Cargando…
Independent effects of white matter hyperintensities on cognitive, neuropsychiatric, and functional decline: a longitudinal investigation using the National Alzheimer’s Coordinating Center Uniform Data Set
BACKGROUND: Longitudinal investigations are needed to improve understanding of the contributions of cerebral small vessel disease to the clinical manifestation of Alzheimer’s disease, particularly in the early disease stages. This study leveraged the National Alzheimer’s Coordinating Center Uniform...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661103/ https://www.ncbi.nlm.nih.gov/pubmed/31351489 http://dx.doi.org/10.1186/s13195-019-0521-0 |
_version_ | 1783439409688870912 |
---|---|
author | Puzo, Christian Labriola, Caroline Sugarman, Michael A. Tripodis, Yorghos Martin, Brett Palmisano, Joseph N. Steinberg, Eric G. Stein, Thor D. Kowall, Neil W. McKee, Ann C. Mez, Jesse Killiany, Ronald J. Stern, Robert A. Alosco, Michael L. |
author_facet | Puzo, Christian Labriola, Caroline Sugarman, Michael A. Tripodis, Yorghos Martin, Brett Palmisano, Joseph N. Steinberg, Eric G. Stein, Thor D. Kowall, Neil W. McKee, Ann C. Mez, Jesse Killiany, Ronald J. Stern, Robert A. Alosco, Michael L. |
author_sort | Puzo, Christian |
collection | PubMed |
description | BACKGROUND: Longitudinal investigations are needed to improve understanding of the contributions of cerebral small vessel disease to the clinical manifestation of Alzheimer’s disease, particularly in the early disease stages. This study leveraged the National Alzheimer’s Coordinating Center Uniform Data Set to longitudinally examine the association between white matter hyperintensities and neuropsychological, neuropsychiatric, and functional decline among participants with normal cognition. METHODS: The sample included 465 participants from the National Alzheimer’s Coordinating Center Uniform Data Set who had quantitated volume of white matter hyperintensities from fluid-attenuated inversion recovery MRI, had normal cognition at the time of their MRI, and were administered the National Alzheimer’s Coordinating Center Uniform Data Set neuropsychological test battery within 1 year of study evaluation and had at least two post-MRI time points of clinical data. Neuropsychiatric status was assessed by the Geriatric Depression Scale-15 and Neuropsychiatric Inventory-Questionnaire. Clinical Dementia Rating Sum of Boxes defined functional status. For participants subsequently diagnosed with mild cognitive impairment (MCI) or dementia, their impairment must have been attributed to Alzheimer’s disease (AD) to evaluate the relationships between WMH and the clinical presentation of AD. RESULTS: Of the 465 participants, 56 converted to MCI or AD dementia (average follow-up = 5 years). Among the 465 participants, generalized estimating equations controlling for age, sex, race, education, APOE ε4, and total brain and hippocampal volume showed that higher baseline log-white matter hyperintensities predicted accelerated decline on the following neuropsychological tests in rank order of effect size: Trails B (p < 0.01), Digit Symbol Coding (p < 0.01), Logical Memory Immediate Recall (p = 0.02), Trail Making A (p < 0.01), and Semantic Fluency (p < 0.01). White matter hyperintensities predicted increases in Clinical Dementia Rating Sum of Boxes (p < 0.01) and Geriatric Depression Scale-15 scores (p = 0.01). Effect sizes were comparable to total brain and hippocampal volume. White matter hyperintensities did not predict diagnostic conversion. All effects also remained after including individuals with non-AD suspected etiologies for those who converted to MCI or dementia. CONCLUSIONS: In this baseline cognitively normal sample, greater white matter hyperintensities were associated with accelerated cognitive, neuropsychiatric, and functional decline independent of traditional risk factors and MRI biomarkers for Alzheimer’s disease. |
format | Online Article Text |
id | pubmed-6661103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66611032019-08-01 Independent effects of white matter hyperintensities on cognitive, neuropsychiatric, and functional decline: a longitudinal investigation using the National Alzheimer’s Coordinating Center Uniform Data Set Puzo, Christian Labriola, Caroline Sugarman, Michael A. Tripodis, Yorghos Martin, Brett Palmisano, Joseph N. Steinberg, Eric G. Stein, Thor D. Kowall, Neil W. McKee, Ann C. Mez, Jesse Killiany, Ronald J. Stern, Robert A. Alosco, Michael L. Alzheimers Res Ther Research BACKGROUND: Longitudinal investigations are needed to improve understanding of the contributions of cerebral small vessel disease to the clinical manifestation of Alzheimer’s disease, particularly in the early disease stages. This study leveraged the National Alzheimer’s Coordinating Center Uniform Data Set to longitudinally examine the association between white matter hyperintensities and neuropsychological, neuropsychiatric, and functional decline among participants with normal cognition. METHODS: The sample included 465 participants from the National Alzheimer’s Coordinating Center Uniform Data Set who had quantitated volume of white matter hyperintensities from fluid-attenuated inversion recovery MRI, had