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 Alzheimerâ€™s disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with Lewy bodies (AD-DLB) or Alzheimerâ€™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 â€œpureâ€ 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 (Î² = -0.69, 95% CI: -1.05, -0.33, p<0.001) while the AD-DLB group did not (Î² = -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.
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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; and al., et, "Faster Cognitive Decline in Dementia Due to Alzheimer Disease With Clinically Undiagnosed Lewy Body Disease" (2019). Neurology. 243.