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Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome

IMPORTANCE: Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established. OBJECTIVE: To examine clinical progress...

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Autores principales: Videla, Laura, Benejam, Bessy, Pegueroles, Jordi, Carmona-Iragui, María, Padilla, Concepción, Fernández, Susana, Barroeta, Isabel, Altuna, Miren, Valldeneu, Silvia, Garzón, Diana, Ribas, Laia, Montal, Víctor, Arranz Martínez, Javier, Rozalem Aranha, Mateus, Alcolea, Daniel, Bejanin, Alexandre, Iulita, Maria Florencia, Videla Cés, Sebastià, Blesa, Rafael, Lleó, Alberto, Fortea, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356319/
https://www.ncbi.nlm.nih.gov/pubmed/35930282
http://dx.doi.org/10.1001/jamanetworkopen.2022.25573
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author Videla, Laura
Benejam, Bessy
Pegueroles, Jordi
Carmona-Iragui, María
Padilla, Concepción
Fernández, Susana
Barroeta, Isabel
Altuna, Miren
Valldeneu, Silvia
Garzón, Diana
Ribas, Laia
Montal, Víctor
Arranz Martínez, Javier
Rozalem Aranha, Mateus
Alcolea, Daniel
Bejanin, Alexandre
Iulita, Maria Florencia
Videla Cés, Sebastià
Blesa, Rafael
Lleó, Alberto
Fortea, Juan
author_facet Videla, Laura
Benejam, Bessy
Pegueroles, Jordi
Carmona-Iragui, María
Padilla, Concepción
Fernández, Susana
Barroeta, Isabel
Altuna, Miren
Valldeneu, Silvia
Garzón, Diana
Ribas, Laia
Montal, Víctor
Arranz Martínez, Javier
Rozalem Aranha, Mateus
Alcolea, Daniel
Bejanin, Alexandre
Iulita, Maria Florencia
Videla Cés, Sebastià
Blesa, Rafael
Lleó, Alberto
Fortea, Juan
author_sort Videla, Laura
collection PubMed
description IMPORTANCE: Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established. OBJECTIVE: To examine clinical progression along the AD continuum and its related cognitive decline and to explore the presence of practice effects and floor effects with repeated assessments. DESIGN, SETTING, AND PARTICIPANTS: This is a single-center cohort study of adults (aged >18 years) with DS with different ID levels and at least 6 months of follow-up between November 2012 and December 2021. The data are from a population-based health plan designed to screen for AD in adults with DS in Catalonia, Spain. Individuals were classified as being asymptomatic, having prodromal AD, or having AD dementia. EXPOSURES: Neurological and neuropsychological assessments. MAIN OUTCOMES AND MEASURES: The main outcome was clinical change along the AD continuum. Cognitive decline was measured by the Cambridge Cognitive Examination for Older Adults With Down Syndrome and the modified Cued Recall Test. RESULTS: A total of 632 adults with DS (mean [SD] age, 42.6 [11.4] years; 292 women [46.2%]) with 2847 evaluations (mean [SD] follow-up, 28.8 [18.7] months) were assessed. At baseline, there were 436 asymptomatic individuals, 69 patients with prodromal AD, and 127 with AD dementia. After 5 years of follow-up, 17.1% (95% CI, 12.5%-21.5%) of asymptomatic individuals progressed to symptomatic AD in an age-dependent manner (0.6% [95% CI, 0%-1.8%] for age <40 years; 21.1% [95% CI, 8.0%-32.5%] for age 40-44 years; 41.4% [95% CI, 23.1%-55.3%] for age 45-49 years; 57.5% [95% CI, 38.2%-70.8%] for age ≥50 years; P < .001), and 94.1% (95% CI, 84.6%-98.0%) of patients with prodromal AD progressed to dementia with no age dependency. Cognitive decline in the older individuals was most common among those who progressed to symptomatic AD and symptomatic individuals themselves. Importantly, individuals with mild and moderate ID had no differences in longitudinal cognitive decline despite having different performance at baseline. This study also found practice and floor effects, which obscured the assessment of longitudinal cognitive decline. CONCLUSIONS AND RELEVANCE: This study found an association between the development of symptomatic AD and a high risk of progressive cognitive decline among patients with DS. These results support the need for population health plans to screen for AD-related cognitive decline from the fourth decade of life and provide important longitudinal data to inform clinical trials in adults with DS to prevent AD.
