Skin cancer and Parkinson's disease

The report of an increased frequency of melanoma during the clinical development of rasagiline prompted a renewed interest in a possible association between skin cancer and Parkinson's disease (PD). The evaluation of this risk ended in a recommendation to perform a periodic dermatological examination as a follow‐up measure of their treatment. The recognition of this safety concern lead to the need to clarify if the risk of skin cancer is indeed associated with PD and if levodopa or other anti‐parkinsonian drugs might contribute to increase such risk. To answer these questions, we critically reviewed all clinical studies available concerning the association between skin cancer and PD. We found 26 studies on cancer occurrence in PD. The best data available suggest the risk of cancer is reduced in PD patients. However, specific cancers like thyroid and the female breast were reported at higher‐than‐expected rates. Additionally, it was suggested that PD patients have a higher frequency of melanoma and non‐melanoma skin cancers than the general population. The data on non‐melanoma skin cancer are less robust than the data on melanoma. Causal factors remain unknown. Due to the weak association between skin cancer and PD, no robust recommendation can be made regarding the need for periodic dermatological screening. © 2010 Movement Disorder Society     

Skin conditions in early Parkinson's disease

ObjectiveSkin conditions have been associated with increased risk of Parkinson's disease (PD). Little is known about clinical and biomarker differences according to presence of skin conditions among PD patients. Studying these differences might provide insight into PD pathogenesis.MethodsWe examined the association between common skin conditions and risk of PD in a case-control study of 423 early drug-naïve PD cases and 196 healthy controls (HC) in the Parkinson's Progression Markers Initiative (PPMI). Among PD participants, we examined if skin conditions were associated with clinical and PD-relevant biomarkers.ResultsSkin conditions occurred more frequently among PD participants (41%) relative to HC (32%). In multivariate analyses, we observed an association between any skin condition and PD (OR = 1.49, 95% CI = 1.03–2.16) and basal cell carcinoma and PD (OR = 2.05, 95% CI = 1.02–4.08). PD participants who reported skin conditions were older (OR = 1.68, 95% CI = 1.21–2.35) more educated (OR = 1.70, 95% CI = 0.99–2.91), had higher Semantic Fluency Test (SFT) scores (OR = 1.45, 95% CI = 1.07–1.96) and Hopkins Verbal Learning Test (HVLT) retention scores (OR = 1.55, 95% CI = 1.09–2.22) compared to PD patients without skin conditions. None of the associations remained significant after Bonferroni correction for multiple comparisons.ConclusionsWe observed a positive association between any skin condition as well as basal cell carcinoma and PD. PD participants with skin conditions were older, more educated, had higher SFT and HVLT retention scores compared to those without skin conditions. However, all associations were no longer significant after Bonferroni multiple comparisons correction. Observed associations should be confirmed in larger, longitudinal studies.     

Melanin and Neuromelanin: Linking Skin Pigmentation and Parkinson's Disease

Neuromelanin-containing dopaminergic neurons in the substantia nigra pars compacta (SNpc) are the most vulnerable neurons in Parkinson's disease (PD). Recent work suggests that the accumulation of oxidized dopamine and neuromelanin mediate the convergence of mitochondrial and lysosomal dysfunction in patient-derived neurons. In addition, the expression of human tyrosinase in mouse SNpc led to the formation of neuromelanin resulting in the degeneration of nigral dopaminergic neurons, further highlighting the importance of neuromelanin in PD. The potential role of neuromelanin in PD pathogenesis has been supported by epidemiological observations, whereby individuals with lighter pigmentation or cutaneous malignant melanoma exhibit higher incidence of PD. Because neuromelanin and melanin share many functional characteristics and overlapping biosynthetic pathways, it has been postulated that genes involved in skin pigmentation and melanin formation may play a role in the susceptibility of vulnerable midbrain dopaminergic neurons to neurodegeneration. Here, we highlight potential mechanisms that may explain the link between skin pigmentation and PD, focusing on the role of skin pigmentation genes in the pathogenesis of PD. We also discuss the importance of genetic ancestry in assessing the contribution of pigmentation-related genes to risk of PD. © 2022 International Parkinson and Movement Disorder Society.     

Malignant melanoma in early Parkinson's disease: the DATATOP trial.

