Abstract
Many subjects with neuropathologically-confirmed dementia with Lewy bodies (DLB) are never diagnosed during life, instead being categorized as Alzheimer’s disease dementia (ADD) or unspecified dementia. Unrecognized DLB therefore is a critical impediment to clinical studies and treatment trials of both ADD and DLB. There are studies that suggest that olfactory function tests may be able to distinguish DLB from ADD, but few of these had neuropathological confirmation of diagnosis. We compared University of Pennsylvania Smell Identification Test (UPSIT) results in 257 subjects that went on to autopsy and neuropathological examination. Consensus clinicopathological diagnostic criteria were used to define ADD and DLB, as well as Parkinson’s disease with dementia (PDD), with (PDD+AD) or without (PDD-AD) concurrent AD; a group with ADD and Lewy body disease (LBD) not meeting criteria for DLB (ADLB) and a clinically normal control group were also included. The subjects with DLB, PDD+AD and PDD-AD all had lower (one-way ANOVA p < 0.0001, pairwise Bonferroni p < 0.05) first and mean UPSIT scores than the ADD, ADLB or control groups. For DLB subjects with first and mean UPSIT scores less than 20 and 17, respectively, Firth logistic regression analysis, adjusted for age, gender and mean MMSE score, conferred statistically significant odds ratios of 17.5 and 18.0 for the diagnosis, vs ADD. For other group comparisons (PDD+AD and PDD-AD vs ADD) and UPSIT cutoffs of 17, the same analyses resulted in odds ratios ranging from 16.3 to 31.6 (p < 0.0001). To our knowledge, this is the largest study to date comparing olfactory function in subjects with neuropathologically-confirmed LBD and ADD. Olfactory function testing may be a convenient and inexpensive strategy for enriching dementia studies or clinical trials with DLB subjects, or conversely, reducing the inclusion of DLB subjects in ADD studies or trials.
Highlights
In this study we sought to determine the diagnostic utility of hyposmia as a diagnostic predictor of neuropathologically-identified dementia with Lewy bodies (DLB) with comorbid Alzheimer’s disease dementia (ADD), as compared with ADD alone, using the largest set to date of neuropathologically-examined subjects
In this study we sought to determine the diagnostic utility of hyposmia as a diagnostic predictor of neuropathologically-identified ADD/DLB, using considerably larger subject numbers than previous studies
Our results confirm those of the prior studies, where subjects with ADD/DLB have been repeatedly found to have worse olfactory function than ADD
Summary
Dementia due to AD (ADD) is often associated with comorbid brain disease that may affect clinical presentation, rate of cognitive decline, and response to therapeutic agents [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]. More than one-half or more of all those meeting clinicopathological ADD diagnostic criteria have α-synuclein pathology [9,23,24,25] with morphological features similar to Parkinson’s disease (PD) This is broadly termed “Lewy body disease” (LBD). In the majority of subjects with ADD and DLB (ADD/DLB), the typical clinical signs and symptoms of DLB [43,44] are absent and this co-existence is recognized only at autopsy [22,45,46,47] This clinical inability to separate ADD from DLB hampers clinical trials for both conditions. There is a critical need for better clinical differentiation of these two conditions
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