A Prospective Study on the Relationship between Iron Supplement Intake, Hemoglobin Concentration, and Risk of Parkinsonism.

The findings regarding whether the greater iron level or intake is a risk factor to Parkinson's disease (PD) or parkinsonism was not clear. The purpose of this study is to establish a consistent association between iron supplementation and parkinsonism risk, we conducted a large-scale prospective cohort study using comprehensive longitudinal data from the UK Biobank. The longitudinal cohort data of 385,898 participants (including 911 cases) who were middle to old aged British adults and joined the UK Biobank study from 2006 to 2010 and were followed up until 2018 was analyzed. The associations between iron supplement intake, hemoglobin levels and all cause subsequent parkinsonism risk after corrections of potential confounders (sex, age, household income, education length, employment status, deprivation level, body mass index, physical activity level, household numbers, smoking and drinking levels, health status, blood pressure) were investigated. Analyses revealed that (a) iron supplementation was significantly associated with higher parkinsonism risk, (b) greater hemoglobin was weakly and insignificantly associated with lower parkinsonism risk, and (c) multivitamin or vitamin C supplement intake was not significantly associated with parkinsonism risk. Regardless of whether the subjects were classified as anemic, normal, or polycythemic or in the hemoglobin level quintile, there was no nonlinear association between hemoglobin and parkinsonism risk. Parkinsonism risk did not differ between participants reporting supplementary iron intake with or without vitamin C or multivitamin supplement intake. Furthermore, polygenic risk score of PD negatively correlated with hemoglobin level, while it did not associate with intake of iron supplement or multivitamin or vitamin C supplement intake. The results suggest excessive iron intake may increase parkinsonism risk. Interventional studies are warranted to examine whether iron intake restriction is beneficial for individuals without clinical iron deficiency.

Annonaceae Consumption Worsens Disease Severity and Cognitive Deficits in Degenerative Parkinsonism.

BACKGROUND: High consumption of Annona muricata fruit has been previously identified as a risk factor for atypical parkinsonism in the French Caribbean islands. OBJECTIVE: We tested whether consumption of Annonaceae products could worsen the clinical phenotype of patients with any form of degenerative parkinsonism. METHODS: We analyzed neurological data from 180 Caribbean parkinsonian patients and specifically looked for dose effects of lifelong, cumulative Annonaceae consumption on cognitive performance. Using unsupervised clustering, we identified one cluster with mild/moderate symptoms (N = 102) and one with severe symptoms including cognitive impairment (N = 78). RESULTS: We showed that even low cumulative consumption of fruits/juices (>0.2 fruit-years) or any consumption of herbal tea from Annonaceae worsen disease severity and cognitive deficits in degenerative parkinsonism including Parkinson's disease (OR fruits-juices: 3.76 [95% CI: 1.13-15.18]; OR herbal tea: 2.91 [95% CI: 1.34-6.56]). CONCLUSION: We suggest that more restrictive public health preventive recommendations should be made regarding the consumption of Annonaceae products. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A Neural Signature of Parkinsonism in Patients With Schizophrenia Spectrum Disorders: A Multimodal MRI Study Using Parallel ICA.

Motor abnormalities in schizophrenia spectrum disorders (SSD) have increasingly attracted scientific interest in the past years. However, the neural mechanisms underlying parkinsonism in SSD are unclear. The present multimodal magnetic resonance imaging (MRI) study examined SSD patients with and without parkinsonism, as defined by a Simpson and Angus Scale (SAS) total score of ≥4 (SAS group, n = 22) or <4 (non-SAS group, n = 22). Parallel independent component analysis (p-ICA) was used to examine the covarying components among gray matter volume maps computed from structural MRI (sMRI) and fractional amplitude of low-frequency fluctuations (fALFF) maps computed from resting-state functional MRI (rs-fMRI) patient data. We found a significant correlation (P = .020, false discovery rate [FDR] corrected) between an sMRI component and an rs-fMRI component, which also significantly differed between the SAS and non-SAS group (P = .042, z = -2.04). The rs-fMRI component comprised the cortical sensorimotor network, and the sMRI component included predominantly a frontothalamic/cerebellar network. Across the patient sample, correlations adjusted for the Positive and Negative Syndrome Scale (PANSS) total scores showed a significant relationship between tremor score and loadings of the cortical sensorimotor network, as well as between glabella-salivation score, frontothalamic/cerebellar and cortical sensorimotor network loadings. These data provide novel insights into neural mechanisms of parkinsonism in SSD. Aberrant bottom-up modulation of cortical motor regions may account for these specific motor symptoms, at least in patients with SSD.

Food toxins and the Caribbean Parkinson plus types.