The available epidemiological data on the incidence of malignant melanoma in Parkinson's disease are contradictory. The role of levodopa therapy in this context has been debated. We identified all known cases of malignant melanoma (N = 5) in the DATATOP clinical trial cohort and compared that to published expected values (N = 1.5) for a standard healthy population. The standardized event ratio was 3.3 (95% confidence interval, 1.1-7.8), indicating that incidence of malignant melanoma was higher than expected. We found no association between levodopa therapy and the incidence of melanoma.     

Development of Parkinson's disease in patients with blepharospasm.

The liability to develop parkinsonian symptoms was evaluated in 105 outpatients with idiopathic blepharospasm (IBS; 54 cases) or IBS associated to oromandibular dystonia (Meige's syndrome; 51 cases) mean age 70.3 +/- 9.6 years, and compared with an age- and sex-matched population. Eleven patients developed Parkinson's disease in the blepharospasm group, whereas only 2 of 105 patients were affected in the control group. Our results suggest that patients with IBS either isolated or associated with oromandibular dystonia are more prone to develop parkinsonian symptoms.     

Cognitive profile of Parkinson's disease patients: a comparative study between early-onset and late-onset Parkinson's disease

Aim: To investigate the influence of onset age on the occurrence and progression of cognitive dysfunction using neuropsychological tests and the electrophysiological component P300 in both early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD) patients. Methods: A cohort of 76 EOPD patients and 166 LOPD patients was recruited for this study. Demographic information and clinical features, including age, disease duration, education level, family history, the Unified Parkinson's Disease Rating Scale, the Hoehn and Yahr stage, and depression scores were documented for each patient. The Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale – Revised, Chinese version (WAIS-RC) and Wechsler Memory Scale – Revised, Chinese version (WMS-RC) were used. In addition, P300 was also examined to assess cognitive function. Results: Although EOPD patients had longer disease duration, their cognitive dysfunction progressed more slowly. The MoCA tests revealed that EOPD patients had higher scores in visuospatial function, attention, delayed recall, and orientation than the LOPD patients. The difference between the two groups on the WMS-RC test did not reach significance, whereas the scores in executive function, visuospatial function and attention as measured on the WAIS-RC test were significantly lower in the LOPD group. In addition, P300 latencies were markedly delayed and P300 amplitudes were reduced in the LOPD group. Conclusions: The current findings demonstrated that cognitive dysfunction progressed more slowly in the EOPD group. Although the LOPD patients exhibited shorter disease durations, their cognitive abilities, including executive function, visuospatial function and attention, may have been impaired.     

Suicide in patients with Parkinson's disease

The purpose of this study was to estimate the risk of suicide for patients with Parkinson's disease (PD) in Denmark compared with that in the background population. The study involved 458 patients with a PD diagnosis, 226 men and 232 women. The follow-up period to either death or end of follow-up on December 31, 1990 was 0 to 17 years, mean 5.7 years. Deaths in the follow-up period amounted to 254, 135 men and 119 women. Two women committed suicide. The number of expected suicides was 1.06 for men and 0.55 for women, a total of 1.62. Neither for men nor for women was the difference between expected and observed suicides statistically significant.     

Use of nutritional supplements in Parkinson's disease patients.

The use of nutritional supplements has almost doubled in the elderly population in the United States (US) in the past decade. We evaluated the use of nutritional supplements in Parkinson's disease (PD) patients to determine the prevalence of their use and whether patients were aware of possible side effects and drug interactions in the supplements they were taking. Consecutively selected PD patients from an academic movement disorders center completed a 33-item questionnaire regarding their use of nutritional supplements. A total of 120 PD patients completed the questionnaire and were included in the data analysis (mean age +/- SD = 68.2 +/- 11.65 years, 67 [55.8%] men and 53 women). Seventy-six patients (63%) took nutritional supplements at the time of data collection. Vitamins were the most common nutritional supplements used, and vitamin E was the most commonly used vitamin. Thirty-six patients (47%) who took nutritional supplements consulted with their doctor before taking them, and only 4% of patients who took nutritional supplements were aware of possible side effects from their use. Twenty patients (16.7%) reported that they were currently taking nutritional supplements because of symptoms related to their Parkinson's disease. The vast majority of PD patients surveyed were not aware that nutritional supplements could cause adverse side effects. Less than half of the patients who took nutritional supplements consulted their physician before starting them. Greater awareness of nutritional supplement use in PD patients is warranted to avoid potentially harmful effects and drug interactions.     

