evidence implicate the basal ganglia in procedural learning. Selective impairment has more recently been described in patients with frontal lesions. The performance of 20 demented patients and 15 matched normal controls was studied in the serial reaction time task (SRTT). Performance on procedural task was further compared with that of 9 normal controls and with patients' performance on tests assessing explicit memory, executive functions and global efficiency. The group of patients with PD showed impaired procedural learning. The difference of response time between the repeated and the non-repeated blocks was smaller in PD when compared to controls. Subsequent analyses separated PD patients into two subgroups according to their performance on SRTT, measured by the rebound effect. PD patients whose learning was normal differed from PD patients whose learning was...

Detection of volume loss in hippocampal layers in Alzheimer's disease using 7 T MRI: A feasibility study

NeuroImage: Clinical, 2014

In Alzheimer3s disease (AD), the hippocampus is an early site of tau pathology and neurodegenerat... more In Alzheimer3s disease (AD), the hippocampus is an early site of tau pathology and neurodegeneration. Histological studies have shown that lesions are not uniformly distributed within the hippocampus. Moreover, alterations of different hippocampal layers may reflect distinct pathological processes. 7 T MRI dramatically improves the visualization of hippocampal subregions and layers. In this study, we aimed to assess whether 7 T MRI can detect volumetric changes in hippocampal layers in vivo in patients with AD. We studied four AD patients and seven control subjects. MR images were acquired using a whole-body 7 T scanner with an eight channel transmitreceive coil. Hippocampal subregions were manually segmented from coronal T2*-weighted gradient echo images with 0.3 × 0.3 × 1.2 mm 3 resolution using a protocol that distinguishes between layers richer or poorer in neuronal bodies. Five subregions were segmented in the region of the hippocampal body: alveus, strata radiatum, lacunosum and moleculare (SRLM) of the cornu Ammonis (CA), hilum, stratum pyramidale of CA and stratum pyramidale of the subiculum. We found strong bilateral reductions in the SRLM of the cornu Ammonis and in the stratum pyramidale of the subiculum (p b 0.05), with average cross-sectional area reductions ranging from −29% to −49%. These results show that it is possible to detect volume loss in distinct hippocampal layers using segmentation of 7 T MRI. 7 T MRI-based segmentation is a promising tool for AD research.

P3-13 Taxonomie de l’apathie dans les démences neurodégénératives

Revue Neurologique, 2005

Objectif : Évaluer les performances de l'association Memory Impairment Screen (MIS) et Set Test d... more Objectif : Évaluer les performances de l'association Memory Impairment Screen (MIS) et Set Test d'Isaacs (STI) dans la détection de tous les types de démence. Matériel et méthode : 356 sujets contrôles et 542 patients ayant une maladie d'Alzheimer ou une autre démence (mixte, vasculaire, lewy, fronto-temporale) ont tous passé le MIS, le STI, le MMSE et une batterie neuropsychologique. Le calcul des cut-off pour chaque test a été effectué à l'aide de courbes ROC (Receiver Operating Characteristics Curves). Une régression logistique a été utilisée pour évaluer l'efficacité du couple MIS/STI. Résultats : La sensibilité du couple MIS < 6 et/ou STI < 25 est de 0.92 et sa spécificité de 0.89. La sensibilité est de 0.88 pour les stades légers (CDR = 1), 0.93 pour les stades modérés (CDR = 2) et de 0.98 pour les stades sévères (CDR = 3). La régression logistique montre une sensibilité globale de 0.91 et une spécificité de 0.92. Conclusion :

Similar beta-amyloid burden in posterior cortical atrophy and Alzheimer's disease

