Early childhood adversity in adult patients with metastatic lung cancer: Cross-sectional analysis of symptom burden and inflammation

ObjectivePsychological and physical symptoms commonly occur in patients with metastatic lung cancer and are associated with reduced quality of life and decreased survival. Previous work has associated these symptoms with inflammation. The experience of Early Childhood Adversity (ECA) is linked to chronic inflammation and may identify adult cancer patients who are at-risk for psychological and physical symptoms. We thus hypothesized that ECA in lung cancer patients would be associated with increased psychological symptoms (distress, anxiety, and depression) and physical symptoms and that this relationship would be explained by inflammation.MethodsPatients with metastatic lung cancer (n = 92) were evaluated for ECA using the Risky Families Questionnaire. Concomitant assessments were made of distress (Distress Thermometer and Problem List [DT&PL]), anxiety (Generalized Anxiety Disorder-7), depression (Patient Hospital Questionniare-9), physical symptoms (DT&PL), and inflammation (C-reactive protein [CRP]). Multivariate models were created to explain associations of ECA with depression, anxiety, distress, number of physical problems, and inflammation.ResultsECA was associated with distress (r = 0.24, p = .03), anxiety (r = 0.30, p = .004), depression (r = 0.35, p = .001), greater physical problems (r = 0.25, p = .03), younger age (r = -0.29, p = .006), and elevated CRP (r = 0.22, p = .04). Multivariate analyses of outcomes found that depression severity was independently explained by both ECA and inflammation (β = 0.37, p = .001) but not distress or anxiety, while controlling for age and sex. Number of physical problems were also associated with ECA (β = 0.35, p = .004) but not inflammation. The association between ECA and physical problems was not significant after controlling for depression.ConclusionECA is associated with increased depression and physical symptoms independent of inflammation. Moreover, depression appears to mediate the impact of ECA on physical symptoms. ECA may identify patients at risk for psychological and physical symptoms.     

Detecting inspiratory flow limitation with temporal features of nasal airflow

BackgroundInspiratory flow limitation is a breathing pattern during sleep caused by upper airway (UA) narrowing that occurs during snoring and various degrees of obstructive sleep apnea (OSA). Clinical examination of flow limitation relies on identifying patterns of airflow contour, however this process is subjective and lacks physiological evidence of UA narrowing. Our objective is to derive the temporal features of nasal airflow contour that characterize flow limitation. The features that correlate with UA narrowing can be used to develop machine learning classifiers to detect flow limitation with physiological support.MethodsSixteen healthy adult men underwent full daytime polysomnography where the nasal airflow was recorded. Before and after sleep, we measured UA anatomical parameters including neck circumference (NC) and upper-airway cross-sectional area (UA-XSA). We extracted various temporal features of airflow and investigated their relationships with the UA anatomical parameters.ResultsWe found that three features were correlated with the anatomical parameters associated with UA narrowing: deviation index vs. baseline UA-XSA (r = −0.67, p = 0.01), peak amplitude variability vs. baseline UA-XSA (r = −0.69, p < 0.01), peak amplitude variability vs. ΔNC (r = 0.74, p < 0.01) and peak number vs. baseline UA-XSA (r = −0.54, p = 0.04).ConclusionsTemporal features of airflow were associated with UA narrowing. Future studies could utilize the features to develop classifiers to detect flow limitation and assess the severity of breathing disorders during sleep in high-risk populations such as pregnant women and children.     

Impulsivity is associated with blood pressure and waist circumference among adolescents with bipolar disorder

