Longitudinal Analysis of Brain-Predicted Age in Amnestic and Non-amnestic Sporadic Early-Onset Alzheimer's Disease
Objective: Predicted age difference (PAD) is a score computed by subtracting chronological age from “brain” age, which is estimated using neuroimaging data. The goal of this study was to evaluate the PAD as a marker of phenotypic heterogeneity and severity among early-onset Alzheimer's disease...
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.729635/full |
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| author | Morgan Gautherot Grégory Kuchcinski Grégory Kuchcinski Grégory Kuchcinski Cécile Bordier Adeline Rollin Sillaire Adeline Rollin Sillaire Xavier Delbeuck Mélanie Leroy Mélanie Leroy Xavier Leclerc Xavier Leclerc Xavier Leclerc Jean-Pierre Pruvo Jean-Pierre Pruvo Jean-Pierre Pruvo Florence Pasquier Florence Pasquier Florence Pasquier Renaud Lopes Renaud Lopes |
| author_facet | Morgan Gautherot Grégory Kuchcinski Grégory Kuchcinski Grégory Kuchcinski Cécile Bordier Adeline Rollin Sillaire Adeline Rollin Sillaire Xavier Delbeuck Mélanie Leroy Mélanie Leroy Xavier Leclerc Xavier Leclerc Xavier Leclerc Jean-Pierre Pruvo Jean-Pierre Pruvo Jean-Pierre Pruvo Florence Pasquier Florence Pasquier Florence Pasquier Renaud Lopes Renaud Lopes |
| author_sort | Morgan Gautherot |
| collection | DOAJ |
| description | Objective: Predicted age difference (PAD) is a score computed by subtracting chronological age from “brain” age, which is estimated using neuroimaging data. The goal of this study was to evaluate the PAD as a marker of phenotypic heterogeneity and severity among early-onset Alzheimer's disease (EOAD) patients.Methods: We first used 3D T1-weighted (3D-T1) magnetic resonance images (MRI) of 3,227 healthy subjects aged between 18 and 85 years to train, optimize, and evaluate the brain age model. A total of 123 participants who met the criteria for early-onset (<65 years) sporadic form of probable Alzheimer's disease (AD) and presented with two distinctive clinical presentations [an amnestic form (n = 74) and a non-amnestic form (n = 49)] were included at baseline and followed-up for a maximum period of 4 years. All the participants underwent a work-up at baseline and every year during the follow-up period, which included clinical examination, neuropsychological testing and genotyping, and structural MRI. In addition, cerebrospinal fluid biomarker assay was recorded at baseline. PAD score was calculated by applying brain age model to 3D-T1 images of the EOAD patients and healthy controls, who were matched based on age and sex. At baseline, between-group differences for neuropsychological and PAD scores were assessed using linear models. Regarding longitudinal analysis of neuropsychological and PAD scores, differences between amnestic and non-amnestic participants were analyzed using linear mixed-effects modeling.Results: PAD score was significantly higher for non-amnestic patients (2.35 ± 0.91) when compared to amnestic patients (2.09 ± 0.74) and controls (0.00 ± 1). Moreover, PAD score was linearly correlated with the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Sum of Boxes (CDR-SB), for both amnestic and non-amnestic sporadic forms. Longitudinal analyses showed that the gradual development of the disease in patients was accompanied by a significant increase in PAD score over time, for both amnestic and non-amnestic patients.Conclusion: PAD score was able to separate amnestic and non-amnestic sporadic forms. Regardless of the clinical presentation, as PAD score was a way of quantifying an early brain age acceleration, it was an appropriate method to detect the development of AD and follow the evolution of the disease as a marker of severity as MMSE and CDR-SB. |
| first_indexed | 2024-12-19T20:09:05Z |
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| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-19T20:09:05Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-45e242480d8447318a806c0756b174582022-12-21T20:07:22ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-11-011310.3389/fnagi.2021.729635729635Longitudinal Analysis of Brain-Predicted Age in Amnestic and Non-amnestic Sporadic Early-Onset Alzheimer's DiseaseMorgan Gautherot0Grégory Kuchcinski1Grégory Kuchcinski2Grégory Kuchcinski3Cécile Bordier4Adeline Rollin Sillaire5Adeline Rollin Sillaire6Xavier Delbeuck7Mélanie Leroy8Mélanie Leroy9Xavier Leclerc10Xavier Leclerc11Xavier Leclerc12Jean-Pierre Pruvo13Jean-Pierre Pruvo14Jean-Pierre Pruvo15Florence Pasquier16Florence Pasquier17Florence Pasquier18Renaud Lopes19Renaud Lopes20UMS 2014–US 41–PLBS–Plateformes Lilloises en Biologie & Santé, University of Lille, Lille, FranceUMS 2014–US 41–PLBS–Plateformes Lilloises en Biologie & Santé, University of Lille, Lille, FranceInserm, U1172–LilNCog–Lille Neuroscience & Cognition, University of Lille, Lille, FranceNeuroradiology Department, Lille University Medical Centre, Lille, FranceInserm, U1172–LilNCog–Lille Neuroscience & Cognition, University of Lille, Lille, FranceMemory Center, DISTALZ, Lille, FranceNeurology Department, Lille University Medical Centre, Lille, FranceMemory Center, DISTALZ, Lille, FranceInserm, U1172–LilNCog–Lille Neuroscience & Cognition, University of Lille, Lille, FranceMemory Center, DISTALZ, Lille, FranceUMS 2014–US 41–PLBS–Plateformes Lilloises en Biologie & Santé, University of Lille, Lille, FranceInserm, U1172–LilNCog–Lille Neuroscience & Cognition, University of Lille, Lille, FranceNeuroradiology Department, Lille University Medical Centre, Lille, FranceUMS 2014–US 41–PLBS–Plateformes Lilloises en Biologie & Santé, University of Lille, Lille, FranceInserm, U1172–LilNCog–Lille Neuroscience & Cognition, University of Lille, Lille, FranceNeuroradiology Department, Lille University Medical Centre, Lille, FranceInserm, U1172–LilNCog–Lille Neuroscience & Cognition, University of Lille, Lille, FranceMemory Center, DISTALZ, Lille, FranceNeurology Department, Lille University Medical Centre, Lille, FranceUMS 2014–US 41–PLBS–Plateformes Lilloises en Biologie & Santé, University of Lille, Lille, FranceInserm, U1172–LilNCog–Lille Neuroscience & Cognition, University of Lille, Lille, FranceObjective: Predicted age difference (PAD) is a score computed by subtracting chronological age from “brain” age, which is estimated using neuroimaging data. The goal of this study was to evaluate the PAD as a marker of phenotypic heterogeneity and severity among early-onset Alzheimer's disease (EOAD) patients.Methods: We first used 3D T1-weighted (3D-T1) magnetic resonance images (MRI) of 3,227 healthy subjects aged between 18 and 85 years to train, optimize, and evaluate the brain age model. A total of 123 participants who met the criteria for early-onset (<65 years) sporadic form of probable Alzheimer's disease (AD) and presented with two distinctive clinical presentations [an amnestic form (n = 74) and a non-amnestic form (n = 49)] were included at baseline and followed-up for a maximum period of 4 years. All the participants underwent a work-up at baseline and every year during the follow-up period, which included clinical examination, neuropsychological testing and genotyping, and structural MRI. In addition, cerebrospinal fluid biomarker assay was recorded at baseline. PAD score was calculated by applying brain age model to 3D-T1 images of the EOAD patients and healthy controls, who were matched based on age and sex. At baseline, between-group differences for neuropsychological and PAD scores were assessed using linear models. Regarding longitudinal analysis of neuropsychological and PAD scores, differences between amnestic and non-amnestic participants were analyzed using linear mixed-effects modeling.Results: PAD score was significantly higher for non-amnestic patients (2.35 ± 0.91) when compared to amnestic patients (2.09 ± 0.74) and controls (0.00 ± 1). Moreover, PAD score was linearly correlated with the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Sum of Boxes (CDR-SB), for both amnestic and non-amnestic sporadic forms. Longitudinal analyses showed that the gradual development of the disease in patients was accompanied by a significant increase in PAD score over time, for both amnestic and non-amnestic patients.Conclusion: PAD score was able to separate amnestic and non-amnestic sporadic forms. Regardless of the clinical presentation, as PAD score was a way of quantifying an early brain age acceleration, it was an appropriate method to detect the development of AD and follow the evolution of the disease as a marker of severity as MMSE and CDR-SB.https://www.frontiersin.org/articles/10.3389/fnagi.2021.729635/fullbrain agedeep learningstructural MRIlongitudinal analysisearly-onset Alzheimer's diseasephenotypic variants |
| spellingShingle | Morgan Gautherot Grégory Kuchcinski Grégory Kuchcinski Grégory Kuchcinski Cécile Bordier Adeline Rollin Sillaire Adeline Rollin Sillaire Xavier Delbeuck Mélanie Leroy Mélanie Leroy Xavier Leclerc Xavier Leclerc Xavier Leclerc Jean-Pierre Pruvo Jean-Pierre Pruvo Jean-Pierre Pruvo Florence Pasquier Florence Pasquier Florence Pasquier Renaud Lopes Renaud Lopes Longitudinal Analysis of Brain-Predicted Age in Amnestic and Non-amnestic Sporadic Early-Onset Alzheimer's Disease Frontiers in Aging Neuroscience brain age deep learning structural MRI longitudinal analysis early-onset Alzheimer's disease phenotypic variants |
| title | Longitudinal Analysis of Brain-Predicted Age in Amnestic and Non-amnestic Sporadic Early-Onset Alzheimer's Disease |
| title_full | Longitudinal Analysis of Brain-Predicted Age in Amnestic and Non-amnestic Sporadic Early-Onset Alzheimer's Disease |
| title_fullStr | Longitudinal Analysis of Brain-Predicted Age in Amnestic and Non-amnestic Sporadic Early-Onset Alzheimer's Disease |
| title_full_unstemmed | Longitudinal Analysis of Brain-Predicted Age in Amnestic and Non-amnestic Sporadic Early-Onset Alzheimer's Disease |
| title_short | Longitudinal Analysis of Brain-Predicted Age in Amnestic and Non-amnestic Sporadic Early-Onset Alzheimer's Disease |
| title_sort | longitudinal analysis of brain predicted age in amnestic and non amnestic sporadic early onset alzheimer s disease |
| topic | brain age deep learning structural MRI longitudinal analysis early-onset Alzheimer's disease phenotypic variants |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.729635/full |
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