Elderly subjects have a delayed antibody response and prolonged viraemia following yellow fever vaccination: a prospective controlled cohort study

Background

Yellow fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to yellow fever vaccine develops more slowly in elderly than in younger subjects.

Method

We vaccinated young volunteers (18–28 yrs, N = 30) and elderly travelers (60–81 yrs, N = 28) with YF-17D and measured their neutralizing antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5, 10, 14 and 28 days after vaccination.

Results

Ten days after vaccination seroprotection was attained by 77% (23/30) of the young participants and by 50% (14/28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean Titer of younger participants was higher than the GMT of the elderly participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8–4.7, p = 0.00004) and at day 14 +1.8 IU/ml (95% CI 1.1–2.9, p = 0.02, using a mixed linear model. Viraemia was more common in the elderly (86%, 24/28) than in the younger participants (60%, 14/30) (p = 0.03) with higher YF-17D RNA copy numbers in the elderly participants.

Conclusions

We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD.

Trial Registration

Trialregitser.nl NTR1040     

Relationship between Changes in Body Fat and a Decline of Renal Function in the Elderly

Obesity is a risk factor for chronic kidney disease, and its prevalence among the elderly is increasing. We investigated the effects of changes in body fat percentage (BFP) on the longitudinal changes in the estimated glomerular filtration rate (eGFR) in the elderly. This prospective cohort study included 390 participants aged >65 years who underwent bioelectrical impedance analysis at baseline and follow-up as a part of the Korean Longitudinal Study on Health and Aging. After a median follow-up period of 5.3 years, BFP was significantly higher than that at the start point (P<0.05). Participants who had the largest increase in BFP had the highest BMI and waist circumference (WC) (P<0.001). The highest tertile had the highest white blood cell count and erythrocyte sedimentation rate, incidence of rapid progression, and decline in eGFR >25% (P≤0.017, P = 0.025, P = 0.005, respectively). The lowest tertile had the lowest triglyceride and highest high-density lipoprotein levels (P<0.05). The adjusted decline rate in eGFR was correlated with a change in BFP (P = 0.039), but not with that in BMI or WC. The highest tertile had a 4.875-fold increase in the risk for rapid progression to a decline in eGFR (95% CI: 1.366–17.397) and a 4.931-fold decrease in the risk to a decline in eGFR>25% (95% CI: 1.617–15.037), when compared with the lowest tertile. In subgroup analysis, the incidence of renal outcomes was significantly increased according to the increase in BFP in patients with lower eGFR (P≤0.010). A change in BFP may be associated with inflammation and dyslipidemia development, and longitudinal changes in body fat are related to a decrease in eGFR in the elderly.     

Diethylhexyl Phthalates Is Associated with Insulin Resistance via Oxidative Stress in the Elderly: A Panel Study

Background

Insulin resistance (IR) is believed to be the underlying mechanism of metabolic syndrome and type 2 diabetes mellitus (DM). Recently, a few studies have demonstrated that phthalates could cause oxidative stress which would contribute to the development of IR. Therefore, we evaluated whether exposure to phthalates affects IR, and oxidative stress is involved in the phthalates-IR pathway.

Methods

We recruited 560 elderly participants, and obtained blood and urine samples during repeated medical examinations. For the determination of phthalate exposure, we measured urinary levels of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) as metabolites of diethylhexyl phthalates (DEHP), and mono-n-butyl phthalate (MnBP) as a metabolite of di-butyl phthalate (DBP). Malondialdehyde (MDA), an oxidative stress biomarker, was also measured in urine samples. We measured serum levels of fasting glucose and insulin, and derived the homeostatic model assessment (HOMA) index to assess IR. A mixed-effect model and penalized regression spline were used to estimate the associations among phthalate metabolites, MDA, and IR.

Results

The molar sum of MEHHP and MEOHP (∑DEHP) were significantly associated with HOMA (β = 0.26, P = 0.040), and the association was apparent among participants with a history of DM (β = 0.88, P = 0.037) and among females (β = 0.30, P = 0.022). However, the relation between MnBP and HOMA was not found. When we evaluated whether oxidative stress is involved in increases of HOMA by ∑DEHP, MDA levels were significantly associated with increases of ∑DEHP (β = 0.11, P<0.001) and HOMA (β = 0.49, P = 0.049).