ObjectiveCardiovascular risk factors (CVRFs) and impulsivity are common in bipolar disorder (BD), and CVRFs are also linked with impulsivity through a number of mechanisms, both behavioral and biological. This study examines the association between CVRFs and impulsivity in adolescents with BD.MethodsSubjects were 34 adolescents with BD and 35 healthy control (HC) adolescents. CVRFs were based on International Diabetes Federation metabolic syndrome criteria (triglycerides, high-density lipoprotein cholesterol, waist circumference, blood pressure (BP) and glucose). Impulsivity was measured using the computerized Cambridge Gambling Task (CGT). Analyses controlled for age, IQ, lifetime attention deficit hyperactivity disorder, and current antipsychotic use.ResultsAdolescents with BD had higher diastolic BP (73.36 ± 9.57 mmHg vs. 67.91 ± 8.74 mmHg, U = 401.0, p = 0.03), higher triglycerides (1.13 ± 0.60 mmol/L vs. 0.78 ± 0.38 mmol/L, U = 373.5, p = 0.008), and were more likely to meet high-risk criteria for waist circumference (17.6% vs. 2.9%, p = 0.04) vs. HC. Within the BD group, CGT sub-scores were correlated with CVRFs. For example, overall proportion bet was positively correlated with systolic (r = 0.387, p = 0.026) and diastolic (ρ = 0.404, p = 0.020) BP. Quality of decision-making was negatively correlated with systolic BP (ρ = −0.401, p = 0.021) and waist circumference (ρ = −0.534, p = 0.003). Significant interactions were observed, such that BD diagnosis moderates the relationship between both waist circumference and BP with CGT sub-scores.ConclusionBP and waist circumference are associated with impulsivity in BD adolescents, but not in HC adolescents. Future studies are warranted to determine temporality and to evaluate whether optimizing CVRFs improves impulsivity among BD adolescents.     

MRI Characteristics Predicting Seizure Threshold in Patients Undergoing Electroconvulsive Therapy: A Prospective Study

BackgroundIn electroconvulsive therapy (ECT), the electrical current must pass the scalp, skull, cerebrospinal fluid (CSF) and brain tissues, to sufficiently exceed the seizure threshold (ST).ObjectiveTo investigate the relationship between these anatomical strata of the head and the level of the ST, in both right unilateral (RUL) and bifrontotemporal (BL) ECT.MethodsObservational prospective study among 74 mainly depressed patients. STs were measured at the 1st (initial ST), 6th, 12th, 18th and 24th session. MRI scans were acquired before the 1st session. Scalp and skull thickness at electrode sites were measured on T₂-weighted images. Volumes of intracranial space (ICV), CSF, gray and white matter, and white matter hyperintensities were estimated using whole brain isovoxel T₁-weighted images. Separate multivariate regression analyses for RUL (n = 55) and BL (n = 19) treated groups were used to estimate the predictive values of the MRI variables.ResultsThe patients had a mean age of 57.7 ± 14.8 years, and 39% were men. After adjustment for age, gender and ICV, CSF volume strongly and independently predicted initial ST in both RUL (β = 0.31; P = 0.049) and BL ECT (β = 0.64; P = 0.007). Using multilevel regression analysis, CSF volume was associated with ST during the remaining RUL ECT course (β = 0.20; P = 0.02).ConclusionsTaking into account the limitations in the titration method and MRI analysis, volume of CSF strongly and independently predicted initial ST. Therefore, the exclusive use of age-based ECT dosing methods may result in suboptimal electrical stimulus dosage in patients with CSF volumes that are not within the average range.     

Structural changes induced by electroconvulsive therapy are associated with clinical outcome

BackgroundElectroconvulsive therapy (ECT) is the most effective treatment option for major depressive disorder, so understanding whether its clinical effect relates to structural brain changes is vital for current and future antidepressant research.ObjectiveTo determine whether clinical response to ECT is related to structural volumetric changes in the brain as measured by structural magnetic resonance imaging (MRI) and, if so, which regions are related to this clinical effect. We also determine whether a similar model can be used to identify regions associated with electrode placement (unilateral versus bilateral ECT).MethodsLongitudinal MRI and clinical data (Hamilton Depression Rating Scale) was collected from 10 sites as part of the Global ECT-MRI research collaboration (GEMRIC). From 192 subjects, relative changes in 80 (sub)cortical areas were used as potential features for classifying treatment response. We used recursive feature elimination to extract relevant features, which were subsequently used to train a linear classifier. As a validation, the same was done for electrode placement. We report accuracy as well as the structural coefficients of regions included in the discriminative spatial patterns obtained.ResultsA pattern of structural changes in cortical midline, striatal and lateral prefrontal areas discriminates responders from non-responders (75% accuracy, p < 0.001) while left-sided mediotemporal changes discriminate unilateral from bilateral electrode placement (81% accuracy, p < 0.001).ConclusionsThe identification of a multivariate discriminative pattern shows that structural change is relevant for clinical response to ECT, but this pattern does not include mediotemporal regions that have been the focus of electroconvulsive therapy research so far.     

