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  1. Article ; Online: The Emergence of a New Conceptual Framework for Alzheimer's Disease.

    Dubois, Bruno

    Journal of Alzheimer's disease : JAD

    2017  Volume 62, Issue 3, Page(s) 1059–1066

    Abstract: The New Criteria for the diagnosis of Alzheimer's disease (AD), published by a group of experts in 2007, have resulted in a revolution in the comprehension of the disease. Before 2007, the diagnosis of AD dementia was done through a process of exclusion: ...

    Abstract The New Criteria for the diagnosis of Alzheimer's disease (AD), published by a group of experts in 2007, have resulted in a revolution in the comprehension of the disease. Before 2007, the diagnosis of AD dementia was done through a process of exclusion: it was considered in the case of patients with a dementia syndrome without identified etiologies. This traditional algorithm had three major limitations that penalize the disease: 1) a low accuracy of the performance which may share responsibility for negative results in clinical trials; 2) a late identification of the patients only when they reach the threshold of dementia which may delay the activation of optimal care; and last but not least, 3) an absence of clear recognition of AD as a disease because of the lack of specific arguments for its identification. Since 2007, the disease has gained a clear definition based on positive evidence: a specific clinical phenotype (the amnestic syndrome of the hippocampal type) and the presence of biomarkers, considered as a biological signature of the disease. Thanks to these positive arguments, AD is a clinically and biologically well-delineated disease, no longer defined as "probable". It is now possible to certify that a given patient has or does not have the disease. Like diabetes, cancer, hyperthyroidism or any other disorder, AD has now a clear definition with well-defined borders. The disease has entered the world of medicine with identified diseases with a biological fingerprint. This is the story of this adventure that we will present now.
    MeSH term(s) Alzheimer Disease/diagnosis ; Humans ; Models, Biological ; Prodromal Symptoms ; Terminology as Topic
    Language English
    Publishing date 2017-10-16
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-170536
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Complications neurocognitives de l’alcoolisme.

    Epelbaum, Stéphane / Dubois, Bruno

    La Revue du praticien

    2021  Volume 71, Issue 1, Page(s) e29–e30

    Title translation Neurocognitive complications of alcoholism.
    MeSH term(s) Alcoholism/complications ; Cognition Disorders ; Humans ; Neuropsychological Tests
    Language French
    Publishing date 2021-06-23
    Publishing country France
    Document type Journal Article
    ZDB-ID 205365-2
    ISSN 2101-017X ; 0035-2640
    ISSN (online) 2101-017X
    ISSN 0035-2640
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  3. Article ; Online: Démences chez le sujet jeune.

    Epelbaum, Stéphane / Dubois, Bruno

    La Revue du praticien

    2021  Volume 71, Issue 1, Page(s) e30

    Title translation Dementias in young people.
    MeSH term(s) Adolescent ; Alcoholism ; Dementia ; Ethanol ; Humans
    Chemical Substances Ethanol (3K9958V90M)
    Language French
    Publishing date 2021-06-23
    Publishing country France
    Document type Journal Article
    ZDB-ID 205365-2
    ISSN 2101-017X ; 0035-2640
    ISSN (online) 2101-017X
    ISSN 0035-2640
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Confusion, démences.

    Epelbaum, Stéphane / Dubois, Bruno

    La Revue du praticien

    2021  Volume 71, Issue 1, Page(s) e21–e28

    Title translation Confusion, dementias.
    MeSH term(s) Alzheimer Disease ; Dementia/diagnosis ; Humans ; Tomography, X-Ray Computed
    Language French
    Publishing date 2021-06-23
    Publishing country France
    Document type Journal Article
    ZDB-ID 205365-2
    ISSN 2101-017X ; 0035-2640
    ISSN (online) 2101-017X
    ISSN 0035-2640
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  5. Article ; Online: The Memory Binding Test Detects Early Subtle Episodic Memory Decline in Preclinical Alzheimer's Disease: A Longitudinal Study.

    Rapos Pereira, Filipa / George, Nathalie / Dalla Barba, Gianfranco / Dubois, Bruno / La Corte, Valentina

    Journal of Alzheimer's disease : JAD

    2024  Volume 98, Issue 2, Page(s) 465–479

    Abstract: Background: The asymptomatic at-risk phase might be the optimal time-window to establish clinically meaningful endpoints in Alzheimer's disease (AD).: Objective: We investigated whether, compared with the Free and Cued Selective Reminding Test (FCSRT) ...

