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1.

Introduction

The impact of prediabetes and diabetes on cognitive decline and the potential underlying mechanisms remain unclear. We investigated whether prediabetes and diabetes accelerate cognitive decline and brain aging, and the initial pathological changes linked to microvascular processes.

Methods

Nine-year longitudinal data from the Swedish National Study on Aging and Care-Kungsholmen (n = 2746, age ≥60 years) and the magnetic resonance imaging subsample (n = 455) were used. Cognitive function was assessed with Mini-Mental State Examination. Brain magnetic resonance imaging markers included total brain tissue, white matter, gray matter, white matter hyperintensities, and hippocampal volumes.

Results

Compared with diabetes-free status, prediabetes and diabetes were independently associated with accelerated cognitive decline. Prediabetes was cross-sectionally associated with smaller total brain tissue volume (P < .01), particularly smaller white matter volume. Diabetes was associated with larger white matter hyperintensities volume. Longitudinally, diabetes was associated with faster white matter hyperintensities accumulation. No associations between prediabetes or diabetes and hippocampal volume were found.

Discussion

Diabetes and prediabetes accelerate cognitive decline and might predict microvascular lesions among dementia-free older adults.  相似文献   

2.

Introduction

Nonhuman primates may serve as excellent models of sporadic age-associated brain β-amyloid deposition and Alzheimer's disease pathologic changes. We examined whether a vervet nonhuman primate model recapitulated pathologic, physiologic, and behavioral features of early Alzheimer's disease.

Methods

Nine middle-aged (mean = 11.2 years) and nine aged (mean = 21.7 years) female vervet/African green monkeys underwent cerebrospinal fluid collection, gait speed measurement, and neuroimaging before neuropathologic assessment.

Results

β-amyloid plaques were identified in all aged vervets and paired helical filament tau immunoreactivity was observed in all animals. Cerebrospinal fluid β-amyloid42 and gait speed correlated negatively with age and plaque density. Greater plaque and paired helical filament tau burden predicted reduced volumes and CMRg in several brain regions.

Discussion

We observed a coordinated set of relationships among neuropathologic, cerebrospinal fluid, imaging, and behavioral modalities consistent with early Alzheimer's disease. Our results support future use of the vervet model to explore disease mechanisms, biomarkers, and novel therapeutic strategies.  相似文献   

3.

Introduction

Little is known about dementia incidence in diverse populations of oldest-old, the age group with highest dementia incidence.

Methods

Incident dementia diagnoses from 1/1/2010 to 9/30/2015 were abstracted from medical records for 2350 members of an integrated health care system in California (n = 1702 whites, n = 375 blacks, n = 105 Latinos, n = 168 Asians) aged ≥90 in 2010. We estimated race/ethnicity-specific age-adjusted dementia incidence rates and implemented Cox proportional hazards models and Fine and Gray competing risk of death models adjusted for demographics and comorbidities in midlife and late-life.

Results

Dementia incidence rates (n = 771 cases) were lowest among Asians (89.9/1000 person-years), followed by whites (96.9/1000 person-years), Latinos (105.8/1000 person-years), and blacks (121.5/1000 person-years). Cox regression and competing risk models estimated 28% and 36% higher dementia risk for blacks versus whites adjusting for demographics and comorbidities.

Discussion

Patterns of racial/ethnic disparities in dementia seen in younger older adults continue after the age of 90 years, though smaller in magnitude.  相似文献   

4.

Introduction

The level of the presynaptic protein growth-associated protein 43 (GAP-43) in cerebrospinal fluid (CSF) has previously been shown to be increased in Alzheimer's disease (AD) and thus may serve as an outcome measure in clinical trials and facilitate earlier disease detection.

Methods

We developed an enzyme-linked immunosorbent assay for CSF GAP-43 and measured healthy controls (n = 43), patients with AD (n = 275), or patients with other neurodegenerative diseases (n = 344). In a subpopulation (n = 93), CSF GAP-43 concentrations from neuropathologically confirmed cases were related to Aβ plaques, tau, α-synuclein, and TDP-43 pathologies.