Conclusions

Our study results suggest that exposure to DEHP in the elderly population increases IR, which is related with oxidative stress, and that participants with a history of DM and females are more susceptible to DEHP exposure.     

Resting-State Neuronal Oscillatory Correlates of Working Memory Performance

Purpose

Working memory (WM) represents the brain’s ability to maintain information in a readily available state for short periods of time. This study examines the resting-state cortical activity patterns that are most associated with performance on a difficult working-memory task.

Methods

Magnetoencephalographic (MEG) band-passed (delta/theta (1–7 Hz), alpha (8–13 Hz), beta (14–30 Hz)) and sensor based regional power was collected in a population of adult men (18–28 yrs, n = 24) in both an eyes-closed and eyes-open resting state. The normalized power within each resting state condition as well as the normalized change in power between eyes closed and open (zECO) were correlated with performance on a WM task. The regional and band-limited measures that were most associated with performance were then combined using singular value decomposition (SVD) to determine the degree to which zECO power was associated with performance on the three-back verbal WM task.

Results

Changes in power from eyes closed to open revealed a significant decrease in power in all band-widths that was most pronounced in the posterior brain regions (delta/theta band). zECO right posterior frontal and parietal cortex delta/theta power were found to be inversely correlated with three-back working memory performance. The SVD evaluation of the most correlated zECO metrics then provided a singular measure that was highly correlated with three-back performance (r = −0.73, p<0.0001).

Conclusion

Our results indicate that there is an association between WM performance and changes in resting-state power (right posterior frontal and parietal delta/theta power). Moreover, an SVD of the most associated zECO measures produces a composite resting-state metric of regional neural oscillatory power that has an improved association with WM performance. To our knowledge, this is the first investigation that has found that changes in resting state electromagnetic neural patterns are highly associated with verbal working memory performance.     

Slower Visuomotor Corrections with Unchanged Latency are Consistent with Optimal Adaptation to Increased Endogenous Noise in the Elderly

We analyzed age-related changes in motor response in a visuomotor compensatory tracking task. Subjects used a manipulandum to attempt to keep a displayed cursor at the center of a screen despite random perturbations to its location. Cross-correlation analysis of the perturbation and the subject response showed no age-related increase in latency until the onset of response to the perturbation, but substantial slowing of the response itself. Results are consistent with age-related deterioration in the ratio of signal to noise in visuomotor response. The task is such that it is tractable to use Bayesian and quadratic optimality assumptions to construct a model for behavior. This model assumes that behavior resembles an optimal controller subject to noise, and parametrizes response in terms of latency, willingness to expend effort, noise intensity, and noise bandwidth. The model is consistent with the data for all young (n = 12, age 20–30) and most elderly (n = 12, age 65–92) subjects. The model reproduces the latency result from the cross-correlation method. When presented with increased noise, the computational model reproduces the experimentally observed age-related slowing and the observed lack of increased latency. The model provides a precise way to quantitatively formulate the long-standing hypothesis that age-related slowing is an adaptation to increased noise.     

Subjective Somatosensory Experiences Disclosed by Focused Attention: Cortical-Hippocampal-Insular and Amygdala Contributions

In order to explore the neurobiological foundations of qualitative subjective experiences, the present study was designed to correlate objective third-person brain fMRI measures with subjective first-person identification and scaling of local, subtle, and specific somatosensory sensations, obtained directly after the imaging procedure. Thus, thirty-four volunteers were instructed to focus and sustain their attention to either provoked or spontaneous sensations of each thumb during the fMRI procedure. By means of a Likert scale applied immediately afterwards, the participants recalled and evaluated the intensity of their attention and identified specific somatosensory sensations (e.g. pulsation, vibration, heat). Using the subject''s subjective scores as covariates to model both attention intensity and general somatosensory experiences regressors, the whole-brain random effect analyses revealed activations in the frontopolar prefrontal cortex (BA10), primary somatosensory cortex (BA1), premotor cortex (BA 6), precuneus (BA 7), temporopolar cortex (BA 38), inferior parietal lobe (BA 39), hippocampus, insula and amygdala. Furthermore, BA10 showed differential activity, with ventral BA10 correlating exclusively with attention (r(32) = 0.54, p = 0.0013) and dorsal BA10 correlating exclusively with somatosensory sensation (r(32) = 0.46, p = 0.007). All other reported brain areas showed significant positive correlations solely with subjective somatosensory experiences reports. These results provide evidence that the frontopolar prefrontal cortex has dissociable functions depending on specific cognitive demands; i.e. the dorsal portion of the frontopolar prefrontal cortex in conjunction with primary somatosensory cortex, temporopolar cortex, inferior parietal lobe, hippocampus, insula and amygdala are involved in the processing of spontaneous general subjective somatosensory experiences disclosed by focused and sustained attention.     

