A SCOPING REVIEW OF ALZHEIMER’S DISEASE HYPOTHESES: THE CASE FOR A MULTI-FACTORIAL THEORY
Notice bibliographique
Résumé
ABSTRACT Introduction There is a common agreement that Alzheimer’s disease (AD) is inherently complex; otherwise, a general disagreement remains on its etiological underpinning, with numerous alternative hypotheses having been proposed. Methods We performed a scoping review of 105 original manuscripts describing hypotheses and theories of AD published in the past decades, characterized them as having a single or multifactorial focus, and tracked their impact. Results Three stages can be discerned in terms of hypotheses generation, with three quarter of studies proposing a hypothesis characterized as being single-focus. The most important theoretical groupings were the Amyloid group, followed by Metabolism and Mitochondrial dysfunction, then Cerebrovascular. Lately, evidence towards Genetics and especially Gut/Brain interactions came to the fore. Discussion When viewed together, these multi-faceted reports reinforce the notion that AD affects multiple sub-cellular, cellular, anatomical, and physiological systems at the same time but at varying degree between individuals. A major impediment remains provide a comprehensive view of all these systems and their interactions to manage its inherent complexity. RESEARCH IN CONTEXT We propose a scoping review of 105 original manuscripts describing hypotheses and theories of Alzheimer’s disease (AD) that have been published in the past decades, characterized as having a single or multifactorial focus. We found that three quarter of studies proposed a hypothesis characterized as being single-focus (77/105), with the most important theoretical groupings being the Amyloid group, followed by Metabolism and Mitochondrial dysfunction, then Cerebrovascular. Three stages can be discerned in terms of hypotheses generation. The first phase (∼1980-1995) included the establishment of the main thrusts that have endured to this day (Amyloid, Glial, Infection, Inflammation, Metabolism, Oxidative stress, and Proteinopathies hypotheses; multifactorality; and neurotoxicity). In the second phase (1995-2005), the importance of the Cerebrovasculature, Mitochondrial dysfunction, and Neurotransmitters were recognized. Lately (2005-2020), evidence towards Genetics (outside of the autosomal dominant form of AD), and especially Gut/Brain interactions came to the fore. When viewed together, these multi-faceted reports reinforce the notion that AD affects multiple sub-cellular, cellular, anatomical, and physiological systems at the same time but at varying degree between individuals. A major impediment remains provide a comprehensive view of all these systems and their interactions to manage its inherent complexity. HIGHLIGHTS - We propose a scoping review of hypotheses and theories for Alzheimer’s disease (AD) - Out of over 11,000 abstracts, we reviewed 105 articles, separated as having a single-focus or multi-factorial approach - The diversity of reports calls for an integrative view of AD in order to encompass its inherent complexity
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,167 | 0,368 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,002 |
| Méta-épidémiologie (sens large) | 0,006 | 0,007 |
| Bibliométrie | 0,040 | 0,030 |
| Études des sciences et des technologies | 0,003 | 0,010 |
| Communication savante | 0,015 | 0,018 |
| Science ouverte | 0,005 | 0,007 |
| Intégrité de la recherche | 0,007 | 0,005 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».