Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease.

• Main Authors: Michael Malek-Ahmadi, Thomas G Beach, Edward Zamrini, Charles H Adler, Marwan N Sabbagh, Holly A Shill, Sandra A Jacobson, Christine M Belden, Richard J Caselli, Brian K Woodruff, Steven Z Rapscak, Geoffrey L Ahern, Jiong Shi, John N Caviness, Erika Driver-Dunckley, Shyamal H Mehta, David R Shprecher, Bryan M Spann, Pierre Tariot, Kathryn J Davis, Kathy E Long, Lisa R Nicholson, Anthony Intorcia, Michael J Glass, Jessica E Walker, Michael Callan, Jasmine Curry, Brett Cutler, Javon Oliver, Richard Arce, Douglas G Walker, Lih-Fen Lue, Geidy E Serrano, Lucia I Sue, Kewei Chen, Eric M Reiman
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2019-01-01
• Series: PLoS ONE
• Online Access: https://doi.org/10.1371/journal.pone.0217566

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.