Although iron-mediated oxidative stress has been proposed as a potential pathomechanism in Parkinson's disease, the global distribution of iron accumulation in Parkinson's disease has not yet been ...elucidated. This study used a new magnetic resonance imaging contrast, quantitative susceptibility mapping, and state-of-the-art methods to map for the first time the whole-brain landscape of magnetostatic alterations as a surrogate for iron level changes in n = 25 patients with idiopathic Parkinson's disease versus n = 50 matched controls. In addition to whole-brain analysis, a regional study including sub-segmentation of the substantia nigra into dorsal and ventral regions and qualitative assessment of susceptibility maps in single subjects were also performed. The most remarkable basal ganglia effect was an apparent magnetic susceptibility increase-consistent with iron deposition-in the dorsal substantia nigra, though an effect was also observed in ventral regions. Increased bulk susceptibility, additionally, was detected in rostral pontine areas and in a cortical pattern tightly concordant with known Parkinson's disease distributions of α-synuclein pathology. In contrast, the normally iron-rich cerebellar dentate nucleus returned a susceptibility reduction suggesting decreased iron content. These results are in agreement with previous post-mortem studies in which iron content was evaluated in specific regions of interest; however, extensive neocortical and cerebellar changes constitute a far more complex pattern of iron dysregulation than was anticipated. Such findings also stand in stark contrast to the lack of statistically significant group change using conventional magnetic resonance imaging methods namely voxel-based morphometry, cortical thickness analysis, subcortical volumetry and tract-based diffusion tensor analysis; confirming the potential of whole-brain quantitative susceptibility mapping as an in vivo biomarker in Parkinson's disease.
We describe one of the first cases of a Posterior reversible encephalopathy syndrome (PRES) under tocilizumab as treatment of Giant cell arteritis (GCA).
A 65-year-old female with known GCA and ...treatment with Tocilizumab (TCZ) developed a convulsive epileptic seizure for the first time. MRI was suggestive of PRES and an associated left sided occipital hemorrhage. Extensive high blood pressure values were not detected. The patient recovered within a week and no further seizures occurred under anticonvulsive medication.
PRES during the treatment with Tocilizumab hasn't been described in GCA so far. There are single reports of an association between TCZ and PRES in other entities. Thus, a link between interleukin-6 and the integrity of the vasculature could be considered. The clinical consequence should be a stringent blood pressure monitoring in the ambulant setting of patients receiving TCZ.
Several lifestyle factors promote protection against Alzheimer's disease (AD) throughout a person's lifespan. Although such protective effects have been described for occupational cognitive ...requirements (OCR) in midlife, it is currently unknown whether they are conveyed by brain maintenance (BM), brain reserve (BR), or cognitive reserve (CR) or a combination of them.
We systematically derived hypotheses for these resilience concepts and tested them in the population-based AgeCoDe cohort and memory clinic-based AD high-risk DELCODE study. The OCR score (OCRS) was measured using job activities based on the O*NET occupational classification system. Four sets of analyses were conducted: (1) the interaction of OCR and APOE-ε4 with regard to cognitive decline (N = 2,369, AgeCoDe), (2) association with differentially shaped retrospective trajectories before the onset of dementia of the Alzheimer's type (DAT; N = 474, AgeCoDe), (3) cross-sectional interaction of the OCR and cerebrospinal fluid (CSF) AD biomarkers and brain structural measures regarding memory function (N = 873, DELCODE), and (4) cross-sectional and longitudinal association of OCR with CSF AD biomarkers and brain structural measures (N = 873, DELCODE).
Regarding (1), higher OCRS was associated with a reduced association of APOE-ε4 with cognitive decline (mean follow-up = 6.03 years), consistent with CR and BR. Regarding (2), high OCRS was associated with a later onset but subsequently stronger cognitive decline in individuals converting to DAT, consistent with CR. Regarding (3), higher OCRS was associated with a weaker association of the CSF Aβ42/40 ratio and hippocampal volume with memory function, consistent with CR. Regarding (4), OCR was not associated with the levels or changes in CSF AD biomarkers (mean follow-up = 2.61 years). We found a cross-sectional, age-independent association of OCRS with some MRI markers, but no association with 1-year-change. OCR was not associated with the intracranial volume. These results are not completely consistent with those of BR or BM.
Our results support the link between OCR and CR. Promoting and seeking complex and stimulating work conditions in midlife could therefore contribute to increased resistance to pathologies in old age and might complement prevention measures aimed at reducing pathology.
Background
Sustained environmental enrichment (EE) through a variety of leisure activities may decrease the risk of developing Alzheimer’s disease. This cross-sectional cohort study investigated the ...association between long-term EE in young adulthood through middle life and microstructure of fiber tracts associated with the memory system in older adults.
Methods
N
= 201 cognitively unimpaired participants (≥ 60 years of age) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) baseline cohort were included. Two groups of participants with higher (
n
= 104) or lower (
n
= 97) long-term EE were identified, using the self-reported frequency of diverse physical, intellectual, and social leisure activities between the ages 13 to 65. White matter (WM) microstructure was measured by fractional anisotropy (FA) and mean diffusivity (MD) in the fornix, uncinate fasciculus, and parahippocampal cingulum using diffusion tensor imaging. Long-term EE groups (lower/higher) were compared with adjustment for potential confounders, such as education, crystallized intelligence, and socio-economic status.