Alzheimers & Dementia, 2011

CSF tau markers are correlated with hippocampal volume in Alzheimer's disease

Neurobiology of aging, 2012

Hippocampal atrophy as assessed by magnetic resonance imaging (MRI) and abnormal cerebrospinal fl... more Hippocampal atrophy as assessed by magnetic resonance imaging (MRI) and abnormal cerebrospinal fluid (CSF) biomarkers are supportive features for the diagnosis of Alzheimer's disease (AD) and are assumed to be indirect pathological markers of the disease. In AD patients, antemortem MRI hippocampal volumes (HVs) correlate with the density of neurofibrillary tangles (but not with senile plaques) at autopsy suggesting that HVs may better correlate with CSF tau and hyperphosphorylated tau (P-tau) levels than CSF amyloid beta protein (Aβ)(42) level. Here, we tested this hypothesis in a well-defined AD group. Patients were selected according to the New Research Criteria for AD, including specific episodic memory deficit and CSF AD profile (defined as abnormal ratio of Aβ(42):tau). MRI was performed within 6 months of lumbar puncture. HVs were obtained using automated segmentation software. Thirty-six patients were included. Left HV correlated with CSF tau (R = -0.53) and P-tau (R = -0...

Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal Alzheimer's disease

by Marie Sarazin and Harald Hampel

Alzheimer's & Dementia, 2015

Background: To study the effect of donepezil on the rate of hippocampal atrophy in prodromal Alzh... more Background: To study the effect of donepezil on the rate of hippocampal atrophy in prodromal Alzheimer's disease (AD). Methods: A double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day) in subjects with suspected prodromal AD. Subjects underwent two brain magnetic resonance imaging scans (baseline and final visit). The primary efficacy outcome was the annualized percentage change (APC) of total hippocampal volume (left 1 right) measured by an automated segmentation method. Results: Two-hundred and sixteen only subjects were randomized across 28 French expert clinical sites. In the per protocol population (placebo 5 92 and donepezil 5 82), the donepezil group exhibited a significant reduced rate of hippocampal atrophy (APC 5 21.89%) compared with the placebo group (APC 5 23.47%), P , .001. There was no significant difference in neuropsychological performance between treatment groups. Conclusions: A 45% reduction of rate of hippocampal atrophy was observed in prodromal AD following 1 year of treatment with donepezil compared with placebo.

Psychiatric Presentation of Frontotemporal Dementia Associated with Inclusion Body Myopathy due to the VCP Mutation (R155H) in a French Family

by Agnès Jacquin and Marie Sarazin

Case Reports in Neurology, 2013

Clinical Investigations in Primary Care

Frontiers of Neurology and Neuroscience, 2009

Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) is a progressive neurodegenerative disorder that represents the most common form of dementia. The most prominent feature of AD is the decline in cognitive function, with an early impairment of episodic memory. The memory deficit of an AD patient is characterized by the amnestic syndrome of the medial temporal type. As the disease progresses, the condition often manifests in language disorders, visuospatial deficits and executive dysfunctions. Patients often have neuropsychiatric disturbances, as apathy and psychotic symptoms. Loss of autonomy follows cognitive impairment. The clinical diagnosis of AD is based on a complete medical examination with a neuropsychological evaluation. The FCSRT (free and cued selective reminding test) is recommended for the identification of the amnestic syndrome of the medial temporal type, which is defined by: (1) a very poor free recall and (2) a decreased total recall due to an insufficient effect of cueing. The neuropsychological tests should also assess other cognitive functions that may be perturbed in AD, such as executive functions, praxis, visuospatial capacities and language. Neuroimaging and biological exams (genetics, biomarkers) are of great utility in the evaluation. Other medical, neurological, or psychiatric disorders which could account for the impairment in memory and related symptoms must be always investigated.

Facteurs pronostiques et évolutifs de la maladie d’Alzheimer : intérêt de l’IRM cérébrale

Revue Neurologique, 2008

P3-39 Profil des biomarqueurs au LCR dans une population avec atrophie corticale postérieure

Revue Neurologique, 2009

P3-38 Le ratio Tau/Ab42 dans le LCR différencie la MA de la DFT avec une spécificité élevée

Revue Neurologique, 2009

Démence sémantique : réflexions d’un groupe de travail pour des critères de diagnostic en français et la constitution d’une cohorte de patients

by Marie Sarazin and Sophie Auriacombe

Revue Neurologique, 2008

Distinct dynamic profiles of microglial activation are associated with progression of Alzheimer's disease

