Search

Background: We have recently demonstrated significant general cognitive recovery with delayed improvement of working memory 10 years after stroke in a unique longitudinal cohort.Aim: This study investigated demographic and clinical characteristics relevant to improved cognitive functions 10-year after a first-ever stroke. Materials and Methods: A prospective longitudinal cohort study was carried out in 38 middle-aged (mean age =54 at stroke onset) stroke survivors. Cognition was assessed thrice at one week, seven months, and ten years after the stroke. Working memory and visuospatial function were assessed with the Digit Span and Block Design subtests, respectively. General cognition was evaluated with the Mini-Mental State Examination at the two later time points. Multivariate linear regression was used to identify the variables that may significantly predict improved cognitive functions at 10-year follow-up. Results: We found that having a full-time job prior to the stroke, suffering an ischemic (as opposed to a hemorrhagic) stroke, and having a university education predicted significantly superior general cognitive function 10 years after stroke (R2 of 0.77, p <0.001), while working memory and visuospatial function at 1 week after stroke significantly predicted their respective functions at 10-year follow-up (R2 of 0.41, p = 0.003). Conclusions: Our results indicate that premorbid employment status and higher education as well as having suffered from an ischemic rather than a hemorrhagic stroke might predict superior cognitive recovery among middle-aged individuals 10 years after stroke.

Aim: This study aimed to investigate executive functioning (EF) among patients 10 years after stroke onset through comparing subjective patients’ and informants’ perceptions as well as objective neuropsychological assessments (NPAs). Materials and Method: One month prior to the neuropsychological assessment, 36 patients and their informants completed the Behaviour Rating Inventory of Executive Function - Adult Version (Brief-A) around 10 years after stroke onset. The patients’ EF was assessed with verbal fluency (FAS), backward Digit span backward and Trail making test (TMT)-B. Results: We found no significant differences between patient and informant ratings on EF on a group level, but more patients reported clinically significant executive dysfunctions (T > 65) than their informants. Only poor to slight agreements were observed between the patient and informant ratings of the BRIEF-A. Digit span backward was the only executive test that demonstrated significant improvement of EF 10 years post-stroke in the cohort. Neither patient nor informant ratings on EF showed any significant association with objective EF test performance. Conclusions: Mismatch patient-informant agreement on perceived executive dysfunction showed no clear association with EF test performance in this study. This may indicate the complexity of EF among persons with stroke at chronic phase.

Background and Objective: Fatigue is common among stroke survivors; and has significant negative consequences. However, long-term follow-up on post-stroke fatigue and it's association with cognitive and physiological parameters remains vague. Methods: A prospective cohort study was carried out on 38 young stroke survivors (aged 18–65 at stroke onset) living in the community 10 years after first-ever stroke. Fatigue was assessed by Fatigue assessment scale (FAS). Global cognition and cognitive sub-domains were assessed repeatedly at 1 week, 7 months, and 10 years after their first-ever stroke. Univariate correlation analysis was used to investigate associations and multivariate regression was used to investigate predictors and association with fatigue. Results: At 10-years follow-up after stroke onset, more than half of the 38 participants suffered from fatigue [with median score 25 on FAS with 25–75% percentile (21–28)]. Most of them were independent in their everyday life [mRS median score 1 (0–2)]. In univariate correlation analyses, higher fatigue score was significantly correlated to higher independence in the daily activity, higher BMI, anxiety, higher scores on global cognition and better working memory at 10-years follow-up as well as better visuospatial functions after 7 months and 10-years. In a multiple regression analysis, only visuospatial function at 7-months follow-up was a significant predictor of fatigue 10 years after stroke onset [F = 23.07, p < 0.009], with adjusted (R2 = 0.815) i.e., higher scores on Block design were associated with more fatigue. Conclusion: Our results extended the time course of post-stroke fatigue up to 10 years after stroke onset. The participants with more fatigue performed better in cognitive assessments and daily activity, which indicated dissociation between fatigue and fatigability among stroke patients. Visuospatial function at the sub-acute phase predicted independently late post-stroke fatigue. This may offer a br