Results

GAP-43 was significantly increased in AD compared to controls and most neurodegenerative diseases and correlated with the magnitude of neurofibrillary tangles and Aβ plaques in the hippocampus, amygdala, and cortex. GAP-43 was not associated to α-synuclein or TDP-43 pathology.

Discussion

The presynaptic marker GAP-43 is associated with both diagnosis and neuropathology of AD and thus may be useful as a sensitive and specific biomarker for clinical research.  相似文献   

5.

Background

Maternal cortisol during pregnancy has the potential to influence rapidly developing fetal brain systems that are commonly altered in neurodevelopmental and psychiatric disorders. Research examining maternal cortisol concentrations across pregnancy and offspring neurodevelopment proximal to birth is needed to advance understanding in this area and lead to insight into the etiology of these disorders.

Methods

Participants were 70 adult women recruited during early pregnancy and their infants born after 34 weeks gestation. Maternal cortisol concentrations were assessed serially over 4 days in early, mid, and late gestation. Resting state functional connectivity magnetic resonance imaging of the neonatal amygdala was examined. Mothers reported on children’s internalizing behavior problems at 24 months of age.

Results

Maternal cortisol concentrations during pregnancy were significantly associated with neonatal amygdala connectivity in a sex-specific manner. Elevated maternal cortisol was associated with stronger amygdala connectivity to brain regions involved in sensory processing and integration, as well as the default mode network in girls, and with weaker connectivity to these brain regions in boys. Elevated maternal cortisol was associated with higher internalizing symptoms in girls only, and this association was mediated by stronger neonatal amygdala connectivity.

Conclusions

Normative variation in maternal cortisol during pregnancy is associated with the coordinated functioning of the amygdala soon after birth in a sex-specific manner. The identified pathway from maternal cortisol to higher internalizing symptoms in girls via alterations in neonatal amygdala connectivity may be relevant for the etiology of sex differences in internalizing psychiatric disorders, which are more prevalent in women.  相似文献   

6.

Background

Repetitive transcranial magnetic stimulation (rTMS) is considered as an effective treatment for adults with major depressive disorder. However, it remains unknown whether rTMS has comparable or better efficacy in adolescents.

Objective

The current naturalistic study aimed to investigate the efficacy and clinical outcome of add-on rTMS in a large sample of adolescent patients compared to adult patients.

Methods

This study included 117 patients (42 adolescents vs. 75 adults) with mood or anxiety disorders who were treated with at least 10 sessions of rTMS. rTMS was applied over the left dorsolateral prefrontal cortex (10?Hz). Symptoms of depression and anxiety were measured using the Hamilton Rating Scale for Depression (HAMD) and the Hamilton Rating Scale for Anxiety (HAMA) respectively, at baseline and after 2 and 4 weeks of follow-up. Comparisons of clinical improvement and rates of response/remission were made across age groups.

Major findings and conclusions

All the age groups showed significant improvements in clinical symptoms. No safety or tolerability concerns were identified. Symptomatic improvements and response/remission rates were more significant in adolescent patients than in adults. Decrease in HAMD and HAMA scores after 2 weeks and 4 weeks of rTMS treatment were positively correlated in adolescents, but not in adults. General linear model repeated measures demonstrated significant effect of time?×?age group interaction on the HAMD score, in response to 10 sessions of rTMS. Add-on rTMS is feasible, tolerable, effective and more applicable to adolescents with mood or anxiety disorders. However, double-blinded and sham-controlled trials are needed for validating this conclusion.  相似文献   

7.

Introduction

Associations between the Mediterranean-DASH diet Intervention for Neurological Delay (MIND) diet and incidence of cognitive impairment have not been evaluated outside the United States.

Methods

We investigated MIND and Mediterranean diet relations with 12-year incidence of Alzheimer's disease/Vascular dementia (National Institute of Neurological Disorders criteria) and mild cognitive impairment (Winbald criteria) in the Personality and Total Health (PATH) Through Life cohort (n = 1220) set in Canberra, Australia: wave-1 2001-2002; wave-2 2005-2006; wave-3 2009-2010; and wave-4 2013-2014.MIND diet and two alternate Mediterranean diet scores were calculated from the baseline food frequency questionnaire responses. Higher dietary scores signified greater adherence.