Brain : a journal of neurology, 2018

Although brain neuroinflammation may play an instrumental role in the pathophysiology of Alzheime... more Although brain neuroinflammation may play an instrumental role in the pathophysiology of Alzheimer's disease, its actual impact on disease progression remains controversial, being reported as either detrimental or protective. This work aimed at investigating the temporal relationship between microglial activation and clinical progression of Alzheimer's disease. First, in a large cohort of patients with Alzheimer's disease we analysed the predictive value of microglial activation assessed by 18F-DPA-714 PET imaging on functional, cognitive and MRI biomarkers outcomes after a 2-year follow-up. Second, we analysed the longitudinal progression of 18F-DPA-714 binding in patients with Alzheimer's disease by comparison with controls, and assessed its influence on clinical progression. At baseline, all participants underwent a clinical assessment, brain MRI, 11C-PiB, 18F-DPA-714 PET imaging and TSPO genotyping. Participants were followed-up annually for 2 years. At the end o...

Distinct amyloid and tau PET signatures are associated with diverging clinical and imaging trajectories in patients with amnestic syndrome of the hippocampal type

Translational Psychiatry, 2021

We aimed to investigate the amyloid and tau PET imaging signatures of patients with amnestic synd... more We aimed to investigate the amyloid and tau PET imaging signatures of patients with amnestic syndrome of the hippocampal type (ASHT) and study their clinical and imaging progression according to their initial PET imaging status. Thirty-six patients with a progressive ASHT and 30 controls underwent a complete neuropsychological assessment, 3 T brain MRI, [11C]-PiB and [18F]-Flortaucipir PET imaging. Subjects were clinically followed-up annually over 2 years, with a second 3 T MRI (n = 27 ASHT patients, n = 28 controls) and tau-PET (n = 20 ASHT patients) at the last visit. At baseline, in accordance with the recent biological definition of Alzheimer’s disease (AD), the AD PET signature was defined as the combination of (i) positive cortical amyloid load, and (ii) increased tau tracer binding in the entorhinal cortices and at least one of the following regions: amygdala, parahippocampal gyri, fusiform gyri. Patients who did not meet these criteria were considered to have a non-AD patho...

P2-8 Déclineurs rapides et déclineurs lents : intérêt de l’étude en VBM dans la maladie d’alzheimer

Revue Neurologique, 2005

Identification of Atrophy Patterns in Alzheimer’s Disease Based on SVM Feature Selection and Anatomical Parcellation

Lecture Notes in Computer Science, 2008

In this paper, we propose a fully automated method to individually classify patients with Alzheim... more In this paper, we propose a fully automated method to individually classify patients with Alzheimer's disease (AD) and elderly control subjects based on anatomical magnetic resonance imaging (MRI). Our approach relies on the identification of gray matter (GM) atrophy patterns using whole-brain parcellation into anatomical regions and the extraction of GM characteristics in these regions. Discriminative features are identified using different feature selection (FS) methods and used in a Support Vector Machine (SVM) for individual classification. We compare two different types of parcellations corresponding to two different levels of anatomical details. We validate our approach with two distinct groups of subjects: an initial cohort of 16 AD patients and 15 elderly controls and a second cohort of 17 AD patients and 13 controls. We used the first cohort for training and region selection and the second cohort for testing and obtained high classification accuracy (90%).

Importance of lack of interest in patients with mild cognitive impairment

by Philippe Robert and Marie Sarazin

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2008

Apathy is one of the most common behavioral symptoms in mild cognitive impairment (MCI). The aim ... more Apathy is one of the most common behavioral symptoms in mild cognitive impairment (MCI). The aim of the authors' study was to examine the influence of the apathy dimensions, i.e., emotional blunting, lack of initiative, and lack of interest, on the risk of developing of Alzheimer disease (AD) in patients with MCI. Longitudinal study. Fourteen French memory clinics. Apathy was assessed in 214 MCI patients. The main endpoint considered was the development of AD during the 3-year follow-up. The neuropsychiatric evaluation included the Goldberg anxiety scale and the Montgomery and Asberg Depression Rating Scale; apathy was assessed with the Apathy Inventory. After 3 years, 59 patients (27.2%) had developed AD. The risk of conversion to AD was significantly higher for patients with lack of interest. Using Cox analyses, controlling for age, gender and education, the difference between survival curves was significant for lack of interest. Lack of interest, a mild behavioral sign, could...