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spelling pubmed-93563192022-08-22 Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome Videla, Laura Benejam, Bessy Pegueroles, Jordi Carmona-Iragui, María Padilla, Concepción Fernández, Susana Barroeta, Isabel Altuna, Miren Valldeneu, Silvia Garzón, Diana Ribas, Laia Montal, Víctor Arranz Martínez, Javier Rozalem Aranha, Mateus Alcolea, Daniel Bejanin, Alexandre Iulita, Maria Florencia Videla Cés, Sebastià Blesa, Rafael Lleó, Alberto Fortea, Juan JAMA Netw Open Original Investigation IMPORTANCE: Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established. OBJECTIVE: To examine clinical progression along the AD continuum and its related cognitive decline and to explore the presence of practice effects and floor effects with repeated assessments. DESIGN, SETTING, AND PARTICIPANTS: This is a single-center cohort study of adults (aged >18 years) with DS with different ID levels and at least 6 months of follow-up between November 2012 and December 2021. The data are from a population-based health plan designed to screen for AD in adults with DS in Catalonia, Spain. Individuals were classified as being asymptomatic, having prodromal AD, or having AD dementia. EXPOSURES: Neurological and neuropsychological assessments. MAIN OUTCOMES AND MEASURES: The main outcome was clinical change along the AD continuum. Cognitive decline was measured by the Cambridge Cognitive Examination for Older Adults With Down Syndrome and the modified Cued Recall Test. RESULTS: A total of 632 adults with DS (mean [SD] age, 42.6 [11.4] years; 292 women [46.2%]) with 2847 evaluations (mean [SD] follow-up, 28.8 [18.7] months) were assessed. At baseline, there were 436 asymptomatic individuals, 69 patients with prodromal AD, and 127 with AD dementia. After 5 years of follow-up, 17.1% (95% CI, 12.5%-21.5%) of asymptomatic individuals progressed to symptomatic AD in an age-dependent manner (0.6% [95% CI, 0%-1.8%] for age <40 years; 21.1% [95% CI, 8.0%-32.5%] for age 40-44 years; 41.4% [95% CI, 23.1%-55.3%] for age 45-49 years; 57.5% [95% CI, 38.2%-70.8%] for age ≥50 years; P < .001), and 94.1% (95% CI, 84.6%-98.0%) of patients with prodromal AD progressed to dementia with no age dependency. Cognitive decline in the older individuals was most common among those who progressed to symptomatic AD and symptomatic individuals themselves. Importantly, individuals with mild and moderate ID had no differences in longitudinal cognitive decline despite having different performance at baseline. This study also found practice and floor effects, which obscured the assessment of longitudinal cognitive decline. CONCLUSIONS AND RELEVANCE: This study found an association between the development of symptomatic AD and a high risk of progressive cognitive decline among patients with DS. These results support the need for population health plans to screen for AD-related cognitive decline from the fourth decade of life and provide important longitudinal data to inform clinical trials in adults with DS to prevent AD. American Medical Association 2022-08-05 /pmc/articles/PMC9356319/ /pubmed/35930282 http://dx.doi.org/10.1001/jamanetworkopen.2022.25573 Text en Copyright 2022 Videla L et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Videla, Laura
Benejam, Bessy
Pegueroles, Jordi
Carmona-Iragui, María
Padilla, Concepción
Fernández, Susana
Barroeta, Isabel
Altuna, Miren
Valldeneu, Silvia
Garzón, Diana
Ribas, Laia
Montal, Víctor
Arranz Martínez, Javier
Rozalem Aranha, Mateus
Alcolea, Daniel
Bejanin, Alexandre
Iulita, Maria Florencia
Videla Cés, Sebastià
Blesa, Rafael
Lleó, Alberto
Fortea, Juan
Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome
title Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome
title_full Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome
title_fullStr Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome
title_full_unstemmed Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome
title_short Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome
title_sort longitudinal clinical and cognitive changes along the alzheimer disease continuum in down syndrome
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356319/
https://www.ncbi.nlm.nih.gov/pubmed/35930282
http://dx.doi.org/10.1001/jamanetworkopen.2022.25573
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