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Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease
BACKGROUND: Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimer’s disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with Lewy bodies (AD-DLB) or Alzheimer’s disease with Lewy bodies (AD-LB), the latter represent...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592515/ https://www.ncbi.nlm.nih.gov/pubmed/31237877 http://dx.doi.org/10.1371/journal.pone.0217566 |
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author | Malek-Ahmadi, Michael Beach, Thomas G. Zamrini, Edward Adler, Charles H. Sabbagh, Marwan N. Shill, Holly A. Jacobson, Sandra A. Belden, Christine M. Caselli, Richard J. Woodruff, Brian K. Rapscak, Steven Z. Ahern, Geoffrey L. Shi, Jiong Caviness, John N. Driver-Dunckley, Erika Mehta, Shyamal H. Shprecher, David R. Spann, Bryan M. Tariot, Pierre Davis, Kathryn J. Long, Kathy E. Nicholson, Lisa R. Intorcia, Anthony Glass, Michael J. Walker, Jessica E. Callan, Michael Curry, Jasmine Cutler, Brett Oliver, Javon Arce, Richard Walker, Douglas G. Lue, Lih-Fen Serrano, Geidy E. Sue, Lucia I. Chen, Kewei Reiman, Eric M. |
author_facet | Malek-Ahmadi, Michael Beach, Thomas G. Zamrini, Edward Adler, Charles H. Sabbagh, Marwan N. Shill, Holly A. Jacobson, Sandra A. Belden, Christine M. Caselli, Richard J. Woodruff, Brian K. Rapscak, Steven Z. Ahern, Geoffrey L. Shi, Jiong Caviness, John N. Driver-Dunckley, Erika Mehta, Shyamal H. Shprecher, David R. Spann, Bryan M. Tariot, Pierre Davis, Kathryn J. Long, Kathy E. Nicholson, Lisa R. Intorcia, Anthony Glass, Michael J. Walker, Jessica E. Callan, Michael Curry, Jasmine Cutler, Brett Oliver, Javon Arce, Richard Walker, Douglas G. Lue, Lih-Fen Serrano, Geidy E. Sue, Lucia I. Chen, Kewei Reiman, Eric M. |
author_sort | Malek-Ahmadi, Michael |
collection | PubMed |
description | BACKGROUND: Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimer’s disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with Lewy bodies (AD-DLB) or Alzheimer’s disease with Lewy bodies (AD-LB), the latter representing subjects with ADD and LBD not meeting neuropathological distribution and density thresholds for DLB. Although it has been established that ADD subjects with undifferentiated LBD have a more rapid cognitive decline than those with ADD alone, it is still unknown whether AD-LB subjects, who represent the majority of LBD and approximately one-third of all those with ADD, have a different clinical course. METHODS: Subjects with dementia included those with “pure” ADD (n = 137), AD-DLB (n = 64) and AD-LB (n = 114), all with two or more complete Mini Mental State Examinations (MMSE) and a full neuropathological examination. RESULTS: Linear mixed models assessing MMSE change showed that the AD-LB group had significantly greater decline compared to the ADD group (β = -0.69, 95% CI: -1.05, -0.33, p<0.001) while the AD-DLB group did not (β = -0.30, 95% CI: -0.73, 0.14, p = 0.18). Of those with AD-DLB and AD-LB, only 66% and 2.1%, respectively, had been diagnosed with LBD at any point during their clinical course. Compared with clinically-diagnosed AD-DLB subjects, those that were clinically undetected had significantly lower prevalences of parkinsonism (p = 0.046), visual hallucinations (p = 0.0008) and dream enactment behavior (0.013). CONCLUSIONS: The probable cause of LBD clinical detection failure is the lack of a sufficient set of characteristic core clinical features. Core DLB clinical features were not more common in AD-LB as compared to ADD. Clinical identification of ADD with LBD would allow stratified analyses of ADD clinical trials, potentially improving the probability of trial success. |
format | Online Article Text |