P2-004: Brain perfusion SPECT profile in posterior cortical atrophy

Background: Diffraction enhanced imaging (DEI) is a new imaging modality that generates contrast ... more Background: Diffraction enhanced imaging (DEI) is a new imaging modality that generates contrast from the refraction of ϫ-rays. DEI's images show enhanced soft tissue contrast as compared to conventional radiography. Objective: We tested the hypothesis that amyloid deposits (A␤ plaques), one of the hallmarks of Alzheimer's disease (AD), can be visualized by DEI when applied in the micro-computed tomography (microCT) mode. Methods: Formalin-fixed brains excised from the skull of AD-model [B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J, male, 6 months] and age-matched wild-type mouse brains were imaged whole using 20 keV ϫ-rays on the DEI system at the National Synchrotron Light Source. Volumetric refraction microCT data sets of the mouse brains were generated with a voxel size of 9 m. Post-imaging, the brains were sectioned using a cryotome and immunostained to mark the A␤ plaques. Images from the refraction microCT data set were compared to the corresponding digitized histological sections using anatomical landmarks and processing software. Several anatomical structures within the brain, such as hippocampal subregions and white matter tracks, were visualized. Importantly, structures resembling small 'nodules' were seen in the refraction microCT images of the AD-model mouse brain but not in the wild-type brain. The size and physical density of the nodules were measured and compared to A␤ plaques on the histological sections. Results: Histological stained brain sections corresponding to the refraction microCT slice images demonstrated that the nodule-like structures in the cortex and hippocampus of the ADmodel mouse brain corresponded to locations of A␤ plaques. The size of the plaques, as determined from the refraction microCT data, was 44 Ϯ 13 m. The difference in density between the plaques and the surrounding brain tissue was 21 Ϯ 4 mg/cc. Conclusions: We have demonstrated that the DEI technique can be used both to visualize A␤ plaques and measure their density. As such, it provides novel physical information which is not currently available with other imaging tech-niques. This technique can be extended to in vivo imaging of mice allowing for tracking and characterizing A␤ plaques over time.

DIAGNOSIS VALUE OF HIPPOCAMPAL VOLUME IN BIOLOGICALLY CONFIRMED AD

Alzheimer's & Dementia, 2014

computed with the BMAS algorithm in a "leave-one out" fashion. Segmentation accuracy was assessed... more computed with the BMAS algorithm in a "leave-one out" fashion. Segmentation accuracy was assessed using Dice and relative volume error (RVE) with the provided hippocampal segmentations as reference. Pearson's correlation between computed and reference volumes was also calculated. Finally cohort separation power was measured with the area under the ROC curve (AUC). Results: As detailed in Tables 1 and 2, accuracy of the proposed BMAS segmentation was high (Dice¼ 86.59% 6 1.80) and total hippocampal volumes (right + left) were very close to the reference volumes (RVE¼3.96% 6 3.31). BMAS hippocampus segmentations were highly correlated to the reference hippocampus segmentations (r¼0.96 with p<0.001). Similar ability for subject cohort separation was observed for the reference and BMAS hippocampus segmentations (see ). Conclusions: The implementation of BMAS based on the new 100 atlases from the hippocampal protocol was straightforward and successful. BMAS results were highly correlated with those of the harmonized hippocampal protocol and its ability to separate subject cohorts was also very similar. The newly released library of atlases generated based on the hippocampal protocol can be used as the new gold standard for benchmarking various segmentation methods in terms of accuracy and reproducibility and as the reference library for processing MRI scans in prospective AD trials.

by Marie Sarazin and Sophie Auriacombe

[Procedural learning and Parkinson disease: implication of striato-frontal loops]