Results
Reported participation in higher long-term EE was associated with greater fornix microstructure, as indicated by higher FA (standardized β = 0.117,
p
= 0.033) and lower MD (β = −0.147,
p
= 0.015). Greater fornix microstructure was indirectly associated (FA: unstandardized
B
= 0.619,
p
= 0.038; MD:
B
= −0.035,
p
= 0.026) with better memory function through higher long-term EE. No significant effects were found for the other WM tracts.
Conclusion
Our findings suggest that sustained participation in a greater variety of leisure activities relates to preserved WM microstructure in the memory system in older adults. This could be facilitated by the multimodal stimulation associated with the engagement in a physically, intellectually, and socially enriched lifestyle. Longitudinal studies will be needed to support this assumption.
INTRODUCTION
Soluble amyloid beta (Aβ) oligomers have been suggested as initiating Aβ related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological ...sequence within the AD continuum remain unclear.
METHODS
A total of 526 participants in early clinical stages of AD and controls from a longitudinal cohort were neurobiologically classified for amyloid and tau pathology applying the AT(N) system. Aβ and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface‐based fluorescence intensity distribution analysis (sFIDA) technology.
RESULTS
Across groups, highest Aβ oligomer levels were found in A+ with subjective cognitive decline and mild cognitive impairment. Aβ oligomers were significantly higher in A+T− compared to A−T− and A+T+. APOE ε4 allele carriers showed significantly higher Aβ oligomer levels. No differences in tau oligomers were detected.
DISCUSSION
The accumulation of Aβ oligomers in the CSF peaks early within the AD continuum, preceding tau pathology. Disease‐modifying treatments targeting Aβ oligomers might have the highest therapeutic effect in these disease stages.
Highlights
Using surface‐based fluorescence intensity distribution analysis (sFIDA) technology, we quantified Aβ oligomers in cerebrospinal fluid (CSF) samples of the DZNE‐Longitudinal Cognitive Impairment and Dementia (DELCODE) cohort
Aβ oligomers were significantly elevated in mild cognitive impairment (MCI)
Amyloid‐positive subjects in the subjective cognitive decline (SCD) group increased compared to the amyloid‐negative control group
Interestingly, levels of Aβ oligomers decrease at advanced stages of the disease (A+T+), which might be explained by altered clearing mechanisms
To identify radiological and laboratory hallmarks in patients with primary Sjögren's syndrome (pSS) presenting with spinal cord involvement.
Clinical and laboratory routine parameters were analyzed ...in a retrospective multicenter case series of four patients who developed myelitis associated with pSS. Serological and cerebrospinal fluid (CSF) measurements of pSS associated anti-SSA(Ro)-antibodies were initiated, and CSF neurofilament light chain (NFL) levels were assessed. NFL values were compared with results from 15 sex- and age-matched healthy controls. Radiological assessment was performed using multi-sequence spinal cord magnetic resonance imaging.
Three of the four patients initially developed neurological signs suggestive of myelitis and were subsequently diagnosed with pSS. All patients presented a longitudinal spinal T2-hyperintense lesion in the cervical spinal cord, whereas only two patients showed pleocytosis and oligoclonal bands in the CSF. Median (range) CSF-NFL levels were significantly elevated in patients compared to controls (6672 pg/mL (621-50000) vs. 585 pg/mL (357-729),
= 0.009). One patient showed sustained, highly increased NFL levels (50000 pg/mL) in the initial assessment when radiological signs of axonal injury were still absent. Anti-SSA(Ro)-antibodies were found in the serum of three patients, while two patients additionally presented intrathecal anti-SSA(Ro)-antibody production. Elevated CSF-NFL levels and intrathecal synthesis of anti-SSA(Ro)-antibodies were associated with a relapsing and treatment-resistant disease course.
Inflammatory spinal cord lesions associated with pSS are a rare but serious disease leading to severe disability. NFL and anti-SSA(Ro)-antibodies in CSF might serve as prognostic biomarkers and should be routinely assessed in patients with pSS.
Remote monitoring of cognition holds the promise to facilitate case-finding in clinical care and the individual detection of cognitive impairment in clinical and research settings. In the context of ...Alzheimer's disease, this is particularly relevant for patients who seek medical advice due to memory problems. Here, we develop a remote digital memory composite (RDMC) score from an unsupervised remote cognitive assessment battery focused on episodic memory and long-term recall and assess its construct validity, retest reliability, and diagnostic accuracy when predicting MCI-grade impairment in a memory clinic sample and healthy controls. A total of 199 participants were recruited from three cohorts and included as healthy controls (n = 97), individuals with subjective cognitive decline (n = 59), or patients with mild cognitive impairment (n = 43). Participants performed cognitive assessments in a fully remote and unsupervised setting via a smartphone app. The derived RDMC score is significantly correlated with the PACC5 score across participants and demonstrates good retest reliability. Diagnostic accuracy for discriminating memory impairment from no impairment is high (cross-validated AUC = 0.83, 95% CI 0.66, 0.99) with a sensitivity of 0.82 and a specificity of 0.72. Thus, unsupervised remote cognitive assessments implemented in the neotiv digital platform show good discrimination between cognitively impaired and unimpaired individuals, further demonstrating that it is feasible to complement the neuropsychological assessment of episodic memory with unsupervised and remote assessments on mobile devices. This contributes to recent efforts to implement remote assessment of episodic memory for case-finding and monitoring in large research studies and clinical care.