Longitudinal Neurostimulation in Older Adults Improves Working Memory

An increasing concern affecting a growing aging population is working memory (WM) decline. Consequently, there is great interest in improving or stabilizing WM, which drives expanded use of brain training exercises. Such regimens generally result in temporary WM benefits to the trained tasks but minimal transfer of benefit to untrained tasks. Pairing training with neurostimulation may stabilize or improve WM performance by enhancing plasticity and strengthening WM-related cortical networks. We tested this possibility in healthy older adults. Participants received 10 sessions of sham (control) or active (anodal, 1.5 mA) tDCS to the right prefrontal, parietal, or prefrontal/parietal (alternating) cortices. After ten minutes of sham or active tDCS, participants performed verbal and visual WM training tasks. On the first, tenth, and follow-up sessions, participants performed transfer WM tasks including the spatial 2-back, Stroop, and digit span tasks. The results demonstrated that all groups benefited from WM training, as expected. However, at follow-up 1-month after training ended, only the participants in the active tDCS groups maintained significant improvement. Importantly, this pattern was observed for both trained and transfer tasks. These results demonstrate that tDCS-linked WM training can provide long-term benefits in maintaining cognitive training benefits and extending them to untrained tasks.     

In the Elderly,Failure to Update Internal Models Leads to Over-Optimistic Predictions about Upcoming Actions

Before an action is performed, the brain simulates the body''s dynamic behavior in relation to the environment, estimates the possible outcomes and assesses the feasibility of potential actions. Here, we tested a hypothesis whereby age-related changes in sensorimotor abilities result in failure to update internal models of action in the elderly. Young and older adults were required to judge in advance whether or not they could stand on an inclined plane (Experiment 1). Relative to young adults, elderly adults overestimated their postural capabilities: although the two groups made similar feasibility judgments, elderly participants showed significantly worse postural performance levels. This tendency to overestimate their own ability persisted when elderly adults had to not only estimate the feasibility of an action but also endanger themselves by walking towards an obstacle that was too high for them to clear (Experiment 2). An age-related failure to update internal models may prompt the elderly to make over-optimistic predictions about upcoming actions. In turn, this may favor risky motor decision-making and promote falls.     

Hand Dominance and Age Have Interactive Effects on Motor Cortical Representations

Older adults exhibit more bilateral motor cortical activity during unimanual task performance than young adults. Interestingly, a similar pattern is seen in young adults with reduced hand dominance. However, older adults report stronger hand dominance than young adults, making it unclear how handedness is manifested in the aging motor cortex. Here, we investigated age differences in the relationships between handedness, motor cortical organization, and interhemispheric communication speed. We hypothesized that relationships between these variables would differ for young and older adults, consistent with our recent proposal of an age-related shift in interhemispheric interactions. We mapped motor cortical representations of the right and left first dorsal interosseous muscles using transcranial magnetic stimulation (TMS) in young and older adults recruited to represent a broad range of the handedness spectrum. We also measured interhemispheric communication speed and bimanual coordination. We observed that more strongly handed older adults exhibited more ipsilateral motor activity in response to TMS; this effect was not present in young adults. Furthermore, we found opposing relationships between interhemispheric communication speed and bimanual performance in the two age groups. Thus, handedness manifests itself differently in the motor cortices of young and older adults and has interactive effects with age.     