Revue Neurologique

To investigate procedural learning in non demented patients with idiopathic Parkinson's disea... more To investigate procedural learning in non demented patients with idiopathic Parkinson's disease (PD). Experimental evidence implicate the basal ganglia in procedural learning. Selective impairment has more recently been described in patients with frontal lesions. The performance of 20 demented patients and 15 matched normal controls was studied in the serial reaction time task (SRTT). Performance on procedural task was further compared with that of 9 normal controls and with patients' performance on tests assessing explicit memory, executive functions and global efficiency. The group of patients with PD showed impaired procedural learning. The difference of response time between the repeated and the non-repeated blocks was smaller in PD when compared to controls. Subsequent analyses separated PD patients into two subgroups according to their performance on SRTT, measured by the rebound effect. PD patients whose learning was normal differed from PD patients whose learning was...

Detection of volume loss in hippocampal layers in Alzheimer's disease using 7 T MRI: A feasibility study

NeuroImage: Clinical, 2014

In Alzheimer3s disease (AD), the hippocampus is an early site of tau pathology and neurodegenerat... more In Alzheimer3s disease (AD), the hippocampus is an early site of tau pathology and neurodegeneration. Histological studies have shown that lesions are not uniformly distributed within the hippocampus. Moreover, alterations of different hippocampal layers may reflect distinct pathological processes. 7 T MRI dramatically improves the visualization of hippocampal subregions and layers. In this study, we aimed to assess whether 7 T MRI can detect volumetric changes in hippocampal layers in vivo in patients with AD. We studied four AD patients and seven control subjects. MR images were acquired using a whole-body 7 T scanner with an eight channel transmitreceive coil. Hippocampal subregions were manually segmented from coronal T2*-weighted gradient echo images with 0.3 × 0.3 × 1.2 mm 3 resolution using a protocol that distinguishes between layers richer or poorer in neuronal bodies. Five subregions were segmented in the region of the hippocampal body: alveus, strata radiatum, lacunosum and moleculare (SRLM) of the cornu Ammonis (CA), hilum, stratum pyramidale of CA and stratum pyramidale of the subiculum. We found strong bilateral reductions in the SRLM of the cornu Ammonis and in the stratum pyramidale of the subiculum (p b 0.05), with average cross-sectional area reductions ranging from −29% to −49%. These results show that it is possible to detect volume loss in distinct hippocampal layers using segmentation of 7 T MRI. 7 T MRI-based segmentation is a promising tool for AD research.

P3-13 Taxonomie de l’apathie dans les démences neurodégénératives

Revue Neurologique, 2005

Objectif : Évaluer les performances de l'association Memory Impairment Screen (MIS) et Set Test d... more Objectif : Évaluer les performances de l'association Memory Impairment Screen (MIS) et Set Test d'Isaacs (STI) dans la détection de tous les types de démence. Matériel et méthode : 356 sujets contrôles et 542 patients ayant une maladie d'Alzheimer ou une autre démence (mixte, vasculaire, lewy, fronto-temporale) ont tous passé le MIS, le STI, le MMSE et une batterie neuropsychologique. Le calcul des cut-off pour chaque test a été effectué à l'aide de courbes ROC (Receiver Operating Characteristics Curves). Une régression logistique a été utilisée pour évaluer l'efficacité du couple MIS/STI. Résultats : La sensibilité du couple MIS < 6 et/ou STI < 25 est de 0.92 et sa spécificité de 0.89. La sensibilité est de 0.88 pour les stades légers (CDR = 1), 0.93 pour les stades modérés (CDR = 2) et de 0.98 pour les stades sévères (CDR = 3). La régression logistique montre une sensibilité globale de 0.91 et une spécificité de 0.92. Conclusion :

Similar beta-amyloid burden in posterior cortical atrophy and Alzheimer's disease

