Parkinson Disease: Doty RL

Doty RL. · Smell and Taste Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · Parkinsonism Relat Disord. · Pubmed #18267240 No free full text.

Abstract: It has become increasingly apparent that Parkinson's disease (PD) can no longer be considered purely a motor disease, as numerous sensory alterations accompany this disorder either before or early in its clinical progression. Most notable among such disturbances are decrements in smell function. Such anomalies have been documented in approximately 90% of patients with early-stage sporadic PD and appear to progress little, if at all, with the development of the more classic PD-related motor symptoms. In this paper, I briefly review the nature of the olfactory dysfunction observed in PD and current theories as to its pathological basis.

Doty RL. · Smell and Taste Center and Department of Otorhinolaryngology, Head and Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · Ann Neurol. · Pubmed #18232016 No free full text.

Abstract: Environmental agents, including viruses, prions, and toxins, have been implicated in the cause of a number of neurodegenerative diseases, most notably Alzheimer's and Parkinson's diseases. The presence of smell loss and the pathological involvement of the olfactory pathways in the formative stages of Alzheimer's and Parkinson's diseases, together with evidence that xenobiotics, some epidemiologically linked to these diseases, can readily enter the brain via the olfactory mucosa, have led to the hypothesis that Alzheimer's and Parkinson's diseases may be caused or catalyzed by agents that enter the brain via this route. Evidence for and against this concept, the "olfactory vector hypothesis," is addressed in this review.

Siderowf A, Jennings D, Connolly J, Doty RL, Marek K, Stern MB. · Parkinson's Disease and Movement Disorders Center, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Mov Disord. · Pubmed #17876851 No free full text.

Abstract: Our objective was to assess the association between risk factors for Parkinson's disease (PD) and abnormal olfaction in first-degree relatives of patients with PD. Factors including lower cigarette smoking and lower caffeine consumption have been associated with increased risk of PD. Idiopathic hyposmia has also been associated with an increased risk of PD. The relationship between risk factors for PD and impaired olfactory function has not been evaluated in relatives of PD patients. We conducted a mail survey of odor identification ability in 173 first-degree relatives of PD patients using the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Respondents also completed a questionnaire inquiring about risk factors for PD including caffeine consumption, tobacco use, exercise, and exposures to heavy metals, well-water, and pesticides. There was a direct relationship between olfactory performance and lifetime caffeine intake. After adjustment for age, gender, and smoking status, subjects who reported drinking 2 to 3 cups of caffeinated beverages per day (2.6 points higher 95% CI: 0.5, 4.5) and 4 or more cups per day (3.7 points higher, 95% CI: 0.6, 6.7) had significantly better UPSIT scores than those who consumed less than 1 cup per day. There was no significant relationship between olfactory performance and other risk factors. In conclusion, abnormal olfaction is associated with significantly lower lifetime caffeine consumption in first-degree relatives of PD patients. Further research is warranted to determine whether a history of lower caffeine consumption confers additional risk for the development of PD in hyposmic relatives of PD patients.

Antunes MB, Bowler R, Doty RL. · Smell and Taste Center, 5University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA. · Neurology. · Pubmed #17875916 No free full text.

Abstract: BACKGROUND: The sense of smell can be damaged by airborne xenobiotics, including aerosolized heavy metals, reflecting the direct exposure of its receptors to the outside environment. OBJECTIVES: To determine whether professional welders working in confined spaces exhibit olfactory dysfunction. To determine whether such dysfunction, if present, is related to indices of metal exposure associated with welding, as well as measures of neurologic and neuropsychological function. METHODS: The University of Pennsylvania Smell Identification Test (UPSIT) and a battery of neurologic and neuropsychological tests were administered to 43 welders who worked for 1 to 2 years on the San Francisco/Oakland Bay Bridge. Blood levels of Mn, Fe, Cu, and Pb were obtained. RESULTS: Relative to matched controls, the welders had significantly lower UPSIT scores, with a mean (SEM) of 29.51 (0.90) for welders and 36.55 (0.88) for controls. Eighty-eight percent scored below their individually matched controls. As in idiopathic Parkinson disease, the welders' olfactory test scores were unrelated to a broad spectrum of neurologic and neuropsychological test measures, as determined by principal components analysis. Although blood levels of Mn were associated with the time spent working on the bridge, workers with the highest Mn blood levels exhibited better olfactory function than those with the lowest Mn blood levels. The basis of this paradox, which has been observed previously, is unknown. CONCLUSIONS: Professional welders may be at risk for loss of smell function, although such loss seems to be unrelated to neurologic and neuropsychological test performance.

Bowler RM, Roels HA, Nakagawa S, Drezgic M, Diamond E, Park R, Koller W, Bowler RP, Mergler D, Bouchard M, Smith D, Gwiazda R, Doty RL. · San Francisco State University, El Cerrito, CA 94530, USA. · Occup Environ Med. · Pubmed #17018581 No free full text.

