Changes in MEG resting-state networks are related to cognitive decline in type 1 diabetes mellitus patients

OBJECTIVE: Integrity of resting-state functional brain networks (RSNs) is important for proper cognitive functioning. In type 1 diabetes mellitus (T1DM) cognitive decrements are commonly observed, possibly due to alterations in RSNs, which may vary according to microvascular complication status. Thus, we tested the hypothesis that functional connectivity in RSNs differs according to clinical status and correlates with cognition in T1DM patients, using an unbiased approach with high spatio-temporal resolution functional network.; METHODS: Resting-state magnetoencephalographic (MEG) data for T1DM patients with (n=42) and without (n=41) microvascular complications and 33 healthy participants were recorded. MEG time-series at source level were reconstructed using a recently developed atlas-based beamformer. Functional connectivity within classical frequency bands, estimated by the phase lag index (PLI), was calculated within eight commonly found RSNs. Neuropsychological tests were used to assess cognitive performance, and the relation with RSNs was evaluated.; RESULTS: Significant differences in terms of RSN functional connectivity between the three groups were observed in the lower alpha band, in the default-mode (DMN), executive control (ECN) and sensorimotor (SMN) RSNs. T1DM patients with microvascular complications showed the weakest functional connectivity in these networks relative to the other groups. For DMN, functional connectivity was higher in patients without microangiopathy relative to controls (all p<0.05). General cognitive performance for both patient groups was worse compared with healthy controls. Lower DMN alpha band functional connectivity correlated with poorer general cognitive ability in patients with microvascular complications.; DISCUSSION: Altered RSN functional connectivity was found in T1DM patients depending on clinical status. Lower DMN functional connectivity was related to poorer cognitive functioning. These results indicate that functional connectivity may play a key role in T1DM-related cognitive dysfunction

Ultra-pure digital sideband separation at sub-millimeter wavelengths

Deep spectral-line surveys in the mm and sub-mm range can detect thousands of lines per band uncovering the rich chemistry of molecular clouds, star forming regions and circumstellar envelopes, among others objects. The ability to study the faintest features of spectroscopic observation is, nevertheless, limited by a number of factors. The most important are the source complexity (line density), limited spectral resolution and insufficient sideband (image) rejection (SRR). Dual Sideband (2SB) millimeter receivers separate upper and lower sideband rejecting the unwanted image by about 15 dB, but they are difficult to build and, until now, only feasible up to about 500 GHz (equivalent to ALMA Band 8). For example ALMA Bands 9 (602-720 GHz) and 10 (787-950 GHz) are currently DSB receivers. Aims: This article reports the implementation of an ALMA Band 9 2SB prototype receiver that makes use of a new technique called calibrated digital sideband separation. The new method promises to ease the manufacturing of 2SB receivers, dramatically increase sideband rejection and allow 2SB instruments at the high frequencies currently covered only by Double Sideband (DSB) or bolometric detectors. Methods: We made use of a Field Programmable Gate Array (FPGA) and fast Analog to Digital Converters (ADCs) to measure and calibrate the receiver's front end phase and amplitude imbalances to achieve sideband separation beyond the possibilities of purely analog receivers. The technique could in principle allow the operation of 2SB receivers even when only imbalanced front ends can be built, particularly at very high frequencies. Results: This digital 2SB receiver shows an average sideband rejection of 45.9 dB while small portions of the band drop below 40 dB. The performance is 27 dB (a factor of 500) better than the average performance of the proof-of-concept Band 9 purely-analog 2SB prototype receiver.Comment: 5 page

Wearable technologies to measure clinical outcomes in multiple sclerosis: A scoping review

Wearable technology refers to any sensor worn on the person, making continuous and remote monitoring available to many people with chronic disease, including multiple sclerosis (MS). Daily monitoring seems an ideal solution either as an outcome measure or as an adjunct to support rater-based monitoring in both clinical and research settings. There has been an increase in solutions that are available, yet there is little consensus on the most appropriate solution to use in either MS research or clinical practice. We completed a scoping review (using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines) to summarise the wearable solutions available in MS, to identify those approaches that could potentially be utilised in clinical trials, by evaluating the following: scalability, cost, patient adaptability and accuracy. We identified 35 unique products that measure gait, cognition, upper limb function, activity, mood and fatigue, with most of these solutions being phone applications