Adipokines,metabolic dysfunction and illness course in bipolar disorder

Replicated evidence indicates that individuals with BD are differentially affected by metabolic comorbidities and that its occurrence is a critical mediator and/or moderator of BD outcomes. This study aimed to explore the role of adipokines on bipolar disorder (BD) course and its relationship with metabolic comorbidities (i.e. type 2 diabetes mellitus, obesity). We measured plasma levels of adiponectin and leptin, as well as anthropometric and metabolic parameters of 59 patients with BD and 28 healthy volunteers. Our results showed that, in female participants, adiponectin was lower in individuals with BD, relative to healthy controls (p = 0.017). In the BD population, adiponectin levels were correlated with fasting glucose (r = −0.291, p = 0.047), fasting insulin (r = −0.332, p = 0.023), C-peptide (r = 0.040, p = 0.040), homeostatic model assessment-insulin resistance (r = −0.411, p = 0.004), HDL (r = 0.508, p < 0.001), VLDL (r = −0.395, p = 0.005) and triglycerides (r = −0.310, p = 0.030). After adjustment for age, gender and BMI, individuals with BD and low adiponectin levels (i.e. < 7.5 μg/ml), had a higher number of mood episodes (p < 0.001), lower number of psychiatric hospitalizations (p = 0.007), higher depressive symptoms (p < 0.001) and lower levels of functioning (p = 0.020). In conclusion, adiponectin levels, either directly or as a proxy of metabolic dysfunction, is independently associated with an unfavorable course of illness in BD.     

Long-term auditory processing outcomes in early implanted young adults with cochlear implants: The mismatch negativity vs. P300 response

ObjectiveLong-term outcomes of early implanted, young adult cochlear implant (CI) users remain variable. We measured auditory discrimination by means of event-related potentials in this population to examine whether variability at the level of cortical auditory processing helps to explain speech abilities.MethodsUsing an auditory oddball paradigm, the P300 and Mismatch Negativity (MMN) were measured in 8 young adult CI users and 14 normal-hearing peers. We related P300 amplitude and latency to clinical speech perception scores in quiet and to duration of deafness.ResultsAll individuals showed P300 responses. The MMN response was less robust in both groups. There was no evidence for differences in P300 responses between CI users and controls. P300 amplitude was associated with speech perception scores (r = 0.70, p = .05) and duration of deafness (r = −0.83, p = .009).ConclusionsEarly CI implantation yields good auditory processing outcomes at young adult age and, in contrast to MMN, the P300 provides a robust measure for auditory processing on an individual level.SignificanceAt the cortical level, early implanted, long-term CI users have good auditory discrimination, leaving variability in implantation outcomes unexplained. This group provides unique insight into the long-term neurophysiological underpinnings of early implantation.     

A dissociation between anterograde and retrograde amnesia after treatment with electroconvulsive therapy: a naturalistic investigation

OBJECTIVE: The aim of the present study is to investigate the cumulative effects of a clinically determined course of electroconvulsive therapy (ECT) on anterograde and retrograde amnesia. In this study, mood and memory were examined in the context of a protocol driven by therapeutic response, rather than by preordained research criteria. METHODS: Twenty-two patients with major depressive disorder and 18 nondepressed controls were taught a series of faces and names before the initiation of ECT, and their retention of this information was examined after the end of treatment. Anterograde (ie, new learning) and retrograde memory (ie, recall of information learned before ECT) were assessed. Eleven ECT patients underwent unilateral (UL) stimulation, and 11 had a combination of UL and bilateral stimulation. Major depressive disorder patients and nondepressed controls participants were matched according to baseline memory abilities. Unilateral and unilateral/bilateral (UB) ECT patients were matched according to baseline depression and memory abilities. RESULTS: Treatment with ECT resulted in a dissociation between anterograde and retrograde memory; after treatment, major depressive disorder patients demonstrated significant retrograde amnesia, whereas there was no change in their anterograde memory. Unilateral and UB ECT patients performed equally well on tasks of anterograde memory. Contrary to our expectation, UB ECT was not associated with greater retrograde memory loss than was UL ECT treatment. However, a trend toward a group difference was present on 1 memory measure. CONCLUSIONS: Results of the study suggest that a clinical course of ECT is associated with isolated impairment for information learned before treatment (ie, retrograde memory), whereas there was no effect of ECT on posttreatment learning abilities (ie, anterograde memory).     

