Background The prevalence of neurodegenerative diseases increases significantly with increasing age. Neurodegeneration is the progressive loss of function of neurons that eventually leads to cell... Show moreBackground The prevalence of neurodegenerative diseases increases significantly with increasing age. Neurodegeneration is the progressive loss of function of neurons that eventually leads to cell death, which in turn leads to cognitive disfunction. Cognitive performance can therefore also be considered age dependent. The current study investigated if the NeuroCart can detect age related decline on drug-sensitive CNS-tests in healthy volunteers (HV), and whether there are interactions between the rates of decline and sex. This study also investigated if the NeuroCart was able to differentiate disease profiles of neurodegenerative diseases, compared to age-matched HV and if there is age related decline in patient groups. Methods This retrospective study encompassed 93 studies, performed at CHDR between 2005 and 2020 that included NeuroCart measurements, which resulted in data from 2729 subjects. Five NeuroCart tests were included in this analysis: smooth and saccadic eye movements, body sway, adaptive tracking, VVLT and N-back. Data from 84 healthy male and female volunteer studies, aged 16-90, were included. Nine studies were performed in patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) or vascular dementia (VaD). The data were analyzed with regression analyses on age by group, sex, sex by age, group by sex and group by sex by age. Least square means (LSMs) and 95% confidence intervals (CIs) were calculated for each group at the average age of the group, and at the average age of each of the other groups, and per sex. Results Mean age and standard deviation (SD) for all groups was: HV 36.2 years (19.3), AD 68.3 years (8), PD 62.7 years (8.5), HD 51.4 years (9.8) and VaD 66.9 years (8.1). Performance on all NeuroCart tests decreased significantly each year in HV. Saccadic peak velocity (SPV) was increased in AD compared to age-matched HV (+26.28 degrees/s, p =0.007), while SPV was decreased for PD and HD compared to age-matched HV (PD: -15.87 degrees/s, p=0.038, HD: -22.52 degrees/s, p=0.018). In HD patients SPV decreased faster with age compared to HV. On saccadic peak velocity the slopes between HD vs HV were significantly different, indicating a faster decline in performance on this task for HD patients compared to HV per age year. Smooth pursuit showed an overall significant difference between subject groups (p=0.037. Significantly worse performance was found for AD (-12.87%, p=<0.001), PD (-4.45%, p=<0.001) and VaD (-5.69%, p=0.005) compared to age-matched HV. Body sway significantly increased with age (p=0.021). Postural stability was decreased for both PD and HD compared to age-matched HV (PD: +38.8%, p=<0.001, HD: 154.9%, p=<0.001). The adaptive tracking was significantly decreased with age (p=<0.001). Adaptive tracking performance by AD (-7.54%, p=<0.001), PD (-8.09%, p=<0.001), HD (-5.19%, p=<0.001) and VaD (-5.80%, p=<0.001) was decreased compared to age-matched HV. Adaptive tracking in PD patients vs HV and in PD vs HD patients was significantly different, indicating a faster decline on this task per age year for PD patients compared to HV and HD. The VVLT delayed word recall showed an overall significant effect of subject group (p=0.006. Correct delayed word recall was decreased for AD (-5.83 words, p=<0.001), HD (-3.40 words, p=<0.001) and VaD (-5.51 words, p=<0.001) compared to age-matched HV. Conclusion This study showed that the NeuroCart can detect age-related decreases in performance in HV, which were not affected by sex. The NeuroCart was able to detect significant differences in performance between AD, PD, HD, VaD and age-matched HV. Disease durations were unknown, therefore this cross-sectional study was not able to show age-related decline after disease onset. This article shows the importance of investigating age-related decline on digitalized neurocognitive test batteries. Performance declines with age, which emphasizes the need to correct for age when including HV in clinical trials. Patients with different neurogenerative diseases have distinct performance patterns on the NeuroCart , which this should be considered when performing NeuroCart tasks in patients with AD, PD, HD and VaD. Show less
Hiele, K. van der; Gorp, D.A.M. van; Egmond, E.E.A. van; Jongen, P.J.; Reneman, M.F.; Klink, J.J.L. van der; ... ; Visser, L.H. 2021
Background: Multiple sclerosis (MS) poses a major threat to sustainable employability. Identifying conditions and factors that promote work participation is of great importance. Our objective was... Show moreBackground: Multiple sclerosis (MS) poses a major threat to sustainable employability. Identifying conditions and factors that promote work participation is of great importance. Our objective was to explore the contribution of personality traits in explaining occupational functioning in MS. Methods: 241 participants with relapsing-remitting MS (78% female, median age: 42.0 years, median EDSS: 2.0) and 60 healthy controls (70% female, median age: 45.0 years) underwent neuropsychological and neurological examinations and completed questionnaires. Multivariate logistic and linear regression analyses were conducted to examine relations between