Plasma IGFBP-2 Levels after Postoperative Combined Radiotherapy and Chemotherapy Predict Prognosis in Elderly Glioblastoma Patients

It has been found that preoperative plasma IGFBP-2 levels correlate with prognosis in glioma patients. The prognostic value of plasma IGFBP-2 after postoperative combined radiotherapy and chemotherapy in glioma patients is unknown. Plasma IGFBP-2 levels in 83 glioblastoma patients after postoperative radiotherapy plus chemotherapy were analyzed using an IGFBP-2 ELISA kit. We found that after standard therapy plasma IGFBP-2 levels significantly correlated with the patient''s age (R = 0.738, P<0.001) and Karnofsky performance status (KPS, R = −0.633, P<0.05). Cox proportional hazards models were used to calculate hazard ratios (HRs) of death according to plasma IGFBP-2 levels adjusted for patient clinical characteristics. Plasma IGFBP-2 levels significantly correlated with overall survival in glioblastoma patients (multivariate HR = 1.035; 95% CI, 1.024–1.047; P<0.001). The effect of plasma IGFBP-2 levels on survival seemed to differ according to patients'' age. Among patients older than 60, high plasma IGFBP-2 levels were associated with a significant increase in overall mortality (HR = 1.097; 95% CI, 1.055–1.140; P<0.001). In contrast, plasma IGFBP-2 levels conferred no significant effect on mortality among patients younger than 60. Elevated plasma IGFBP-2 levels after combined postoperative radiotherapy and chemotherapy in elderly glioblastoma patients correlate with poor KPS score and predicts poor prognosis.     

Computerized Cognitive Training in Cognitively Healthy Older Adults: A Systematic Review and Meta-Analysis of Effect Modifiers

Background

New effective interventions to attenuate age-related cognitive decline are a global priority. Computerized cognitive training (CCT) is believed to be safe and can be inexpensive, but neither its efficacy in enhancing cognitive performance in healthy older adults nor the impact of design factors on such efficacy has been systematically analyzed. Our aim therefore was to quantitatively assess whether CCT programs can enhance cognition in healthy older adults, discriminate responsive from nonresponsive cognitive domains, and identify the most salient design factors.

Methods and Findings

We systematically searched Medline, Embase, and PsycINFO for relevant studies from the databases'' inception to 9 July 2014. Eligible studies were randomized controlled trials investigating the effects of ≥4 h of CCT on performance in neuropsychological tests in older adults without dementia or other cognitive impairment. Fifty-two studies encompassing 4,885 participants were eligible. Intervention designs varied considerably, but after removal of one outlier, heterogeneity across studies was small (I ² = 29.92%). There was no systematic evidence of publication bias. The overall effect size (Hedges'' g, random effects model) for CCT versus control was small and statistically significant, g = 0.22 (95% CI 0.15 to 0.29). Small to moderate effect sizes were found for nonverbal memory, g = 0.24 (95% CI 0.09 to 0.38); verbal memory, g = 0.08 (95% CI 0.01 to 0.15); working memory (WM), g = 0.22 (95% CI 0.09 to 0.35); processing speed, g = 0.31 (95% CI 0.11 to 0.50); and visuospatial skills, g = 0.30 (95% CI 0.07 to 0.54). No significant effects were found for executive functions and attention. Moderator analyses revealed that home-based administration was ineffective compared to group-based training, and that more than three training sessions per week was ineffective versus three or fewer. There was no evidence for the effectiveness of WM training, and only weak evidence for sessions less than 30 min. These results are limited to healthy older adults, and do not address the durability of training effects.

Conclusions

CCT is modestly effective at improving cognitive performance in healthy older adults, but efficacy varies across cognitive domains and is largely determined by design choices. Unsupervised at-home training and training more than three times per week are specifically ineffective. Further research is required to enhance efficacy of the intervention. Please see later in the article for the Editors'' Summary     

Features of temporal dynamics of oscillatory brain activity during creative problem solving in young and elderly adults

Considering evidence from psychological research, successful aging is accompanied by long-term preservation of creative potential despite slowing of mental processes; however, the neurophysiological mechanisms that ensure the maintenance of those abilities are unclear. In this study, we compared temporal dynamics of changes induced by divergent task electrical activity (event-related spectral perturbations, ERSP) in a wide range of EEG frequencies in the younger (YA, N = 80, 22.6 ± 3 years) and older (OA, N = 80, 63.4 ± 6.7 years) age groups. The groups were sex-matched. EEG was recorded while participants performed the “alternate uses task”. The time ranges 200–400, 400–600 and 600–800 ms after stimulus presentation were analyzed. It was found that task performance was associated with distinct patterns of ERSP changes in the θ and α₃ rhythms in young and elderly subjects. The elderly subjects exhibited smaller θ-desyn-chronization of anterior brain areas at the initial stage of creative thinking as compared to young participants. The gradient of fronto-parietal activation was unchanged during the entire interval of analysis in the elderly subjects, whereas it was observed in young adults in the interval 200–400 ms only. Decrease in desynchronization of the parieto-occipital area in the α₃ rhythm in the interval 600–800 ms in elderly subjects was revealed, and it resulted in disappearance of differences between parietal and fronto-temporal areas, while they were preserved in the young group. Significant correlations between ERSP in the α₃ band and originality, in the β₁ band and solution rate were obtained in old adults exclusively. Identified age-related changes in oscillatory activity may be the basis of different strategies in solving creative task in young and elderly adults.     

