Cognitive-behavioral therapy for depression in Parkinson's disease: a pilot study.

The present study was conducted to examine the feasibility and effect of an individual cognitive-behavioral treatment (CBT) for depression that was modified to meet the unique needs of the PD patient and incorporated a separate social support intervention for caregivers. Fifteen PD patients with Major Depressive Disorder participated in the study with a caregiver. Patients received 10-14 sessions of modified individual CBT. Caregivers attended 3-4 psychoeducational sessions, occurring separately from the patients treatment sessions, which focused on strategies for offering appropriate support, and ways to respond to the patients' negative thoughts in a targeted manner. Patients experienced a significant reduction in depressive symptoms and negative cognitions, and an increased perception of social support over the course of treatment. Gains were maintained at 1-month follow-up. In conclusion, individual CBT, when modified appropriately, may be a feasible and effective option for PD depression. Larger, randomized controlled trials are needed to further evaluate the efficacy of this intervention and to identify specific mechanisms of change.     

Associations between family history of Parkinson's disease and dementia and risk of dementia in Parkinson's disease: A community-based, longitudinal study.

Dementia is common in patients with Parkinson's disease (PDD). The etiology of PDD is still unclear, but exciting advances have been made in discovering pathogenetic components in Parkinson's disease (PD), implicating the role of genetic factors. It is, however, still controversial whether genetic factors also contribute to the development of dementia in PD. Thus, we investigated the association between development of dementia and a positive family history of PD or dementia in a community-based study of PD in Rogaland County, Norway (n = 219). The patients were followed prospectively with neurological and neuropsychological assessments. Dementia was more common in patients with a strong family association of PD (first-degree relatives > second-degree relatives > no family history; P < 0.05). However, time to dementia did not differ between the two groups. No associations between dementia in PD and familial occurrence of dementia could be shown. Further studies with larger samples are needed to explore a possible relationship between a family history of PD and development of dementia in PD and its potential pathogenetic mechanisms.     

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.     

Risk factors for Parkinson's disease and impaired olfaction in relatives of patients with Parkinson's disease.

Our objective was to assess the association between risk factors for Parkinson's disease (PD) and abnormal olfaction in first-degree relatives of patients with PD. Factors including lower cigarette smoking and lower caffeine consumption have been associated with increased risk of PD. Idiopathic hyposmia has also been associated with an increased risk of PD. The relationship between risk factors for PD and impaired olfactory function has not been evaluated in relatives of PD patients. We conducted a mail survey of odor identification ability in 173 first-degree relatives of PD patients using the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Respondents also completed a questionnaire inquiring about risk factors for PD including caffeine consumption, tobacco use, exercise, and exposures to heavy metals, well-water, and pesticides. There was a direct relationship between olfactory performance and lifetime caffeine intake. After adjustment for age, gender, and smoking status, subjects who reported drinking 2 to 3 cups of caffeinated beverages per day (2.6 points higher 95% CI: 0.5, 4.5) and 4 or more cups per day (3.7 points higher, 95% CI: 0.6, 6.7) had significantly better UPSIT scores than those who consumed less than 1 cup per day. There was no significant relationship between olfactory performance and other risk factors. In conclusion, abnormal olfaction is associated with significantly lower lifetime caffeine consumption in first-degree relatives of PD patients. Further research is warranted to determine whether a history of lower caffeine consumption confers additional risk for the development of PD in hyposmic relatives of PD patients.     

Novel compound heterozygous FBXO7 mutations in a family with early onset Parkinson's disease