id | pubmed-6592515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-65925152019-07-05 Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease Malek-Ahmadi, Michael Beach, Thomas G. Zamrini, Edward Adler, Charles H. Sabbagh, Marwan N. Shill, Holly A. Jacobson, Sandra A. Belden, Christine M. Caselli, Richard J. Woodruff, Brian K. Rapscak, Steven Z. Ahern, Geoffrey L. Shi, Jiong Caviness, John N. Driver-Dunckley, Erika Mehta, Shyamal H. Shprecher, David R. Spann, Bryan M. Tariot, Pierre Davis, Kathryn J. Long, Kathy E. Nicholson, Lisa R. Intorcia, Anthony Glass, Michael J. Walker, Jessica E. Callan, Michael Curry, Jasmine Cutler, Brett Oliver, Javon Arce, Richard Walker, Douglas G. Lue, Lih-Fen Serrano, Geidy E. Sue, Lucia I. Chen, Kewei Reiman, Eric M. PLoS One Research Article BACKGROUND: Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimer’s disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with Lewy bodies (AD-DLB) or Alzheimer’s disease with Lewy bodies (AD-LB), the latter representing subjects with ADD and LBD not meeting neuropathological distribution and density thresholds for DLB. Although it has been established that ADD subjects with undifferentiated LBD have a more rapid cognitive decline than those with ADD alone, it is still unknown whether AD-LB subjects, who represent the majority of LBD and approximately one-third of all those with ADD, have a different clinical course. METHODS: Subjects with dementia included those with “pure” ADD (n = 137), AD-DLB (n = 64) and AD-LB (n = 114), all with two or more complete Mini Mental State Examinations (MMSE) and a full neuropathological examination. RESULTS: Linear mixed models assessing MMSE change showed that the AD-LB group had significantly greater decline compared to the ADD group (β = -0.69, 95% CI: -1.05, -0.33, p<0.001) while the AD-DLB group did not (β = -0.30, 95% CI: -0.73, 0.14, p = 0.18). Of those with AD-DLB and AD-LB, only 66% and 2.1%, respectively, had been diagnosed with LBD at any point during their clinical course. Compared with clinically-diagnosed AD-DLB subjects, those that were clinically undetected had significantly lower prevalences of parkinsonism (p = 0.046), visual hallucinations (p = 0.0008) and dream enactment behavior (0.013). CONCLUSIONS: The probable cause of LBD clinical detection failure is the lack of a sufficient set of characteristic core clinical features. Core DLB clinical features were not more common in AD-LB as compared to ADD. Clinical identification of ADD with LBD would allow stratified analyses of ADD clinical trials, potentially improving the probability of trial success. Public Library of Science 2019-06-25 /pmc/articles/PMC6592515/ /pubmed/31237877 http://dx.doi.org/10.1371/journal.pone.0217566 Text en © 2019 Malek-Ahmadi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Malek-Ahmadi, Michael Beach, Thomas G. Zamrini, Edward Adler, Charles H. Sabbagh, Marwan N. Shill, Holly A. Jacobson, Sandra A. Belden, Christine M. Caselli, Richard J. Woodruff, Brian K. Rapscak, Steven Z. Ahern, Geoffrey L. Shi, Jiong Caviness, John N. Driver-Dunckley, Erika Mehta, Shyamal H. Shprecher, David R. Spann, Bryan M. Tariot, Pierre Davis, Kathryn J. Long, Kathy E. Nicholson, Lisa R. Intorcia, Anthony Glass, Michael J. Walker, Jessica E. Callan, Michael Curry, Jasmine Cutler, Brett Oliver, Javon Arce, Richard Walker, Douglas G. Lue, Lih-Fen Serrano, Geidy E. Sue, Lucia I. Chen, Kewei Reiman, Eric M. Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease |
title | Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease |
title_full | Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease |
title_fullStr | Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease |
title_full_unstemmed | Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease |
title_short | Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease |
title_sort | faster cognitive decline in dementia due to alzheimer disease with clinically undiagnosed lewy body disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592515/ https://www.ncbi.nlm.nih.gov/pubmed/31237877 http://dx.doi.org/10.1371/journal.pone.0217566 |
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