Investigation of familiarity performance as an early cognitive marker of Alzheimer's Disease neurodegeneration
Bibliographic record
Abstract
Alzheimer's Disease (AD) is the most common form of dementia.This age-related neurodegenerative disorder leads to progressive cognitive impairments and functional disabilities.AD neurodegenerative processes progress under a silent, or pre-clinical, phase for a prolonged period of time.It is hoped that detecting AD at an earlier stage will facilitate the efficiency and development of therapeutic strategies for this disease.For this reason, the identification of reliable markers of early stages of AD is critical.In this thesis we used the dual-process theory of recognition to investigate a new potential cognitive marker of early stages of AD.The dual-process theory posits that two distinct and independent cognitive processes contribute to recognition performance: recollection and familiarity.Neuroanatomical studies have revealed a functional dissociation of these two processes within separate medial temporal lobe regions.Precisely, these studies have indicated that, while recollection is associated with hippocampal functional and structural integrity, familiarity is associated with the integrity of the rhinal cortex.Because the rhinal cortex is the first region to be targeted by neurofibrillary tangles, one of AD's core neuropathological features, the assessment of familiarity performance could allow the detection of the earliest cognitive symptoms of AD.Through four different articles, this thesis investigated the potential utility of recollection and familiarity assessment in the identification of aging individuals at risk of AD.Article 1 provides a review of the past literature examining recollection and familiarity in aging individuals with mild cognitive impairments and AD.Article 2 characterizes recollection and familiarity ii! performance in cognitively normal aging individuals, in contrast to young adults.As to obtain a confirmation of neuroanatomical correlates of recollection and familiarity in aging individuals, this article further explores relationships between these two processes and structural integrity of medial temporal lobe regions.Article 3 examines recollection and familiarity performance in cognitively intact aging individuals presenting a genetic risk for AD, the APOE ε4.As a followup investigation, Article 4 investigates associations between familiarity deficits in individuals with APOE ε4 and medial temporal lobe's structural integrity.The evidence presented in this thesis indicates that familiarity is well-preserved, and even increased, during normal aging.However, in aging individuals with a genetic risk for AD, we outlined selective deficits in familiarity, in the absence of other cognitive impairments.In accordance with the progression of neurofibrillary tangles in the course of AD, familiarity impairments in this at-risk sample were related to the structural integrity of rhinal areas.This suggests that familiarity deficits might represent one of the first cognitive manifestations of AD and, consequently, be a useful cognitive marker of early stages of this disease.Future studies using longitudinal designs and incorporating validated biomarkers of AD pathology are needed to confirm the presence of selective familiarity deficits in aging individuals with pre-clinical AD.iii! RÉSUMÉ La Maladie d'Alzheimer (MA) est la forme la plus courante de démence.Ce trouble neurodégénératif lié au vieillissement entraîne des déficits cognitifs et des incapacités fonctionnelles progressifs.Les processus neurodégénératifs de la MA progressent sous une phase silencieuse, ou pré-clinique, pendant une période prolongée.Il est espéré que la détection précoce de la MA facilitera l'efficacité et le développement de stratégies thérapeutiques visant à contrer cette maladie.Pour cette raison, l'identification de marqueurs fiables des stades précoces de la MA est critique.Dans cette thèse, nous nous sommes basés sur la théorie de la reconnaissance à double-processus afin d'étudier un nouveau marqueur cognitif potentiel des premiers stades de la MA.La théorie de la reconnaissance à double-processus postule que deux fonctions cognitives distinctes et indépendantes contribuent à la performance en reconnaissance: la recollection et la familiarité.Des études neuroanatomiques ont révélé une dissociation fonctionnelle entre ces deux processus dans des régions distinctes des lobes temporaux médians.Précisément, ces études ont indiqué que, bien que la recollection soit associée à l'intégrité fonctionnelle et structurale de l'hippocampe, la familiarité est associée à l'intégrité du cortex du entorhinal.Puisque le cortex rhinal est la première région à être ciblée par les enchevêtrements neurofibrillaires, l'une des principales caractéristiques neuropathologiques de la MA, l'évaluation de la performance en familiarité pourrait permettre la détection de symptômes cognitifs précoces associés à la MA.À travers quatre différents articles, cette thèse étudie l'utilité potentielle de l'évaluation de la recollection et de la familiarité dans l'identification des personnes vieillissantes à risque de MA. iv! L'Article 1 fournit une revue de la littérature passée examinant la recollection et la familiarité chez des personnes vieillissantes avec des troubles cognitifs légers (TCL) et MA.L'Article 2 caractérise la performance en matière de recollection et de familiarité chez des individus vieillissants avec une cognition normale, en contraste avec celle de jeunes adultes.Afin d'obtenir une confirmation des corrélats neuroanatomiques de la recollection et de la familiarité chez les individus vieillissants, cet article explore également les relations entre ces deux processus et l'intégrité structurale de régions précises des lobes temporaux médians.L'Article 3 évalue les performances de recollection et de familiarité chez des individus vieillissants avec une cognition normale présentant un risque génétique pour la MA, l'APOE ε4.Enfin, pour approfondir ce dernier article, l'
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".