Functional Optical Hemodynamic Imaging of the Olfactory Cortex in Patients with Parkinson’s Disease

Author(s):  
Masayuki Karaki ◽  
Eiji Kobayashi ◽  
Ryuichi Kobayashi ◽  
Kosuke Akiyama ◽  
Tetsuo Toge ◽  
...  

Olfactory dysfunction is a frequent non-motor symptom in Parkinson’s disease (PD). This symptom is considered to be an early manifestation of the disease. The aim of this study was to establish the cortical basis of olfactory function in patients with PD. This study was conducted on ten healthy, normosmic subjects and seven patients with PD (one with subjective olfactory dysfunction and nine without subjective olfactory dysfunction). We employed a 22-channel near-infrared spectroscopy (NIRS) device with eight light-incident fibers and seven light-detector fibers, each with an inter-optode distance of 2.5 centimeters on the frontal head. Isovaleric acid was used as the odor stimulant. We measured the change in total hemoglobin concentrations (totalHb) from pre-baseline values and compared the results obtained for healthy normosmic subjects and patients with PD. In all healthy normosmic subjects and three patients with PD, isovaleric acid caused remarkable changes in (totalHb), especially in the lower areas of the frontal cortex. However, in four patients with PD, isovaleric acid caused no changes. This result indicates that subjective symptoms are different from objective test results in patients with PD. These activated areas may be related to the orbitofrontal cortex corresponding to the olfactory cortices. This study suggests that normosmic subjects with PD already have damage to their olfactory function.

Author(s):  
Karaki Masayuki ◽  
Kobayashi Eiji ◽  
Touge Tetsuo ◽  
Mori Nozomu

Hyposmia, psychiatric disorders, and cognitive problems are common non-motor manifestations of Parkinson’s disease (PD), but how they are related to the progression of PD remains unclear. Olfactory dysfunction, which is a common non-motor symptom of Parkinson’s disease, is considered to be an early manifestation of this disease. The aim of this study is to investigate the usefulness of near-infrared spectroscopy (NIRS) in measuring olfaction in PD patients and to establish the cortical basis of olfactory function in PD patients. This study was conducted on 9 healthy normosmic volunteers and 24 patients with PD. The authors employed a 22-channel NIRS device with eight light-incident fibers and seven light-detection fibers and placed fibers every 2.5 cm on the forehead of volunteers. Isovaleric acid was used as the odor stimulant. The authors measured the changes in total hemoglobin (tHb) concentration from baseline values and compared the results obtained from healthy normosmic volunteers with those from PD patients. PD patients had higher scores in the subjective olfactory test and smaller changes in tHb concentrations compared with normal volunteers. In particular, no changes in tHb concentration were detected in patients with the awareness of the sense of smell disorder.


2020 ◽  
Vol 14 ◽  
Author(s):  
Runcheng He ◽  
Yuwen Zhao ◽  
Yan He ◽  
Yangjie Zhou ◽  
Jinxia Yang ◽  
...  

Background and Objective:Olfactory dysfunction (hyposmia) is an important non-motor symptom of Parkinson’s disease (PD). To investigate the potential prognostic value of hyposmia as a marker for disease progression, we prospectively assessed clinical manifestations and longitudinal changes of hyposmic PD patients and normosmic ones.MethodsOlfactory function was evaluated with the Sniffin’ Sticks in PD patients at baseline. One hundred five hyposmic PD patients and 59 normosmic PD patients were enrolled and followed up for 2 years. They were subsequently evaluated at baseline and during follow-up periods with neurological and neuropsychological assessments. Clinical manifestations and disease progressions were compared between hyposmic and normosmic patients. In addition, the relationship between disease progressions and olfactory function was analyzed.ResultsOur study suggested that hyposmic PD patients and normosmic ones were similar in gender, age, education levels, age of onset, disease duration, and clinical features at baseline. Hyposmic PD patients exhibited more severe Unified Parkinson’s Disease Rating Scale Part II–III (UPDRS II-III) scores, higher levodopa equivalent dose (LED) needs, and poorer Mini-Mental State Examination (MMSE) score at follow-up visits compared to those in normosmic PD patients. Hyposmia also showed greater rates in the increase of LED needs, improvement of UPDRS III score, and deterioration of MMSE score. Both improvement of UPDRS III score and decline of MMSE score were associated with poorer odor identification.ConclusionOur prospective study demonstrated that hyposmic PD patients showed a relatively worse clinical course compared with normosmic patients. Olfactory dysfunction is a useful predictor of disease progression.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247443
Author(s):  
Mutsumi Iijima ◽  
Yasuyuki Okuma ◽  
Keisuke Suzuki ◽  
Fumihito Yoshii ◽  
Shigeru Nogawa ◽  
...  

