Magdalena Eriksson Domellöf

Cognitive function in early Parkinson's disease: a population-based study

Background and purpose:  The study aims to describe the frequency, pattern and determinants of cognitive function in patients with newly diagnosed Parkinson’s disease (PD); to compare patients with impaired cognition to patients with intact cognition; and to compare to matched healthy controls.

The relation between cognition and motor dysfunction in drug-naive newly diagnosed patients with parkinson's disease

Recent studies have reported cognitive decline to be common in the early phase of Parkinsons disease. Imaging data connect working memory and executive functioning to the dopamine system. It has also been suggested that bradykinesia is the clinical manifestation most closely related to the nigrostriatal lesion. Exploring the relationship between motor dysfunction and cognition can help us find shared or overlapping systems serving different functions. This relationship has been sparsely investigated in population‐based studies of untreated Parkinsons disease. The aim of the present study was to investigate the association between motor signs and cognitive performance in the early stages of Parkinsons disease before the intake of dopaminergic medication. Patients were identified in a population‐based study of incident cases with idiopathic parkinsonism. Patients with the postural instability and gait disturbances phenotype were compared with patients with the tremor‐dominant phenotype on demographics and cognitive measures. Associations between cognitive and motor scores were investigated, with age, education, and sex controlled for. Bradykinesia was associated with working memory and mental flexibility, whereas axial signs were associated with episodic memory and visuospatial functioning. No significant differences in the neuropsychological variables were found between the postural instability and gait disturbances phenotype and the tremor phenotype. Our results indicate a shared system for slow movement and inflexible thinking that may be controlled by a dopaminergic network different from dopaminergic networks involved in tremor and/or rigidity. The association between axial signs and memory and visuospatial function may point to overlapping systems or pathologies related to these abilities.

Cognitive function in the early phase of Parkinson's disease, a five‐year follow‐up

Presence of mild cognitive impairment (MCI) as a predictor for Parkinsons disease dementia (PDD) has been discussed from a clinical perspective. Recently, a Movement Disorder Society (MDS) commissioned Task Force published guidelines for PD‐MCI. However, long‐term follow‐ups of the PD‐MCI guidelines for the prediction of PDD have been sparse.

Cerebrospinal Fluid Patterns and the Risk of Future Dementia in Early, Incident Parkinson Disease

IMPORTANCE Alterations in cerebrospinal fluid (CSF) have been found in Parkinson disease (PD) and in PD dementia (PDD), but the prognostic importance of such changes is not well known. In vivo biomarkers for disease processes in PD are important for future development of disease-modifying therapies. OBJECTIVE To assess the diagnostic and prognostic value of a panel of CSF biomarkers in patients with early PD and related disorders. DESIGN, SETTING, AND PARTICIPANTS Regional population-based, prospective cohort study of idiopathic parkinsonism that included patients diagnosed between January 1, 2004, and April 30, 2009, by a movement disorder team at a university hospital that represented the only neurology clinic in the region. Participants were 128 nondemented patients with new-onset parkinsonism (104 with PD, 11 with multiple system atrophy, and 13 with progressive supranuclear palsy) who were followed up for 5 to 9 years. At baseline, CSF from 30 healthy control participants was obtained for comparison. MAIN OUTCOMES AND MEASURES Cerebrospinal fluid concentrations of neurofilament light chain protein, Aβ1-42, total tau, phosphorylated tau, α-synuclein, and heart fatty acid-binding protein were quantified by 2 blinded measurements (at baseline and after 1 year). Follow-up included an extensive neuropsychological assessment. As PD outcome variables, mild cognitive impairment and incident PDD were diagnosed based on published criteria. RESULTS Among the 128 study participants, the 104 patients with early PD had a different CSF pattern compared with the 13 patients with progressive supranuclear palsy (baseline area under the receiver operating characteristic curve, 0.87; P < .0001) and the 30 control participants (baseline area under the receiver operating characteristic curve, 0.69; P = .0021). A CSF biomarker pattern associated with the development of PDD was observed. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid-binding protein at baseline were related to future PDD as analyzed by Cox proportional hazards regression models. Combined, these early biomarkers predicted PDD with high accuracy (hazard ratio, 11.8; 95% CI, 3.3-42.1; P = .0001) after adjusting for possible confounders. CONCLUSIONS AND RELEVANCE The analyzed CSF biomarkers have potential usefulness as a diagnostic tool in patients with parkinsonism. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid-binding protein were related to future PDD, providing new insights into the etiology of PDD.

Longitudinal changes in task-evoked brain responses in Parkinson's disease patients with and without mild cognitive impairment

Cognitive deficits are common in Parkinsons disease. Previous cross-sectional research has demonstrated a link between cognitive impairments and fronto-striatal dopaminergic dysmodulation. However, longitudinal studies that link disease progression with altered task-evoked brain activity are lacking. Therefore, our objective was to longitudinally evaluate working-memory related brain activity changes in Parkinsons disease patients with and without mild cognitive impairment (MCI). Patients were recruited within a longitudinal cohort study of incident patients with idiopathic parkinsonism. We longitudinally (at baseline examination and at 12-months follow-up) compared 28 patients with Parkinsons disease without MCI with 11 patients with Parkinsons disease and MCI. Functional MRI blood oxygen level dependent signal was measured during a verbal two-back working-memory task. Patients with MCI under-recruited bilateral medial prefrontal cortex at both time-points (main effect of group: p < 0.001, uncorrected). Critically, a significant group-by-time interaction effect (p < 0.001, uncorrected) was found in the right fusiform gyrus, indicating that working-memory related activity decreased for patients with Parkinsons disease and MCI between baseline and follow-up, while patients without MCI were stable across time-points. The functional connectivity between right fusiform gyrus and bilateral caudate nucleus was stronger for patients without MCI relative to patients with MCI. Our findings support the view that deficits in working-memory updating are related to persistent fronto-striatal under-recruitments in patients with early phase Parkinsons disease and MCI. The longitudinal evolution of MCI in Parkinsons disease translates into additional task-evoked posterior cortical changes.