In the 90's, clinico pathological studies have considerably improved the diagnosis of specific and rare neurodegenerative diseases. After a training in Parkinsons' disease in Paris, the author moved to French West Indies (Guadeloupe) and observed a high incidence of atypical parkinsonism with dementia, unresponsive to levodopa. Similar features were observed in Martinique. An environmental origin has been suspected with the exposure to toxins of annonaceae leaves and seeds. The candidate toxins are acetogenins acting as mitochondrial poison. This was demonstrated in neuronal cell cultures, and in animals. However, the agency for food security did not conclude that Annonaceae should not be used for herbal (medicinal) tea, even if the population is now aware about the possible risk of parkinsonism after exposure to annonaceae acetogenins.

Brain atrophy and strategic lesion location increases risk of parkinsonism in cerebral small vessel disease.

INTRODUCTION: Incident parkinsonism in patients with comparable cerebral small vessel disease (SVD) burden is not fully explained by presence of SVD alone. We therefore investigated if severity of SVD, SVD location, incidence of SVD and/or brain atrophy plays a role in this distinct development of parkinsonism. METHODS: Participants were from the RUN DMC study, a prospective cohort of 503 individuals with SVD. Parkinsonism was diagnosed according to the UKPDS brain bank criteria. Fine and Gray method was used to assess the association between SVD and incident parkinsonism. Differences in white matter hyperintensities (WMH) progression and brain atrophy were calculated with a linear mixed effect analysis. RESULTS: After a median follow-up of 8.6 years, 32 of 501 participants developed parkinsonism (6.4%). The highest WMH load was found in the frontal lobe for both groups. Presence of more than one lacune at baseline was higher in the group who developed parkinsonism, especially in the frontal lobe (22% versus 3%, p < 0.001) and basal ganglia (12.5% versus 1%, p-value <0.001). The annual rate of total brain atrophy was significantly higher for those who developed parkinsonism compared to those who did not (8.7 ml [95%CI 7.1-10.3] and 4.9 ml [95%CI 4.5-5.3], respectively). While WMH progression was not different, incidence of lacunes and microbleeds was higher in the group with parkinsonism. CONCLUSION: The risk of parkinsonism in patients with SVD is especially increased when WMH and lacunes are present in the frontal lobe. A higher brain atrophy rate might further increase this risk.

Palliative Care and Nonmotor Symptoms in Parkinson's Disease and Parkinsonism.

The term palliative care (PC) is defined as a collection of interventions and strategies that helps to improve and sustain the quality of life of patients and caregivers in situations and scenarios associated with life-threatening illness. This is usually implemented by means of early identification and treatment of relevant motor and nonmotor issues such as pain, sleep, and autonomic dysfunction, dementia, and depression. In addition, a holistic PC program also includes delivery of physical, psychosocial, and spiritual support. PC as a specific discipline, as well as a treatment strategy for long-term neurological conditions such as Parkinson's disease (PD), is relatively new, but very important as neurodegenerative disorders in the United Kingdom alone affects approximately 10 million people and there are over 130,000 people with PD. With longer life expectancy, the burden of long duration and late stage PD is even more evident, bringing in focus the need for PC. However, the concept of PC in PD is still poorly defined and although there are pockets of excellence, the strategy is poorly implemented into routine clinical practice. The variable progressive nature of the disease, the heterogeneity of clinical subtypes, and also the burden of nonmotor symptoms create challenges for effective PC delivery in PD, but recent clinical trials have started addressing PC in PD and are to be welcomed.

Trends in the Incidence of Parkinson Disease in the General Population: The Rotterdam Study.

We investigated trends in the incidence of parkinsonism and Parkinson disease (PD) by comparing data from the first 2 subcohorts of the Rotterdam Study, a prospective, population-based cohort study (first subcohort: baseline 1990 with 10 years of follow-up; second subcohort, baseline 2000 with 10 years of follow-up). From the baseline years, we observed differences in the second subcohort that were associated with a lower risk of PD for some but not all baseline risk factors. Participants in both subcohorts were followed for a maximum of 10 years and monitored for the onset of parkinsonism, the onset of dementia, or death, until January 1, 2011. We used Poisson regression models to compare the incidences of parkinsonism, both overall and by cause (PD and secondary causes), and competitive events (incident dementia and death) as well as the mortality of parkinsonism patients in the 2 subcohorts. In the 1990 subcohort, there were 182 cases of parkinsonism (84 of which were PD) during 57,052 person-years. In the 2000 subcohort, we observed 28 cases of parkinsonism (10 with PD) during 22,307 person-years. The overall age- and sex-adjusted incidence of parkinsonism was lower in the 2000 subcohort (incidence rate ratio = 0.55, 95% confidence interval: 0.36, 0.81), and PD incidence declined sharply (incidence rate ratio = 0.39, 95% confidence interval: 0.19, 0.72). Competitive event rates were lower in the 2000 subcohort, and mortality rates among persons with parkinsonism remained stable. These findings suggest that the incidence of parkinsonism in general, and of PD in particular, decreased between 1990 and 2011.