BackgroundMutations in the F-box protein 7 (FBXO7) gene result in autosomal recessive parkinsonism. This usually manifests as early-onset parkinsonian-pyramidal syndrome but patients exhibit high phenotypic variability. Here we describe the findings of a Yemeni family with two novel FBXO7 mutations.MethodsClinical data and DNA were available for three siblings with early-onset parkinsonism together with their parents and three unaffected siblings. A targeted next generation sequencing panel was used to screen the proband for mutations in 14 genes known to cause a parkinsonian disorder. In addition, SNCA, PARK2, PINK1, and PARK7 were screened for copy number variants.ResultsThe proband carried two novel compound heterozygous FBXO7 mutations: a missense mutation in exon 1 (p.G39R; c.115G > A) and a frameshift mutation in exon 5 (p.L280fs; c.838del). The mutations segregated with disease in the family with the exception of a potentially pre-symptomatic individual whose age was below the age of onset in two of their three affected siblings. P.G39R occurred at a highly conserved amino acid residue and both mutations were predicted to be deleterious in silico. In contrast to most reported families, the phenotype in this pedigree was consistent with clinically typical Parkinson's disease (PD) with a lack of pyramidal signs and good response to dopaminergic therapy.ConclusionsOur study expands the phenotype associated with FBXO7 to include early-onset PD and broadens the list of causative mutations. These data suggest that FBXO7 should be included in clinical genetic testing panels for PD, particularly in patients with early onset or a recessive inheritance pattern.     

Clinical diagnostic criteria for dementia associated with Parkinson's disease.

Dementia has been increasingly more recognized to be a common feature in patients with Parkinson's disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD-D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD-D. The Task Force members were assigned to sub-committees and performed a systematic review of the literature, based on pre-defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point-prevelance is close to 30%, older age and akinetic-rigid form are associated with higher risk. PD-D is characterized by impairment in attention, memory, executive and visuo-spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body-type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD-D are proposed.     

Atypical clinical presentation of pathologically proven Parkinson's disease: The role of Parkinson's disease related metabolic pattern

Regional changes in brain metabolism upgraded with measurements of specific metabolic brain patterns and automated diagnostic algorithms can help to differentiate among neurodegenerative parkinsonisms, but with few reports on pathological confirmation. Here we describe a parkinsonian patient with atypical presentation and ¹⁸F-FDG-PET imaging consistent with idiopathic Parkinson's disease. The latter was confirmed at the pathohistological examination.     

Compound heterozygous variants in Wiskott-Aldrich syndrome like (WASL) gene segregating in a family with early onset Parkinson's disease

BackgroundKnowledge of genetic determinants in Parkinson's disease is still limited. Familial forms of the disease continue to provide a rich resource to capture the genetic spectrum in disease pathogenesis, and this approach is exploited in this study.MethodsInformative members from a three-generation family of Indian ethnicity manifesting a likely autosomal recessive mode of inheritance of Parkinson's disease were used for whole exome sequencing. Variant data analysis and in vitro functional characterisation of variant(s) segregating with the phenotype were carried out in HEK-293 and SH-SY5Y cells using gene constructs of interest.ResultsTwo compound heterozygous variants, a rare missense (c.1139C > T:p.P380L) and a novel splice variant (c.1456 + 2 delTAGA, intron10) in Wiskott-Aldrich syndrome like gene (WASL, 7q31), both predicted to be deleterious were shared among the proband and two affected siblings. WASL, a gene not previously linked to a human Mendelian disorder is known to regulate actin polymerisation via Arp2/3 complex. Based on exon trapping assay using pSPL3 vector in HEK-293 cells, the splice variant showed skipping of exon10. Characterisation of the missense variant in SH-SY5Y cells demonstrated: i) significant alterations in neurite length and number; ii) decreased reactive oxygen species tolerance in mutation carrying cells on Tetrabutylphosphonium hydroxide induction and iii) increase in alpha-synuclein protein. Screening for WASL variants in two independent PD cohorts identified four individuals with heterozygous but none with biallelic variants.ConclusionWASL, with demonstrated functional relevance in neurons may be yet another strong candidate gene for autosomal recessive PD encouraging assessment of its contribution across populations.     

SPECT findings in Alzheimer's disease and Parkinson's disease with dementia

We examined, with single photon emission tomography (SPECT) and (^99mTc)-HMPAO, 18 patients with idiopathic Parkinson's disease and no dementia (PD), 12 patients with PD and dementia, 24 patients with probable Alzheimer's disease (AD) and 14 controls. While the three patient groups showed significantly lower perfusion in frontal inferior and temporal inferior areas as compared to controls, both demented groups showed significantly more severe bilateral hypoperfusion in superior frontal, superior temporal and parietal areas as compared to non-demented PD patients and controls. On the other hand, no significant differences in cerebral perfusion were found between patients with AD and patients with PD and dementia. In conclusion, our findings demonstrated specific but similar cerebral perfusion deficits in demented patients with either AD or PD.     