Background Rapid eye movement sleep behavior disorder (RBD) and olfactory dysfunction are useful for early diagnosis of Parkinson’s disease (PD). RBD and severe olfactory dysfunction are also regarded as risk factors for cognitive impairment in PD. This study aimed to assess the associations between RBD, olfactory function, and clinical symptoms in patients with PD. Methods The participants were 404 patients with non-demented PD. Probable RBD (pRBD) was determined using the Japanese version of the RBD screening questionnaire (RBDSQ-J) and the RBD Single-Question Screen (RBD1Q). Olfactory function was evaluated using the odor identification test for Japanese. Clinical symptoms were evaluated using the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts I–IV. Results In total, 134 (33.2%) patients indicated a history of pRBD as determined by the RBD1Q and 136 (33.7%) by the RBDSQ-J based on a cutoff value of 6 points. Moreover, 101 patients were diagnosed as pRBD by both questionnaires, 35 by the RBDSQ-J only, and 33 by the RBD1Q only. The MDS-UPDRS parts I–III scores were significantly higher and disease duration significantly longer in the pRBD group. pRBD was significantly associated with male gender and the MDS-UPDRS part I score. The olfactory identification function was significantly reduced in the pRBD group. Conclusions About 33% of the patients with PD had pRBD based on the questionnaires, and both motor and non-motor functions were significantly decreased in these patients. These results suggest that more extensive degeneration occurred in patients with non-demented PD with RBD.


2018 ◽  
Vol 27 (5) ◽  
pp. 831-839 ◽  
Author(s):  
Soohyun Wi ◽  
Jang Woo Lee ◽  
MinGi Kim ◽  
Chang-Hwan Park ◽  
Sung-Rae Cho

Parkinson’s disease (PD) features nonmotor symptoms such as olfactory dysfunction referred to as hyposmia, an initial sign of disease progression. Metabolic dysfunction can contribute to neurodegenerative diseases, and various xenobiotics and endogenous compounds are also involved in the pathogenesis of PD. Although aerobic exercise was found to induce preservation or improvement in olfactory function in PD patients in a recent study, the exact underlying mechanism for this effect is not clear. We aimed to investigate the influence of an enriched environment (EE) on olfactory dysfunction especially via metabolic pathways related to detoxification enzymes. Eight-month-old transgenic (Tg) PD mice that overexpress human A53T α-synuclein (α-syn) were randomly allocated to an EE or standard conditions for 2 mo. The buried food test showed that EE group had significantly improved olfactory function compared to the control group. Reverse transcription polymerase chain reaction (PCR) and real-time quantitative PCR showed that expression of the detoxification enzymes–– cytochrome P450 family 1 subfamily A member 2, paraoxonase 1, alcohol dehydrogenase 1, UDP glucuronosyltransferase family 2 member A1 complex locus, aldehyde oxidase homolog 2, and aldehyde glutathione peroxidase 6––was significantly increased in the olfactory bulb (OB) of the PD control group, but these enzymes were normalized in the EE group. Immunohistochemical staining of the OB showed that oxidative stress and nitrated α-syn were significantly increased in the control group but decreased in the EE group. In conclusion, we suggest that exposure to an EE decreases both oxidative stress and nitrated α-syn, resulting in normalized detoxification enzymes and amelioration of olfactory dysfunction.


2021 ◽  
Author(s):  
Cécilia Tremblay ◽  
Johannes Frasnelli

Abstract Olfactory dysfunction (OD) is a highly frequent early non-motor symptom of Parkinson’s disease (PD). An important step to potentially use OD for the development of early diagnostic tools of PD is to differentiate PD-related OD from other forms of non-parkinsonian OD (NPOD: post-viral, sinunasal, post-traumatic and idiopathic OD). Measuring non-olfactory chemosensory modalities, especially the trigeminal system, may allow to characterize a PD-specific olfactory profile.We here review the literature on PD-specific chemosensory alteration patterns compared to NPOD. Specifically, we focused on the impact of PD on the trigeminal system and particularly on the interaction between olfactory and trigeminal systems. As this interaction is seemingly affected in a disease-specific manner, we propose a model of interaction between both chemosensory systems that is distinct for PD-related OD and NPOD. These patterns of chemosensory impairment still need to be confirmed in prodromal PD; nevertheless, appropriate chemosensory tests may eventually help to develop diagnostic tools to identify individuals at risks for PD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Su ◽  
Kai Li ◽  
Chun-Mei Li ◽  
Xin-Xin Ma ◽  
Hong Zhao ◽  
...  

