A meta‐analysis of 142 positron emission tomography and single photon emission computed tomography studies that have investigated striatal presynaptic dopamine function in Parkinson disease (PD) was ...performed. Subregional estimates of striatal dopamine metabolism are presented. The aromatic L‐amino‐acid decarboxylase (AADC) defect appears to be consistently smaller than the dopamine transporter and vesicular monoamine transporter 2 defects, suggesting upregulation of AADC function in PD. The correlation between disease severity and dopamine loss appears linear, but the majority of longitudinal studies point to a negative exponential progression pattern of dopamine loss in PD. Ann Neurol 2017;82:873–882
Parkinson's disease and other Lewy body spectrum diseases (LBDs) are associated with a specific risk for clinical depression. In the present clinicopathological study with 73 patients with LBD, we ...observed that the substantia nigra pars compacta dopamine neuron density was markedly lower in patients who had comorbid depression antemortem than in nondepressed patients (1.52 vs 2.32 n/mm2, p = 0.004). There were no differences in cognition, motor disease severity, antiparkinsonian medications, or disease duration between groups. The results implicate the substantia nigra as an important psychomotor modulatory area of mood in patients with Lewy body disorders. ANN NEUROL 2021;;89:1046–1050
Objective
The nigral lesion and the resulting contralateral motor signs of Parkinson's disease (PD) are remarkably asymmetric. This study investigated the prevalence of patients with “wrong‐sided” ...lesions, that is, patients with symptoms on the side ipsilateral to the predominant dopaminergic nigrostriatal deficit.
Methods
The analyzed sample included 434 early unmedicated PD patients from the Parkinson's Progression Markers Initiative database. Asymmetry indices of motor function and putamen 123IFP‐CIT SPECT were calculated from the screening visit data.
Results
Ipsilateral deficits were unexpectedly common even when only patients with clear motor and dopaminergic asymmetries were included in the analysis (8.1%, n = 24/295). When patients with any asymmetry were included in the analysis, the prevalence of ipsilateral deficits was 15.4% (n = 65/423). Wrong‐sided symptoms were not associated with the PD motor subtype. However, the dataset was heavily biased toward tremor‐dominant patients (85% of patients). Right‐handed PD patients had predominantly right‐sided motor symptoms and left‐sided dopamine defects, whereas the effect was opposite in left‐handed patients (P = 0.005 and 0.028, respectively).
Interpretation
The results indicate that the side of the predominant motor symptoms and the corresponding side of the dopaminergic defects in PD are not random, but are directed by brain lateralization. Importantly, the traditional pathogenetic model of nigral degeneration causing primarily contralateral motor symptoms may be inadequate in many patients.
Abstract Introduction Movement disorder specialists can achieve a high level of accuracy when clinically diagnosing parkinsonism syndromes. However, data about the diagnostic accuracy among general ...neurologists is limited. Objectives This study investigated the recent diagnostic accuracy of parkinsonism syndromes by general neurologists. Methods A retrospective examination of 1362 post-mortem cases diagnosed in the years 2000–2012 by neuropathologists was performed. Out of these cases, we identified 111 patients who received a clinical parkinsonism diagnosis during life and 122 patients who received a neuropathological diagnosis of a parkinsonism syndrome post-mortem including 11 incidental cases. Results Fifty-eight (75.3%) of the 77 patients who had received clinical Parkinson's disease (PD) diagnoses were confirmed after the neuropathological examination. The sensitivity of the clinical diagnosis for idiopathic Parkinson's disease (PD) was 89.2% and the specificity was 57.8%. The corresponding numbers for progressive supranuclear palsy (PSP) were 52.9% and 100%, and for multiple system atrophy (MSA) were 64.3% and 99.0%, respectively. Conclusions Parkinson's disease is heavily overdiagnosed by general neurologists, whereas parkinsonism plus syndromes are underdiagnosed. Despite improvements in the diagnostic methods during recent decades and the development of diagnostic clinical criteria for parkinsonian syndromes, the diagnostic accuracy of Parkinson's disease remains relatively low, and 1/4 of diagnoses are incorrect.
