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

Abstract

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 (β-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 β-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.

Dysosmia Is a Predictor of Motor Function and Quality of Life in Patients with Parkinson’s Disease

“…The PDQ-39 COG dimension has been shown to correlate with individual neuropsychological tests [ 38 ], individual cognitive domains [ 39 ], and depression [ 39 ]. Our previous studies suggested there is a close relationship between dysosmia and impaired cognition according to neuropsychological testing [ 13 , 14 ], but there seemed to be a lack of correlation between dysosmia and depression [ 13 , 40 ]. The findings in our study revealed similar results.…”

“…These non-motor symptoms include cognition, psychiatric, sleep, autonomic disturbance, and pain symptoms. Although anxiety, apathy, sleep, and autonomic disturbance have been correlated with dysomia [ 3 , 4 , 44 ], depression is still a matter of debate [ 3 , 4 , 13 , 40 ]. Furthermore, there is no pathophysiological basis for the relationship between pain and dysosmia at present.…”

“…It primarily spreads to the anterior olfactory nucleus [ 6 ], which connects to various locations, including the entorhinal cortices, olfactory tubercles, substantia nigra (SN), amygdala, dorsal motor nucleus of the vagus nerve, raphe nuclei, and locus coeruleus [ 7 ]. However, there is conflicting evidence regarding the correlation between dysosmia in PD with motor dysfunction [ 1 , 2 , 3 , 4 , 5 , 8 , 9 , 10 , 11 , 12 ] and depression [ 3 , 4 , 13 ], although there is a consistent correlation between dysosmia and cognitive dysfunction in PD [ 3 , 4 , 5 , 13 , 14 ]. A cohort study showed that only 51–83% of autopsies of PD patients followed the Braak staging, while another cohort showed that 6.3% deviated from the Braak staging but showed prominent involvement of olfactory structures and amygdala [ 15 ].…”

Olfactory Impairment Correlates with Executive Functions Disorders and Other Specific Cognitive Dysfunctions in Parkinson’s Disease

“…Although previous studies evaluated the correlation between olfactory deficit and cognitive impairment in PD [8][9][10][11][12][13] demonstrating that olfactory dysfunction may increase the risk of dementia up to ten years after PD diagnosis regardless of baseline cognitive function [14], the involved specific cognitive domains are largely undetermined. To date, only a single study explored whether Mild Cognitive Impairment (MCI) and the involvement of each single cognitive domain may influence olfactory function in PD patients [15].…”

Unveiling the knowledge domain and emerging trends of olfactory dysfunction with depression or anxiety: A bibliometrics study

“…The olfactory bulbs project to brain regions that play a vital role in emotion and cognition, such as the orbitofrontal cortex, hippocampus, and amygdala ( Kohli et al, 2016 ). A large amount of evidence shows that OD is related to various neuropsychiatric disorders, including depression and anxiety ( Fang et al, 2021 ). Functional and structural damage to the olfactory system, particularly the olfactory bulbs and olfactory epithelium, are common in patients suffering from depression ( Zuo et al, 2018 ).…”