Abstract: BACKGROUND: Although adverse neuropsychological and neurological health effects are well known among workers with high manganese (Mn) exposures in mining, ore-processing and ferroalloy production, the risks among welders with lower exposures are less well understood. METHODS: Confined space welding in construction of a new span of the San Francisco-Oakland Bay Bridge without adequate protection was studied using a multidisciplinary method to identify the dose-effect relationship between adverse health effects and Mn in air or whole blood. Bridge welders (n = 43) with little or no personal protection equipment and exposed to a welding fume containing Mn, were administered neurological, neuropsychological, neurophysiological and pulmonary tests. Outcome variables were analysed in relation to whole blood Mn (MnB) and a Cumulative Exposure Index (CEI) based on Mn-air, duration and type of welding. Welders performed a mean of 16.5 months of welding on the bridge, were on average 43.8 years of age and had on average 12.6 years of education. RESULTS: The mean time weighted average of Mn-air ranged from 0.11-0.46 mg/m(3) (55% >0.20 mg/m(3)). MnB >10 microg/l was found in 43% of the workers, but the concentrations of Mn in urine, lead in blood and copper and iron in plasma were normal. Forced expiratory volume at 1s: forced vital capacity ratios (FEV(1)/FVC) were found to be abnormal in 33.3% of the welders after about 1.5 years of welding at the bridge. Mean scores of bradykinesia and Unified Parkinson Disease Rating Scale exceeded 4 and 6, respectively. Computer assisted tremor analysis system hand tremor and body sway tests, and University of Pennsylvania Smell Identification Test showed impairment in 38.5/61.5, 51.4 and 88% of the welders, respectively. Significant inverse dose-effect relationships with CEI and/or MnB were found for IQ (p<or=0.05), executive function (p<or=0.03), sustaining concentration and sequencing (p<or=0.04), verbal learning (p<or=0.01), working (p<or=0.04) and immediate memory (p<or=0.02), even when adjusted for demographics and years of welding before Bay Bridge. Symptoms reported by the welders while working were: tremors (41.9%); numbness (60.5%); excessive fatigue (65.1%); sleep disturbance (79.1%); sexual dysfunction (58.1%); toxic hallucinations (18.6%); depression (53.5%); and anxiety (39.5%). Dose-effect associations between CEI and sexual function (p<0.05), fatigue (p<0.05), depression (p<0.01) and headache (p<0.05) were statistically significant. CONCLUSIONS: Confined space welding was shown to be associated with neurological, neuropsychological and pulmonary adverse health effects. A careful enquiry of occupational histories is recommended for all welders presenting with neurological or pulmonary complaints, and a more stringent prevention strategy should be considered for Mn exposure due to inhalation of welding fume.

Siderowf A, Newberg A, Chou KL, Lloyd M, Colcher A, Hurtig HI, Stern MB, Doty RL, Mozley PD, Wintering N, Duda JE, Weintraub D, Moberg PJ. · Parkinson Disease and Movement Disorders Center, Department of Neurology, University of Pennsylvania, Philadelphia, USA. · Neurology. · Pubmed #15911797 No free full text.

Abstract: BACKGROUND: In vivo imaging of the dopamine transporter with [99mTc]TRODAT-1 (TRODAT) and olfactory testing have both been proposed as potential biomarkers in Parkinson disease (PD). OBJECTIVE: To evaluate the relationship between TRODAT SPECT imaging, odor identification skills, and motor function in patients with early PD. METHODS: Twenty-four patients with a clinical diagnosis of early-stage PD (mean Hoehn & Yahr stage = 1.4) underwent TRODAT imaging, Unified PD Rating Scale (UPDRS) ratings of motor function, and administration of the University of Pennsylvania Smell Identification Test (UPSIT). Brain images were obtained using a standardized processing protocol and specific uptake ratios for striatal regions of interest were calculated. Partial correlations between the imaging indices, disease duration, UPSIT scores, and UPDRS motor scores were then calculated. RESULTS: UPSIT scores were correlated with TRODAT uptake in the striatum as a whole (r = 0.66, p = 0.001). The putamen showed the strongest correlation with the UPSIT (r = 0.74; p < 0.001). The correlation between dopamine transporter density in the caudate and UPSIT was moderate (r = 0.36, p = 0.11), but was not significant. CONCLUSIONS: Olfactory function is highly correlated with dopamine transporter imaging abnormalities in early Parkinson disease (PD). Further studies are warranted to determine whether changes over time in these two measures are also correlated in early PD.

Doty RL. · No affiliation provided · Am J Psychiatry. · Pubmed #11532759 links to  free full text

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