Results

In adjusted logistic regression models, MIND diet (OR = 0.47, 95% CI 0.24, 0.91), but not Mediterranean diet, was associated with reduced odds of 12-year cognitive impairment.

Discussion

Preliminary evidence suggests that protective effects of the MIND diet are geographically generalizable. Additional prospective studies are needed in diverse samples to determine the relative effects of the MIND and the Mediterranean diets against cognitive decline.  相似文献   

8.

Background

Inhibitory deficits in motor cortex in schizophrenia have been well demonstrated using short-interval intracortical inhibition (SICI) by transcranial magnetic stimulation. However, it remains unknown whether these deficits originate from dysfunction of motor cortex itself or reflect abnormal modulations of motor cortex by other schizophrenia-related brain areas.

Methods

The study was completed by 24 patients with schizophrenia spectrum disorders and 30 healthy control subjects. SICI was obtained by delivering transcranial magnetic stimulation over the left motor cortex. Resting-state functional magnetic resonance imaging and diffusion tensor imaging fractional anisotropy were used to measure functional connectivity (FC) and white matter microstructures, respectively. Stimulation sites for SICI at motor cortex were used as the seeds to obtain whole-brain FC maps. Clinical symptoms were assessed with the Brief Psychiatric Rating Scale.

Results

In schizophrenia, left prefrontal cortex–motor cortex FC was inversely associated with SICI but positively associated with the underlying white matter microstructure at the left corona radiata and also associated with overall symptoms (all corrected p < .05). Mediation analysis showed that the prefrontal-motor cortex FC significantly mediated the corona radiata white matter effects on SICI (p = .007).

Conclusions

Higher resting-state left prefrontal-motor cortex FC, accompanied by a higher fractional anisotropy of left corona radiata, predicted fewer inhibitory deficits, suggesting that the inhibitory deficits in motor cortex in schizophrenia may in part be mediated by a top-down prefrontal influence. SICI may serve as a robust biomarker indexing inhibitory dysfunction at anatomic as well as circuitry levels in schizophrenia.  相似文献   

9.

Background

Previous studies have shown associations between maternal infections during pregnancy and increased risks of schizophrenia and autism spectrum disorder in the offspring. However, large-scale studies investigating an association between parental infections both during and outside the pregnancy period and the risk of any mental disorder in the child are lacking.

Methods

A nationwide Danish cohort study identified 1,206,600 children born between 1996 and 2015 and followed them to a maximum of 20 years of age. Exposure included all maternal and paternal infections treated with anti-infective agents or hospital contacts before, during, or after pregnancy. The main outcome was a diagnosis of any mental disorder in the child. Hazard ratios (HRs) were calculated using Cox regression analysis.

Results

Maternal infections during pregnancy treated with anti-infective agents (n = 567,016) increased the risk of mental disorders (n = 70,037) in the offspring (HR, 1.09; 95% confidence interval [CI], 1.06–1.12), which was more elevated (p < .001) than after paternal infections (n = 350,835; HR, 1.01; 95% CI, 0.98–1.03). Maternal hospital contacts for infections (n = 39,753) conferred an increased HR of 1.21 (95% CI, 1.14–1.28), which was not significantly (p = .08) different from the risk after paternal infections (n = 8559; HR, 1.07; 95% CI, 0.95–1.20). The increased risks observed during pregnancy were not different from the similarly increased risks for maternal and paternal infections before and after pregnancy. The risk of mental disorders increased in a dose-response relationship with the number of maternal infections treated with anti-infective agents, particularly during and after pregnancy (both p < .001).

Conclusions

Maternal infections were associated with an increased risk of mental disorder in the offspring; however, there were similar estimates during and outside the pregnancy period.  相似文献   

10.

Introduction

Psychogenic non-epileptic seizures (PNES) are paroxysms of either altered subjective or objective manifestations that may mimic epileptic seizures (ES), without abnormal neuronal epileptiform activity. In this report, we present the case of a 39-year-old woman with PNES and functional movement disorders, who was successfully treated with neuro-guided transcranial direct current stimulation (tDCS).

