The greatest loss of unpleasant smells may be related to the risk of more severe PD symptoms.

Background: Limited research has explored the relationship between the valence of olfactory dysfunction and PD clinical symptoms. This study aimed to investigate correlations between the emotional valence of olfactory impairment and different domains of PD symptoms. Methods: PD patients who fulfilled the clinically probable PD diagnostic criteria of the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease were recruited from the Center for Parkinson and Movement Disorders at Taichung Veterans General Hospital between October 2016 and April 2022. Demographic data and serial clinical assessments were collected, including the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Thirty-five odors from the UPSIT-TC were classified into neutral, pleasant or unpleasant groups. Group comparisons, correlation analyses, and linear regression analyses were conducted to examine the relationship between olfactory impairment of UPSIT-TC odors, considering emotional valence, and MDS-UPDRS subscores across various domains. Results: A total of 176 PD patients were recruited for analysis. Patients in the predominantly neutral/unpleasant odor impairment groups had higher MDS-UPDRS part III scores compared to those in the predominantly pleasant odor impairment group (pleasant vs. neutral vs. unpleasant odor impairment groups: 26.79 ± 13.59 vs. 35.33 ± 16.36 vs. 31.57 ± 12.37, p = 0.009). This trend was also noted in MDS-UPDRS rigidity, bradykinesia, and akinetic-rigid subscores (p = 0.003, p = 0.012, and p = 0.001, respectively). Correlation analysis revealed a weak but significant correlation between rigidity/akinetic-rigid subscores and misidentification numbers for neutral/unpleasant odors (all p < 0.05), with age, gender, LEDD, and disease duration as covariates. All significances were retained in the linear regression analysis. Conclusion: Our results emphasize the link between olfactory impairment of specific emotional valence, neutral/unpleasant odors, and PD severity, particularly with respect to akinetic-rigid symptoms. A concise olfactory test that focuses on both neutral and unpleasant odors may offer deeper insights into PD symptoms.

UPSIT subitems may predict motor progression in Parkinson's disease.

Background: The relationship between hyposmia and motor progression is controversial in Parkinson's disease (PD). The aim of this study was to investigate whether preserved identification of Chinese-validated University of Pennsylvania Smell Identification Test (UPSIT) odors could predict PD motor progression. Methods: PD patients with two consecutive clinical visits while taking medication were recruited. Based on mean changes in Movement Disorder Society Unified Parkinson's Disease Rating Scale part 3 score and levodopa equivalent daily dosage, the participants were categorized into rapid progression, medium progression, and slow progression groups. Odors associated with the risk of PD motor progression were identified by calculating the odds ratios of UPSIT item identification between the rapid and slow progression groups. Receiver operating characteristic curve analysis of these odors was conducted to determine an optimal threshold for rapid motor progression. Results: A total of 117 PD patients were screened for group classification. Preserved identification of neutral/pleasant odors including banana, peach, magnolia, and baby powder was significantly correlated with rapid motor progression. The risk of rapid progression increased with more detected risk odors. Detection of ≥1.5 risk odors could differentiate rapid progression from slow progression with a sensitivity of 85.7%, specificity of 45.8%, and area under the receiver operating characteristic curve of 0.687. Conclusion: Preserved identification of neutral/pleasant odors may help to predict PD motor progression, and detection of ≥1.5 UPSIT motor progression risk odors could improve the predictive power. In PD patients with a similar level of motor disability during initial screening, preserved pleasant/neutral odor identification may imply relatively better cortical odor discriminative function, which may suggest the body-first (caudo-rostral) subtype with faster disease progression.

Sequential change in olfaction and (non) motor symptoms: the difference between anosmia and non-anosmia in Parkinson's disease.

Introduction: Hyposmia is a common prodrome in patients with Parkinson's disease (PD). This study investigates whether olfactory changes in PD differ according to the degree of olfactory dysfunction and whether there are changes in motor and non-motor symptoms. Methods: The 129 subjects with PD were divided into two groups: anosmia and non-anosmia. All cases were reassessed within 1-3 years after the initial assessment. The assessment included the MDS-Unified PD Rating Scale (MDS-UPDRS), the University of Pennsylvania Smell Identification Test (UPSIT), Beck's Depression Inventory-II (BDI-II), Montreal Cognitive Assessment (MoCA), and equivalence dose of daily levodopa (LEDD). The generalized estimating equation (GEE) model with an exchangeable correlation structure was used to analyze the change in baseline and follow-up tracking and the disparity in change between these two groups. Results: The anosmia group was older and had a longer disease duration than the non-anosmia group. There was a significant decrease in UPSIT after follow-up in the non-anosmia group (ß = -3.62, p < 0.001) and a significant difference in the change between the two groups (group-by-time effect, ß = 4.03, p < 0.001). In the third part of the UPDRS motor scores, there was a tendency to increase the score in the non-anosmia group compared to the anosmia group (group-by-time effect, ß = -4.2, p < 0.038). There was no significant difference in the group-by-time effect for UPDRS total score, LEDD, BDI-II, and MoCA scores. Discussion: In conclusion, this study found that olfactory sensation may still regress in PD with a shorter disease course without anosmia, but it remains stable in the anosmia group. Such a decline in olfaction may not be related to cognitive status but may be associated with motor progression.

The Association of Olfactory Dysfunction With Depression, Cognition, and Disease Severity in Parkinson's Disease.