Objective: The striatum is unevenly impaired bilaterally in Parkinson's disease (PD). Because the striatum plays a key role in cortico-striatal circuits, we assume that lateralization affects cortico-striatal functional connectivity in PD. The present study sought to evaluate the effect of lateralization on various cortico-striatal circuits through resting-state functional magnetic resonance imaging (fMRI).Methods: Thirty left-onset Parkinson's disease (LPD) patients, 27 right-onset Parkinson's disease (RPD) patients, and 32 normal controls with satisfactory data were recruited. Their demographic, clinical, and neuropsychological information was collected. Resting-state fMRI was performed, and functional connectivity changes of seven subdivisions of the striatum were explored in the two PD groups. In addition, the associations between altered functional connectivity and various clinical and neuropsychological characteristics were analyzed by Pearson's or Spearman's correlation.Results: Directly comparing the LPD and RPD patients demonstrated that the LPD patients had lower FC between the left dorsal rostral putamen and the left orbitofrontal cortex than the RPD patients. In addition, the LPD patients showed aberrant functional connectivity involving several striatal subdivisions in the right hemisphere. The right dorsal caudate, ventral rostral putamen, and superior ventral striatum had decreased functional connectivity with the cerebellum and parietal and occipital lobes relative to the normal control group. The comparison between RPD patients and the controls did not obtain significant difference in functional connectivity. The functional connectivity between the left dorsal rostral putamen and the left orbitofrontal cortex was associated with contralateral motor symptom severity in PD patients.Conclusions: Our findings provide new insights into the distinct characteristics of cortico-striatal circuits in LPD and RPD patients. Lateralization of motor symptoms is associated with lateralized striatal functional connectivity.


2020 ◽  
Vol 45 (5) ◽  
pp. 401-406 ◽  
Author(s):  
Emilie Aubry-Lafontaine ◽  
Cécilia Tremblay ◽  
Pascali Durand-Martel ◽  
Nicolas Dupré ◽  
Johannes Frasnelli

Abstract Olfactory dysfunction (OD) in Parkinson’s disease (PD) appears several years before the presence of motor disturbance. Olfactory testing has the potential to serve as a tool for early detection of PD, but OD is not specific to PD as it affects up to 20% of the general population. Olfaction includes an orthonasal and a retronasal components; in some forms of OD, retronasal olfactory function is preserved. We aimed to evaluate whether combined testing components allows for discriminating between PD-related OD and non-Parkinsonian OD (NPOD). The objective of this study is to orthonasal and retronasal olfactory function in PD patients and compare them to a NPOD group and to healthy controls. We hypothesized that this combined testing allows to distinguish PD patients from both other groups. We included 32 PD patients, 25 NPOD patients, and 15 healthy controls. Both olfactory components were impaired in PD and NPOD patients, compared with controls; however, NPOD patients had significantly better orthonasal scores than PD patients. Furthermore, the ratio of retronasal/orthonasal score was higher in PD than in both other groups. In the NPOD group, orthonasal and retronasal scores were significantly correlated; no such correlation could be observed in PD patients. In summary, PD patients seem to rely on compensatory mechanisms for flavor perception. Combined orthonasal and retronasal olfactory testing may contribute to differentiate PD patients from patients with NPOD.


2021 ◽  
pp. 1-9
Author(s):  
Laura P. Hughes ◽  
Marilia M.M. Pereira ◽  
Deborah A. Hammond ◽  
John B. Kwok ◽  
Glenda M. Halliday ◽  
...  

Background: Reduced activity of lysosomal glucocerebrosidase is found in brain tissue from Parkinson’s disease patients. Glucocerebrosidase is also highly expressed in peripheral blood monocytes where its activity is decreased in Parkinson’s disease patients, even in the absence of GBA mutation. Objective: To measure glucocerebrosidase activity in cryopreserved peripheral blood monocytes from 30 Parkinson’s disease patients and 30 matched controls and identify any clinical correlation with disease severity. Methods: Flow cytometry was used to measure lysosomal glucocerebrosidase activity in total, classical, intermediate, and non-classical monocytes. All participants underwent neurological examination and motor severity was assessed by the Movement Disorders Society Unified Parkinson’s Disease Rating Scale. Results: Glucocerebrosidase activity was significantly reduced in the total and classical monocyte populations from the Parkinson’s disease patients compared to controls. GCase activity in classical monocytes was inversely correlated to motor symptom severity. Conclusion: Significant differences in monocyte glucocerebrosidase activity can be detected in Parkinson’s disease patients using cryopreserved mononuclear cells and monocyte GCase activity correlated with motor features of disease. Being able to use cryopreserved cells will facilitate the larger multi-site trials needed to validate monocyte GCase activity as a Parkinson’s disease biomarker.


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