Methods

We used a PET-guided tDCS approach, as a hypometabolism of the frontal region was revealed by FDG TEP scan. TDCs was performed 5 days/week, 2 times/day, during 3 weeks. All clinical manifestations were reported in a seizure diary. We also assessed dissociation, depression, alexithymia, psychotraumatic scales, and involuntary movements.

Results

The treatment was followed by a decrease of both psychogenic involuntary movements and PNES at 5 weeks. At the same time, PTSD symptoms, dissociative symptoms, depression and alexithymia improved.

Conclusion

PET-scan and tDCS seems to be promising tools for the evaluation and treatment of PNES in clinical practice, and may have a specific role on dissociative symptoms.  相似文献   

11.

Introduction

We evaluated whether hospitalization with or without surgery increases risk for dementia or Alzheimer's disease.

Methods

A clinical sample (843 clinically diagnosed dementia cases; 1686 matched nondemented individuals) was identified from Swedish Twin Registry studies. A register-based sample (4293 cases; 21,465 matched controls) was identified by linkage of Swedish Twin Registry to Swedish Patient Registry records. Apolipoprotein E (APOE) status and within-pair comparisons of dementia discordant twins indicated genetic susceptibility.

Results

Nonsurgical hospitalization is associated with greater dementia risk than hospitalization with surgical intervention. In the register sample, thoracic, abdominal, and major orthopedic procedures entailed dementia risk; in the clinical sample, orthopedic alone. Within-pair analyses indicate that associations in part reflect genetic susceptibility in common to hospitalization and dementia. Potential gene-environment interactions were indicated by greater risk due to hospitalization among APOE ε4 noncarriers.

Discussion

We confirm hospitalization as a risk factor for dementia, with repeated hospitalizations a more important risk factor than surgery.  相似文献   

12.

Background

Elevated striatal dopamine synthesis capacity has been implicated in the etiology and antipsychotic response in psychotic illness. The effects of antipsychotic medication on dopamine synthesis capacity are poorly understood, and no prospective studies have examined this question in a solely first-episode psychosis sample. Furthermore, it is unknown whether antipsychotic efficacy is linked to reductions in dopamine synthesis capacity. We conducted a prospective [18F]-dihydroxyphenyl-L-alanine positron emission tomography study in antipsychotic naïve/free people with first-episode psychosis commencing antipsychotic treatment.

Methods

Dopamine synthesis capacity (indexed as influx rate constant) and clinical symptoms (measured using Positive and Negative Syndrome Scale) were measured before and after at least 5 weeks of antipsychotic treatment in people with first-episode psychosis. Data from a prior study indicated that a sample size of 13 would have >80% power to detect a statistically significant change in dopamine synthesis capacity at alpha = .05 (two tailed).

Results

A total of 20 people took part in the study, 17 of whom were concordant with antipsychotic medication at therapeutic doses. There was no significant effect of treatment on dopamine synthesis capacity in the whole striatum (p = .47), thalamus, or midbrain, nor was there any significant relationship between change in dopamine synthesis capacity and change in positive (ρ = .35, p = .13), negative, or total psychotic symptoms.

Conclusions

Dopamine synthesis capacity is unaltered by antipsychotic treatment, and therapeutic effects are not mediated by changes in this aspect of dopaminergic function.  相似文献   

13.

Introduction

Few population studies have investigated whether longitudinal decline after delirium in mid-to-late life might affect specific cognitive domains.

Methods

Participants from a birth cohort completing assessments of search speed, verbal memory, and the Addenbrooke's Cognitive Examination at age 69 were asked about delirium symptoms between ages 60 and 69 years. Linear regression models estimated associations between delirium symptoms and cognitive outcomes.

Results

Period prevalence of delirium between 60 and 69 years was 4% (95% confidence interval 3.2%–4.9%). Self-reported symptoms of delirium over the seventh decade were associated with worse scores in the Addenbrooke's Cognitive Examination (?1.7 points; 95% confidence interval ?3.2, ?0.1; P = .04). In association with delirium symptoms, verbal memory scores were initially lower, with subsequent decline in search speed by the age of 69 years. These effects were independent of other Alzheimer's risk factors.

Discussion

Delirium symptoms may be common even at relatively younger ages, and their presence may herald cognitive decline, particularly in search speed, over this time period.  相似文献   

14.

