Years Of Parkinson's Disease Research Articles

Clinical spectrum of levodopa-induced complications.

The first years of Parkinson disease (PD) treatment are marked by good and sustained responses to dopaminergic therapy. With disease progression and longer exposure to levodopa (l-dopa), patients develop a range of l-dopa-induced complications that include motor and non-motor symptoms. Motor complications include motor fluctuations, characterized by periods of reduced benefit from the medication, and l-dopa-induced dyskinesia, characterized by emergence of hyperkinetic involuntary movements. Dyskinesia can occur at peak effect of l-dopa, at the beginning and end of dose, or between doses. These motor complications are often associated with fluctuations in non-motor symptoms, particularly fluctuations in neuropsychiatric, autonomic, and sensory symptoms. Recognizing such complications and understanding their relationship with the timing of l-dopa doses is essential for adequate diagnosis and management. Society.

CSF biomarkers and clinical progression of Parkinson disease.

To investigate whether certain CSF biomarkers at baseline can predict future progression of motor symptoms and cognitive decline in patients with Parkinson disease (PD). Patients and controls were recruited from hospitals in southern Sweden as part of the prospective and longitudinal Swedish BioFinder Study. In the present study, we included 42 patients with PD and 69 controls who had clinical assessment and lumbar puncture at baseline. Baseline CSF samples were analyzed for α-synuclein (αSyn), β-amyloid 1-42 (Aβ42), tau, phosphorylated tau, and neurofilament light. Associations between CSF markers at baseline and change in clinical characteristics after 2 years of follow-up were investigated using multivariate models adjusting for age, sex, disease duration, and levodopa-equivalent daily dose. Higher levels of αSyn within the PD group were associated with progression of motor symptoms and cognitive decline over 2 years, indicated by significant relationships between αSyn and change in Hoehn and Yahr (β = 0.394, p = 0.043), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (β = 0.449, p = 0.013), Timed Up and Go (β = 0.406, p = 0.023), and A Quick Test of Cognitive Speed (β = 0.423, p = 0.018). Lower levels of Aβ42 were associated with worsening of performance on delayed memory recall (F = 5.834, p = 0.022). Finally, high levels of phosphorylated tau were associated with worsening in motor symptoms (UPDRS-III, β = 0.350, p = 0.045; Hoehn and Yahr, β = 0.366, p = 0.038). We found evidence of a link between higher levels of αSyn at baseline and worsening of motor symptoms and cognitive speed over 2 years in PD. Increased αSyn might be a marker of more intense synaptic degeneration in PD. The results indicate that cortical amyloid pathology (low CSF Aβ42) is associated with memory decline.

Functional connectivity and cognitive decline over 3 years in Parkinson disease.

To evaluate fMRI whole-brain resting-state functional connectivity changes in relation to cognitive decline in Parkinson disease (PD) over a 3-year period. Resting-state fMRI scans were acquired in 55 patients with PD (mean age 65.8 years, SD 6.37; average disease duration 9.24 years, SD 3.96) and 15 matched controls (mean age 64.4 years, SD 8.65). We first performed overall (i.e., 1 whole-brain mean) as well as regional (i.e., for all individual regions of interest) functional connectivity analyses, in which we compared subject groups cross-sectionally. After a 3-year follow-up period, 36 patients with PD and 12 controls were rescanned to study functional connectivity changes over time and correlate the changes in functional connectivity with deteriorating cognitive and motor function in the PD sample. In the cross-sectional analysis, we found widespread decreases of resting-state functional connectivity in patients with PD in comparison to controls. Subsequent comparison between the 2 timepoints revealed that patients with PD displayed further decreases in functional connectivity independent of aging effects. These functional connectivity changes were most prominent for posterior parts of the brain and correlated across time with clinical measures of disease progression, especially cognitive decline. In this fMRI study in PD, we demonstrated a progressive loss of resting-state functional connectivity over a period of 3 years for multiple brain regions, especially in posterior parts of the brain. The strong correlation with decreasing cognitive performance supports the pathophysiologic role of reduced functional connectivity in cognitive decline and the development of dementia in PD.

