Cognitive markers for the distinction between asymptomatic and prodromal Alzheimer's disease in Down syndrome: Correlations with volumetric brain changes

Abstract INTRODUCTION Motivated by the difficulties in detecting cognitive deterioration in the context of Down syndrome (DS), we aimed to identify markers of prodromal Alzheimer's disease (AD) in this population. METHODS Sixty‐two participants with DS (age > 45) distributed in three groups...

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Main Authors: Javier García‐Alba, Elisa M. Molanes‐López, Pilar Zuluaga, Cristina Bell‐Fenellos, Lucía Vaquero, Eva Alfayate, Felipe García, Gloria Mateo, Fernando Modenhauer, José M. Galván‐Román, Ricardo Bajo, Alberto Fernández
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
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Online Access:https://doi.org/10.1002/dad2.70084
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author Javier García‐Alba
Elisa M. Molanes‐López
Pilar Zuluaga
Cristina Bell‐Fenellos
Lucía Vaquero
Eva Alfayate
Felipe García
Gloria Mateo
Fernando Modenhauer
José M. Galván‐Román
Ricardo Bajo
Alberto Fernández
author_facet Javier García‐Alba
Elisa M. Molanes‐López
Pilar Zuluaga
Cristina Bell‐Fenellos
Lucía Vaquero
Eva Alfayate
Felipe García
Gloria Mateo
Fernando Modenhauer
José M. Galván‐Román
Ricardo Bajo
Alberto Fernández
author_sort Javier García‐Alba
collection DOAJ
description Abstract INTRODUCTION Motivated by the difficulties in detecting cognitive deterioration in the context of Down syndrome (DS), we aimed to identify markers of prodromal Alzheimer's disease (AD) in this population. METHODS Sixty‐two participants with DS (age > 45) distributed in three groups (asymptomatic [ADS], prodromal [PDS], and dementia [DDS]) completed the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities, Cambridge Cognitive Examination for older adults with Down's Syndrome, and Barcelona Test for Intellectual Disability tests and a magnetic resonance imaging scan. RESULTS Although temporal orientation showed significant differences among groups, only a predictive diagnostic model based on verbal short‐term memory tasks (relying on “cued” recall) allowed the correct classification of 88.5% of ADS, 75.0% of PDS, and 95% of DDS individuals. Cognitive decline strongly correlated with brain volume reductions in orbitofrontal, medial‐temporal, and bilateral thalamus within the DDS group. DISCUSSION Neuropsychological results showed that PDS cases were characterized by a significant deterioration of verbal memory and temporal orientation, compared to ADS. This pattern might be crucial to support diagnosis in clinical settings. Highlights Detecting signs of prodromal dementia is a major challenge in Down syndrome. Such challenge is due to a poor definition of the early cognitive manifestations. Memory tasks relying on “cued” recall allowed the detection of prodromal cases. A pattern of temporal disorientation was also evident in the prodromal phase. These cognitive deficits preceded volumetric brain changes only present in dementia.
