Send to

Choose Destination
PLoS One. 2019 Jun 25;14(6):e0217566. doi: 10.1371/journal.pone.0217566. eCollection 2019.

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

Author information

Banner Alzheimer Institute, Phoenix, Arizona, United States of America.
Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
Department of Neurology, Mayo Clinic, Scottsdale, Arizona, United States of America.
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada, United States of America.
Barrow Neurological Institute, Phoenix, Arizona, United States of America.
Department of Neurology, University of Arizona, Tucson, Arizona, United States of America.
Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan.
Shanghai Green Valley Pharmaceutical, Shanghai, China.
Arizona State University School of Mathematics and Statistics, Tempe, Arizona, United States of America.
College of Medicine-Phoenix, University of Arizona, Phoenix, Arizona, United States of America.
Beijing Normal University, Beijing, China.



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.


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.


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).


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.

Conflict of interest statement

We have the following interests: Dr. Kewei Chen is employed by Shanghai Green Valley Pharmaceutical. Dr. Malek-Ahmadi is a consultant to Shanghai Green Valley Pharmaceutical. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center