DNA methylation changes at TREM2 intron 1 and TREM2 mRNA expression in patients with Alzheimer's disease

ObjectivesRecent genome-wide association studies revealed that Triggering receptor expressed on myeloid cells 2 (TREM2) was associated with Alzheimer's disease (AD) and other neurodegenerative diseases. We previously reported that TREM2 mRNA is highly expressed in leukocytes of AD patients compared to those in healthy controls. However, the mechanism of TREM2 expression change is still not known. In this study, we examined the involvement of the DNA methylation status of TREM2 in its high gene expression.Materials and methodsFifty AD subjects and age- and sex-matched control subjects were recruited (25 males, 25 females; 79.9 ± 5.27 and 79.4 ± 3.92 years old, respectively). TREM2 mRNA expression and the percentage of DNA methylation at four CpG sites in intron 1 of TREM2 were studied using their peripheral leukocytes.ResultsWe confirmed that TREM2 mRNA expression in leukocytes was significantly higher in AD patients than in controls (p = 0.007). The percentage methylation at three CpG sites in TREM2 intron 1 was significantly lower in AD subjects than in control: CpG1, 9.4 ± 3.2 vs 11.9 ± 4.0 (p = 0.001); CpG2, 15.4 ± 4.9 vs 19.1 ± 4.8 (p = 0.001); CpG3, 20.8 ± 5.5 vs 25.5 ± 5.4 (p < 0.001); and the average percentage methylation of all CpG sites: 13.5 ± 3.7 vs 16.1 ± 3.8 (p = 0.002), respectively. In addition, there were significant negative correlations between TREM2 mRNA expression and the percentage DNA methylation of each of CpG sites (CpG1, r = −0.416, p < 0.001; CpG2, r = −0.510, p < 0.001; CpG3, r = −0.504, p < 0.001; CpG4, r = −0.356, p < 0.001).ConclusionsLower DNA methylation at TREM2 intron 1 caused higher TREM2 mRNA expression in the leukocytes of AD subjects versus controls and may be a biomarker for AD.     

Cerebral perfusion is related to antidepressant effect and cognitive side effects of Electroconvulsive Therapy

BackgroundThe mechanisms underlying the antidepressant effect and cognitive side effects of Electroconvulsive Therapy (ECT) remain elusive. The measurement of cerebral perfusion provides an insight into brain physiology.ObjectiveWe investigated ECT-related perfusion changes in depressed patients and tested whether these changes correlate with clinical effects.MethodsA sample of 22 in-patients was examined at three time points: 1) within two days before, 2) within one week after, and 3) six months after an ECT series. Cerebral perfusion was quantified using arterial spin labeling magnetic resonance imaging. The primary regions of interest were the bilateral dorsolateral prefrontal cortices (DL-PFC) and hippocampi. The depression severity was assessed by the six-item Hamilton Depression Rating Scale, and cognitive performance by the Screen for Cognitive Impairment in Psychiatry. A linear mixed model and partial correlation were used for statistical analyses.ResultsFollowing an ECT series, perfusion decreased in the right (?6.0%, p = .01) and left DL-PFC (?5.6%, p = .001). Perfusion increased in the left hippocampus (4.8%, p = .03), while on the right side the increase was insignificant (2.3%, p = .23). A larger perfusion reduction in the right DL-PFC correlated with a better antidepressant effect, and a larger perfusion increase in the right hippocampus with worse cognitive impairment.ConclusionECT-induced attenuation of prefrontal activity may be related to clinical improvement, whereas a hippocampal process triggered by the treatment is likely associated with cognitive side effects.     