A comparison of caregiver burden in older persons and persons with Parkinson's disease or dementia in sub-Saharan Africa

Caregiver burden includes the many physical, mental and socio-economic problems arising from caring for individuals with chronic and disabling diseases. Being a carer in sub-Saharan Africa (SSA), where little is known about chronic neurological conditions, may be extremely demanding. Conversely, multigenerational living may allow sharing of care among many caregivers. We wished to determine the relative burden of caring for two chronic neurodegenerative conditions (Parkinson's disease (PD) and dementia) in rural Tanzania. All surviving patients from a PD prevalence study, newly identified people with PD from a neurological disorders study and all people with dementia from a dementia prevalence study in Hai, rural Tanzania, were invited to participate. The Zarit Burden Interview (ZBI) was used to determine level of caregiver strain (higher score reflects more strain). Of 25 PD patients ZBI was recorded in 20 (14 male). Five had no identifiable carer as they were largely independent. Three had PD dementia (PDD). Of 75 people with dementia (excluding 3 PDD), 43 (32 female) completed the ZBI. For the other 32, the caregivers felt the care they provided was a normal intergenerational expectation. Median ages were 78.5 and 85 years for PD and dementia, respectively. Median ZBI was 30.5 for PD and 14 for dementia (U = 166.0, z = -3.913, p < 0.001). Disease duration and disease type (PD or dementia) were univariate predictor of ZBI score, although only disease type was predictive by multivariable linear regression. Caring for an individual with PD may be more burdensome than caring for an individual with dementia in SSA. People with more advanced PD had higher caregiver burden.

Effects of a physical therapy home-based exercise program for Parkinson's disease

INTRODUCTION: Parkinson's disease (PD) is a neurological disorder that causes loss of functional abilities and independence. The aim of this study was to evaluate the effects of a physical therapist-supervised home-based exercise program in patients with PD using the UPDRS scale. MATERIALS AND METHODS: Thirty-three PD patients in the 1.5 to 3 Hoehn and Yahr stages participated in the trial. The patients and their relatives received a booklet with a 12-week home program, with a series of strengthening, stretching and flexibility exercises. The patients were trained by a physical therapist, and each session took 60 minutes, three times a week. RESULTS: We classified our patients in four groups: Group 1 - patients under 60 years of age and less than five years of PD; Group 2 - patients under 60 years of age and more than five years of PD; Group 3 - patients over 60 years of age and less than five years of the disease; and Group 4 - patients over 60 years of age and more than five years of PD. Significant improvement was found in group 1 in mentation, activities of daily living and motor function (p &gt; 0.05). Group 3 presented statistically significant differences in motor function subscale (p &gt; 0.05) and Group 4 showed no worsening in mentation subscale (p &gt; 0.05). Group 2, however, presented no difference in all subscales (p &lt; 0.05). CONCLUSION: Although not all patients improved their UPDRS scores, our data support the use of a home program as an alternative method of physical therapy treatment for PD patients.

Linking LINGO1 to essential tremor

Linking LINGO1 to essential tremor

Ectopic expression of α‐synuclein affects the migration of neural stem cells in mouse subventricular zone

α-Synuclein (α-syn) is a key protein in Parkinson's disease (PD), and its abnormal accumulation is implicated only not in the loss of dopaminergic neurons in the substantia nigra but also in impairment of olfactory bulb (OB) in PD. Olfactory dysfunction could arise from these OB changes as an early symptom in PD. We reported previously the impairment of neuronal stem cell (NSC) proliferation in the subventricular zone, which is upstream of OB in PD models. Reduction of NSC generation could potentially lead to olfactory dysfunction, which is commonly associated with and precedes the motor symptoms by several years in PD. Here, we investigated neurosphere formation in vitro and migration of NSCs in vivo after transduction of α-syn-encoding retroviral vector to characterize the function of α-syn in NSC. Over-expression of α-syn caused less effective formation of neurospheres and induced morphological changes. Fluorescence-activated cell sorting showed diminished NSC cell cycle progression induced by over-expression of α-syn. Intriguingly, suppression of NSC migration along the rostral migratory stream was observed when the α-syn-encoding vector was directly injected into the subventricular zone of mice in vivo. These results indicate that α-syn affects the generation of NSC and suggest that this protein could serve as a tool for the design of potentially useful therapy for PD patients.