Background: Non-motor subtypes of Parkinson's disease (PD) include the limbic, cognitive, and brainstem phenotype, which may have different pathological pathways with olfaction. In this work, we aim to clarify the association between olfactory dysfunction, depression, cognition, and disease severity in PD. Methods: A total of 105 PD subjects were included and divided into anosmia and non-anosmic groups, using the University of Pennsylvania Smell Identification Test (UPSIT). All patients were evaluated with the movement disorder society unified Parkinson's disease rating scale (MDS-UPDRS), the Beck depression inventory (BDI)-II, and the Montreal cognitive assessment (MoCA). Results: The BDI-II and UPSIT scores had a trend of reverse correlation without statistical significance (ß-coefficient -0.12, p = 0.232). However, the odds ratio (OR) in anosmia was 2.74 (95% CI 1.01-7.46) for depression and 2.58 (95% CI 1.06-6.29) for cognitive impairment. For the MDS-UPDRS total and Part 3 score, the anosmia had a ß-coefficient of 12.26 (95% CI 5.69-18.82) and 8.07 (95% CI 3.46-12.67), respectively. Neither depression nor cognitive impairment is associated with motor symptoms. Conclusion: More severe olfactory dysfunction in PD is associated with cognitive impairment and greater disease severity. Depression in PD may involve complex pathways, causing relatively weak association with olfactory dysfunction.

Is either anosmia or constipation associated with cognitive dysfunction in Parkinson's disease?

OBJECTIVE: To clarify the association of anosmia or constipation with cognitive dysfunction and disease severity in patients with Parkinson's disease (PD). METHODS: Newly diagnosed patients with PD (less than 5 years) without a clinical diagnosis of dementia were included from February 2017 to August 2018. The subjects were further divided into subgroups based on whether anosmia occurred and the grade of constipation. The severity of PD motor symptoms was rated using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and cognitive functions were evaluated by Montreal Cognitive Assessment (MoCA). Statistical analyses including t-tests, chi-square tests, multiple linear regression, and binary logistic regression were used to determine statistical significance. RESULTS: A total of 107 newly diagnosed PD patients were included in this study. The MoCA score was significantly lower in the anosmia group (p < 0.001). Constipation was associated with impaired olfaction in a post-hoc test. The correlation coefficient between MoCA and UPSIT score was 0.41 (p < 0.001). Total anosmia and age were associated with cognitive dysfunction (MoCA < 26) (odds ratio, 2.63, p = 0.003; 1.10, p < 0.001, respectively). The anosmia group had a higher MDS-UPDRS part 3 score with ß coefficient of 7.30 (p = 0.02). Furthermore, grade 3 constipation was associated with a higher MDS-UPDRS total score with ß coefficient of 14.88 (p = 0.02). CONCLUSIONS: Anosmia but not constipation was associated with cognitive impairment in PD patients. Nevertheless, severe constipation was associated with impaired olfaction and PD disease severity. We suggest that the propagation of α-synuclein from the olfactory route is distinct from the enteric nervous system, but the intercommunication between these two routes is complex.

Altered Functional Connectivity and Sensory Processing in Blepharospasm and Hemifacial Spasm: Coexistence and Difference.

Background: Blepharospasm (BSP) and hemifacial spasm (HFS) are both facial hyperkinesia however BSP is thought to be caused by maladaptation in multiple brain regions in contrast to the peripherally induced cause in HFS. Plausible coexisting pathophysiologies between these two distinct diseases have been proposed. Objectives: In this study, we compared brain resting state functional connectivity (rsFC) and quantitative thermal test (QTT) results between patients with BSP, HFS and heathy controls (HCs). Methods: This study enrolled 12 patients with BSP, 11 patients with HFS, and 15 HCs. All subjects received serial neuropsychiatric evaluations, questionnaires determining disease severity and functional impairment, QTT, and resting state functional MRI. Image data were acquired using seed-based analyses using the CONN toolbox. Results: A higher cold detection threshold was found in the BSP and HFS patients compared to the HCs. The BSP and HFS patients had higher rsFC between the anterior cerebellum network and left occipital regions compared to the HCs. In all subjects, impaired cold detection threshold in the QTT of lower extremities had a correlation with higher rsFC between the anterior cerebellar network and left lingual gyrus. Compared to the HCs, increased rsFC in right postcentral gyrus in the BSP patients and decreased rsFC in the right amygdala and frontal orbital cortex in the HFS subjects were revealed when the anterior cerebellar network was used as seed. Conclusions: Dysfunction of sensory processing detected by the QTT is found in the BSP and HSP patients. Altered functional connectivity between the anterior cerebellar network and left occipital region, especially the Brodmann area 19, may indicate the possibility of shared pathophysiology among BSP, HFS, and impaired cold detection threshold. Further large-scale longitudinal study is needed for testing this theory in the future.

Risk of Dementia in Patients with Depression or Parkinson's Disease: A Retrospective Cohort Study.

BACKGROUND: This study aimed to clarify whether Parkinson's disease (PD) and depression were independent risk factors or with synergic effects in dementia. METHODS: Newly diagnosed PD (n = 1213) patients and control subjects (n = 4852) were selected from the Taiwan National Health Insurance Research Database from January 2001 through December 2008. Follow-up ended in 2011 with an outcome of dementia occurring or not. This cohort was divided into controls with or without depression, PD only, and PD with depression. The incident rate of dementia and hazard ratio (HR) using Cox's regression analysis were calculated for each group. RESULTS: When compared with controls without depression as HR 1.00, the adjusted HR for dementia was 3.29 (p < 0.001) in the PD only group, 2.77 (p < 0.001) in the PD with depression group, and 1.55 (p=0.024) in the depression only group. The incident rate of dementia was 29.2 (per 1000 person-years) in the PD only group and 13.2 in the PD with depression group. The effect of PD on dementia in the depression group produced a HR of 0.97 (p=0.905). CONCLUSIONS: Parkinson's disease served as a risk factor for dementia. By comparison, depression was not a risk factor for dementia in PD patients, although it did act as a risk factor for dementia.