Impaired Prefrontal Hemodynamic Maturation in Autism and Unaffected Siblings

Background

Dysfunctions of the prefrontal cortex have been previously reported in individuals with autism spectrum disorders (ASD). Previous studies reported that first-degree relatives of individuals with ASD show atypical brain activity during tasks associated with social function. However, developmental changes in prefrontal dysfunction in ASD and genetic influences on the phenomena remain unclear. In the present study, we investigated the change in hemoglobin concentration in the prefrontal cortex as measured with near-infrared spectroscopy, in children and adults with ASD during the letter fluency test. Moreover, to clarify the genetic influences on developmental changes in the prefrontal dysfunction in ASD, unaffected siblings of the ASD participants were also assessed.

Methodology/Principal Findings

Study participants included 27 individuals with high-functioning ASD, age- and IQ-matched 24 healthy non-affected siblings, and 27 unrelated healthy controls aged 5 to 39 years. The relative concentration of hemoglobin ([Hb]) in the prefrontal cortex was measured during the letter fluency task. For children, neither the [oxy-Hb] change during the task nor task performances differed significantly among three groups. For adults, the [oxy-Hb] increases during the task were significantly smaller in the bilateral prefrontal cortex in ASD than those in control subjects, although task performances were similar. In the adult siblings the [oxy-Hb] change was intermediate between those in controls and ASDs.

Conclusion/Significance

Although indirectly due to a cross-sectional design, the results of this study indicate altered age-related change of prefrontal activity during executive processing in ASD. This is a first near-infrared spectroscopy study that implies alteration in the age-related changes of prefrontal activity in ASD and genetic influences on the phenomena.     

Shear Modulus Estimation on Vastus Intermedius of Elderly and Young Females over the Entire Range of Isometric Contraction

Elderly people often suffer from sarcopenia in their lower extremities, which gives rise to the increased susceptibility of fall. Comparing the mechanical properties of the knee extensor/flexors on elderly and young subjects is helpful in understanding the underlying mechanisms of the muscle aging process. However, although the stiffness of skeletal muscle has been proved to be positively correlated to its non-fatiguing contraction intensity by some existing methods, this conclusion has not been verified above 50% maximum voluntary contraction (MVC) due to the limitation of their measurement range. In this study, a vibro-ultrasound system was set up to achieve a considerably larger measurement range on muscle stiffness estimation. Its feasibility was verified on self-made silicone phantoms by comparing with the mechanical indentation method. The system was then used to assess the stiffness of vastus intermedius (VI), one of the knee extensors, on 10 healthy elderly female subjects (56.7±4.9 yr) and 10 healthy young female subjects (27.6±5.0 yr). The VI stiffness in its action direction was confirmed to be positively correlated to the % MVC level (R² = 0.999) over the entire range of isometric contraction, i.e. from 0% MVC (relaxed state) to 100% MVC. Furthermore, it was shown that there was no significant difference between the mean VI shear modulus of the elderly and young subjects in a relaxed state (p>0.1). However, when performing step isometric contraction, the VI stiffness of young female subjects was found to be larger than that of elderly participants (p<0.001), especially at the relatively higher contraction levels. The results expanded our knowledge on the mechanical property of the elderly’s skeletal muscle and its relationship with intensity of active contraction. Furthermore, the vibro-ultrasound system has a potential to become a powerful tool for investigating the elderly’s muscle diseases.     

Low-Grade Albuminuria Is Associated with Metabolic Syndrome and Its Components in Middle-Aged and Elderly Chinese Population

Background

Micro-albuminuria has been well established as one of the risk factors of metabolic syndrome (MetS). However, the association of MetS and its components with low-grade albuminuria among those with normal urinary albumin excretion has not been clearly elucidated in Chinese population.

