Eva Elgh

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.

Cognitive Dysfunction, Hippocampal Atrophy and Glucocorticoid Feedback in Alzheimer’s Disease

BACKGROUND The hippocampal formation is damaged early in Alzheimers disease (AD). An association between temporal lobe volume and cognitive function has been shown in several studies. Increased limbic-hypothalamic-pituitary-adrenal (LHPA) axis function has been suggested to be related to hippocampal atrophy and cognitive impairment. Our hypothesis was that there is a clear link between hippocampal volume -- notably of the CA1 region -- memory (episodic and visuospatial) and decreased feedback sensitivity in the LHPA axis in AD. METHODS Sixteen medication-free outpatients with mild to moderate AD were included. Hippocampal volume was measured with magnetic resonance imaging. Dexamethasone suppression tests were performed using .5 mg and .25 mg dexamethasone. Three different components in the neuropsychological battery -- Rey 15 item memory test, Alzheimers Disease Assessment Scale (ADAS) word recall and spatial span from Wechsler Adult Intelligence Scale - Revised neuropsychological instrument (WAIS-R NI) -- were found to represent episodic and visuospatial memory. RESULTS Low hippocampal CA1 volume and high post-dexamethasone cortisol levels in combination were significantly associated with Rey 15 item memory and spatial span test outcomes. No association was found between LHPA feedback and hippocampal volume. CONCLUSIONS Low hippocampal volume and a disturbed negative feedback in the LHPA axis link to specific cognitive impairments in Alzheimers disease.

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.

Temporal dynamics of basal ganglia under-recruitment in Parkinson's disease: transient caudate abnormalities during updating of working memory

Using hybrid-blocked/event-related fMRI and the 2-back task we aimed to decompose tonic and phasic temporal dynamics of basal ganglia response abnormalities in working memory associated with early untreated Parkinsons disease. In view of the tonic/phasic dopamine hypothesis, which posits a functional division between phasic D(2)-dependent striatal updating processes and tonic D(1)-dependent prefrontal context-maintenance processes, we predicted that newly diagnosed, drug-naïve Parkinsons disease patients, with selective striatal dopamine deprivation, would demonstrate transient rather than sustained activation changes in the basal ganglia during 2-back performance. Task-related activation patterns within discrete basal ganglia structures were directly compared between patients and healthy elderly controls. The obtained results yielded uniquely transient underactivation foci in caudate nuclei, putamen and globus pallidus in Parkinsons disease patients, which indicates suboptimal phasic implementation of striatal D(2)-dependent gating mechanisms during updating. Sustained underactivation was only seen in the anterior putamen, which may reflect initial signs of tonic control impairment. No significant changes were exhibited in prefrontal cortex. The present findings resonate well with the tonic/phasic dopamine account and suggest that basal ganglia under-recruitment associated with executive dysfunction in early Parkinsons disease might predominantly stem from deficiencies in phasic executive components subserved by striatum.

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.

Altered Prefrontal Brain Activity in Persons at Risk for Alzheimer's Disease: An fMRI Study

BACKGROUND Early diagnosis of Alzheimers disease (AD) is critical for adequate treatment and care. Recently it has been shown that functional magnetic resonance imaging (fMRI) can be important in preclinical detection of AD. The purpose of this study was to examine possible differences in memory-related brain activation between persons with high versus low risk for AD. This was achieved by combining a validated neurocognitive screening battery (the 7-minutes test) with memory assessment and fMRI. METHODS One hundred two healthy community-living persons with subjective memory complaints were recruited through advertisement and tested with the 7-minutes test. Based on their test performance they were classified as having either high (n = 8) or low risk (n = 94) for AD. Six high-risk individuals and six age-, sex-, and education-matched low-risk individuals were investigated with fMRI while engaged in episodic memory tasks. RESULTS The high-risk individuals performed worse than low-risk individuals on tests of episodic memory. Patterns of brain activity during episodic encoding and retrieval showed significant group differences (p < .05 corrected). During both encoding and retrieval, the low-risk persons showed increased activity relative to a baseline condition in prefrontal brain regions that previously have been implicated in episodic memory. By contrast, the high-risk persons did not significantly activate any prefrontal regions, but instead showed increased activity in visual occipito-temporal regions. CONCLUSION Patterns of prefrontal brain activity related to episodic memory differ between persons with high versus low risk for AD, and lowered prefrontal activity may predict subsequent disease.

One-year follow-up of mild traumatic brain injury : cognition, disability and life satisfaction of patients seeking consultation.

OBJECTIVE To investigate cognitive function, symptoms, disabilities and life satisfaction of patients with mild traumatic brain injury who accepted consultation one year post-trauma. DESIGN Prospective study. PATIENTS Sixty-nine patients (16 accepted the consultation offered, 53 declined). METHODS At follow-up, the patients answered questionnaires about symptoms, disabilities (RHFUQ) and life satisfaction (LiSat-11). The patients who underwent consultation and their healthy control subjects were administered a neuropsychological evaluation. RESULTS In the group undergoing consultation, the number of cognitive tests with outcomes below cut-off limits (-1.5 SD) was statistically significantly higher compared with a control group (21 tests in 11 patients vs 8 tests in 7 control subjects; p=0.025). The number of patients with one or more disability was statistically significantly higher among patients with consultation than without (94% and 34%, respectively; p<0.001). Total RHFUQ score was statistically significantly higher for the group with consultation than without (5.9 +/- 3.7 and 1.1 +/- 2.3, respectively, p<0.001). The group with consultation exhibited a lower level of life satisfaction (41.5 +/- 10.4 vs 45.8 +/- 13.8 for the non-consulting group; p=0.057). CONCLUSION The high frequency of occurrence of disabilities and lower cognitive functioning, together with the lower level of life satisfaction, appear to characterize patients choosing consultation 1 year post-injury. This highlights the importance of offering consultation for persons suffering mild head injuries.

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.

Effects of interactivity and 3D-motion on mental rotation brain activity in an immersive virtual environment

The combination of virtual reality (VR) and brain measurements is a promising development of HCI, but the maturation of this paradigm requires more knowledge about how brain activity is influenced by parameters of VR applications. To this end we investigate the influence of two prominent VR parameters, 3d-motion and interactivity, while brain activity is measured for a mental rotation task, using functional MRI (fMRI). A mental rotation network of brain areas is identified, matching previous results. The addition of interactivity increases the activation in core areas of this network, with more profound effects in frontal and preparatory motor areas. The increases from 3d-motion are restricted to primarily visual areas. We relate these effects to emerging theories of cognition and potential applications for brain-computer interfaces (BCIs). Our results demonstrate one way to provoke increased activity in task-relevant areas, making it easier to detect and use for adaptation and development of HCI.

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.