The rarity of primary angiitis of the central nervous system (PACNS) demands diagnostic and prognostic biomarkers. We retrospectively measured Neurofilament light chain (NFL) concentrations in ...cerebrospinal fluid in a severely relapsing PACNS patient at multiple time points during the course of the disease. A marked increase in NFL levels preceding the onset of neuro‐axonal damage and arterial‐vessel abnormalities was observed with magnetic resonance imaging as well as with MR‐ and conventional angiography. Thus, marked elevation of NFL in PACNS seems to occur ahead of definitive radiological abnormalities and might serve as a diagnostic biomarker.
Abstract
Background
Patients with Alzheimer’s disease (AD) often show problems in spatial navigation. However, spatial navigation is rarely investigated in real world settings and in people at early ...disease stages. Capitalizing on recent advancements in digital technologies, we measured the performance of healthy younger (YA) and older adults (OA), as well as older adults with subjective cognitive decline (SCD) while they solved a smartphone‐based wayfinding task.
Method
Using the novel smartphone application “Explore”, we tracked GPS data and other behavioral indicators in 24 YAs, 25 OAs, and 23 SCDs, while they were asked to find points of interest on the medical campus in Magdeburg. In our analyses, we first quantified similarities between the GPS trajectories and identified wayfinding styles using k‐medoids clustering. Next, we extracted navigation profiles with aggregated performance measures as input features (e.g., wayfinding distance and number of help function calls) in a latent profile analysis. Mixed effect models were fitted to evaluate group differences for each performance measure separately. We then fed the performance measure that showed the largest groups differences into a multinomial logistic regression model to predict age and diagnostic group in unknown users via leave‐one‐out cross‐validation.
Result
The GPS data could be clustered into three wayfinding styles. However, the correspondence to our groups was rather low (Figure 1a). In contrast, navigation profiles obtained from the latent profile analysis showed a higher correspondence (Figure 1b). Particularly the number of brief stops during navigation differed between the groups, all p ≤ .006 (Figure 2), and predicted age group, p = .015, and diagnostic group above chance, p = .004 (Figure 3). The leave‐one‐out cross‐validation confirmed the successful prediction of group membership in unknown participants, accuracy = 0.57 (chance level 0.33).
Conclusion
Here, we show how information about the cognitive health status of an individual can be inferred from smartphone‐data, obtained during a brief episode of a frequently performed everyday behavior. In particular, the number of short stops during wayfinding could be used to distinguish between YA, OA, and SCDs. Hence, real‐world navigation data, obtained from mobile devices, might help to identify individuals at increased risk for developing AD.
Background
Patients with Alzheimer’s disease (AD) often show problems in spatial navigation. However, spatial navigation is rarely investigated in real world settings and in people at early disease ...stages. Capitalizing on recent advancements in digital technologies, we measured the performance of healthy younger (YA) and older adults (OA), as well as older adults with subjective cognitive decline (SCD) while they solved a smartphone‐based wayfinding task.
Method
Using the novel smartphone application “Explore”, we tracked GPS data and other behavioral indicators in 24 YAs, 25 OAs, and 23 SCDs, while they were asked to find points of interest on the medical campus in Magdeburg. In our analyses, we first quantified similarities between the GPS trajectories and identified wayfinding styles using k‐medoids clustering. Next, we extracted navigation profiles with aggregated performance measures as input features (e.g., wayfinding distance and number of help function calls) in a latent profile analysis. Mixed effect models were fitted to evaluate group differences for each performance measure separately. We then fed the performance measure that showed the largest groups differences into a multinomial logistic regression model to predict age and diagnostic group in unknown users via leave‐one‐out cross‐validation.
Result
The GPS data could be clustered into three wayfinding styles. However, the correspondence to our groups was rather low (Figure 1a). In contrast, navigation profiles obtained from the latent profile analysis showed a higher correspondence (Figure 1b). Particularly the number of brief stops during navigation differed between the groups, all p = .006 (Figure 2), and predicted age group, p = .015, and diagnostic group above chance, p = .004 (Figure 3). The leave‐one‐out cross‐validation confirmed the successful prediction of group membership in unknown participants, accuracy = 0.57 (chance level 0.33).
Conclusion
Here, we show how information about the cognitive health status of an individual can be inferred from smartphone‐data, obtained during a brief episode of a frequently performed everyday behavior. In particular, the number of short stops during wayfinding could be used to distinguish between YA, OA, and SCDs. Hence, real‐world navigation data, obtained from mobile devices, might help to identify individuals at increased risk for developing AD.
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