Long Leukocyte Telomere Length at Diagnosis Is a Risk Factor for Dementia Progression in Idiopathic Parkinsonism

Telomere length (TL) is regarded as a marker of cellular aging due to the gradual shortening by each cell division, but is influenced by a number of factors including oxidative stress and inflammation. Parkinsons disease and atypical forms of parkinsonism occur mainly in the elderly, with oxidative stress and inflammation in afflicted cells. In this study the relationship between blood TL and prognosis of 168 patients with idiopathic parkinsonism (136 Parkinsons disease [PD], 17 Progressive Supranuclear Palsy [PSP], and 15 Multiple System Atrophy [MSA]) and 30 controls was investigated. TL and motor and cognitive performance were assessed at baseline (diagnosis) and repeatedly up to three to five years follow up. No difference in TL between controls and patients was shown at baseline, nor any significant difference in TL stability or attrition during follow up. Interestingly, a significant relationship between TL at diagnosis and cognitive phenotype at follow up in PD and PSP patients was found, with longer mean TL at diagnosis in patients that developed dementia within three years.

Olfactory Function, Eating Ability, and Visceral Obesity Associated with MMSE Three Years after Parkinson's Disease Diagnosis.

ObjectiveThis study examines whether risk factors for poor nutrition are associated with global cognitive function three years after confirmed Parkinson’s disease (PD) diagnosis.DesignThe follow-up investigations for this prospective community-based study were conducted three years after PD diagnosis.SettingThe study participants lived in Västerbotten County, a region in northern Sweden with 142,000 inhabitants.ParticipantsThis study population consisted of 118 PD outpatients from the study of Newly Diagnosed PD in Umeå (NYPUM).MeasurementsGlobal cognition was assessed with the Mini Mental State Examination (MMSE) at baseline and at follow-up. Anthropometry, nutrition (Mini Nutritional Assessment, MNA, 3-day food registration, 3-FDR), olfactory function (Brief Smell Identification Test, B-SIT), and swallowing, cutting food, and salivation (single questions from the Unified Parkinson’s Disease Rating Scale, UPDRS) were used as markers for nutritional status.ResultsThe MMSE score decreased over three years (–1.06±3.38, p=0.001). Olfactory function at baseline was associated to MMSE at three years (B=0.365, p=0.004). Changes in waist/hip ratio (B=113.29, p=0.017), swallowing (B=1.18, P=0.033), and cutting food (B=-1.80, p=0.000) were associated with MMSE at follow-up.ConclusionThis study indicates that olfactory function, cutting food, swallowing, and visceral obesity are associated with MMSE three years after PD diagnosis.

PITX3 genotype and risk of dementia in Parkinson's disease : A population-based study

Dementia is a devastating manifestation of Parkinsons disease (PD). This study investigates whether a common polymorphism in the PITX3 gene (rs2281983), which is of importance for the function of dopaminergic neurons, affects the risk of developing dementia in PD and whether it affects dopamine transporter (DAT) uptake. We PITX3 genotyped 133 patients with new-onset, idiopathic PD, participating in a population-based study in Sweden. Patients were followed prospectively during 6-11years with extensive investigations, including neuropsychology and DAT-imaging with 123I FP-CIT. The primary outcome was the incidence of PD dementia (PDD), diagnosed according to published criteria, studied by the Kaplan-Meier method and Cox proportional hazards. Performance in individual cognitive domains, the incidence of visual hallucinations, disease progression and striatal DAT uptake on imaging was also investigated. PD patients carrying the PITX3 C allele had an increased risk of developing PDD (hazard ratio: 2.87, 95% CI: 1.42-5.81, p=0.003), compared to the PD patients homozygous for the T-allele. Furthermore, the PITX3 C allele carriers with PD had a poorer cognitive performance in the visuospatial domain (p<0.001) and a higher incidence of visual hallucinations. A trend towards a lower striatal DAT uptake in the PITX3 C allele carriers was suggested, but could not be confirmed. Our results show that a common polymorphism in the PITX3 gene affects the risk of developing PDD and visuospatial dysfunction in idiopathic PD. If validated, these findings can provide new insights into the neurobiology and genetics of non-motor symptoms in PD.

A FRONTO-STRIATAL WORKOUT IN A PATIENT WITH PARKINSON DISEASE: IMPROVED WORKING-MEMORY UPDATING AND ACTIVITY INCREASES IN STRIATUM

balance performance in all four conditions. Conclusions: Impaired visual acuity leads to balance deficits through impaired EF in people with AD. Specifically, participants with poorer vision had poorer EF and participants with impaired EF had greater postural instability. In addition, the influence of EF on the relationship between visual acuity and postural instability was progressively larger as the challenge to the sensory systems increased.

Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease

Both polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinsons disease.