    Abstract Background: The asymptomatic at-risk phase might be the optimal time-window to establish clinically meaningful endpoints in Alzheimer's disease (AD).
    Objective: We investigated whether, compared with the Free and Cued Selective Reminding Test (FCSRT), the Memory Binding Test (MBT) can anticipate the diagnosis of emergent subtle episodic memory (EM) deficits to an at-risk phase.
    Methods: Five-year longitudinal FCSRT and MBT scores from 45 individuals matched for age, education, and gender, were divided into 3 groups of 15 subjects: Aβ-/controls, Aβ+/stable, and Aβ+/progressors (preclinical-AD). The MBT adds an associative memory component (binding), particularly sensitive to subtle EM decline.
    Results: In the MBT, EM decline started in the Aβ+/progressors (preclinical-AD) up to 4 years prior to diagnosis in delayed free recall (FR), followed by decline in binding-associated scores 1 year later. Conversely, in the FCSRT, EM-decline began later, up to 3 years prior to diagnosis, in the same group on both immediate and delayed versions of FR, while on total recall (TR) and intrusions decline started only 1 year prior to diagnosis.
    Conclusions: The MBT seems more sensitive than the FCSRT for early EM-decline detection, regarding the year of diagnosis and the number of scores showing AD-linked EM deficits (associated with the AD-characteristic amnesic hippocampal syndrome). Considering the MBT as a detection tool of early subtle EM-decline in an asymptomatic at-risk phase, and the FCSRT as a classification tool of stages of EM-decline from a preclinical phase, these tests ought to potentially become complementary diagnostic tools that can foster therapies to delay cognitive decline. Clinical trial registration title: Electrophysiological markers of the progression to clinical Alzheimer disease in asymptomatic at-risk individuals: a longitudinal event-related potential study of episodic memory in the INSIGHT pre-AD cohort (acronym: ePARAD).
    MeSH term(s) Humans ; Alzheimer Disease/metabolism ; Memory, Episodic ; Longitudinal Studies ; Neuropsychological Tests ; Mental Recall/physiology ; Cognitive Dysfunction/diagnosis ; Memory Disorders/diagnosis ; Memory Disorders/etiology
    Language English
    Publishing date 2024-02-23
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-230921
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Explaining the Variability of Alzheimer Disease Fluid Biomarker Concentrations in Memory Clinic Patients Without Dementia.

    Bouteloup, Vincent / Pellegrin, Isabelle / Dubois, Bruno / Chene, Genevieve / Planche, Vincent / Dufouil, Carole

    Neurology

    2024  Volume 102, Issue 8, Page(s) e209219

    Abstract: Background and objectives: Patients' comorbidities can affect Alzheimer disease (AD) blood biomarker concentrations. Because a limited number of factors have been explored to date, our aim was to assess the proportion of the variance in fluid biomarker ... ...

    Abstract Background and objectives: Patients' comorbidities can affect Alzheimer disease (AD) blood biomarker concentrations. Because a limited number of factors have been explored to date, our aim was to assess the proportion of the variance in fluid biomarker levels explained by the clinical features of AD and by a large number of non-AD-related factors.
    Methods: MEMENTO enrolled 2,323 individuals with cognitive complaints or mild cognitive impairment in 26 French memory clinics. Baseline evaluation included clinical and neuropsychological assessments, brain MRI, amyloid-PET, CSF (optional), and blood sampling. Blood biomarker levels were determined using the Simoa-HDX analyzer. We performed linear regression analysis of the clinical features of AD (cognition, AD genetic risk score, and brain atrophy) to model biomarker concentrations. Next, we added covariates among routine biological tests, inflammatory markers, demographic and behavioral determinants, treatments, comorbidities, and preanalytical sample handling in final models using both stepwise selection processes and least absolute shrinkage and selection operator (LASSO).
    Results: In total, 2,257 participants were included in the analysis (median age 71.7, 61.8% women, 55.2% with high educational levels). For blood biomarkers, the proportion of variance explained by clinical features of AD was 13.7% for neurofilaments (NfL), 11.4% for p181-tau, 3.0% for Aβ-42/40, and 1.4% for total-tau. In final models accounting for non-AD-related factors, the variance was mainly explained by age, routine biological tests, inflammatory markers, and preanalytical sample handling. In CSF, the proportion of variance explained by clinical features of AD was 24.8% for NfL, 22.3% for Aβ-42/40, 19.8% for total-tau, and 17.2% for p181-tau. In contrast to blood biomarkers, the largest proportion of variance was explained by cognition after adjustment for covariates. The covariates that explained the largest proportion of variance were also the most frequently selected with LASSO. The performance of blood biomarkers for predicting A+ and T+ status (PET or CSF) remained unchanged after controlling for drivers of variance.
    Discussion: This comprehensive analysis demonstrated that the variance in AD blood biomarker concentrations was mainly explained by age, with minor contributions from cognition, brain atrophy, and genetics, conversely to CSF measures. These results challenge the use of blood biomarkers as isolated stand-alone biomarkers for AD.
    MeSH term(s) Humans ; Female ; Male ; Alzheimer Disease/genetics ; tau Proteins ; Amyloid beta-Peptides ; Biomarkers ; Cognitive Dysfunction/psychology ; Atrophy ; Peptide Fragments
    Chemical Substances tau Proteins ; Amyloid beta-Peptides ; Biomarkers ; Peptide Fragments
    Language English
    Publishing date 2024-03-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000209219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Correspondance à propos de l'éditorial de Gilles Chopart et al. « Diagnostic précoce de la maladie d'Alzheimer : l'arbre qui cache la forêt ? »