Hyperhidrosis in Parkinson's disease.

We studied the sudomotor skin response (SSR) in patients with Parkinson's disease with and without symptomatic hyperhidrosis. The study was carried out in 13 patients who complained of excessive sweating and in 37 patients who did not have excessive sweating. Patients were matched for age, sex, degree of impairment, duration of the disease, and number and severity of autonomic disturbances. Excessive sweating involved mainly the face, head, and trunk. The SSR was recorded from the palm of the hands to electrical stimulation of the median nerve at the wrist. We analyzed onset latency, peak to peak amplitude, and waveform. Patients with hyperhidrosis had more often absent responses (chi(2) = 5.292; P = 0.021), their responses were of lower mean amplitude (analysis of variance [ANOVA]; F[2,101] = 11.678; P < 0.001), and they had a reduced number of responses with a predominantly negative component (chi(2) = 8.493; P = 0.004) than patients who did not complain of sweating disturbances. Our results indicate that excessive sweating in Parkinson's disease concurs with decreased activation of sweat glands in the palms of the hands and suggests that axial hyperhidrosis could be a compensatory phenomenon for reduced sympathetic function in the extremities.     

Reduced mind wandering in patients with Parkinson's disease

BackgroundMind Wandering (MW) refers to the process of disengaging from the immediate external environment and participating in internally driven mentation. This process has been suggested to be supported by a distributed set of brain regions, collectively referred to as the Default Mode Network (DMN). Recently, reduced recruitment and connectivity of the DMN has been described in Parkinson's disease (PD) patients compared to healthy controls. We thus aimed to explore whether PD patients with normal cognitive test scores show differential MW capabilities compared to healthy controls.MethodsThirty PD patients and thirty age-matched controls, all with a Montreal cognitive assessment (MoCA) score of 26 or above, performed a novel yet validated thought-sampling paradigm used to assess the frequency and extent of MW irrespective of cognitive load in which participants were asked to observe a series of geometric shapes and describe their thoughts after watching them. Shapes were presented one at a time for varying durations across nine trials.ResultsPD patients showed significantly less MW compared to the control. ANCOVA revealed a significant interaction indicating that the difference in MW scores was driven by trials with short stimulus presentation times.ConclusionsThese findings provide evidence for decreased MW in PD patients. We propose that this is due to difficulties in performing MW within short time frames.     

Visual symptoms in Parkinson's disease and Parkinson's disease dementia

Visual symptoms are common in PD and PD dementia and include difficulty reading, double vision, illusions, feelings of presence and passage, and complex visual hallucinations. Despite the established prognostic implications of complex visual hallucinations, the interaction between cognitive decline, visual impairment, and other visual symptoms remains poorly understood. Our aim was to characterize the spectrum of visual symptomatology in PD and examine clinical predictors for their occurrence. Sixty-four subjects with PD, 26 with PD dementia, and 32 age-matched controls were assessed for visual symptoms, cognitive impairment, and ocular pathology. Complex visual hallucinations were common in PD (17%) and PD dementia (89%). Dementia subjects reported illusions (65%) and presence (62%) more frequently than PD or control subjects, but the frequency of passage hallucinations in PD and PD dementia groups was equivalent (48% versus 69%, respectively; P = 0.102). Visual acuity and contrast sensitivity was impaired in parkinsonian subjects, with disease severity and age emerging as the key predictors. Regression analysis identified a variety of factors independently predictive of complex visual hallucinations (e.g., dementia, visual acuity, and depression), illusions (e.g., excessive daytime somnolence and disease severity), and presence (e.g., rapid eye movement sleep behavior disorder and excessive daytime somnolence). Our results demonstrate that different "hallucinatory" experiences in PD do not necessarily share common disease predictors and may, therefore, be driven by different pathophysiological mechanisms. If confirmed, such a finding will have important implications for future studies of visual symptoms and cognitive decline in PD and PD dementia.     