Genetic analysis of TRIM family genes for early-onset Parkinson's disease in Chinese population

IntroductionAmounting evidence has suggested the Tripartite Motif (TRIM) family proteins as related to Parkinson's disease (PD). However, many of the risk genes were still awaiting further explorations, and their genetic role in PD has not been investigated yet.MethodsHere, we aimed to systematically evaluate the genetic associations of TRIMs with PD in a large Chinese early-onset PD (EOPD, age at onset < 50 years) cohort. We identified rare variants (minor allele frequency < 0.01) in 743 unrelated EOPD patients using whole exome sequencing, and evaluated the association between rare variants and EOPD at allele and gene levels.ResultsTotally 123 rare variants were identified in 13 TRIM protein family members, including TRIM3, TRIM6, TRIM8, TRIM9, TRIM10, TRIM11, TRIM17, TRIM24, TRIM27, TRIM28, TRIM34, TRIM40 and TRIM41. At the allele level, three variants were nominally associated with PD, namely p.R65H in TRIM10, p.P467S in TRIM11, and p.I425V in TRIM24. Gene-based burden analysis showed a clear enrichment of rare variants of TRIM24 in EOPD.ConclusionThese results demonstrate TRIM24 as a potential risk gene for PD, provide a better understanding for the genetic involvement of TRIM protein family members in EOPD and broaden the current mutation spectrum of PD.     

Caregiver burden in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that imposes an important burden upon the patient's caregiver. This study aims at assessing caregiver burden (CB) and analyzing its relationship with sociodemographic, emotional, and functional factors, as well as health-related quality of life (HRQoL). The following measures were applied to 80 patients with PD: the Hospital Anxiety and Depression Scale (HADS); the EuroQoL (for HRQoL); and PD-specific measures (Hoehn and Yahr staging and SCOPA-Motor ADL subscale). Patients' main caregivers completed the HADS, SF-36, EuroQoL, and Zarit CB Inventory (ZCBI). The ZCBI was found to be a valid and reliable measure in the context of PD. There was a significant association between CB and caregivers' HRQoL (r = -0.29 to -0.64). Mental aspects of caregivers' HRQoL and burden were affected by disability and disease severity. The presence of caregivers' depression had a significant negative effect on both CB and HRQoL. The main predictors of CB were caregivers' psychological well-being, patients' mood and clinical aspects of PD (disability and severity), and HRQoL of patients and caregivers. This study underscores the need to consider the impact of PD on caregivers' well-being.     

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.     

Depressive symptom profile in Parkinson's disease: a comparison with depression in elderly patients without Parkinson's disease

OBJECTIVE: Depression is a common neuropsychiatric syndrome in Parkinson's disease (PD), and may be etiologically related to the neurochemical changes accompanying this disease. It is still unclear whether the disturbances of neurotransmitter activities lead to a specific profile of depressive symptoms, that is characteristic for PD and differs from that in depressed patients without PD. METHOD: We compared the individual depressive symptoms of 145 non-demented depressed patients with PD and 100 depressed patients without PD by comparing item scores on the Montgomery-Asberg Depression Rating Scale by way of MANCOVA. RESULTS: The severity of depression and the level of cognitive functioning in depressed PD patients were comparable with that of depressed control subjects. However, patients with PD showed significant less reported sadness, less anhedonia, less feelings of guilt and, slightly less loss of energy, but more concentration problems than depressed control subjects. CONCLUSION: The profile of depressive symptoms in PD differs from that in depressed subjects without PD. This finding is important for the conceptualisation and clinical diagnosis of depression in PD.     

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.     

Acupuncture therapy for the symptoms of Parkinson's disease.

