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1.

Introduction

Information on anticipated survival time after dementia diagnosis among racially/ethnically diverse patients is needed to plan for care and evaluate disparities.

Methods

Dementia-free health care members aged ≥64 years were followed (1/1/2000–12/31/2013) for dementia diagnosis and subsequent survival (n = 23,032 Asian American; n = 18,778 African American; n = 21,000 Latino; n = 4543 American Indian/Alaska Native; n = 206,490 white). Kaplan–Meier curves were estimated for survival after dementia diagnosis by race/ethnicity. We contrasted mortality patterns among people with versus without dementia using Cox proportional hazards models.

Results

After dementia diagnosis (n = 59,494), whites had shortest median survival (3.1 years), followed by American Indian/Alaska Natives (3.4 years), African Americans (3.7 years), Latinos (4.1 years), and Asian Americans (4.4 years). Longer postdiagnosis survival among racial/ethnic minorities compared with whites persisted after adjustment for comorbidities. Racial/ethnic mortality inequalities among dementia patients mostly paralleled mortality inequalities among people without dementia.

Discussion

Survival after dementia diagnosis differs by race/ethnicity, with shortest survival among whites and longest among Asian Americans.  相似文献   

2.

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   

3.

Background

Ambulation is an essential aspect of daily living and is often impaired after brain and spinal cord injuries. Despite the implementation of standard neurorehabilitative care, locomotor recovery is often incomplete.

Objective

In this randomized, sham-controlled, double-blind, parallel design study, we aimed to determine if anodal transcutaneous spinal direct current stimulation (anodal tsDCS) could improve training effects on locomotion compared to sham (sham tsDCS) in healthy subjects. Methods: 43 participants underwent a single backwards locomotion training (BLT) session on a reverse treadmill with concurrent anodal (n = 22) or sham (n = 21) tsDCS. The primary outcome measure was speed gain measured 24 h post-training. We hypothesized that anodal tsDCS + BLT would improve training effects on backward locomotor speed compared to sham tsDCS + BLT. A subset of participants (n = 31) returned for two additional training days of either anodal (n = 16) or sham (n = 15) tsDCS and underwent (n = 29) H-reflex testing immediately before, immediately after, and 30 min post-training over three consecutive days.

Results

A single session of anodal tsDCS + BLT elicited greater speed gain at 24 h relative to sham tsDCS + BLT (p = 0.008, two-sample t-test, adjusted for one interim analysis after the initial 12 subjects). Anodal tsDCS + BLT resulted in higher retention of the acquired skill at day 30 relative to sham tsDCS + BLT (p = 0.002) in the absence of significant group differences in online or offline learning over the three training days (p = 0.467 and p = 0.131). BLT resulted in transient down-regulation of H-reflex amplitude (Hmax/Mmax) in both test groups (p < 0.0001). However, the concurrent application of anodal-tsDCS with BLT elicited a longer lasting effect than sham-tsDCS + BLT (p = 0.050).

Conclusion

tsDCS improved locomotor skill acquisition and retention in healthy subjects and prolonged the physiological exercise-mediated downregulation of excitability of the alpha motoneuron pool. These results suggest that this strategy is worth exploring in neurorehabilitation of locomotor function.  相似文献   

4.

Background

Repetitive convergent inputs to a single post-synaptic neuron can induce long-term potentiation (LTP) or depression (LTD) of synaptic activity in a spike timing-dependent manner.

Objective

Here we set a protocol of visual paired associative stimulation (vPAS) of the primary visual cortex (V1) in humans to induce persistent changes in the excitatory properties of V1 with a spike timing rule.

Methods

We provided convergent inputs to V1 by coupling transcranial magnetic stimulation (TMS) pulses of the occipital cortex with peripheral visual inputs, at four interstimulus intervals of ?50/-25/+25/+50 ms relative to the visual evoked potential (VEP) P1 latency. We analysed VEP amplitude and delayed habituation before and up to 10 min after each vPAS protocol.

Results

VEP amplitude was reduced after vPAS+25. Delayed VEP habituation was increased after vPAS-25 while it was reduced after vPAS+25.

Conclusions

We provide evidence that associative bidirectional synaptic plasticity is a feature not only of the sensorimotor but also of the human visual system.  相似文献   

5.

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   

6.

Introduction

Staging preclinical Alzheimer disease (AD) by the expected years to symptom onset (EYO) in autosomal dominant AD (ADAD) through biomarker correlations is important.

Methods

We estimated the correlation matrix between EYO/cognition and imaging/CSF biomarkers, and searched for the EYO cutoff where a change in the correlations occurred before and after the cutoff among the asymptomatic mutation carriers of ADAD. We then estimated the longitudinal rate of change for biomarkers/cognition within each preclinical stage defined by the EYO.