OBJECTIVE The Computerized General Neuropsychological INPH Test (CoGNIT) provides the clinician and the researcher with standardized and accessible cognitive assessments in patients with idiopathic normal pressure hydrocephalus (INPH). CoGNIT includes tests of memory, executive functions, attention, manual dexterity, and psychomotor speed. Investigations of the validity and reliability of CoGNIT have been published previously. The aim of this study was to evaluate CoGNIT's sensitivity to cognitive change after shunt surgery in patients with INPH. METHODS Forty-one patients with INPH (median Mini-Mental State Examination score 26) were given CoGNIT preoperatively and at a postoperative follow-up 4 months after shunt surgery. Scores were compared to those of 44 healthy elderly control volunteers. CoGNIT was administered by either a nurse or an occupational therapist. RESULTS Improvement after shunt surgery was seen in all cognitive domains: memory (10-word list test, p < 0.01); executive functions (Stroop incongruent color and word test, p < 0.01); attention (2-choice reaction test, p < 0.01); psychomotor speed (Stroop congruent color and word test, p < 0.01); and manual dexterity (4-finger tapping, p < 0.01). No improvement was seen in the Mini-Mental State Examination score. Preoperative INPH test scores were significantly impaired compared to healthy control subjects (p < 0.001 for all tests). CONCLUSIONS In this study the feasibility for CoGNIT to detect a preoperative impairment and postoperative improvement in INPH was demonstrated. CoGNIT has the potential to become a valuable tool in clinical and research work.

Background and objective: The trajectories of long-term and domain-specific cognitive alterations over a decade after stroke are largely unknown. This study aims to investigate the dynamic alterations of domain-specific cognitive performance among young stroke survivors over 10 years after their first stroke. Methods: A prospective cohort study was carried out on 38 young stroke survivors (aged 18-65 at stroke onset) living in the community at 10 years after their first stroke. The cognitive outcomes were assessed repeatedly at 1 week, 7 months, and 10 years after their first stroke on the sub-domains: process speed (Symbol search and Coding from WAIS, TMT-A), visual attention (Bells test), visuospatial function (Block design from WAIS, RCFT), executive function (TMT-B, verbal fluency), verbal function [Letter fluency (FAS) from D-KEFS and CD], working memory (Digit Span from WAIS), immediate memory (RCFT and CD), and delayed memory (RCFT and CD). Global cognition was evaluated with Mini mental state examination at the two later time-points. Results: We found a delayed significant improvement of working memory with total recovery 10 years after participants' stroke. Visuospatial function recovered already at 7 months and remained stable at 10-year follow-up. Process speed demonstrated a significant decrease at 10 years compared to 7 months after stroke onset, a decrease which could be compensated by enhancements of other cognitive domains. No further deterioration was found in verbal function, immediate-, and delayed memory, and executive function during 10-year follow-up. Global cognition improved by on average two points between 7 months and 10 years. Education level and fatigue showed low to moderate positive correlations with cognitive improvements. Conclusions: The concordance of cognitive improvements between domain-specific and global cognitions strongly suggest that some young stroke survivors do improve their cognitive outcome over a 10-year period followin

Objectives: Cognitive decline is common in Parkinson's disease (PD), but the underlying mechanisms for this complication are incompletely understood. Genotypes affecting dopamine transmission may be of importance. This study investigates whether genotypes associated with reduced prefrontal dopaminergic tone and/or reduced dopamine D2-receptor availability (Catechol-O-methyltransferase [COMT] Val(158)Met genotype and DRD2 (CT)-T-957 genotype) affect the development of cognitive deficits in PD. Materials and methods: One hundred and 34 patients with idiopathic PD, participating in a regional, population-based study of incident parkinsonism, underwent genotyping. After extensive baseline investigations (including imaging and biomarker analyses), the patients were followed prospectively during 6-10 years with neuropsychological evaluations, covering six cognitive domains. Cognitive decline (defined as the incidence of either Parkinson's disease mild cognitive impairment [PD-MCI] or dementia [PDD], diagnosed according to published criteria and blinded to genotype) was studied as the primary outcome. Results: Both genotypes affected cognition, as shown by Cox proportional hazards models. While the COMT(158)Val/Val genotype conferred an increased risk of mild cognitive impairment in patients with normal cognition at baseline (hazard ratio: 2.13, P=.023), the DRD2(957)T/T genotype conferred an overall increased risk of PD dementia (hazard ratio: 3.22, P<.001). The poorer cognitive performance in DRD2(957)T/T carriers with PD occurred mainly in episodic memory and attention. Conclusions: The results favor the hypothesis that dopamine deficiency in PD not only relate to mild cognitive deficits in frontostriatal functions, but also to a decline in memory and attention. This could indicate that dopamine deficiency impairs a wide network of brain areas.