The relationship between gross motor function impairment in cerebral palsy and sleeping issues of children and caregivers

AimTo investigate, among children and adolescents with cerebral palsy (CP), the relationship between impairment of the gross motor function and: (i) child sleep disorders; (ii) the need for nocturnal support; and (iii) the quality of sleep of their caregivers.MethodsFor children, we considered their scores on the gross motor function measure (GMFM-88) and on the sleep disturbance scale for children (SDSC), besides analyzing qualitative features about their sleep. For caregivers, we considered their scores in the Pittsburgh sleep quality index (PSQI).ResultsOur sample was comprised of 87 participants with mean age of 11.4 years old (±3.4). We observed correlations between GMFM-88 and disorders of initiating and maintaining sleep (DIMS) (r = −0.22; p = 0.039), sleep–wake transition disorders (SWTD) (r = 0.26; p = 0.017) and disorders of arousal (DA) (r = 0.23; p = 0.033). Children receiving nocturnal support presented lower scores in the GMFM-88 (p = 0.001) and higher scores in the SDSC (p = 0.029). For the caregivers, we found no correlation between GMFM-88 and PSQI. Nonetheless, their PSQI scores correlated with the SDSC scores (r = 0.24; p = 0.027).ConclusionImpairment of the gross motor function correlated with DIMS and the need for nocturnal support but might not have an impact on the caregivers’ sleep, which in turn correlated with child sleep disorders.     

Does REM sleep behavior disorder change in the progression of Parkinson’s disease?

Objectives/backgroundRapid eye movement (REM) Sleep Behavior Disorder (RBD) in Parkinson's disease (PD) may be associated with a malignant phenotype. Despite its prognostic value, little is known about the time course of RBD in PD. In this study, we aimed to ascertain whether or not RBD is a stable feature in PD. In this study, we prospectively evaluated clinical and neurophysiological features of RBD, including REM Sleep Without Atonia (RSWA), in PD patients with RBD at baseline and after three years then assessed whether the changes in measures of RSWA parallel the progression of PD.Patients/methodsIn sum, 22 (17M, mean age 64.0 ± 6.9 years) moderate-to-advanced PD patients (mean PD duration at baseline:7.6±4.8 years) with RBD, underwent a video-polysomnography (vPSG) recording and clinical and neuropsychological assessment at baseline and after three years.ResultsAt follow-up, the self-assessed frequency of RBD symptoms increased in six patients, decreased in six and remained stable in 10, while RSWA measures significantly increased in all subjects. At follow-up, patients showed worse H&Y stage (p = 0.02), higher dopaminergic doses (p = 0.05) and they performed significantly worse in phonetic and semantic fluency tests (p = 0.02; p = 0.04). Changes in RSWA correlated significantly with the severity in levodopa-induced dyskinesia (r = 0.61,p = 0.05) and motor fluctuation (r = 0.54,p = 0.03) scores, and with the worsening of executive functions (r = 0.78,p = 0.001) and visuo-spatial perception (r = −0.57,p = 0.04).ConclusionDespite the subjective improvement of RBD symptoms in one-fourth of PD patients, all RSWA measures increased significantly at follow-up, and their changes correlated with the clinical evolution of motor and non-motor symptoms. RBD is a long-lasting feature in PD and RSWA is a marker of the disease's progression.     

Neurophysiological and behavioral effects of multisession prefrontal tDCS and concurrent cognitive remediation training in patients with autism spectrum disorder (ASD): A double-blind,randomized controlled fNIRS study

BackgroundThe clinical effects and neurophysiological mechanisms of prefrontal tDCS and concurrent cognitive remediation training in individuals with autism spectrum disorder (ASD) remain unclear.ObjectiveThis two-armed, double-blind, randomized, sham-controlled trial aimed to investigate the beneficial effects of tDCS combined with concurrent cognitive remediation training on adolescents and young adults with ASD.MethodsParticipants were randomly assigned to either active or sham tDCS groups and received 1.5 mA prefrontal tDCS with left dorsolateral prefrontal cortex (dlPFC) cathode placement and right supraorbital region anode placement for 20 minutes over two consecutive weeks. tDCS was delivered concurrently with a computerized cognitive remediation training program. Social functioning and its underlying cognitive processes, as well as prefrontal resting-state functional connectivity (rsFC), were measured.ResultsThe results from 41 participants indicated that multisession prefrontal tDCS, compared to sham tDCS, significantly enhanced the social functioning of ASD individuals [F(1,39) = 4.75, p = .035, η_p² = 0.11]. This improvement was associated with enhanced emotion recognition [F(1,39) = 8.34, p = .006, η_p² = 0.18] and cognitive flexibility [F(1,39) = 4.91, p = .033, η_p² = 0.11]. Specifically, this tDCS protocol optimized information processing efficiency [F(1,39) = 4.43, p = .042, η_p² = 0.10], and the optimization showed a trend to be associated with enhanced rsFC in the right medial prefrontal cortex (ρ = 0.339, pFDR = .083).ConclusionMultisession tDCS with left dlPFC cathode placement and right supraorbital region anode placement paired with concurrent cognitive remediation training promoted social functioning in individuals with ASD. This appeared to be associated with the enhancement of the functional connectivity of the right medial PFC, a major hub for flexible social information processing, allowing these individuals to process information more efficiently in response to different social situations.Trial registrationClinicalTrials.gov (ID: NCT03814083)     