Interest in alternative medical treatments, including acupuncture, is increasing. Alternative treatments must be subjected to the same objective standards as all medical treatments. A non-blinded pilot study of the safety, tolerability, and efficacy of acupuncture (ACUPX) for the symptoms of (PD) was performed. Twenty PD patients (mean age, 68 years; disease duration, 8.5 years; Hoehn and Yahr [H&Y] stage, 2.2; Unified Parkinson's Disease Rating Scale score [UPDRS], 38.7) each received acupuncture treatments by a licensed acupuncturist. All patients were treated with two acupuncture treatment sessions per week. The first seven patients received 10 treatments and the last 13 patients 16 treatments. Patients were evaluated before and after ACUPX with the Sickness Impact Profile (SIP); UPDRS; H & Y; Schwab and England (S & E); Beck Anxiety Inventory (BAI); Beck Depression Inventory (BDI); quantitative motor tests, including timed evaluations of arm pronation supination movements, finger dexterity, finger movements between two fixed measured points, and the stand-walk-sit test; and a patient questionnaire designed for the study. Following ACUPX, there were no significant changes in the UPDRS, H&Y, S&E, BAI, BDI, quantitative motor tests, total SIP or the two SIP Dimension scores. Analysis of the 12 SIP categories not corrected for multiple comparisons revealed a post-ACUPX improvement in the sleep and rest category only (P = 0.03). On the patient questionnaire, 85% of patients reported subjective improvement of individual symptoms including tremor, walking, handwriting, slowness, pain, sleep, depression, and anxiety. There were no adverse effects. ACUPX therapy is safe and well tolerated in PD patients. A range of PD and behavioral scales failed to show improvement following ACUPX other than sleep benefit, although patients reported other discrete symptomatic improvements. A broad battery of tests in PD patients suggested that ACUPX resulted in improvement of sleep and rest only. This finding needs to be verified using more in-depth and controlled evaluation of ACUPX for PD-related sleep disturbance.     

Identification of a panel of five serum miRNAs as a biomarker for Parkinson's disease

Background and objectiveParkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease. The aim of this work was to determine whether the differences of serum miRNAs profiling could distinguish PD patients from healthy individuals.MethodsWe collected serum samples from 106 sporadic PD patients and 91 age/gender-matched healthy controls. Serum miRNAs were analysed by Solexa sequencing followed by a qRT-PCR examination. The qRT-PCR assay, which was divided into two phases, was used to validate the expression of miRNAs screened by Solexa sequencing. Receiver operating characteristic (ROC) curve analysis and clustering analysis were performed to determine the diagnostic usefulness of the selected miRNAs for PD.ResultsIn this study, we generated a profile of 5 serum miRNAs: miR-195 was up-regulated, and miR-185, miR-15b, miR-221 and miR-181a were down-regulated.ConclusionThis group of five miRNAs can precisely distinguish PD patients from health individuals and may be used as a potential serum-based biomarker for the diagnosis of PD.     

Neural networks associated with quality of life in patients with Parkinson's disease

IntroductionThe neural underpinnings of health-related quality of life in Parkinson's disease remain unclear. This study was conducted to unravel which motor and non-motor symptoms in Parkinson's disease influence health-related quality of life and reveal neural networks most likely linked to it.MethodsComprehensive clinical assessments were conducted for 247 Parkinson's disease patients and image analyses were performed for 181 patients. Clinical scores commonly used to assess various symptoms related to health-related quality of life were investigated. Factor and resting-state functional magnetic resonance imaging analyses were reviewed to reveal health-related quality of life-associated brain networks.ResultsThe Spearman's rank correlation coefficient for the Parkinson's disease Questionnaire-39 summary index was high in the Activities-specific Balance Confidence Scale, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 2, Freezing of Gait Questionnaire, and Self-reported Autonomic Symptoms in Parkinson's disease. Multiple regression and Random Forest regression analyses indicated that health-related quality of life-associated factors were Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 1, Depression Rating Scales, and the above-mentioned scales. The resting-state functional magnetic resonance imaging analysis revealed decreased functional connectivity between the anterior cingulate cortex and right temporo-parietal junction as health-related quality of life worsened.ConclusionFear of falling, daily living activities, gait freezing, and autonomic dysfunction have notable effects on health-related quality of life in Parkinson's disease. Brain networks consisting of the anterior cingulate cortex and temporo-parietal junction may be associated with the emotion-related and social factors of health-related quality of life in Parkinson's disease.     

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.     

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.