normal cognition at the time of their MRI, and were administered the National Alzheimer’s Coordinating Center Uniform Data Set neuropsychological test battery within 1 year of study evaluation and had at least two post-MRI time points of clinical data. Neuropsychiatric status was assessed by the Geriatric Depression Scale-15 and Neuropsychiatric Inventory-Questionnaire. Clinical Dementia Rating Sum of Boxes defined functional status. For participants subsequently diagnosed with mild cognitive impairment (MCI) or dementia, their impairment must have been attributed to Alzheimer’s disease (AD) to evaluate the relationships between WMH and the clinical presentation of AD. RESULTS: Of the 465 participants, 56 converted to MCI or AD dementia (average follow-up = 5 years). Among the 465 participants, generalized estimating equations controlling for age, sex, race, education, APOE ε4, and total brain and hippocampal volume showed that higher baseline log-white matter hyperintensities predicted accelerated decline on the following neuropsychological tests in rank order of effect size: Trails B (p < 0.01), Digit Symbol Coding (p < 0.01), Logical Memory Immediate Recall (p = 0.02), Trail Making A (p < 0.01), and Semantic Fluency (p < 0.01). White matter hyperintensities predicted increases in Clinical Dementia Rating Sum of Boxes (p < 0.01) and Geriatric Depression Scale-15 scores (p = 0.01). Effect sizes were comparable to total brain and hippocampal volume. White matter hyperintensities did not predict diagnostic conversion. All effects also remained after including individuals with non-AD suspected etiologies for those who converted to MCI or dementia. CONCLUSIONS: In this baseline cognitively normal sample, greater white matter hyperintensities were associated with accelerated cognitive, neuropsychiatric, and functional decline independent of traditional risk factors and MRI biomarkers for Alzheimer’s disease. BioMed Central 2019-07-27 /pmc/articles/PMC6661103/ /pubmed/31351489 http://dx.doi.org/10.1186/s13195-019-0521-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Puzo, Christian Labriola, Caroline Sugarman, Michael A. Tripodis, Yorghos Martin, Brett Palmisano, Joseph N. Steinberg, Eric G. Stein, Thor D. Kowall, Neil W. McKee, Ann C. Mez, Jesse Killiany, Ronald J. Stern, Robert A. Alosco, Michael L. Independent effects of white matter hyperintensities on cognitive, neuropsychiatric, and functional decline: a longitudinal investigation using the National Alzheimer’s Coordinating Center Uniform Data Set |
title | Independent effects of white matter hyperintensities on cognitive, neuropsychiatric, and functional decline: a longitudinal investigation using the National Alzheimer’s Coordinating Center Uniform Data Set |
title_full | Independent effects of white matter hyperintensities on cognitive, neuropsychiatric, and functional decline: a longitudinal investigation using the National Alzheimer’s Coordinating Center Uniform Data Set |
title_fullStr | Independent effects of white matter hyperintensities on cognitive, neuropsychiatric, and functional decline: a longitudinal investigation using the National Alzheimer’s Coordinating Center Uniform Data Set |
title_full_unstemmed | Independent effects of white matter hyperintensities on cognitive, neuropsychiatric, and functional decline: a longitudinal investigation using the National Alzheimer’s Coordinating Center Uniform Data Set |
title_short | Independent effects of white matter hyperintensities on cognitive, neuropsychiatric, and functional decline: a longitudinal investigation using the National Alzheimer’s Coordinating Center Uniform Data Set |
title_sort | independent effects of white matter hyperintensities on cognitive, neuropsychiatric, and functional decline: a longitudinal investigation using the national alzheimer’s coordinating center uniform data set |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661103/ https://www.ncbi.nlm.nih.gov/pubmed/31351489 http://dx.doi.org/10.1186/s13195-019-0521-0 |
work_keys_str_mv | AT puzochristian independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT labriolacaroline independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT sugarmanmichaela independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT tripodisyorghos independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT martinbrett independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT palmisanojosephn independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT steinbergericg independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT steinthord independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT kowallneilw independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT mckeeannc independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT mezjesse independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT killianyronaldj independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT sternroberta independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset AT aloscomichaell independenteffectsofwhitematterhyperintensitiesoncognitiveneuropsychiatricandfunctionaldeclinealongitudinalinvestigationusingthenationalalzheimerscoordinatingcenteruniformdataset |