Olfaction, cholinergic basal forebrain degeneration, and cognition in early Parkinson disease

Murphy, Justin M.; Zhang, Jeffrey; Blair, Jamie C.; Flanigan, Joseph L.; Nawaz, Huma; Dalrymple, W. Alex; Sperling, Scott A.; Patrie, James T.; Druzgal, T. Jason

doi:10.1016/j.parkreldis.2021.07.024

Cited by 8 publications

(5 citation statements)

References 31 publications

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“…Hyposmia typically precedes the presence of the cardinal motor features of PD by several years, and affects up to 96% of patients ( 2 ). The literature supports that impaired olfaction is caused by the spread of Lewy body pathology to the olfactory bulb and anterior olfactory nucleus ( 3 ), as well as the degeneration of cholinergic circuits ( 4 , 5 ). While hyposmia has been suggested to be a biomarker for cognitive impairment ( 6 ), its association with parkinsonian motor deficits remains controversial ( 7 – 9 ).…”

Section: Introductionmentioning

confidence: 95%

UPSIT subitems may predict motor progression in Parkinson’s disease

Lin,

Fang,

Lei

et al. 2023

Front. Neurol.

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BackgroundThe 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.MethodsPD 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.ResultsA 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.ConclusionPreserved 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.

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Section: Introductionmentioning

confidence: 95%

UPSIT subitems may predict motor progression in Parkinson’s disease

Lin,

Fang,

Lei

et al. 2023

Front. Neurol.

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“…Additionally, amygdala mean diffusivity was positively associated with the UPDRS scores for non-motor symptoms as well as activities of daily living impairment, indicating that amygdala changes may affect movement through the regulation of affective states [ 57 ]. Dysfunction of the amygdala has further been demonstrated through affected nodal centrality [ 58 , 59 ] and, in line with the diverse functions of the amygdala, studies also report impaired olfaction, sleep disturbances, and autonomic dysfunction in combination with amygdala alterations [ 60 , 61 ].…”

Section: Regions Of the Limbic Systemmentioning

confidence: 99%

“…In face of this detrimental symptom, extensive research has addressed pathological changes in the hippocampus. Morphological studies have reported reduced hippocampal volume in PD patients, whereby atrophy has inconsistently been reported in early-PD but becomes more pronounced with increasing disease duration and is strongly linked to cognitive decline including memory, spatial working memory, and language impairments [ 29 , 31 , 36 , 37 , 54 , 60 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. The severity of volume loss has also been found to be predictive of conversion to dementia [ 53 , 98 , 99 ].…”

Section: Regions Of the Limbic Systemmentioning

confidence: 99%

“…As mentioned earlier, changes in the hippocampus do not only result in cognitive deficits but manifest in other nonmotor symptoms. Hyposmia and sleep disturbance have been associated with hippocampal dysfunction [ 60 , 92 , 111 , 112 , 113 , 114 , 115 ] and modulation of the parasympathetic outflow seems to be impaired as well [ 116 ]. In addition, decreased left hippocampal volume and altered functional connectivity were reported in depressed individuals [ 46 , 117 ].…”

Section: Regions Of the Limbic Systemmentioning

confidence: 99%

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Imaging the Limbic System in Parkinson’s Disease—A Review of Limbic Pathology and Clinical Symptoms

et al. 2022

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The limbic system describes a complex of brain structures central for memory, learning, as well as goal directed and emotional behavior. In addition to pathological studies, recent findings using in vivo structural and functional imaging of the brain pinpoint the vulnerability of limbic structures to neurodegeneration in Parkinson’s disease (PD) throughout the disease course. Accordingly, dysfunction of the limbic system is critically related to the symptom complex which characterizes PD, including neuropsychiatric, vegetative, and motor symptoms, and their heterogeneity in patients with PD. The aim of this systematic review was to put the spotlight on neuroimaging of the limbic system in PD and to give an overview of the most important structures affected by the disease, their function, disease related alterations, and corresponding clinical manifestations. PubMed was searched in order to identify the most recent studies that investigate the limbic system in PD with the help of neuroimaging methods. First, PD related neuropathological changes and corresponding clinical symptoms of each limbic system region are reviewed, and, finally, a network integration of the limbic system within the complex of PD pathology is discussed.

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“…Moreover, olfaction deficits are a common non-motor symptom in PDD. According to a recent study, hyposmia is associated to degeneration of the cholinergic system of basal forebrain and bilateral cortex, amygdala, and hippocampus in PD and this may provide a link to the co-occurrence of impaired olfaction and cognitive decline [31].…”

Section: Epidemiology Clinical Characteristics Timing and Neurobiolog...mentioning

confidence: 99%