Severe hyposmia distinguishes neuropathologically confirmed dementia with Lewy bodies from Alzheimer’s disease dementia

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

Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies

“…Olfactory impairment has been demonstrated in a plethora of neurological disorders, including AD, Parkinson’s disease (PD) and DLB [ 8 , 9 ]. Although not currently implemented in the clinic, olfactory assessment has been postulated as a promising tool for the differential diagnosis of AD and DLB [ 10 , 11 , 12 , 13 , 14 ]. Previous clinicopathological studies have shown that olfactory dysfunction is associated with Lewy body pathology in limbic and neocortical regions [ 15 ], and to date, most of the studies have revealed that olfactory deficits are more severe in DLB than in AD [ 8 , 13 , 14 , 16 ].…”

“…Although not currently implemented in the clinic, olfactory assessment has been postulated as a promising tool for the differential diagnosis of AD and DLB [ 10 , 11 , 12 , 13 , 14 ]. Previous clinicopathological studies have shown that olfactory dysfunction is associated with Lewy body pathology in limbic and neocortical regions [ 15 ], and to date, most of the studies have revealed that olfactory deficits are more severe in DLB than in AD [ 8 , 13 , 14 , 16 ]. However, despite the great attention that has caught in the last decade, the sense of smell is often undermine in the clinical diagnosis, and clinicians rarely test this deficit in patients with suspicion of neurological disease.…”

Olfaction in Neuropathologically Defined Progressive Supranuclear Palsy

“…Hyposmia is likely to begin at prodromal disease stages as it is present in subjects with incidental Lewy body disease and often predates the appearance of motor features. [1][2][3][4][5][6][7][8] On the contrary, patients with clinically determined progressive supranuclear palsy (PSP) have been reported to have normal olfaction. [9][10][11][12][13] However, there is a lack of studies performed regarding pathological confirmation of disease state.…”

The challenges of COVID‐19 for people with dementia with Lewy bodies and family caregivers

“…Secondary pneumonias may be more common given that people with DLB often have a pharyngeal-type dysfunction, which results in a high prevalence of silent aspiration. 12 This could contribute to diagnostic difficulty especially in conjunction with anosmia, another symptom commonly associated with DLB, 13 and which is also indicative of COVID-19.…”