Infratentorial Abnormalities in Vascular Dementia

Background and Purpose—Infratentorial abnormalities may cause cognitive deficits, but current research criteria for vascular dementia (VaD) do not consider them. Our purposes were to determine the prevalence of infratentorial abnormalities in VaD, their relation with supratentorial abnormalities, and whether they are relevant to cognition. Methods—We examined 182 patients (120 men, mean age 73 years, SD 8) with probable VaD at inclusion into a multicenter clinical trial. MRI scans were evaluated for infratentorial vascular abnormalities, midbrain atrophy, cerebellar atrophy, basilar artery diameter and tortuosity, and supratentorial abnormalities. Cognitive testing included the mini–mental state examination (MMSE) and the vascular dementia assessment scale (VaDAS-cog). Results—One hundred forty-one (77.5%) patients had infratentorial abnormalities: 119 (65.4%) had focal infratentorial vascular lesions, 65 (35.7%) had diffuse pontine vascular abnormalities hyperintense on T2-weighted images, 20 (11.0%) had midbrain atrophy, and 16 (8.8%) had cerebellar atrophy. Significant correlations were found between number of infratentorial vascular lesions and basilar artery diameter (rs 0.26; P 0.0001), infratentorial and basal ganglia (including thalamus) vascular abnormalities (rs 0.30; P 0.0001), as well as between midbrain atrophy and global supratentorial atrophy (rs 0.27; P 0.0001). Infratentorial vascular abnormalities and cerebellar atrophy were not significantly associated with cognitive impairment. Patients with midbrain atrophy performed worse on cognitive tests than those without midbrain atrophy. After correction for sex, age, education, supratentorial abnormalities, and center, midbrain atrophy remained significantly associated with lower MMSE scores (P 0.05). Conclusions—Infratentorial abnormalities often occur in patients with VaD, but only midbrain atrophy was found to be relevant to cognitio

Thalamic Lesions in Vascular Dementia: Low Sensitivity of Fluid-Attenuated Inversion Recovery (FLAIR) Imaging

Background and Purpose—The criteria of the National Institute of Neurological Disorders and Stroke (NINDS)– Association Internationale pour la Recherche et l’Enseignement en Neurosciences (AIREN) include thalamic lesions for the diagnosis of vascular dementia (VaD). Although studies concerning VaD and brain aging advocate the use of fluid-attenuated inversion recovery (FLAIR) or T2-weighted images (T2-WI) to detect ischemic lesions, none compared the sensitivity of these sequences to depict thalamic lesions. Methods—We performed a blinded review of T2-WI and FLAIR images in 73 patients fulfilling the radiological part of the NINDS-AIREN criteria (mean age, 71 years; range, 49 to 83 years). This sample was drawn from a large multicenter trial on VaD and was expected to have a high prevalence of thalamic lesions. In a side-by-side review, including T1-weighted images as well, lesions were classified according to presumed underlying pathology. Results—The total number of thalamic lesions was 214. Two hundred eight (97%) were detected on T2-WI, but only 117 (55%) were detected on FLAIR ( 2 5.1; P 0.05). Although the mean size of lesions detected on T2-WI and not on FLAIR (4.4 mm) was significantly lower than the mean size of lesions detected on both sequences (6.7 mm) (P 0.001), 5 of the 29 lesions 10 mm on T2-WI were not visible on FLAIR. FLAIR detected only 81 (51%) of the 158 probable ischemic lesions and 30 (60%) of the 50 probable microbleeds. Conclusions—FLAIR should not be used as the only T2-weighted sequence to detect thalamic lesions in patients suspected of having VaD

Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy

Background: Progressive multifocal leukoencephalopathy (PML) was reported to have developed in three patients treated with natalizumab. We conducted an evaluation to determine whether PML had developed in any other treated patients. Methods: We invited patients who had participated in clinical trials in which they received recent or long-term treatment with natalizumab for multiple sclerosis, Crohn's disease, or rheumatoid arthritis to participate. The clinical history, physical examination, brain magnetic resonance imaging (MRI), and testing of cerebrospinal fluid for JC virus DNA were used by an expert panel to evaluate patients for PML. We estimated the risk of PML in patients who completed at least a clinical examination for PML or had an MRI. Results: Of 3417 patients who had recently received natalizumab while participating in clinical trials, 3116 (91 percent) who were exposed to a mean of 17.9 monthly doses underwent evaluation for PML. Of these, 44 patients were referred to the expert panel because of clinical findings of possible PML, abnormalities on MRI, or a high plasma viral load of JC virus. No patient had detectable JC virus DNA in the cerebrospinal fluid. PML was ruled out in 43 of the 44 patients, but it could not be ruled out in one patient who had multiple sclerosis and progression of neurologic disease because data on cerebrospinal fluid testing and follow-up MRI were not available. Only the three previously reported cases of PML were confirmed (1.0 per 1000 treated patients; 95 percent confidence interval, 0.2 to 2.8 per 1000). Conclusions: A detailed review of possible cases of PML in patients exposed to natalizumab found no new cases and suggested a risk of PML of roughly 1 in 1000 patients treated with natalizumab for a mean of 17.9 months. The risk associated with longer treatment is not known

Cognitive Functioning and Hippocampal Connectivity in Patients With Longstanding Type 1 Diabetes and Apolipoprotein E ε4