Dementia is a devastating manifestation of Parkinson's 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 6-11 years with extensive investigations, including neuropsychology and DAT-imaging with I-123 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.

BACKGROUND: Presence of mild cognitive impairment (MCI) as a predictor for Parkinson's 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. METHOD: In a community-based cohort of PD, the MDS guidelines for PD-MCI and consensus criteria for PDD were applied on 147 subjects. The predictive ability of PD-MCI for PDD was investigated. Additionally, baseline comparisons were conducted between MCI that converted to PDD and those who did not, and evolvement of motor function was investigated. RESULTS: One fourth of the population developed PDD. MCI and age at baseline predicted later occurrence of PDD, and baseline results of tests measuring episodic memory, visuospatial function, semantic fluency, and mental flexibility differed between MCI converters and non-converters. Postural instability/gait (PIGD) phenotype and education did not predict later occurrence of PDD, but increased postural/gait disturbances were shown across time in those developing dementia. CONCLUSION: The new PD-MCI guidelines are useful to detect patients at risk for developing PDD. The PIGD phenotype at diagnosis was not a predictor of PDD within 5 years, but the study supports a temporal association between postural/gait disturbances and PDD. Older patients with PD-MCI at baseline with decline in episodic memory, semantic fluency, and mental flexibility need to be carefully monitored regarding cognition and likely also for fall risk.

BACKGROUND: A tool for standardized and repeated neuropsychological assessments in patients with idiopathic normal pressure hydrocephalus (INPH) is needed. The objective of this study was to develop a computerized neuropsychological test battery designed for INPH and to evaluate its reliability, validity and patient's ability to complete the tests. METHODS: Based on a structured review of the literature on neuropsychological testing in INPH, the eight tests most sensitive to the INPH cognitive profile were implemented in a computerized format. The Geriatric Depression Scale (GDS) was also included. Tests were presented on a touch-screen monitor, with animated instructions and speaker sound. The battery was evaluated with the following cohorts: A. Test-retest reliability, 44 healthy elderly; B. Validity against standard pen and pencil testing, 28 patients with various cognitive impairments; C. Ability to complete test battery, defined as completion of at least seven of the eight tests, 40 investigated for INPH. RESULTS: A. All except the figure copy test showed good test-retest reliability, r = 0.67-0.90; B. A high correlation was seen between conventional and computerized tests (r = 0.66-0.85) except for delayed recognition and figure copy task; C. Seventy-eight percent completed the computerized battery; Patients diagnosed with INPH (n = 26) performed worse on all tests, including depression score, compared to healthy controls. CONCLUSIONS: A new computerized neuropsychological test battery designed for patients with communicating hydrocephalus and INPH was introduced. Its reliability, validity for general cognitive impairment and completion rate for INPH was promising. After exclusion of the figure copy task, the battery is ready for clinical evaluation and as a next step we suggest validation for INPH and a comparison before and after shunt surgery. TRIAL REGISTRATION: ClinicalTrials.org NCT01265251.

Cognitive deficits are common in Parkinson's 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 Parkinson's 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 Parkinson's disease without MCI with 11 patients with Parkinson's 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 Parkinson's 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 Parkinson's disease and MCI. The longitudinal evolution of MCI in Parkinson's disease translates into additional task-evoked posterior cortical changes.