Comorbid cancer in Parkinson's disease

The aim of this article was to evaluate cancer occurrence before and after diagnosis of Parkinson's disease (PD). We investigated 692 patients newly diagnosed with PD and 761 age‐ and sex‐matched control subjects identified during two periods (1994–1995 and 2000–2003) within Kaiser Permanente Medical Care Program of Northern California. Primary cancers were searched and dated, and all participants were followed up until the end of membership, death, or December 31, 2008. We used unconditional logistic regression to evaluate the PD–cancer association before the date of PD diagnosis or the index date and Cox proportional hazards regression to evaluate the PD–cancer association after the index date. Nearly 20% (140 of 692) of the PD patients and 25% (188 of 761) of the non‐PD controls had ever had a cancer diagnosis. Before the index date, the prevalence of cancer was not significantly lower in patients with PD (8.1% PD vs. 9.2% controls; OR = 0.83; 95% CI 0.54–1.3). After the index date, the risk of developing a cancer did not differ between PD cases and controls (relative risk [RR] = 0.94; 95% CI 0.70–1.3). Among specific cancers, melanoma was more common among PD cases (before PD, OR = 1.5; 95% CI 0.40–5.2; after PD, RR = 1.6; 95% CI 0.71–3.6), but independent of dopaminergic therapy. Cancer occurrence is not significantly lower among patients with PD. The positive association between PD and subsequent melanoma merits further investigation, as it does not seem to be attributable to dopaminergic therapy, pigmentation, or confounding by smoking. © 2010 Movement Disorder Society.     

Osteoporosis in Parkinson's disease.

There are few studies of osteoporosis in Parkinson's disease (PD). We assessed the prevalence of osteoporosis in a PD clinic cohort. All subjects with a confirmed diagnosis of PD attending a clinic were invited to participate. All consenting subjects had bone density measured by dual energy X-ray absorptiometry scanning. Further data, including demography, disease duration, and disease severity, were collected. One hundred five subjects participated; median age was 75 (54-92) years. Fifty-one (49%) patients were men. Of the men: median T score, -1.3 (range, -4.7 to 3.8); median Z score, 0.0 (-3.2 to 4.7); diagnostic categories: osteoporosis, 20%; osteopenia, 41%; normal, 39%. Of the women: median T score -2.7 (-4.7 to 1.4); median Z score, -0.25 (-2.6 to 4.2); diagnostic categories: osteoporosis, 63%; osteopenia, 28%; and normal, 9%. Whole sample: osteoporosis, 42%; osteopenia, 34%; and normal, 24%. There were associations between age, depression, disease duration, and osteoporosis but not with disease severity. Female gender was an independent predictor of osteoporosis. The prevalence of osteoporosis/osteopenia is considerable in PD patients but does not exceed that of other people of similar age. Osteoporosis/osteopenia was present in almost all women of this age group with PD.     

Assessing comorbidity in patients with Parkinson's disease.

The aim of this study was to assess the accuracy of an interview-based assessment of comorbidity, in patients with Parkinson's disease (PD). The Cumulative Illness Rating Scale-Geriatric (CIRS-G) was completed (1) in an interview with 31 PD patients and their caregivers, and (2) by reviewing the patient's medical charts from their general practitioners. Based on the interview, all patients had some comorbidity, 84% had one or more moderate comorbid diseases. The most frequently affected organ systems were "lower gastrointestinal" and "genitourinary". The mean +/- SD total score of the interview-based (chart-based) CIRS-G was 6.9 +/- 3.8 (7.6 +/- 3.5) with a mean of 4.3 +/- 1.9 (5.0 +/- 1.9) affected organ systems and a mean of 2.1 +/- 1.7 (2.3 +/- 1.6) organ systems with at least moderate comorbidity per patient. The agreement (intraclass correlation coefficients) between the interview-based and chart-based assessments for the six summary scores ranged from 0.69 to 0.81. The agreement for the 14 organ systems ranged from 0.13 to 1.00 (weighted kappa); 12 had a K(w) above 0.40 (moderate agreement). The comorbidity summary scores had a moderate correlation with age and disability. The interview-based assessment of the CIRS-G is easy to apply and is an accurate method to assess comorbidity in patients with PD.     

Body weight in patients with Parkinson's disease.