Deep brain stimulation (DBS) is an effective treatment for Parkinson’s disease (PD) patients with motor fluctuations and dyskinesias. The key DBS efficacy studies were performed in PD patients with ...unknown genotypes; however, given the estimated monogenic mutation prevalence of approximately 5–10%, most commonly
LRRK2, PRKN, PINK1
and
SNCA
, and risk-increasing genetic factors such as
GBA
, proper characterization is becoming increasingly relevant. We performed a systematic review of 46 studies that reported DBS effects in 221 genetic PD patients. The results suggest that monogenic PD patients have variable DBS benefit depending on the mutated gene. Outcome appears excellent in patients with the most common
LRRK2
mutation, p.G2019S, and good in patients with
PRKN
mutations but poor in patients with the more rare
LRRK2
p.R1441G mutation. The overall benefit of DBS in
SNCA, GBA
and
LRRK2
p.T2031S mutations may be compromised due to rapid progression of cognitive and neuropsychiatric symptoms. In the presence of other mutations, the motor changes in DBS-treated monogenic PD patients appear comparable to those of the general PD population.
Abstract To investigate the effects of aging and gender on brain dopamine and serotonin transporter bindings, we analyzed 123 IFP-CIT single-photon emission computed tomography scans of 231 ...Parkinson's disease (PD) patients and 230 controls. An automated region-of-interest–based method (BRASS automated analysis software) was used for striatal regions and a voxel-based method (Statistical Parametric Mapping software, SPM8) for the entire brain. In controls, aging was associated with a decline of 3.6%–4.6% per decade in striatal binding. Multiple extrastriatal regions also showed age-related declines. In PD patients, age-related declines were only observed in the caudate nuclei, thalamus, olfactory, and cingulate cortices with a comparable rate of decline as that in controls. Female subjects had higher caudate nucleus binding compared with males with a similar near-significant difference in the right putamen. The results demonstrate that the aging effect is limited in PD, which is possibly because of disease-related excess variation, and the results do not support the theory of accelerated aging of the dopaminergic system in PD. Women have higher caudate nucleus dopamine transporter binding compared with men in both normal and degenerated dopamine systems.
Alterations in the brain’s μ-opioid receptor (MOR) system have been associated with several neuropsychiatric disorders. Central MOR availability also varies considerably in healthy individuals. ...Multiple epidemiological factors have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive. We compiled 11Ccarfentanil positron emission tomography scans from 204 individuals with no neurologic or psychiatric disorders, and estimated the effects of sex, age, body mass index (BMI) and smoking on 11Ccarfentanil binding potential using between-subject regression analysis. We also examined hemispheric differences in MOR availability. Older age was associated with increase in MOR availability in frontotemporal areas but decrease in amygdala, thalamus, and nucleus accumbens. The age-dependent increase was stronger in males. MOR availability was globally lowered in smokers but independent of BMI. Finally, MOR availability was higher in the right versus the left hemisphere. The presently observed variation in MOR availability may explain why some individuals are prone to develop MOR-linked pathological states, such as chronic pain or psychiatric disorders. Lateralized MOR system may reflect hemispheric work specialization in central emotion and pain processes.
•Sex, age and smoking have regionally specific influence on human μ-opioid receptor (MOR) availability in the brain.•MOR availabilities have regional asymmetries between the two hemispheres, right hemisphere being more abundant in MORs.•Variability in MOR system may explain why some individuals are vulnerable to chronic pain and neuropsychiatric disorders.
Major depressive disorder is associated with lowered mood, anxiety, anhedonia, sleep problems, and cognitive impairments. Many of these functions are regulated by μ-opioid receptor (MOR) system. ...Preclinical, in vivo, and post-mortem studies have however yielded inconclusive results regarding the role of the MOR in depression and anxiety. Moreover, it is not known whether alterations in MOR are already present in subclinical depression and anxiety. In a large-scale retrospective cross-sectional study we pooled data from 135 (113 males and 22 females) healthy subjects whose brain's MOR availability was measured with positron emission tomography (PET) using an agonist radioligand
Ccarfentanil that has high affinity for MORs. Depressive and anxious symptomology was addressed with BDI-II and STAI-X questionnaires, respectively. Both anxiety and depression scores in the subclinical range were negatively associated with MOR availability in cortical and subcortical areas, notably in amygdala, hippocampus, ventral striatum, and orbitofrontal and cingulate cortices. We conclude that dysregulated MOR availability is involved in altered mood and pathophysiology of depression and anxiety disorders.
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