    Dubois, Bruno

    Presse medicale (Paris, France : 1983)

    2014  Volume 43, Issue 9, Page(s) 1026

    Title translation Letter on the editorial by Gilles Chopart et al. "early diagnosis of Alzheimer's disease: are we too close to the tree to see the forest?".
    MeSH term(s) Alzheimer Disease/diagnosis ; Early Diagnosis ; Humans
    Language French
    Publishing date 2014-09
    Publishing country France
    Document type Comment ; Letter
    ZDB-ID 120943-7
    ISSN 2213-0276 ; 0032-7867 ; 0755-4982 ; 0301-1518
    ISSN (online) 2213-0276
    ISSN 0032-7867 ; 0755-4982 ; 0301-1518
    DOI 10.1016/j.lpm.2014.06.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Vers une nouvelle définition de la maladie d'Alzheimer.

    Dubois, Bruno

    Bulletin de l'Academie nationale de medecine

    2013  Volume 197, Issue 1, Page(s) 143–53; discussion 153–6

    Abstract: In 2007 and 2010, the International Working Group on Research Criteria for Alzheimer's Disease introduced a new conceptual framework that included a diagnostic algorithm covering early prodromal stages. There is a growing consensus that Alzheimer's ... ...

    Title translation A new definition for Alzheimer's disease.
    Abstract In 2007 and 2010, the International Working Group on Research Criteria for Alzheimer's Disease introduced a new conceptual framework that included a diagnostic algorithm covering early prodromal stages. There is a growing consensus that Alzheimer's disease (AD) should be considered as a clinical-biological entity characterized by: i) a well-defined clinical phenotype (an amnestic syndrome of the hippocampal type in typical AD), and ii) biomarkers, especially pathophysiological biomarkers, of the underlying disease process. The IWG criteria created the possibility for AD to be diagnosed prior to the onset of dementia, and also integrated biomarkers into the diagnostic framework. Although these criteria were intended for research purposes, they are increasingly used in expert centers for early diagnosis, for example of young-onset AD and complex cases (posterior cortical atrophy, primary progressive aphasia, etc.), where biomarkers can improve the diagnostic accuracy. In this article we present this new approach, together with the results of ongoing validation studies and data obtained by a French research team.
    MeSH term(s) Algorithms ; Alzheimer Disease/classification ; Alzheimer Disease/diagnosis ; Biomarkers ; Humans ; Terminology as Topic
    Chemical Substances Biomarkers
    Language French
    Publishing date 2013-01
    Publishing country Netherlands
    Document type English Abstract ; Journal Article ; Review
    ZDB-ID 213227-8
    ISSN 0001-4079
    ISSN 0001-4079
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  9. Article ; Online: Alzheimer's Disease Including Focal Presentations.

    Villain, Nicolas / Dubois, Bruno

    Seminars in neurology

    2019  Volume 39, Issue 2, Page(s) 213–226

    Abstract: Alzheimer's disease (AD) is the commonest neurodegenerative disease and the most frequent cause of dementia. It affects 30 million people worldwide. Current research criteria focus on biomarkers' status for amyloid and tau using positron emission ... ...