Methodology and Findings

A cross-sectional study was conducted among 9,579 participants with normal urinary albumin excretion, who were recruited from Jia Ding District, Shanghai, China. The single-void first morning urine sample was collected for urinary albumin and creatinine measurements, and urinary albumin-to-creatinine ratio (UACR) was calculated as urinary albumin divided by creatinine. Low-grade albuminuria was classified as sex-specific upper UACR quartile in this population. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence of MetS and its components increased across the UACR quartiles (all P _trend <0.01). A multivariable adjusted logistic regression analysis revealed that the prevalence of MetS was gradually elevated according to the UACR quartiles (adjusted odds ratios [ORs] were 1.14, 1.24 and 1.59 for UACR quartiles 2, 3 and 4, compared with the lowest quartile; P _trend<0.0001). In the further stratified logistic regression analyses, the associations between low-grade albuminuria and MetS were significant in both sex strata (male and female), both age strata (<60 and ≥60 years), both body mass index strata (<24 and ≥24 kg/m²), and both diabetes strata (yes and no). Compared to the lowest UACR quartile, the participants in the highest quartile of UACR had the highest prevalence of central obesity (OR = 1.43; 95%CI = 1.25–1.63), high blood pressure (OR = 1.64; 95%CI = 1.43–1.87), hyperglycemia (OR = 1.52; 95%CI = 1.30–1.78) and high triglycerides (OR = 1.19; 95%CI = 1.04–1.37).

Conclusions and Significance

Low-grade albuminuria was significantly associated with the increasing prevalence of MetS and its components in the middle-aged and elderly Chinese population with normal urinary albumin excretion.     

Prevalence and Correlates of Dental Caries in an Elderly Population in Northeast China

Objectives

The present study aimed to investigate the prevalence and correlates of dental caries in elderly population in northeast China.

Methods

A community-based, cross-sectional study among 2376 elderly subjects (age: 65–74 years) from nine urban areas and nine rural areas in three provinces of northeast China was conducted using multistage stratified random sampling per the World Health Organization oral health survey methodology. Decayed-missing-filled teeth (DMFT) and decayed-filled teeth (DFT) indices were used to evaluate the prevalence of dental caries. Face-to-face questionnaire survey on oral health was performed in a randomly selected subset (n = 1197). T test and chi square test were employed to compare groups for continuous and categorical variables, respectively. Multivariate logistic regression was used to estimate odds ratios (ORs) and corresponding confidence intervals (CIs).

Results

67.5% of elderly subjects reported dental caries (average DFT = 2.68±3.40), and the prevalence was higher in urban areas (P<0.01). Missing teeth accounted for 80.72% of DMFT, and filled teeth due to caries accounted for 2.08% with a rate higher in urban areas (P<0.01). Logistic regression analysis indicated significant association among elderly population in urban areas (OR 1.713; 95% CI 1.337–2.195), smoking (OR 1.779; 95% CI 1.384–2.288), and individuals without dental insurance (OR 2.050; 95% CI 1.120–3.754) with dental caries.

Conclusions

The prevalence of dental caries in the elderly population in northeast China is high. The elderly from urban areas who smoke and who do not have a dental insurance are at a higher risk to develop dental caries.     

Neuroanatomical Heterogeneity of Essential Tremor According to Propranolol Response

Background

Recent studies have suggested that essential tremor (ET) is a more complex and heterogeneous clinical entity than initially thought. In the present study, we assessed the pattern of cortical thickness and diffusion tensor white matter (WM) changes in patients with ET according to the response to propranolol to explore the pathogenesis underlying the clinical heterogeneity of ET.

Methods

A total of 32 patients with drug naive ET were recruited prospectively from the Movement Disorders outpatient clinic. The patients were divided into a propranolol-responder group (n = 18) and a non-responder group (n = 14). We analyzed the pattern of cortical thickness and diffusion tensor WM changes between these two groups and performed correlation analysis between imaging and clinical parameters.

Results

There were no significant differences in demographic characteristics, general cognition, or results of detailed neuropsychological tests between the groups. The non-responder group showed more severe cortical atrophy in the left orbitofrontal cortex and right temporal cortex relative to responders. However, the responders exhibited significantly lower fractional anisotropy values in the bilateral frontal, corpus callosal, and right parietotemporal WM compared with the non-responder group. There were no significant clusters where the cortical thickness or WM alterations were significantly correlated with initial tremor severity or disease duration.