Midlife migraine and late-life parkinsonism: AGES-Reykjavik study.

OBJECTIVE: In the present study, we tested the hypothesis that having migraine in middle age is related to late-life parkinsonism and a related disorder, restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED). METHODS: The AGES-Reykjavik cohort (born 1907-1935) has been followed since 1967. Headaches were classified based on symptoms assessed in middle age. From 2002 to 2006, 5,764 participants were reexamined to assess symptoms of parkinsonism, diagnosis of Parkinson disease (PD), family history of PD, and RLS/WED. RESULTS: Subjects with midlife migraine, particularly migraine with aura (MA), were in later life more likely than others to report parkinsonian symptoms (odds ratio [OR]MA = 3.6 [95% CI 2.7-4.8]) and diagnosed PD (ORMA = 2.5 [95% CI 1.2-5.2]). Women with MA were more likely than others to have a parent (ORMA = 2.26 [95% CI 1.3-4.0]) or sibling (ORMA = 1.78 [95% CI 1.1-2.9]) with PD. Late-life RLS/WED was increased for headache generally. Associations were independent of cardiovascular disease and MRI-evident presumed ischemic lesions. CONCLUSIONS: These findings suggest there may be a common vulnerability to, or consequences of, migraine and multiple indicators of parkinsonism. Additional genetic and longitudinal observational studies are needed to identify candidate pathways that may account for the comorbid constellation of symptoms.

[Muro disease: amyotrophic lateral sclerosis/parkinsonism-dementia complex in Kii peninsula of Japan].

Muro disease refers to the endemic amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) in the high incidence ALS focus in the Muro district of the Kii peninsula. Kii paralysis was first described in the 1680s in a folk literature, and as ALS in the medical literature by Kin-no-suke Miura in 1911. Two high-incidence ALS foci were discovered in 1960s by Kimura and Yase, and retro- and anterospective epidemiological surveys were started. Kii ALS was neuropathologically characterized by classical ALS pathology together with many neurofibrillary tangles (NFTs) in the brain, similar to Guamanian ALS. The incidence rates of ALS dramatically declined during the 1950s and 1980s, resulting in the disappearance of the high-incidence foci. In the early 1990s, however, Kuzuhara found existence of high-incidence of ALS in the region, and, in addition, of a high-incidence of PDC with abundant NFTs, similar to Guamanian PDC. The incidence rates of PDC dramatically rose during the 1980s and 1990s, and PDC replaced ALS. Unsuccessful attempts were made to identify cause and pathogenesis of the disease in minerals and environmental factors. More than 70% of patients in the endemic region had a family history of ALS or PDC; therefore, genetic factors were suspected as the cause. The authors analyzed the causative and risk candidate genes in the affected and unaffected family members, but failed to find genes related to ALS/PDC. The changing pattern of Muro disease from ALS with a younger onset and rapid progression to PDC with a later onset and longer survival suggests that some unknown environmental factor(s) might modulate the disease process, which basically might be programmed in the gene(s).

[Neurorehabilitation in parkinsonian syndromes]. / Neurorééducation des syndromes parkinsoniens.

Parkinson's disease is a frequent and major source of motor disability, for which physical therapies currently involve less than a third of ambulatory patients and are thus underutilized when compared to chemical and surgical treatments. However, dopaminergic therapies alone prove unable to prevent worsening of motor disability after a number of years. There is rising interest about physical neurorehabilitative therapy for Parkinson's disease, for its symptomatic therapeutic properties, but also for its potential neuroprotective effects in the light of compelling, recent animal literature. The approach to therapy in an individual patient may be governed at the most basic level by the disease stage. For moderate stages of Parkinson's disease (ambulatory patients who have retained a certain degree of physical independence), therapy may focus on the teaching of exercises to the patient: strategies established in controlled studies when used over few weeks periods include motor strengthening programs in the lower limb, high intensity aerobic exercises, attentional strategies using in particular verbal instruction sets, sensory cueing, active axial rotation exercises and high-number repetition of specific tasks. A randomized protocol will soon evaluate the concept of asymmetric motor training, combining a strengthening program in extensor, abductor, external rotator and supinator muscles and a stretching program in their antagonists. For advanced stages (individuals with compromised sit-to-stand, ambulation and significant disability), the therapeutic focus may shift to the teaching of compensation strategies to the patient and the caregiver, both to lessen the effects of motor impairment and to optimize safety. A number of these compensatory strategies are reviewed, some being validated in controlled protocols. In idiopathic Parkinson's disease, clinicians must continue evaluating the symptomatic and perhaps neuroprotective value of physical treatment strategies used over the long term. In atypical parkinsonism, physical treatments often remain the only realistic methods to improve motor behavior and reduce functional deficiencies. The relatively short duration of the effects of physical therapies implies that such programs be pursued over long periods of time, or repeated frequently, for their benefits to be maintained over time.

Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes.

Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction.

On the decline and etiology of high-incidence motor system disease in West Papua (southwest New Guinea).

The etiology of a high-incidence focus of amyotrophic lateral sclerosis and parkinsonism-dementia (ALS/P-D) in south West Papua (Irian Jaya, Indonesia), first described in the 1960s and 1970s, has been attributed to mineral deficiencies, hyperparathyroidism, and metal neurotoxicity arising from reliance on drinking water obtained from springs and shallow wells. More recent visits (1987 and 1990) to the south West Papua focus of neurodegenerative disease cast doubt on this explanation by revealing changes in disease prevalence in communities with an unchanged water supply. These communities have experienced a dramatic decline in ALS and a reversal in the relative prevalence of ALS and parkinsonism. The extrapyramidal disorder can be distinguished from Parkinson disease by pyramidal features (and dementia) reminiscent of Guam P-D. Topical use of cycad seed (termed kurru) gametophyte to treat large skin lesions is advanced as a plausible but unproven etiologic factor. Medicinal use of untreated cycad seed (Cycas sp.) has also been linked with ALS foci in Japan (oral use) and Guam (topical use), with the additional consumption on Guam of food items prepared from Cycas sp. seed or animals that consume cycad seed components.

Parkinsonian signs in older people: prevalence and associations with smoking and coffee.

BACKGROUND: Cigarette smoking and coffee consumption may reduce the risk of PD. Parkinsonian signs (tremor, rigidity, bradykinesia) occur in 30 to 40% of the elderly. OBJECTIVE: To determine whether there was an association between cigarette smoking, coffee consumption, and parkinsonian signs in a community population of older people. METHODS: Data on smoking were collected and a neurologic examination performed on 1,339 residents > or = 65 years of age in the Washington Heights-Inwood community in northern Manhattan, NY. Parkinsonian signs were rated with an abbreviated Unified Parkinson's Disease Rating Scale, resulting in a parkinsonian sign score. Coffee consumption was assessed with a semiquantitative food-frequency questionnaire, and caffeine consumption was determined. Analyses were cross-sectional. RESULTS: Mean age was 76.6 years. Parkinsonian signs were present in 537 (40.1%). The odds for presence of parkinsonian signs was lower in smokers than nonsmokers (odds ratio [OR] = 0.58, 95% CI = 0.47 to 0.73). Smokers had a lower mean parkinsonian sign score than nonsmokers (p < 0.001). Coffee drinking and caffeine consumption were not associated with the presence of parkinsonian signs. The odds for presence of parkinsonian signs remained lower in smokers (OR = 0.75, 95% CI = 0.57 to 0.99) after adjusting for age, gender, ethnicity, years of education, adjusted daily caffeine consumption, and dementia. CONCLUSION: The reduced risk of parkinsonian signs in cigarette smokers could reflect a protective effect of smoking on age-related parkinsonian signs in the elderly or an aversion to smoking in elderly persons with mild parkinsonism.

[Vascular parkinsonian syndrome in 21 case studies, two of which were anatomic]. / Syndromes parkinsoniens vasculaires à propos de 21 observations dont 2 cas anatomiques.

A clinicopathological study of parkinsonian syndrome witch occurred after stroke, is done by the authors. That is a retrospective study concerning 2 anatomic cases from 21 vascular parkinsonism. All the patients were admitted in the clinique neurologique de Fann from 1970 to 1990. They were 15 men and 6 women. Their age ranged between 45 to 75 years (mean 59.66). The 2 autopsied cases had lesions located in the thalamus as the superior part and a discreet cortical atrophy in the one case, and in the other case, we can see similar lesions in the right external capsule and in the inferior part of the putamen. Another lesion of haemorrhage infarct was located in the left temporal lobe. The locus niger was macroscopically normal in the 2 cases. Anatomical lesions observed have been localized in the putamen and in the external capsule in the associatical cerebral cortex in the second case and in the first one, lesions are located in the thalamus and in the cortex. These lesions were not well correlated with neurological signs. The different clinical aspects are discussed. From this study, it results that arterial damages associated with hypertension and atheromatosis might touch dopaminergic structures responsible of parkinsonism with sometime good sensitivity to levodopa.