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. Parkinson's 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 Parkinson's 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.

The relation between cognitive and motor functions in Parkinson's disease is not fully understood. In an incidence population of newly diagnosed drug na < ve patients with Parkinson's disease, associations were found between the degree of bradykinesia and postural instability and gait disturbances, measured by the Unified Disease Rating Scale, and different types of cognitive functions. To investigate the stability of these associations over time, we explored the association of differences between baseline and 1-year follow-up in 91 incident cases with Parkinson's disease. The magnitude of change between the two assessments was assessed together with analysis of differences based on which dopaminergic medication was used. Change in bradykinesia was associated with change in working memory and mental flexibility. Changes in postural instability and gait disturbances were associated with change in visuospatial memory. A negative effect of the dopamine agonist pramipexole on phonemic fluency performance was found compared to treatment with other dopaminergic drugs. Change in cognitive and motor functions were associated from time of diagnosis until 1 year after diagnosis. These persisting findings strengthen results from a previous cross-sectional study suggesting similar associations. The effects of dopamine agonists on phonemic fluency should be investigated further.

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.

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. METHODS: Patients were identified in a longitudinal population based study of idiopathic non-drug induced parkinsonism. Eighty-eight newly diagnosed patients with PD and no dementia were included during a four year period. The patients and 30 age- and sex-matched healthy control subjects underwent a comprehensive neuropsychological assessment. RESULTS: Patients performed significantly worse than healthy controls in a majority of neuropsychological tests. Test results in attention, psychomotor function, episodic memory (free recall), executive function and category fluency were significantly lower in the patient group. Comparison with normative data revealed that 30% of the patients had deficits in > or =1 cognitive domain (episodic memory, executive function and verbal function). Seventy per cent of the patients had normal performance. Unified Parkinson's Disease Rating Scale (UPDRS) III sub scores; speech, facial expression, rigidity and bradykinesia were significantly higher, and disease duration shorter amongst the cognitively impaired than amongst the cognitively intact patients. Tremor showed no difference. Education level was an independent predictor of dysfunction in patients with > or =2 cognitive domains affected. CONCLUSION: Cognitive dysfunction is common in untreated patients in early PD, affecting attention, psychomotor function, episodic memory, executive function and category fluency. Education level was an independent predictor of severe cognitive dysfunction.

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.

BACKGROUND: The hippocampal formation is damaged early in Alzheimer's 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, Alzheimer's 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 Alzheimer's disease.

BACKGROUND: Early diagnosis of Alzheimer's 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.

NYPUM

Background We have developed the COmputerized General Neuropsychological INPH Test (CoGNIT) dedicated for patients with idiopathic normal pressure hydrocephalus (INPH). Previously, validity and reliability of included tests have been established. The aim was to evaluate the battery’s sensitivity to detect cognitive changes after shunt surgery in INPH patients. Methods Preoperatively, thirty-one INPH patients were given CoGNIT, which includes tests assessing memory, executive functions, attention, manual dexterity and psychomotor speed. CoGNIT also includes the Geriatric Depression Scale (GDS). Re-examination was done four months after shunt surgery. Scores and test completion were examined and compared to healthy elderly (n=44). Results Preoperative INPH test results were significantly lower in all tests compared to healthy. Improvements after shunt surgery were seen in all cognitive domains: memory (Ten-word list test, p<0,01), executive functions (Stroop incongruent, (p<0.05), attention (Two choice reaction test, p<0.01), psychomotor speed (Stroop congruent, p<0.05) and manual dexterity (Four- finger tapping, p<0.01). No ceiling effects were observed. Depressive symptoms were more common in INPH versus healthy and did not change postoperatively. Preoperatively 81 % of INPH patients completed at least eight of the nine included test. Conclusions CoGNIT is sensitive to cognitive impairment and to investigate changes after shunt surgery in INPH. Completion rates are good. CoGNIT has a potential to be useful in the cognitive assessment of INPH.

NYPUM