Results

Based on the change in the correlations, the preclinical ADAD was divided by EYOs ?7 and ?13 years. Mutation carriers demonstrated a temporal ordering of biomarker/cognition changes across the three preclinical stages.

Discussion

Duration of each preclinical stage can be estimated in ADAD, facilitating better planning of prevention trials with the EYO cutoffs under the recently released FDA guidance. The generalization of these results to sporadic AD warrants further investigation.  相似文献   

7.

Introduction

Cerebrovascular lesions on MRI are common in Alzheimer's disease (AD) dementia, but less is known about their frequency and impact on dementia with Lewy bodies (DLB).

Methods

White-matter hyperintensities (WMHs) and infarcts on MRI were assessed in consecutive DLB (n = 81) and AD dementia (n = 240) patients and compared to age-matched and sex-matched cognitively normal subjects (CN) from a population-based cohort.

Results

DLB had higher WMH volume compared to CN, and WMH volume was higher in the occipital and posterior periventricular regions in DLB compared to AD. Higher WMH volume was associated with history of cardiovascular disease and diabetes but not with clinical disease severity in DLB. Frequency of infarcts in DLB was not different from CN and AD dementia.

Discussion

In DLB, WMH volume is higher than AD and CN and appears to be primarily associated with history of vascular disease.  相似文献   

8.

Objective

The present work aims to evaluate the significance of sleep disturbance and electroencephalogram (EEG) alteration in the early stage of Alzheimer's disease (AD).

Background and Rationale

Sleep disturbance is common in patients with AD. It is not known if it can occur at the early stage of AD and if EEG recording may help identify the early sign of the disease.

Historical Evolution

Sleep disturbance in AD has generally been considered as late consequence of the neurodegenerative process. A growing body of evidence has suggested that the sleep disturbance may occur at the early stage of AD.

Updated Hypothesis

Based on the previous epidemiologic studies and our recent findings, we propose that sleep disturbance may play an important role in the development of AD. Sleep EEG changes may serve as a valuable early sign for AD in the prepathological stage.

Early Experimental Data

Our data suggested that AβPPswe/PS1ΔE9 transgenic AD mice at preplaque stage (3 and 4 months of age) exhibited different profile of sleep architecture and sleep EEG, which preceded the cognitive deficit and AD neuropathology.

Future Experiments and Validation Studies

Future experiments should focus on sleep EEG changes in patients with mild cognitive impairment and early stage of AD. Follow-up studies in high-risk population of the elderly are equally important. In addition, the exact molecular mechanism underlying the sleep disturbance should be thoroughly investigated.

Major Challenges for the Hypothesis

Studies on human participants with early stage of AD, especially the follow-up studies on the presymptomatic elderly in a large population, are difficult and time-consuming.

Linkage to Other Major Theories

Our hypothesis may link previous theories to establish a bidirectional relationship between sleep disorders and AD, which may finally form a new schematic mechanism to understand the disease pathogenesis and disease progression.  相似文献   

9.

Introduction

Recruitment for Alzheimer's disease (AD) prevention research studies is challenging because of lack of awareness among cognitively healthy adults coupled with the high screen fail rate due to participants not having a genetic risk factor or biomarker evidence of the disease. Participant recruitment registries offer one solution for efficiently and effectively identifying, characterizing, and connecting potential eligible volunteers to studies.

Methods

Individuals aged 55-75 years who live in the United States and self-report not having a diagnosis of cognitive impairment such as MCI or dementia are eligible to join GeneMatch. Participants enroll online and are provided a cheek swab kit for DNA extraction and apolipoprotein E (APOE) genotyping. Participants are not told their APOE results, although the results may be used in part to help match participants to AD prevention studies.

Results

As of August 2018, 75,351 participants had joined GeneMatch. Nearly 30% of participants have one APOE4 allele, and approximately 3% have two APOE4 alleles. The percentages of APOE4 heterozygotes and homozygotes are inversely associated with age (P < .001).

Discussion

GeneMatch, the first trial-independent research enrollment program designed to recruit and refer cognitively healthy adults to AD prevention studies based in part on APOE test results, provides a novel mechanism to accelerate prescreening and enrollment for AD prevention trials.  相似文献   

10.

Background

Transcranial magnetic stimulation (TMS) is a non-invasive method to stimulate localized brain regions. Despite widespread use in motor cortex, TMS is seldom performed in sensory areas due to variable, qualitative metrics.

Objective

Assess the reliability and validity of tracing phosphenes, and to investigate the stimulation parameters necessary to elicit decreased visual cortex excitability with paired-pulse TMS at short inter-stimulus intervals.

Methods

Across two sessions, single and paired-pulse recruitment curves were derived by having participants outline elicited phosphenes and calculating resulting average phosphene sizes.

Results

Phosphene size scaled with stimulus intensity, similar to motor cortex. Paired-pulse recruitment curves demonstrated inhibition at lower conditioning stimulus intensities than observed in motor cortex. Reliability was high across sessions.