Alzheimers & Dementia, 2011

CSF tau markers are correlated with hippocampal volume in Alzheimer's disease

Neurobiology of aging, 2012

Hippocampal atrophy as assessed by magnetic resonance imaging (MRI) and abnormal cerebrospinal fl... more Hippocampal atrophy as assessed by magnetic resonance imaging (MRI) and abnormal cerebrospinal fluid (CSF) biomarkers are supportive features for the diagnosis of Alzheimer's disease (AD) and are assumed to be indirect pathological markers of the disease. In AD patients, antemortem MRI hippocampal volumes (HVs) correlate with the density of neurofibrillary tangles (but not with senile plaques) at autopsy suggesting that HVs may better correlate with CSF tau and hyperphosphorylated tau (P-tau) levels than CSF amyloid beta protein (Aβ)(42) level. Here, we tested this hypothesis in a well-defined AD group. Patients were selected according to the New Research Criteria for AD, including specific episodic memory deficit and CSF AD profile (defined as abnormal ratio of Aβ(42):tau). MRI was performed within 6 months of lumbar puncture. HVs were obtained using automated segmentation software. Thirty-six patients were included. Left HV correlated with CSF tau (R = -0.53) and P-tau (R = -0...

Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal Alzheimer's disease

by Marie Sarazin and Harald Hampel

Alzheimer's & Dementia, 2015

Background: To study the effect of donepezil on the rate of hippocampal atrophy in prodromal Alzh... more Background: To study the effect of donepezil on the rate of hippocampal atrophy in prodromal Alzheimer's disease (AD). Methods: A double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day) in subjects with suspected prodromal AD. Subjects underwent two brain magnetic resonance imaging scans (baseline and final visit). The primary efficacy outcome was the annualized percentage change (APC) of total hippocampal volume (left 1 right) measured by an automated segmentation method. Results: Two-hundred and sixteen only subjects were randomized across 28 French expert clinical sites. In the per protocol population (placebo 5 92 and donepezil 5 82), the donepezil group exhibited a significant reduced rate of hippocampal atrophy (APC 5 21.89%) compared with the placebo group (APC 5 23.47%), P , .001. There was no significant difference in neuropsychological performance between treatment groups. Conclusions: A 45% reduction of rate of hippocampal atrophy was observed in prodromal AD following 1 year of treatment with donepezil compared with placebo.

Psychiatric Presentation of Frontotemporal Dementia Associated with Inclusion Body Myopathy due to the VCP Mutation (R155H) in a French Family

by Agnès Jacquin and Marie Sarazin

Case Reports in Neurology, 2013

Clinical Investigations in Primary Care

Frontiers of Neurology and Neuroscience, 2009

Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) is a progressive neurodegenerative disorder that represents the most common form of dementia. The most prominent feature of AD is the decline in cognitive function, with an early impairment of episodic memory. The memory deficit of an AD patient is characterized by the amnestic syndrome of the medial temporal type. As the disease progresses, the condition often manifests in language disorders, visuospatial deficits and executive dysfunctions. Patients often have neuropsychiatric disturbances, as apathy and psychotic symptoms. Loss of autonomy follows cognitive impairment. The clinical diagnosis of AD is based on a complete medical examination with a neuropsychological evaluation. The FCSRT (free and cued selective reminding test) is recommended for the identification of the amnestic syndrome of the medial temporal type, which is defined by: (1) a very poor free recall and (2) a decreased total recall due to an insufficient effect of cueing. The neuropsychological tests should also assess other cognitive functions that may be perturbed in AD, such as executive functions, praxis, visuospatial capacities and language. Neuroimaging and biological exams (genetics, biomarkers) are of great utility in the evaluation. Other medical, neurological, or psychiatric disorders which could account for the impairment in memory and related symptoms must be always investigated.

Facteurs pronostiques et évolutifs de la maladie d’Alzheimer : intérêt de l’IRM cérébrale

Revue Neurologique, 2008

P3-39 Profil des biomarqueurs au LCR dans une population avec atrophie corticale postérieure

Revue Neurologique, 2009

P3-38 Le ratio Tau/Ab42 dans le LCR différencie la MA de la DFT avec une spécificité élevée

Revue Neurologique, 2009

Démence sémantique : réflexions d’un groupe de travail pour des critères de diagnostic en français et la constitution d’une cohorte de patients

by Marie Sarazin and Sophie Auriacombe

Revue Neurologique, 2008