personality traits and self-reported occupational functioning, while accounting for known correlates. Results: Personality traits were not associated with self-reported occupational functioning when correcting for known correlates. A higher impact of fatigue (B = -0.05, p = .005 and B = -0.04, p = .009) and depression (B = -0.22, p = .008 and B = -0.21, p = .01) were associated with no paid job (R2 = 0.13) and considering to reduce work hours (R2 = 0.12). A higher impact of fatigue (B = -0.05, p = .008, beta = 0.46, p = .001 and beta = -0.36, p = .001) was associated with absenteeism from work (R2 = 0.15), more presenteeism (R2 = 0.35) and lower work ability (R2 = 0.25). A higher impact of fatigue (beta = 0.46, p = .001) and anxiety (beta = 0.25, p = .001) were associated with more work difficulties (R2 = 0.54). Conclusion: Personality traits did not explain additional variance in self-reported occupational functioning in persons with relapsing-remitting MS with mild disability. The impact of fatigue was the main and most consistent correlate of occupational functioning, often combined with depression or anxiety. Total explained variance of the Show less
Hiele, K. van der; Gorp, D.A.M. van; Egmond, E.E.A. van; Jongen, P.J.; Reneman, M.F.; Van der Klink, J.; ... ; Visser, L.H. 2021
Background: In management decisions on saccular unruptured intracranial aneurysms (UIAs) the risk of rupture is an important factor. The PHASES score, introduced in 2014, provides absolute 5-year... Show moreBackground: In management decisions on saccular unruptured intracranial aneurysms (UIAs) the risk of rupture is an important factor. The PHASES score, introduced in 2014, provides absolute 5-year risks of rupture based on six easily retrievable patient and aneurysm characteristics. We assessed whether management decisions on UIAs changed after implementation of the PHASES score. Patient and methods: We included all patients with UIAs who were referred to two Dutch tertiary referral centers for aneurysm care in the Netherlands (University Medical Center Utrecht (UMCU) and Leiden University Medical Center (LUMC)) between 2011 and 2017. Analyses were done on an aneurysm level. We calculated the overall proportion of UIAs with a decision to treat before and after PHASES implementation and studied the influence of age and center on post-implementation management changes. Results: We included 623 patients with 803 UIAs. The proportion of UIAs with a decision to treat was 123/360 (34.2%) before and 117/443 (26.4%) after PHASES implementation (absolute risk difference:-7.8%; 95% CI: -14.1 to-1.4). The decision to treat was made at a higher median PHASES score after implementation (7 points (IQR 5;10) pre-versus 8 points (IQR 5;10) post-implementation; p = 0.14). The reduced proportion with a treatment decision after implementation was most pronounced in patients <50 years (-22.3%; 95% CI:-39.2 to -3.4) and was restricted to treatment decisions made at the UMCU (-10.6%; 95% CI:-18.5 to-2.5). Discussion and conclusions: Management of UIAs changed following implementation of the PHASES score, but the impact of PHASES implementation on treatment decisions differed across age subgroups and centers. Show less
Zielonka, D.; Ren, M.; Roos, R.A.C.; Michele, G. de; Marcinkowski, J.T.; Squitieri, F.; ... ; Landwehrmeyer, G.B. 2017
Huntington's disease (HD) is characterized by brain atrophy. Localized atrophy of a specific structure could potentially be a more sensitive biomarker reflecting neuropathologic changes rather than... Show moreHuntington's disease (HD) is characterized by brain atrophy. Localized atrophy of a specific structure could potentially be a more sensitive biomarker reflecting neuropathologic changes rather than global volume variation. We examined 90 TRACK-HD participants of which 30 were premanifest HD, 30 were manifest HD and 30 were controls. Using FMRIB's Integrated Registration and Segmentation Tool, segmentations were obtained for the pallidum, caudate nucleus, putamen, thalamus, accumbens nucleus, amygdala, and hippocampus and overall volumes were calculated. A point distribution model of each structure was obtained using Growing and Adaptive Meshes. Permutation testing between groups was performed to detect local displacement in shape between groups. In premanifest HD overall volume loss occurred in the putamen, accumbens and caudate nucleus. Overall volume reductions in manifest HD were found in all subcortical structures, except the amygdala, as compared to controls. In premanifest HD shape analysis showed small areas of displacement in the putamen, pallidum, accumbens and caudate nucleus. When the premanifest group was split into two groups according to predicted disease onset, the premanifest HD group close to expected disease onset showed more pronounced displacements in caudate nucleus and putamen compared to premanifest HD far from disease onset or the total premanifest group. Analysis of shape in manifest HD showed widespread shape differences, most prominently in the caudal part of the accumbens nucleus, body of the caudate nucleus, putamen and dorsal part of the pallidum. We conclude that shape analysis provides new insights in localized intrastructural atrophy patterns in HD, but can also potentially serve as specific target areas for disease tracking. (C) 2011 Elsevier B.V. All rights reserved. Show less