Conclusions

TMS-induced phosphenes are a valid and reliable tool for measuring cortical excitability and inhibition in early visual areas. Our results also provide appropriate stimulation parameters for measuring short-latency intracortical inhibition in visual cortex.  相似文献   

11.

Introduction

We examined the relation between self-reported hearing loss, hearing aid use, and risk of subjective cognitive function (SCF) decline.

Methods

We conducted an 8-year (2008–2016) longitudinal study of 10,107 men aged ≥62 years who reported their hearing status in 2006 and had no subjective cognitive concerns in 2008. Change in SCF scores was assessed by a 6-item questionnaire, and subjective decline was defined as new report of at least one SCF concern during follow-up.

Results

Hearing loss was associated with higher risk of SCF decline. Compared with no hearing loss, the multivariable-adjusted relative risk (95% CI) of incident SCF decline was 1.30 (1.18, 1.42), 1.42 (1.26, 1.61), and 1.54 (1.22, 1.96) among men with mild, moderate, and severe hearing loss (no hearing aids), respectively (P-trend < .001). Among men with severe hearing loss who used hearing aids, the multivariable-adjusted relative risk (95% CI) was 1.37 (1.18, 1.60).

Discussion

Hearing loss was associated with substantially higher risk of subsequent subjective cognitive decline in men.  相似文献   

12.

Background

Error processing and inhibitory control enable the adjustment of behaviors to meet task demands. Functional magnetic resonance imaging studies report brain activation abnormalities in patients with obsessive-compulsive disorder (OCD) during both processes. However, conclusions are limited by inconsistencies in the literature and small sample sizes. Therefore, the aim here was to perform a meta-analysis of the existing literature using unthresholded statistical maps from previous studies.

Methods

A voxelwise seed-based d mapping meta-analysis was performed using t-maps from studies comparing patients with OCD and healthy control subjects (HCs) during error processing and inhibitory control. For the error processing analysis, 239 patients with OCD (120 male; 79 medicated) and 229 HCs (129 male) were included, while the inhibitory control analysis included 245 patients with OCD (120 male; 91 medicated) and 239 HCs (135 male).

Results

Patients with OCD, relative to HCs, showed longer inhibitory control reaction time (standardized mean difference = 0.20, p = .03, 95% confidence interval = 0.016, 0.393) and more inhibitory control errors (standardized mean difference = 0.22, p = .02, 95% confidence interval = 0.039, 0.399). In the brain, patients showed hyperactivation in the bilateral dorsal anterior cingulate cortex, supplementary motor area, and pre-supplementary motor area as well as right anterior insula/frontal operculum and anterior lateral prefrontal cortex during error processing but showed hypoactivation during inhibitory control in the rostral and ventral anterior cingulate cortices and bilateral thalamus/caudate, as well as the right anterior insula/frontal operculum, supramarginal gyrus, and medial orbitofrontal cortex (all seed-based d mapping z value >2, p < .001).

Conclusions

A hyperactive error processing mechanism in conjunction with impairments in implementing inhibitory control may underlie deficits in stopping unwanted compulsive behaviors in the disorder.  相似文献   

13.

Introduction

The relative importance of structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) to predict diagnosis and cognition in Alzheimer's disease (AD) is unclear.

Methods

We tested 56 cognitively unimpaired controls (including 27 preclinical AD), 32 patients with prodromal AD, and 39 patients with AD dementia. Optimal classifiers were constructed using the least absolute shrinkage and selection operator with 18F-AV-1451 (tau) PET and structural MRI data (regional cortical thickness and subcortical volumes).

Results

18F-AV-1451 in the amygdala, entorhinal cortex, parahippocampal gyrus, fusiform, and inferior parietal lobule had 93% diagnostic accuracy for AD (prodromal or dementia). The MRI classifier involved partly the same regions plus the hippocampus, with 83% accuracy, but did not improve upon the tau classifier. 18F-AV-1451 retention and MRI were independently associated with cognition.

Discussion

Optimized tau PET classifiers may diagnose AD with high accuracy, but both tau PET and structural brain MRI capture partly unique information relevant for the clinical deterioration in AD.  相似文献   

14.

Introduction

Primary progressive aphasia (PPA) is a neurological syndrome, associated with both frontotemporal dementia and Alzheimer's disease, in which progressive language impairment emerges as the most salient clinical feature during the initial stages of disease.

Methods

We screened the main genes associated with Alzheimer's disease and frontotemporal dementia for pathogenic and risk variants in a cohort of 403 PPA cases.

Results

In this case series study, 14 (3.5%) cases carried (likely) pathogenic variants: four C9orf72 expansions, nine GRN, and one TARDBP mutation. Rare risk variants, TREM2 R47H and MAPT A152T, were associated with a three- to seven-fold increase in risk for PPA.