Exploring three levels of interoception in people with functional motor disorders

IntroductionA three-level model of interoception has recently been defined. We aim to study the interoceptive processing in individuals with functional motor disorder (FMD).MethodsTwenty-two patients with FMD were compared to 23 healthy controls. They underwent a protocol measuring different levels of interoception including: accuracy (a heart-beat tracking task), awareness (participant's confidence level) and sensibility (the Body Awareness Questionnaire-BAQ). Depression, anxiety and alexithymia were assessed by means of validated clinical scales.ResultsThe FMD group showed a lower cardiac interoceptive accuracy and sensibility than healthy controls but they did not differ in terms of awareness (p = 0.03 and 0.005 respectively). They were aware of their poor performance in the accuracy task. Cardiac interoceptive accuracy positively correlated with the BAQ sub-scales “Predict Body Reaction” (r = 0.49, p = 0.001) and “Sleep-Wake Cycle” (r = 0.52, p < 0.001). A mediation analysis showed a significant indirect effect of group on cardiac interoceptive accuracy through BAQ “Predict Body Reaction” (b = −2.95, 95% BCa CI[-7.2;-0.2]). The direct effect of group on “Predict Body Reaction” was still significant (b = − 6.95, p = 0.02, 95% CI[-13.18;-0.73]).ConclusionsPeople with FMD have impaired cardiac interoceptive accuracy and sensibility but no difference in metacognitive interoception compared to healthy controls.     

Greater social jetlag associates with higher HbA1c in adults with type 2 diabetes: a cross sectional study

Background/ObjectivesLater chronotype has been associated with poorer glycemic control in type 2 diabetes. It is unclear whether this is a direct relationship, or if personality factors or social jetlag ([SJL], ie, chronic circadian misalignment reflecting the discrepancy between the entrained phase of the circadian clock and socially-determined behavioural cycles) play a role. This study aimed to determine the relationships among chronotype, SJL, personality factors and glycemic control in type 2 diabetes, independently of sleep disturbances and daily caloric distribution.MethodsIn sum, 252 type 2 diabetes patients attending an annual review outpatients' clinic completed questionnaires, including the Munich Chronotype Questionnaire to assess chronotype and SJL, the Pittsburgh Sleep Quality index (PSQI), the Big Five Personality Inventory and the Center for Epidemiologic Studies Depression Scale. Chart review provided information on diabetes duration, Hemoglobin A1c (HbA1c), body mass index (BMI) and other clinical variables. Caloric intake was assessed via 24-h dietary recall.ResultsHierarchical linear regression revealed that SJL, but not chronotype or personality factors, was a significant predictor of HbA1c levels (β = 0.16, p < 0.05). There was a significant relationship between later chronotype and HbA1c levels, but only in patients who had more than 90 min SJL (r = 0.51, p = 0.002). Younger age was associated with a higher HbA1c (r = −0.23, p < 0.001), and this effect was partially mediated through SJL (Pm = 0.22).ConclusionsWe identify SJL as a novel factor that may impact on glycemic control in type 2 diabetes. Further study is needed to determine whether interventions aimed at reducing SJL may lead to improvements in glycemic control.     