OBJECTIVE: While the apolipoprotein E ε4 allele (ApoE-ε4) is related to cognitive and brain decline in the general population, its effect on the brain in type 1 diabetes mellitus (T1DM) remains unclear. Therefore, the aim was to determine the interaction between ApoE-ε4 and T1DM on cognitive performance and hippocampal structure and connectivity as the brain area most vulnerable to ApoE-ε4 effects in adult patients with T1DM. RESEARCH DESIGN AND METHODS: Blood sampling was performed in 104 patients with T1DM and 49 control subjects for ApoE genotyping, neuropsychology, and neuroimaging to determine hippocampal volume and resting-state connectivity. The interaction between T1DM status and ApoE-ε4 presence was investigated and adjusted for age and mean systolic blood pressure. RESULTS: ApoE genotyping could not be performed for three patients with T1DM. Significant interaction effects, indicating a differential effect of ApoE-ε4 between both groups, were found for overall cognitive functioning and for the subdomains of information processing speed and attention. Additionally, interaction effects were present for right hippocampal connectivity with the right posterior cingulate and supramarginal gyri. Subsequent group analysis showed that patients with T1DM with ApoE-ε4 performed worse on these cognitive domains with increased connectivity, relative to their counterparts without ApoE-ε4. In contrast, no cognitive effects, but decreased connectivity, were observed in control subjects with ApoE-ε4. In patients with T1DM, higher right hippocampus connectivity with the posterior cingulate gyrus was related to poorer overall cognitive functioning. CONCLUSIONS: The results may suggest that ApoE-ε4 presence leaves our patients with T1DM more susceptible to cognitive decrements at a younger age, possibly through vascular pathways, warranting further longitudinal studies

Accelerated executive functions decline and gray matter structural changes in middle-aged type 1 diabetes mellitus patients with proliferative retinopathy

Background The aim of the present study was to determine trajectories of cognitive and cortical changes over time in middle‐aged patients with type 1 diabetes mellitus (T1DM) and proliferative retinopathy. Methods Twenty‐five patients and 25 controls underwent neuropsychological assessment and neuroimaging twice in a mean (±SD) of 3.56 ± 0.65 and 3.94 ± 0.91 years, respectively (P = 0.098). Cognitive assessment included the domains of general cognitive ability, memory, information processing speed, executive functions, attention, and motor and psychomotor speed. Symmetrized percentage change in local cortical thickness, surface area, and volume was determined using the FreeSurfer 6 vertex‐wise general linear model method. Analyses were performed uncorrected and corrected for baseline systolic blood pressure and depressive symptoms. Results In patients versus controls, accelerated executive function decline was accompanied by, but not related to, lower left frontal and temporal surface area, left parietal and right frontal thickness, and bilateral frontal and right posterior cingulate volume (family‐wise error [FWE]‐corrected P < 0.05 for all). In patients, lower executive performance was related to loss of right precuneus surface area (PFWE = 0.005). Higher HbA1c during follow‐up was related to executive function decline (r = −0.509, P = 0.016) and loss of left hemisphere surface area (rcorrected analysis = −0.555, P = 0.007). Conclusions After 3.5 years of follow‐up, middle‐aged T1DM patients with proliferative retinopathy, mild focal changes in executive functions, and cortical structure were found, which may indicate accelerated aging

The presence of cerebral white matter lesions and lower skin microvascular perfusion predicts lower cognitive performance in type 1 diabetes patients with retinopathy but not in healthy controls-A longitudinal study

OBJECTIVE: Cognitive impairments in type 1 diabetes may result from hyperglycemia-associated cerebral microangiopathy. We aimed to identify cerebral microangiopathy and skin microvascular dysfunction-as a surrogate marker for generalized microvascular function-as predictors of cognitive performance over time. METHODS: In this prospective cohort study, 25 type 1 diabetes patients with proliferative retinopathy and 25 matched healthy controls underwent neurocognitive testing at baseline and after follow-up (3.8 ± 0.8 years). At baseline, 1.5-T cerebral magnetic resonance imaging was used to detect WML and cerebral microbleeds. Skin capillary perfusion was assessed by means of capillary microscopy. RESULTS: In type 1 diabetes patients, but not in healthy controls, the presence of WML (ß = -0.419; P = 0.037) as well as lower skin capillary perfusion (baseline: ß = 0.753; P < 0.001; peak hyperemia: ß = 0.743; P = 0.001; venous occlusion: ß = 0.675; P = 0.003; capillary recruitment: ß = 0.549; P = 0.022) at baseline was associated with lower cognitive performance over time, independent of age, sex, HbA1c, and severe hypoglycemia. The relationship between WML and lower cognitive performance was significantly reduced after adjusting for capillary perfusion. CONCLUSIONS: These data fit the hypothesis that cerebral microangiopathy is a manifestation of generalized microvascular dysfunction, leading to lower cognitive performance