Apraxia in Parkinson’s disease and multiple system atrophy

To determine praxis function in patients with Parkinson's disease (PD) and multiple system atrophy (MSA). Nineteen patients with PD and 16 patients with probable MSA were recruited into study. Twenty-five age-matched, healthy subjects were included as controls. The Mayo Clinic praxis test battery was applied. Pantomime tasks, including oral/facial, trunk, and upper extremity movement, were used to evaluate ideomotor apraxia (IMA). Sequential tasks, including Luria test for ideational apraxia (IDA) and use of actual objects, were also tested. In addition, Standardized Mini Mental Test (MMSE), Hamilton Depression (HAM-D), and Anxiety (HAM-A) Scales were used. Mean ages of the study participants were 66 +/- 7, 68 +/- 5, and 65 +/- 7 years in PD, MSA, and control groups, respectively. Mean total praxis score was significantly lower for patients with PD (92.4 +/- 4) and MSA (75.9 +/- 18) than for controls (97.4 +/- 2) (P = 0.000). Transitive performances of upper extremities and sequential tasks were significantly impaired in patients with PD compared to control subjects (P < 0.05). There was no correlation between total praxis scores and sum scores of tremor, bradykinesia, and rigidity of both of the upper limbs of patients with PD. Subgroup praxis scores were substantially worse in MSA group (P < 0.0001). Compared to control subjects, mean scores for MMSE, HAM-D, and HAM-A tests were significantly worse in MSA group, but, for PD patient group, only HAM-A scores were worse. Our results indicate that although not a presenting symptom, IMA and IDA may be features of MSA and, to a lesser degree, of PD. Also, it seems to be unrelated to the motor features of patients with PD.

Large differences in levodopa dose requirement in Parkinson’s disease: men use higher doses than women

The characteristics of levodopa dosing are not well described in the literature. The aims were to investigate the use of levodopa in a nationwide Swedish survey and to study the characteristics of low-dose and high-dose patients with Parkinson's disease (PD) in a university hospital. Patients with >or= 1 and >or= 2 purchases of levodopa during 2007 were selected from the prescribed drug register. Daily levodopa doses were estimated. Records of 504 patients with PD who visited the neurology clinic at Uppsala University Hospital during 2006-2007 were examined to select a low-dose group (< or = 400 mg levodopa daily, n = 21) and a high-dose group (>or= 1200 mg daily, n = 26) with at least 5 years of PD duration. In total, 33 534 levodopa users with > or = 1 levodopa purchase were found. Daily levodopa dose range was large; median daily dose was 465 mg for men and 395 mg for women (P < 0.0001). Almost half (46%) of the patients used < 400 mg levodopa daily. Significantly, more men were treated with doses >or= 1200 mg daily. Dose and age correlated negatively (P < 0.0001). Patients with high dose at 5 years PD duration continuously increased their dosage the following years, whereas low-dose patients did not. The occurrence of dyskinesias was about the same in both groups despite the large difference in levodopa dose. We conclude that the levodopa requirement in PD ranges considerably, and that men use higher levodopa dose than women. Levodopa requirement is constant during the progression of the disease in low-dose patients but increases in high-dose patients.

Striatal subregional 6‐[18F]fluoro‐L‐dopa uptake in early Parkinson's disease: A two‐year follow‐up study

Thirty-one drug-naive patients with Parkinson's disease (PD) underwent 6-[18F]fluoro-L-dopa (F-dopa) positron emission tomography (PET) scan at the time of the diagnosis (baseline) and 2 years later in order to investigate F-dopa uptake in striatal and extrastriatal regions during the first years of early PD. Twenty-four healthy controls underwent one F-dopa PET scan. The regional differences in the striatal and extrastriatal regions were analyzed with statistical parametric mapping and automated region of interest analyses. Our study shows that the F-dopa uptake in unmedicated early PD is most severely decreased in the dorsal part of caudal putamen but significant decrease can be seen throughout the striatum compared with controls. During the first years of PD, there is a progressive regional decline in striatal F-dopa uptake, the dorsal part of caudal putamen being still the most severely affected region. The absolute decline is equal between the striatal subregions. This suggests that the decline of dopamine function starts from the dorsocaudal putamen, but once started, the rate of progression is equal between the subregions of the striatum. In contrast to the striatal decline, the increased cortical F-dopa uptake prevails at least during the first years of PD.