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Background and objective: We recently reported improvements of working memory across 10 years post stroke among middle-aged individuals. However, the mechanisms underlying working-memory recovery are largely unknown. This study investigated the associations between long-term improvement of working memory and resting-state functional connectivity in two frontoparietal networks: the frontoparietal network and the dorsal attention network.

Methods: Working memory was repeatedly assessed by the Digit Span Backwards task in 21 persons, within 1 year after stroke onset and again 10 years post stroke onset. Brain functional connectivity was examined by resting state functional magnetic resonance imaging at the 10-year follow-up.

Results: A significant improvement of working memory was found among 21 persons after stroke (median age = 64) at the 10-year follow-up compared to the within-one-year assessment. The magnitude of performance improvement on the Digit Span Backwards task was significantly positively correlated with stronger brain connectivity in the frontoparietal network (r = 0.51, p = 0.018) measured at the 10-year follow-up only. A similar association was observed in the dorsal attention network (r = 0.43, p = 0.052) but not in a visual network (r = -0.17, p = 0.46) that served as a control network. The association between functional connectivity within the above-mentioned networks and Digit Span Backwards scores at 10-year after stroke was in the same direction but did not reach significance.

Conclusions: The present work relate stronger long-term performance improvement on the Digit Span Backwards task with higher integrity of frontoparietal network connectivity.

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. 

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: 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 broad time window for rehabilitation and information about fatigue. The clinical implications of the current findings are worth to be studied further.

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 following their first stroke. This finding fills a gap of knowledge with respect to the dynamic trajectory of post-stroke cognition, with important implications in clinical practice.

Introduction

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

Methods

Four hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis.

Results

A total of 12.0% of patients with Parkinson's disease carried a GBA variant, and nearly half (22/53) of them progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers.

Discussion

GBA variants are of great clinical relevance for the development of dementia in Parkinson's disease, especially due to the relatively higher frequency of these alleles compared with other risk alleles.

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.