Low clinical diagnostic accuracy of early vs advanced Parkinson disease

Adler, Charles H.; Beach, Thomas G.; Hentz, Joseph G.; Shill, Holly A.; Caviness, John N.; Driver‐Dunckley, Erika; Sabbagh, Marwan N.; Sue, Lucia I.; Jacobson, Sandra A.; Belden, Christine M.; Dugger, Brittany N.

doi:10.1212/wnl.0000000000000641

Cited by 409 publications

(379 citation statements)

References 32 publications

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“…However, parkinsonism is also an early sign of other neurodegenerative disorders such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Differentiating between these disorders at early disease stages can be challenging, and clinicopathologic studies show that the clinical diagnosis of PD is often incorrect in the early stages (4). This is problematic, because accurate, early diagnosis is important for patient management, prognosis, and patient selection for clinical trials.…”

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confidence: 99%

Metabolic Imaging in Parkinson Disease

et al. 2016

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This review focuses on recent human 18 F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how 18 F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of 18 F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed.

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confidence: 99%

Metabolic Imaging in Parkinson Disease

et al. 2016

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“…This can make accurate diagnosis challenging, especially in the early stages of disease 8. Since PSP is not known for specific olfactory pathology, this suggests that the UPSIT test might be used for differential diagnosis of PD versus PSP, as demonstrated previously 16.…”

Section: Resultsmentioning

confidence: 98%

“…Previous studies have reported that poor performance on the UPSIT is correlated with PD, but it was previously unclear if this test had enough predictive power to be of clinical value. Part of this uncertainty originates from the use of a purely clinical diagnosis of PD as a gold standard, which may be inaccurate especially in the early stages of the diseases 8. Here we overcame this issue using a postmortem pathological assessment of subjects as a gold standard, made possible by the ongoing AZSAND and BBDP 14…”

Section: Discussionmentioning

confidence: 99%

“…Olfactory dysfunction is thus the proverbial “canary in the coal mine” for PD. Since early clinical diagnosis of PD by standard neurological examination is unreliable,8 this motivates the possibility of improving clinical diagnosis by making better use of potentially informative olfactory information. It may also help to distinguish PD from other disorders that have a motor but not necessarily olfactory component.…”

Section: Introductionmentioning

confidence: 99%

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

Gerkin

Adler

Hentz

et al. 2017

Ann Clin Transl Neurol

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ObjectiveTo assess the predictive potential of the complete response pattern from the University of Pennsylvania Smell Identification Test for the diagnosis of Parkinson's disease.MethodsWe analyzed a large dataset from the Arizona Study of Aging and Neurodegenerative Disorders, a longitudinal clinicopathological study of health and disease in elderly volunteers. Using the complete pattern of responses to all 40 items in each subject's test, we built predictive models of neurodegenerative disease, and we validated these models out of sample by comparing model predictions against postmortem pathological diagnosis.ResultsConsistent with anatomical considerations, we found that the specific test response pattern had additional predictive power compared with a conventional measure – total test score – in Parkinson's disease, but not Alzheimer's disease. We also identified specific test questions that carry the greatest predictive power for disease diagnosis.InterpretationOlfactory ability has typically been assessed with either self‐report or total score on a multiple choice test. We showed that a more accurate clinical diagnosis can be made using the pattern of responses to all the test questions, and validated this against the “gold standard” of pathological diagnosis. Information in the response pattern also suggests specific modifications to the standard test that may optimize predictive power under the typical clinical constraint of limited time. We recommend that future studies retain the individual item responses for each subject, and not just the total score, both to enable more accurate diagnosis and to enable additional future insights.

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“…It will be important to further elucidate the role of p11 in dopamine neurons, particularly in relation to mechanism(s) underlying neurodegeneration. The diagnosis of PD is based solely on clinical assessment (24), which often leads to misdiagnosis (25). Reproducible and robust objective biomarkers to support the diagnosis, classify subtypes, and track disease progression would represent a scientific breakthrough (26).…”

Section: Discussionmentioning

confidence: 99%

Alterations of p11 in brain tissue and peripheral blood leukocytes in Parkinson’s disease

Green

Zhang

Tiklová

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Individuals with Parkinson’s disease (PD) often suffer from comorbid depression. P11 (S100A10), a member of the S100 family of proteins, is expressed widely throughout the body and is involved in major depressive disorder and antidepressant response. Central p11 levels are reduced in postmortem tissue from depressed individuals; however, p11 has not yet been investigated in PD patients with depression or those without depression. We investigated p11 levels in postmortem PD brains and assessed whether peripheral p11 levels correlate with disease severity. Substantia nigra, putamen, and cortical p11 protein levels were assessed in postmortem brain samples from PD patients and matched controls. In a different set of postmortem brains, p11 mRNA expression was measured in dopaminergic cells from the substantia nigra. Both p11 protein and mRNA levels were decreased in PD patients. Peripheral p11 protein levels were investigated in distinct leukocyte populations from PD patients with depression and those without depression. Monocyte, natural killer (NK) cell, and cytotoxic T-cell p11 levels were positively associated with the severity of PD, and NK cell p11 levels were positively associated with depression scores. Given that inflammation plays a role in both PD and depression, it is intriguing that peripheral p11 levels are altered in immune cells in both conditions. Our data provide insight into the pathological alterations occurring centrally and peripherally in PD. Moreover, if replicated in other cohorts, p11 could be an easily accessible biomarker for monitoring the severity of PD, especially in the context of comorbid depression.

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Low clinical diagnostic accuracy of early vs advanced Parkinson disease

Abstract: This study provides Class II evidence that a clinical diagnosis of PD identifies patients who will have pathologically confirmed PD with a sensitivity of 88% and specificity of 68%.

Cited by 409 publications

References 32 publications

Metabolic Imaging in Parkinson Disease

Metabolic Imaging in Parkinson Disease

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

Alterations of p11 in brain tissue and peripheral blood leukocytes in Parkinson’s disease

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