Valproate but not levetiracetam slows the EEG alpha peak frequency – A pharmaco-EEG study

ObjectiveStudies of the effect of valproate (VPA) on the background EEG have shown varying results. Therefore, we compared the effect of VPA and levetiracetam (LEV) on the EEG alpha peak frequency (APF).MethodsWe retrospectively examined the APF in resting-state EEG of patients undergoing inpatient video-EEG monitoring (VEM) during withdrawal of VPA or LEV. We assessed APF trends by computing linear fits across individual patients’ APF as a function of consecutive days, and correlated the APF and daily antiseizure medication (ASM) doses on a single-patient and group level.ResultsThe APF in the VPA-group significantly increased over days with falling VPA doses (p = 0.005, n = 13), but did not change significantly in the LEV-group (p = 0.47, n = 18). APF correlated negatively with daily ASM doses in the VPA-group (average of r = −0.74 ± 0.12 across patients, p = 0.0039), but not in the LEV-group (average of r = −0.17 ± 0.18 across patients, p = 0.4072).ConclusionsOur results suggest that VPA treatment slows the APF. This APF reduction correlates with the daily dose of VPA and is not present in LEV treatment.SignificanceOur study identifies a VPA-related slowing of the APF even in patients without electroencephalographic or overt clinical signs of encephalopathy.     

Longitudinal changes in cognition in early Parkinson's disease patients with REM sleep behavior disorder

IntroductionCognitive decline is common in Parkinson's disease (PD), and identifying patients at highest risk for it is essential. We aimed to examine the effect of possible REM sleep behavior disorder (pRBD) on rate of cognitive decline in early PD, for both global cognition and in specific cognitive domains.MethodsParkinson's Progression Markers Initiative (PPMI) is a multi-site, international study of PD patients untreated at enrollment. pRBD was assessed with the REM sleep behavior disorder questionnaire (RBDSQ). Global cognition was assessed at baseline and annually using the Montreal Cognitive Assessment (MoCA) and a cognitive battery. Linear mixed effects models were used to examine the relationship between pRBD (RBDSQ ≥ 6) and rate of change in cognitive variables. Age, sex, years of education, and baseline motor and cognitive scores were included as covariates.ResultsThe baseline sample consisted of 423 individuals with PD, mean age 61.7 years and 65.5% male. Data was available on 389, 366, and 196 participants at 1-year, 2-year, and 3-year follow-up respectively. Possible RBD occurred in 108 (25.5%) at baseline. In multivariate analyses, baseline RBD was associated with greater annual rate of decline in MoCA score (β = −0.34, 95%CI −0.54, −0.13, p < 0.001), Symbol Digit Modalities Test (β = −0.69, 95%CI −1.3, −0.09, p = 0.024), and Hopkins Verbal Learning Test-Revised, delayed free recall (β = −0.21, 95%CI −0.41, −0.013, p = 0.037).ConclusionsPossible RBD is common in early PD and predicts future cognitive decline, particularly in attention and memory domains.     

Effects of CPAP for patients with OSA on visual sensitivity and retinal thickness

ObjectiveObstructive sleep apnea/hypopnea syndrome (OSA) could compromise oxygenation of the optic nerve and cause glaucomatous optic neuropathy; there has been no study to investigate the microstructure changes of the optic nerve and retina in OSA patients before and after continuous positive airway pressure (CPAP) therapy. In this study, we assess whether treatment with CPAP might improve visual sensitivity and retinal thickness in patients with OSA.MethodsPatients with OSA were prospectively recruited and referred for ophthalmologic evaluation at baseline and three months after CPAP treatment. Each patient underwent an ophthalmological exam, standard automated perimetry (SAP), and optical coherence tomography (OCT) exam. Peripapillary retinal nerve fiber layer (RNFL) and macular layer (ML) thickness parameters were measured. The SAP, RNFL, and ML thickness parameters before and after treatment were compared.ResultsA total of 32 OSA patients were consecutively enrolled. At baseline, the mean deviation (MD) of SAP was −2.15 ± 1.90 dB (dB). After CPAP treatment, the MD was −1.38 ± 1.37 dB (p = 0.017). Regarding the OCT parameters, the inferior quadrant and nasal-inferior sector of RNFL thickness significantly improved after treatment (p = 0.025 and 0.004, respectively). The ML thickness in the superior-inner sector, inferior-outer sector, nasal-outer sector, superior hemisphere, and inferior hemisphere were also significantly improved after treatment. Improvement of ML thickness in the superior-inner sector positively correlated with the apnea/hypopnea index (r = 0.405, p = 0.022) and desaturation index (r = 0.473, p = 0.006) on pre-treatment polysomnography.ConclusionThe treatment of CPAP could improve visual sensitivity and increase retinal thickness in patients with OSA.     