Discussion

Our results show that while pathogenic variants within the most common dementia genes were rarely associated with PPA, these were found almost exclusively in GRN and C9orf72, suggesting that PPA is more TDP43- than tau-related in our series. This is consistent with the finding that PPA frequency in dominantly inherited dementias is the highest in kindreds with GRN variants.  相似文献   

15.

Introduction

Previous studies have demonstrated that an overall high level of mental work demands decreased dementia risk. In our study, we investigated whether this effect is driven by specific mental work demands and whether it is exposure dependent.

Methods

Patients aged 75+ years were recruited from general practitioners and participated in up to seven assessment waves (every 1.5 years) of the longitudinal AgeCoDe study. Analyses of the impact of specific mental work demands on dementia risk were carried out via multivariate regression modeling (n = 2315).

Results

We observed a significantly lower dementia risk in individuals with a higher level of “information processing” (HR, 0.888), “pattern detection” (HR, 0.878), “mathematics” (HR, 0.878), and “creativity” (HR, 0.878). Yet, exposure-dependent effects were only significant for “information processing” and “pattern detection.”

Discussion

Our longitudinal observations suggest that dementia risk may be reduced by some but not all types of mental work demands.  相似文献   

16.

Background

Childhood maltreatment is a major risk factor for psychopathology. However, some maltreated individuals appear remarkably resilient to the psychiatric effects while manifesting the same array of brain abnormalities as maltreated individuals with psychopathology. Hence, a critical aim is to identify compensatory brain alterations that enable resilient individuals to maintain mental well-being despite alterations in stress-susceptible regions.

Methods

Network models were constructed from diffusion tensor imaging and tractography in physically healthy unmedicated 18- to 25-year-old participants (N = 342, n = 192 maltreated) to develop network-based explanatory models.

Results

First, we determined that susceptible and resilient individuals had the same alterations in global fiber stream network architecture using two different definitions of resilience: 1) no lifetime history of Axis I or II disorders, and 2) no clinically significant symptoms of anxiety, depression, anger-hostility, or somatization. Second, we confirmed an a priori hypothesis that right amygdala nodal efficiency was lower in asymptomatic resilient than in susceptible participants or control subjects. Third, we identified eight other nodes with reduced nodal efficiency in resilient individuals and showed that nodal efficiency moderated the relationship between maltreatment and psychopathology. Fourth, we found that models based on global network architecture and nodal efficiency could delineate group membership (control, susceptible, resilient) with 75%, 82%, and 80% cross-validated accuracy.

Conclusions

Together these findings suggest that sparse fiber networks with increased small-worldness following maltreatment render individuals vulnerable to psychopathology if abnormalities occur in specific nodes, but that decreased ability of certain nodes to propagate information throughout the network mitigates the effects and leads to resilience.  相似文献   

17.

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   

18.

Introduction

Rapid growth of the older adult population requires greater epidemiologic characterization of dementia. We developed national prevalence estimates of diagnosed dementia and subtypes in the highest risk United States (US) population.

Methods

We analyzed Centers for Medicare & Medicaid administrative enrollment and claims data for 100% of Medicare fee-for-service beneficiaries enrolled during 2011–2013 and age ≥68 years as of December 31, 2013 (n = 21.6 million).

Results

Over 3.1 million (14.4%) beneficiaries had a claim for a service and/or treatment for any dementia subtype. Dementia not otherwise specified was the most common diagnosis (present in 92.9%). The most common subtype was Alzheimer's (43.5%), followed by vascular (14.5%), Lewy body (5.4%), frontotemporal (1.0%), and alcohol induced (0.7%). The prevalence of other types of diagnosed dementia was 0.2%.

Discussion

This study is the first to document concurrent prevalence of primary dementia subtypes among this US population. The findings can assist in prioritizing dementia research, clinical services, and caregiving resources.  相似文献   

19.

Introduction

We investigated the association between age of onset of hypertension and dementia risk in an oldest-old cohort.

Methods

Participants are from The 90+ Study, a population-based longitudinal study of people aged 90+ who are survivors from the Leisure World Cohort Study. We estimated hypertension onset age using self-reported information from The 90+ Study and Leisure World Cohort Study, collected about 20 years earlier. A total of 559 participants without dementia were followed every 6 months for up to 10 years.

Results

A total of 224 participants developed dementia during follow-up (mean = 2.8 years). Compared with those without hypertension, participants whose hypertension onset age was 80 to 89 years had a lower dementia risk (hazard ratio = 0.58, P = .04) and participants with an onset age of 90+ years had the lowest risk (hazard ratio = 0.37, P = .004).

Discussion

Developing hypertension at older ages may protect against dementia. Understanding the mechanisms for this lower risk is important for determining ways to prevent dementia in the very elderly.  相似文献   

20.
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