Conclusions

The present data suggest that patients with ET have heterogeneous cortical thinning and WM alteration with respect to responsiveness to propranolol, suggesting that propranolol responsiveness may be a predictive factor to determine ET subtypes in terms of neuroanatomical heterogeneity.     

Altered Pattern of Spontaneous Brain Activity in the Patients with End-Stage Renal Disease: A Resting-State Functional MRI Study with Regional Homogeneity Analysis

Purpose

To investigate the pattern of spontaneous neural activity in patients with end-stage renal disease (ESRD) with and without neurocognitive dysfunction using resting-state functional magnetic resonance imaging (rs-fMRI) with a regional homogeneity (ReHo) algorithm.

Materials and Methods

rs-fMRI data were acquired in 36 ESRD patients (minimal nephro-encephalopathy [MNE], n = 19, 13 male, 37±12.07 years; non-nephro-encephalopathy [non-NE], n = 17, 11 male, 38±12.13 years) and 20 healthy controls (13 male, 7 female, 36±10.27 years). Neuropsychological (number connection test type A [NCT-A], digit symbol test [DST]) and laboratory tests were performed in all patients. The Kendall''s coefficient of concordance (KCC) was used to measure the regional homogeneity for each subject. The regional homogeneity maps were compared using ANOVA tests among MNE, non-NE, and healthy control groups and post hoc t -tests between each pair in a voxel-wise way. A multiple regression analysis was performed to evaluate the relationships between ReHo index and NCT-A, DST scores, serum creatinine and urea levels, disease and dialysis duration.

Results

Compared with healthy controls, both MNE and non-NE patients showed decreased ReHo in the multiple areas of bilateral frontal, parietal and temporal lobes. Compared with the non-NE, MNE patients showed decreased ReHo in the right inferior parietal lobe (IPL), medial frontal cortex (MFC) and left precuneus (PCu). The NCT-A scores and serum urea levels of ESRD patients negatively correlated with ReHo values in the frontal and parietal lobes, while DST scores positively correlated with ReHo values in the bilateral PCC/precuneus, MFC and inferior parietal lobe (IPL) (all P<0.05, AlphaSim corrected). No significant correlations were found between any regional ReHo values and disease duration, dialysis duration and serum creatinine values in ESRD patients (all P>0.05, AlphaSim corrected).

Conclusion

Diffused decreased ReHo values were found in both MNE and non-NE patients. The progressively decreased ReHo in the default mode network (DMN), frontal and parietal lobes might be trait-related in MNE. The ReHo analysis may be potentially valuable for elucidating neurocognitive abnormalities of ESRD patients and detecting the development from non-NE to MNE.     

Changes in White Matter Integrity before Conversion from Mild Cognitive Impairment to Alzheimer’s Disease

Background

Mild cognitive impairment (MCI) may represent an early stage of dementia conferring a particularly high annual risk of 15–20% of conversion to Alzheimer’s disease (AD). Recent findings suggest that not only gray matter (GM) loss but also a decline in white matter (WM) integrity may be associated with imminent conversion from MCI to AD.

Objective

In this study we used Voxel-based morphometry (VBM) to examine if gray matter loss and/or an increase of the apparent diffusion coefficient (ADC) reflecting mean diffusivity (MD) are an early marker of conversion from MCI to AD in a high risk population.

Method

Retrospective neuropsychological and clinical data were collected for fifty-five subjects (MCI converters n = 13, MCI non-converters n = 14, healthy controls n = 28) at baseline and one follow-up visit. All participants underwent diffusion weighted imaging (DWI) and T1-weighted structural magnetic resonance imaging scans at baseline to analyse changes in GM density and WM integrity using VBM.

Results

At baseline MCI converters showed impaired performance in verbal memory and naming compared to MCI non-converters. Further, MCI converters showed decreased WM integrity in the frontal, parietal, occipital, as well as the temporal lobe prior to conversion to AD. Multiple regression analysis showed a positive correlation of gray matter atrophy with specific neuropsychological test results.

Conclusion

Our results suggest that additionally to morphological changes of GM a reduced integrity of WM indicates an imminent progression from MCI stage to AD. Therefore, we suggest that DWI is useful in the early diagnosis of AD.