Improved diagnosis of Parkinson's disease from a detailed olfactory phenotype

Gerkin, Richard C.; Adler, Charles H.; Hentz, Joseph G.; Shill, Holly A.; Driver‐Dunckley, Erika; Mehta, Shyamal H.; Sabbagh, Marwan N.; Caviness, John N.; Dugger, Brittany N.; Serrano, Geidy E.; Belden, Christine M.; Smith, Brian H.; Sue, Lucia I.; Davis, Kathryn; Zamrini, Edward; Beach, Thomas G.

doi:10.1002/acn3.447

Cited by 12 publications

(9 citation statements)

References 18 publications

(25 reference statements)

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“…Most subjects had serial standardized research cognitive evaluations, done by teams of nurses, medical assistants, behavioral neurologists, movement disorders neurologists, neuropsychologists and psychometrists using standardized research-quality assessment batteries [93] [95][96][97] every third year on average. The presence or absence of DLB core clinical features [43,44], including the presence or absence of parkinsonism, visual hallucinations, fluctuations in attention or cognition and clinical history consistent with REM sleep behavior disorder (RBD), were recorded for each subject at each visit; to assist with the latter, the Mayo Sleep Questionnaire [98][99][100][101] was administered.…”

Section: Subject Characterizationmentioning

confidence: 99%

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

et al. 2020

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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

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Section: Subject Characterizationmentioning

confidence: 99%

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

et al. 2020

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“…These methods include combination of smell scores with other early, nonmotor PD manifestations, such as constipation, sleep disturbances, and depression [16, 31]. Moreover, another recent study identified a PD-specific response pattern of 12 incorrect UPSIT question/response pairs in PD participants compared to healthy controls [32], which appeared more valuable for PD diagnosis than total mean UPSIT score. Assessing for this sort of disease-specific olfactory loss was beyond the scope of the present study, but would certainly merit further work in the future.…”

Section: Discussionmentioning

confidence: 99%

Screening performance of abbreviated versions of the UPSIT smell test

et al. 2019

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Background Hyposmia can develop with age and in neurodegenerative conditions, including Parkinson’s disease (PD). The University of Pennsylvania Smell Identification Test (UPSIT) is a 40-item smell test widely used for assessing hyposmia. However, in a number of situations, such as identifying hyposmic individuals in large populations, shorter tests are preferable. Methods We assessed the ability of shorter UPSIT subsets to detect hyposmia in 891 healthy participants from the PREDICT-PD study. Shorter subsets included Versions A and B of the 4-item Pocket Smell Test (PST) and 12-item Brief Smell Identification Test (BSIT). Using a data-driven approach, we evaluated screening performances of 23,231,378 combinations of 1–7 smell items from the full UPSIT to derive “winning” subsets, and validated findings separately in another 191 healthy individuals. We then compared discriminatory UPSIT smells between PREDICT-PD participants and 40 PD patients, and assessed the performance of “winning” subsets containing discriminatory smells in PD patients. Results PST Versions A and B achieved sensitivity/specificity of 76.8%/64.9% and 86.6%/45.9%, respectively, while BSIT Versions A and B achieved 83.1%/79.5% and 96.5%/51.8%. From the data-driven analysis, 2 “winning” 7-item subsets surpassed the screening performance of 12-item BSITs (validation sensitivity/specificity of 88.2%/85.4% and 100%/53.5%), while a “winning” 4-item subset had higher sensitivity than PST-A, -B, and even BSIT-A (validation sensitivity 91.2%). Interestingly, several discriminatory smells featured within “winning” subsets, and demonstrated high-screening performances for identifying hyposmic PD patients. Conclusion Using abbreviated smell tests could provide a cost-effective means of large-scale hyposmia screening, allowing more targeted UPSIT administration in general and PD-related settings. Electronic supplementary material The online version of this article (10.1007/s00415-019-09340-x) contains supplementary material, which is available to authorized users.

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“…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.…”

Section: Supporting Datamentioning

confidence: 99%

Olfaction in Neuropathologically Defined Progressive Supranuclear Palsy

et al. 2021

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Background Hyposmia is characteristic of idiopathic Parkinson's disease (PD) and dementia with Lewy bodies (DLBs), whereas progressive supranuclear palsy (PSP) typically has normal sense of smell. However, there is a lack of pathologically confirmed data. Objective The objective is to study hyposmia in pathologically confirmed PSP patients and compare to PD patients and nondegenerative controls. Methods We studied autopsied subjects in the Arizona Study of Aging and Neurodegenerative Disorders who had antemortem olfactory testing and a neuropathological diagnosis of either PD, PSP, or control. Results: This study included 281 cases. Those with neuropathologically confirmed PSP (N = 24) and controls (N = 174) had significantly better sense of smell than those with PD (N = 76). Although most PSP patients had normal olfaction, there were some with hyposmia, resulting in an overall reduced sense of smell in PSP compared to controls. The sensitivity of having PSP pathologically in those presenting with parkinsonism and normosmia was 93.4% with a specificity of 64.7%. Cases with both PSP and PD pathologically had reduced sense of smell similar to PD alone (N = 7). Hyposmic PSP patients had significantly higher Lewy body burden not meeting criteria for additional PD/DLB diagnosis. Conclusions Pathologically confirmed PD had reduced olfaction compared with PSP or controls. In the setting of parkinsonism in this sample, the presence of normosmia had high sensitivity for PSP. Hyposmia in PSP suggests the presence of additional Lewy body pathology. © 2021 International Parkinson and Movement Disorder Society

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Improved diagnosis of Parkinson's disease from a detailed olfactory phenotype

Cited by 12 publications

References 18 publications

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

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

Screening performance of abbreviated versions of the UPSIT smell test

Olfaction in Neuropathologically Defined Progressive Supranuclear Palsy

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