There is some evidence suggesting that Parkinson's disease (PD) patients exhibit lower body weight when compared to age-matched healthy subjects. Low body mass index (BMI) is correlated with low bone mineral density, both of which are major risk factors for hip fractures. Possible determinants of weight loss in PD patients include hyposmia, impaired hand-mouth coordination, difficulty chewing, dysphagia, intestinal hypomotility, depression, decreased reward processing of dopaminergic mesolimbic regions, nausea, and anorexia as the side effects of medication, and increased energy requirements due to muscular rigidity and involuntary movements. It is unclear whether PD patients in general, or only a subgroup of those affected, definitely show lower BMI in the advanced stages of the disease. We therefore recommend that the body weight of PD patients be monitored monthly as the disease progresses, and that a patient's nutrition should be supplemented with sufficient amounts of vitamin D and calcium to reduce the risk of hip fractures and strengthen bone density. Because meal times may coincide with unpredictable off periods associated with akinesia and impaired hand-mouth coordination, PD patients also need flexible food schedules that accommodate the associated symptoms of this disease.     

A prospective study of depression in French patients with Parkinson's disease. The Depar study

To investigate the prevalence and symptomatology of depression in Parkinson's disease (PD), we have studied 506 unselected patients attending the neurology services in French general hospitals during a 5 month period defined for prospective inclusion. 246 patients (48.6%) were suspected of depression according to different methods of evaluation and 168 (33.2%) were defined as definite or probable depression. According to the Montgomery and Asberg scale, 46 cases (9%) had a severity score suggestive of major depression. As a function of the cut-off score defined for severity, these patients represented from 23.2 to 43.7% of the depressive population with PD. There was no significant difference between depressed and non depressed PD patients as a function of the patient's current age or age at onset of PD. A significantly higher rate of depression was found among women with PD. A past history of depression was a risk factor for mood disorder after onset of PD. The severely depressed patients had a significantly longer duration of PD and a higher score of cognitive impairment than mildly or moderately depressed and non depressed patients with PD. Depressed patients had a significantly more advanced stage of disability than non-depressed patients with PD.     

Applause sign in advanced Parkinson's disease

BackgroundThe ‘applause sign’ a tendency to continue applauding in response to instructions to clap three times was described in 1995 and was considered specific to degenerative disease, especially to atypical parkinsonian disorders. In early phase Parkinson's disease (PD) the sign has been reported positive as well. In late stage PD it is unknown whether and to what extent the sign may be elicited and it remains unknown if and to what degree the sign correlates to cognitive impairment and PD related dementia.MethodsNursing home residents with PD (MMSE >17) were included. All patients underwent the clapping test and were tested for cognitive disturbance by making use of accepted clinimetrics (MMSE and Scopa-cog). T-testing was performed with the hypothesis that patients expressing the applause sign would score lower on the MMSE or Scopa-cog.ResultsSeventy three nursing home residents (mainly Hoehn and Yahr 4/5) with a mean disease duration of 10 years and a mean age of 78.7 years were included. The applause sign was found positive in 15 of 73 residents (20.5%). Residents expressing the applause sign had significantly lower mean scores on the MMSE (25.1 vs 22.9 points, p < 0.006) and Scopa-cog (14.8 vs 12.0 points, p < 0.039).ConclusionsThe applause sign is present in late stage PD and correlates with a higher degree of cognitive impairment as established with accepted clinimetric tests. A higher degree of frontal lobe involvement explains the presence of the applause sign.     

Mirror movements in patients with Parkinson's disease

Mirror movements (MM) refer to ipsilateral involuntary movements that appear during voluntary activity in contralateral homologous body regions. This study aimed to compare the frequency and distribution of MM in an unselected sample of 274 patients with Parkinson's disease (PD) and 100 healthy subjects, and to check a possible relationship between MM and parkinsonian features. MM of the hand were scored according to the Woods and Teuber scale. The frequency of MM was lower in PD patients than in healthy subjects (29% vs. 71%, P < 0.0001). The distribution of MM also differed in the two groups being often bilateral in healthy subjects, invariably unilateral in PD patients. When parkinsonian signs were unilateral, MM always manifested on the unaffected side; when parkinsonian signs were bilateral, MM manifested on the less affected side. PD patients manifesting MM scored significantly lower on Hohen and Yahr staging than patients without MM. Likewise, there was a significant inverse correlation between the intensity of MM as rated by the Woods and Teuber score and HY staging (r = ?0.16, P < 0.01). The low frequency of MM in PD probably relates to the complex interactions between the pathophysiological mechanisms leading to parkinsonian signs and the mechanisms responsible for movement lateralization. © 2007 Movement Disorder Society