Background

Schizophrenia is a highly disabling psychiatric disorder characterized by a range of positive “psychosis” symptoms. However, the neurobiology of psychosis and associated systems-level disruptions in the brain remain poorly understood. Here, we test an aberrant saliency model of psychosis, which posits that dysregulated dynamic cross-network interactions among the salience network (SN), central executive network, and default mode network contribute to positive symptoms in patients with schizophrenia.

Methods

Using task-free functional magnetic resonance imaging data from two independent cohorts, we examined 1) dynamic time-varying cross-network interactions among the SN, central executive network, and default mode network in 130 patients with schizophrenia versus well-matched control subjects; 2) accuracy of a saliency model–based classifier for distinguishing dynamic brain network interactions in patients versus control subjects; and 3) the relation between SN-centered network dynamics and clinical symptoms.

Results

In both cohorts, we found that dynamic SN-centered cross-network interactions were significantly reduced, less persistent, and more variable in patients with schizophrenia compared with control subjects. Multivariate classification analysis identified dynamic SN-centered cross-network interaction patterns as factors that distinguish patients from control subjects, with accuracies of 78% and 80% in the two cohorts, respectively. Crucially, in both cohorts, dynamic time-varying measures of SN-centered cross-network interactions were correlated with positive, but not negative, symptoms.

Conclusions

Aberrations in time-varying engagement of the SN with the central executive network and default mode network is a clinically relevant neurobiological signature of psychosis in schizophrenia. Our findings provide strong evidence for dysregulated brain dynamics in a triple-network saliency model of schizophrenia and inform theoretically motivated systems neuroscience approaches for characterizing aberrant brain dynamics associated with psychosis.  相似文献   

15.

Background

Evidence links infections to mental disorders and suicidal behavior. However, knowledge is sparse regarding less severe infections, anti-infective treatment, and deliberate self-harm. Using nationwide Danish longitudinal registers, we estimated associations between infections treated with anti-infective agents and infections requiring hospitalization with the risk of deliberate self-harm.

Methods

A total of 1.3 million people born between 1977 and 2002 were followed during the period from 1995 to 2013. In total, 15,042 individuals were recorded with deliberate self-harm (92% had been treated with anti-infective agents and 19% had been hospitalized for infections) and 114 died by suicide (64% had been treated with anti-infective agents and 13% had been hospitalized for infections). Hazard rate ratios were obtained while adjusting for age, gender, calendar period, education, hospitalizations with infections, prescribed anti-infective agents during childhood, parental mental disorders, and parental deliberate self-harm.

Results

Individuals with infections treated with anti-infective agents had an increased risk of deliberate self-harm with a hazard rate ratio of 1.80 (95% confidence interval = 1.68–1.91). The associations fitted a dose–response relationship (p < .001) and remained significant up to 5 years after last infection. An additive effect was found for individuals with an additional hospitalization for infections with an increased hazard rate ratio of 3.20 (95% confidence interval = 2.96–3.45) for deliberate self-harm.

Conclusions

An increased risk of deliberate self-harm was found among individuals with infections treated with anti-infective agents in temporal and dose–response associations. These results add to the growing literature on a possible link between infections and the pathophysiological mechanisms of suicidal behavior.  相似文献   

16.

Background

Accounts of cognitive processes in judgment and decision-making are frequently based on a dual-process framework, which reflects two qualitatively different types of processing: intuitive (Type 1) and analytical (Type 2) processes.

Objective

The present study investigated the effects of bilateral transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) on judgment and decision-making performance.

Methods

Participants received anodal tDCS stimulation to the right DLPFC, left DLPFC or sham. There were 3 tasks: vignettes measuring heuristic thinking, belief bias syllogisms, and the cognitive reflection test (CRT), a measure of the ability to inhibit automatic responses to reach a correct solution. Fifty-four participants (mean age?=?24.63?±?4.46 years; 29 females) were recruited.

Results

Results showed that anodal tDCS to the right DLPFC was associated with an increase in cognitive reflection performance (Type 2 processing) as compared to left DLPFC and to sham. Logic thinking was reduced following anodal tDCS to the left DLPFC.