    Abstract Alzheimer's disease (AD) is the commonest neurodegenerative disease and the most frequent cause of dementia. It affects 30 million people worldwide. Current research criteria focus on biomarkers' status for amyloid and tau using positron emission tomography and cerebrospinal fluid analysis, independent of clinical status. Current epidemiological data, which mostly rely on biomarker-undetermined AD cases, have highlighted ApoE4 and age as the main risk factors. Rare autosomal dominant mutations also account for a small fraction of early-onset AD. The main clinical phenotype at presentation is the amnestic phenotype targeting episodic memory. This is followed by rarer phenotypes such as posterior cortical atrophy, logopenic variant of primary progressive aphasia, frontal variant AD, corticobasal syndrome, and other even rarer presentations mimicking language variants of frontotemporal dementia. Main differential diagnoses include hippocampal sclerosis with TDP-43, primary age-related tauopathy, argyrophilic grain disease, frontotemporal lobar degeneration, Lewy body disease, chronic traumatic encephalopathy as well as nondegenerative disorders such as cerebrovascular disease, chronic alcohol consumption, limbic encephalitis, medial temporal lobe epilepsy, and others. Co-occurrence of AD pathology with other neurodegenerative and vascular diseases is common and increases with age. This presents a challenge in current clinical practice due to a lack of reliable biomarkers for non-AD neurodegenerative diseases.
    MeSH term(s) Alzheimer Disease/cerebrospinal fluid ; Alzheimer Disease/diagnosis ; Alzheimer Disease/pathology ; Alzheimer Disease/physiopathology ; Humans
    Language English
    Publishing date 2019-03-29
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 603165-1
    ISSN 1098-9021 ; 0271-8235
    ISSN (online) 1098-9021
    ISSN 0271-8235
    DOI 10.1055/s-0039-1681041
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Self-Modulation of Gamma-Band Synchronization through EEG-Neurofeedback Training in the Elderly.

    Andrade, Katia / Houmani, Nesma / Guieysse, Thomas / Razafimahatratra, Solofo / Klarsfeld, André / Dreyfus, Gérard / Dubois, Bruno / Vialatte, François / Medani, Takfarinas

    Journal of integrative neuroscience

    2024  Volume 23, Issue 3, Page(s) 67

    Abstract: Background: Electroencephalography (EEG) stands as a pivotal non-invasive tool, capturing brain signals with millisecond precision and enabling real-time monitoring of individuals' mental states. Using appropriate biomarkers extracted from these EEG ... ...

    Abstract Background: Electroencephalography (EEG) stands as a pivotal non-invasive tool, capturing brain signals with millisecond precision and enabling real-time monitoring of individuals' mental states. Using appropriate biomarkers extracted from these EEG signals and presenting them back in a neurofeedback loop offers a unique avenue for promoting neural compensation mechanisms. This approach empowers individuals to skillfully modulate their brain activity. Recent years have witnessed the identification of neural biomarkers associated with aging, underscoring the potential of neuromodulation to regulate brain activity in the elderly.
    Methods and objectives: Within the framework of an EEG-based brain-computer interface, this study focused on three neural biomarkers that may be disturbed in the aging brain: Peak Alpha Frequency, Gamma-band synchronization, and Theta/Beta ratio. The primary objectives were twofold: (1) to investigate whether elderly individuals with subjective memory complaints can learn to modulate their brain activity, through EEG-neurofeedback training, in a rigorously designed double-blind, placebo-controlled study; and (2) to explore potential cognitive enhancements resulting from this neuromodulation.
    Results: A significant self-modulation of the Gamma-band synchronization biomarker, critical for numerous higher cognitive functions and known to decline with age, and even more in Alzheimer's disease (AD), was exclusively observed in the group undergoing EEG-neurofeedback training. This effect starkly contrasted with subjects receiving sham feedback. While this neuromodulation did not directly impact cognitive abilities, as assessed by pre- versus post-training neuropsychological tests, the high baseline cognitive performance of all subjects at study entry likely contributed to this result.
    Conclusion: The findings of this double-blind study align with a key criterion for successful neuromodulation, highlighting the significant potential of Gamma-band synchronization in such a process. This important outcome encourages further exploration of EEG-neurofeedback on this specific neural biomarker as a promising intervention to counter the cognitive decline that often accompanies brain aging and, eventually, to modify the progression of AD.
    MeSH term(s) Humans ; Aged ; Neurofeedback/methods ; Electroencephalography ; Brain/physiology ; Cognition/physiology ; Alzheimer Disease/therapy ; Biomarkers
    Chemical Substances Biomarkers
    Language English
    Publishing date 2024-03-25
    Publishing country Singapore
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 2136427-8
    ISSN 0219-6352
    ISSN 0219-6352
    DOI 10.31083/j.jin2303067
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