Objective measurement of limb bradykinesia using a marker-less tracking algorithm with 2D-video in PD patients

BackgroundQuantitative measurement of parkinsonian motor symptoms is crucial in clinical practice and in research. However, the widely used Unified PD Rating Scale (UPDRS) part III is based on a semi-quantitative evaluation with high inter- and intra-rater variability. Sensor-based measurements have been widely studied but are limited for their accessibility.MethodsWe analyzed 2D-RGB videos recording finger tapping and leg agility tests in 29 PD patients with a marker-less deep-learning based tracking algorithm. The tracking performance was validated with an accelerometer. Four parameters (mean amplitude, mean interpeak interval, amplitude variability and interpeak interval variability) were calculated from the position tracking.ResultsThe performance of the video-tracking was in good agreement with the accelerometer-based tracking (Intra-class correlation coefficient > 0.9 for the peak amplitude, and >0.6 for the interpeak interval). The video-tracking successfully captured variable aspects of limb bradykinesia that have a distinct correlation with the general parkinsonian motor symptoms and gait. In the finger-tapping task, the mean amplitude (R = −0.6, p = 2.4 × 10⁻⁶), amplitude variability (R = 0.36, p = 0.0092), mean interpeak interval (R = 0.34, p = 0.014), and interpeak interval variability (R = 0.66, p = 1.4 × 10⁻⁷) was significantly correlated with the UPDRS scores. In leg agility test, the mean amplitude (R = −0.58, p = 1.7 × 10⁻⁵), mean interpeak interval (R = 0.37, p = 0.0088) and interpeak interval variability (R = 0.7, p = 6.2 × 10⁻⁸) were significantly correlated with the UPDRS scores, but not with amplitude variability (R = 0.17, p = 0.26). Limb rigidity was significantly correlated with the interpeak interval (R = 0.40, p = 0.0036) and its variability (R = 0.59, p = 4.2 × 10⁻⁶) in the leg agility test.ConclusionThe video-based tracking could objectively measure limb bradykinesia in PD patients.     

Accumulation of affective symptoms and midlife cognitive function: The role of inflammation

BackgroundThe aim of the present study was to test whether C-Reactive Protein (CRP), a proxy measure of inflammation, is elevated in people with higher childhood and adulthood affective symptoms and whether elevated CRP predicts midlife cognitive function.MethodsData were used from the National Child Development Study (n = 6276). Measures of memory, verbal fluency, information processing speed and accuracy were available in midlife (age 50). Affective symptoms were assessed in childhood (ages 7, 11, 16) and in adulthood (ages 23, 33, 42, 50). The level of plasma CRP was measured at age 44. Pathway models, unadjusted and fully adjusted for sex, education, childhood socioeconomic position, childhood cognitive ability and affective symptoms at age 50, were fitted to test direct associations between affective symptoms and midlife cognitive function, and indirect associations via the inflammatory pathway (CRP level).ResultsIn a fully adjusted model, there were significant indirect associations between adulthood affective symptoms and immediate memory (β = −0.01, SE = 0.003, p = .03) and delayed memory (β = −0.01, SE = 0.004, p = .03) via CRP. In addition, there were significant indirect associations between affective symptoms in childhood and immediate memory (β = −0.001, SE = 0.00, p = .03) and delayed memory (β = −0.001, SE = 0.001, p = .03), via adulthood affective symptoms and associated CRP. Independent of CRP, there was a significant direct association between adulthood affective symptoms and information processing errors (β = 0.47, SE = 0.21, p = .02). There were no direct or indirect associations between affective symptoms and verbal fluency or information processing speed.ConclusionsCRP at age 44 is elevated in people with higher affective symptoms from age 7 to 42, and elevated CRP is associated with poorer immediate and delayed memory at age 50.