Conclusion

These findings are broadly consistent with a dual process framework, and cannot be explained by differences in cognitive ability and thinking style. The results demonstrate the involvement of the right DLPFC in cognitive reflection, and suggest the possibility of improving cognitive performance through tDCS.  相似文献   

17.

Introduction

The living environment affects general health and may influence cognitive aging; however, the relationships between neighborhood characteristics and dementia are still poorly understood.

Methods

We used data from a French population–based prospective study (the Three-City cohort) that included 7016 participants aged 65 years and older with a 12-year follow-up. We used principal components analysis of neighborhood composition indicators to construct the Three-City deprivation score. To study its impact on dementia incidence, we performed survival analyses using a marginal Cox model to take into account intraneighborhood correlations. As interaction with sex was significant, analyses were stratified by sex.

Results

Even after controlling on individual factors, women living in deprived neighborhoods were at higher risk of dementia (hazard ratio = 1.29, 95% confidence interval 1.00–1.67) and Alzheimer's disease (hazard ratio = 1.42, 95% confidence interval 1.09–1.84). No association was found for men.

Discussion

Living in a deprived neighborhood is associated with higher risk of dementia in women.  相似文献   

18.

Background

Major depressive disorder (MDD) is a multifactorial disease which often coexists with cognitive deficits. Depression-induced cognitive deficits are known to be associated with aberrant reward processing, neurochemical and structural alterations. Recent studies have shown that chronic electrical stimulation of brain reward areas induces a robust antidepressant effect. However, the effects of repeated electrical self-stimulation of lateral hypothalamus - medial forebrain bundle (LH-MFB) on depression-induced cognitive deficits and associated neurochemical and structural alterations in the prefrontal cortex (PFC) are unknown.

Objectives

We investigated the effect of chronic rewarding self-stimulation of LH-MFB in neonatal clomipramine (CLI) model of depression. During adulthood, neonatal CLI and saline administered rats were implanted with bilateral electrodes stereotaxically in the LH-MFB and trained to receive intracranial self-stimulation (ICSS) for 14 days. The rats were tested for depressive-like behaviors, learning and memory followed by estimation of PFC volumes, levels of monoamines and its metabolites in the PFC.

Results

We found that chronic ICSS of LH-MFB reverses CLI-induced behavioral despair and anhedonia. Interestingly, self-stimulation normalizes the impaired novel object and location recognition memory in CLI rats. The amelioration of learning impairments in CLI rats was associated with the reversal of volume loss and restoration of monoamine metabolism in the PFC.

Conclusion

We demonstrated that repeated intracranial self-stimulation of LH-MFB ameliorates CLI-induced learning deficits, reverses altered monoamine metabolism and the atrophy of PFC. Our results support the hypothesis that chronic brain stimulation rewarding experience might be evolved as a potential treatment strategy for reversal of learning deficits in depression and associated disorders.  相似文献   

19.
20.

Background

Cortical dysfunctioning significantly contributes to the pathogenesis of motor symptoms in Parkinson's disease (PD).

Objective

We aimed at testing whether an acute levodopa administration has measurable and specific cortical effects possibly related to striatal dopaminergic deficit.

Methods

In thirteen PD patients, we measured the electroencephalographic responses to transcranial magnetic stimulation (TMS/EEG) of the supplementary motor area and superior parietal lobule (n?=?8) before and after an acute intake of levodopa. We also performed a single-photon emission computed tomography and [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane to identify the more affected and the less affected brain side in each patient, according to the dopaminergic innervation loss of the putamen. Cortical excitability changes before and after an acute intake of levodopa were computed and compared between the more and the less affected brain side at the single-patient as well as at the group level.

Results

We found that levodopa intake induces a significant increase (P?<?0.01) of cortical excitability nearby the supplementary motor area in the more affected brain side, greater (P?<?0.025) than in the less affected brain side. Notably, cortical excitability changes nearby the superior parietal lobule were not statistically significant.

Conclusions

These results strengthen the idea that dysfunction of specific cortico-subcortical circuits may contribute to pathophysiology of PD symptoms. Most important, they support the use of navigated TMS/EEG as a non-invasive tool to better understand the pathophysiology of PD.  相似文献   

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