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spelling doaj-art-1fbb6c1a04134faebbbf10defb44363d2025-08-20T03:42:18ZengWileyAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring2352-87292025-01-01171n/an/a10.1002/dad2.70084Cognitive markers for the distinction between asymptomatic and prodromal Alzheimer's disease in Down syndrome: Correlations with volumetric brain changesJavier García‐Alba0Elisa M. Molanes‐López1Pilar Zuluaga2Cristina Bell‐Fenellos3Lucía Vaquero4Eva Alfayate5Felipe García6Gloria Mateo7Fernando Modenhauer8José M. Galván‐Román9Ricardo Bajo10Alberto Fernández11Department of Psychology in Education and Research Complutense University of Madrid Madrid SpainDepartment of Statistics and Operational Research Complutense University of Madrid Madrid SpainDepartment of Statistics and Operational Research Complutense University of Madrid Madrid SpainDepartment of Psychology in Education and Research Complutense University of Madrid Madrid SpainDepartment of Experimental Psychology, Cognitive Processes and Speech Therapy; & Research Group in Digital Culture and Social Movements Complutense University of Madrid Madrid SpainNeuroimaging, Reina Sofia Alzheimer Center CIEN Foundation, ISCIII Madrid SpainNeuroimaging, Reina Sofia Alzheimer Center CIEN Foundation, ISCIII Madrid SpainDepartment of Internal Medicine La Princesa University Hospital/La Princesa Biomedical Research Institute Madrid SpainDepartment of Internal Medicine La Princesa University Hospital/La Princesa Biomedical Research Institute Madrid SpainDepartment of Internal Medicine La Princesa University Hospital/La Princesa Biomedical Research Institute Madrid SpainInstitute of Applied Magnetism Complutense University of Madrid Madrid SpainDepartment of Legal Medicine Psychiatry and Pathology, Complutense University of Madrid Madrid SpainAbstract INTRODUCTION Motivated by the difficulties in detecting cognitive deterioration in the context of Down syndrome (DS), we aimed to identify markers of prodromal Alzheimer's disease (AD) in this population. METHODS Sixty‐two participants with DS (age > 45) distributed in three groups (asymptomatic [ADS], prodromal [PDS], and dementia [DDS]) completed the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities, Cambridge Cognitive Examination for older adults with Down's Syndrome, and Barcelona Test for Intellectual Disability tests and a magnetic resonance imaging scan. RESULTS Although temporal orientation showed significant differences among groups, only a predictive diagnostic model based on verbal short‐term memory tasks (relying on “cued” recall) allowed the correct classification of 88.5% of ADS, 75.0% of PDS, and 95% of DDS individuals. Cognitive decline strongly correlated with brain volume reductions in orbitofrontal, medial‐temporal, and bilateral thalamus within the DDS group. DISCUSSION Neuropsychological results showed that PDS cases were characterized by a significant deterioration of verbal memory and temporal orientation, compared to ADS. This pattern might be crucial to support diagnosis in clinical settings. Highlights Detecting signs of prodromal dementia is a major challenge in Down syndrome. Such challenge is due to a poor definition of the early cognitive manifestations. Memory tasks relying on “cued” recall allowed the detection of prodromal cases. A pattern of temporal disorientation was also evident in the prodromal phase. These cognitive deficits preceded volumetric brain changes only present in dementia.https://doi.org/10.1002/dad2.70084Alzheimer's diseasecognitive impairmentDown syndromemagnetic resonance imagingneuropsychological assessmentprodromal Alzheimer's disease
spellingShingle Javier García‐Alba
Elisa M. Molanes‐López
Pilar Zuluaga
Cristina Bell‐Fenellos
Lucía Vaquero
Eva Alfayate
Felipe García
Gloria Mateo
Fernando Modenhauer
José M. Galván‐Román
Ricardo Bajo
Alberto Fernández
Cognitive markers for the distinction between asymptomatic and prodromal Alzheimer's disease in Down syndrome: Correlations with volumetric brain changes
Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
Alzheimer's disease
cognitive impairment
Down syndrome
magnetic resonance imaging
neuropsychological assessment
prodromal Alzheimer's disease
title Cognitive markers for the distinction between asymptomatic and prodromal Alzheimer's disease in Down syndrome: Correlations with volumetric brain changes
title_full Cognitive markers for the distinction between asymptomatic and prodromal Alzheimer's disease in Down syndrome: Correlations with volumetric brain changes
title_fullStr Cognitive markers for the distinction between asymptomatic and prodromal Alzheimer's disease in Down syndrome: Correlations with volumetric brain changes
title_full_unstemmed Cognitive markers for the distinction between asymptomatic and prodromal Alzheimer's disease in Down syndrome: Correlations with volumetric brain changes
title_short Cognitive markers for the distinction between asymptomatic and prodromal Alzheimer's disease in Down syndrome: Correlations with volumetric brain changes
title_sort cognitive markers for the distinction between asymptomatic and prodromal alzheimer s disease in down syndrome correlations with volumetric brain changes
topic Alzheimer's disease
cognitive impairment
Down syndrome
magnetic resonance imaging
neuropsychological assessment
prodromal Alzheimer's disease
url https://doi.org/10.1002/dad2.70084
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