Stress-mediated loss of synaptogenesis in the hippocampus appears to play a role in depressive and mood disorders. However, little is known about the effect of stress/depression on the plasticity and ...survival of cortical neurons. In this report, we have examined whether chronic stress increases the vulnerability of neurons in the rat cortex. We have used a chronic unpredictable mild stress (CMS) as a rat model of depression. CMS (5 weeks treatment) produced anedonia and increased corticosterone levels. These effects were accompanied by a detectable increase in caspase-3 positive neurons in the cerebral cortex, suggesting apoptosis. Desipramine (DMI), a well known antidepressant, reversed the pro-apoptotic effect of CMS. These results suggest that antidepressants may reduce the pathological changes seen in stress-induced depressive disorders.
In Down syndrome (DS) or trisomy of chromosome 21, the β-amyloid (Aβ) peptide product of the amyloid precursor protein (APP) is present in excess. Evidence points to increased APP gene dose and Aβ as ...playing a critical role in cognitive difficulties experienced by people with DS. Particularly, Aβ is linked to the late-life emergence of dementia as associated with neuropathological markers of Alzheimer's disease (AD). At present, no treatment targets Aβ-related pathogenesis in people with DS. Herein we used a vaccine containing the Aβ 1-15 peptide embedded into liposomes together with the adjuvant monophosphoryl lipid A (MPLA). Ts65Dn mice, a model of DS, were immunized with the anti-Aβ vaccine at 5 months of age and were examined for cognitive measures at 8 months of age. The status of basal forebrain cholinergic neurons and brain levels of APP and its proteolytic products were measured. Immunization of Ts65Dn mice resulted in robust anti-Aβ IgG titers, demonstrating the ability of the vaccine to break self-tolerance. The vaccine-induced antibodies reacted with Aβ without detectable binding to either APP or its C-terminal fragments. Vaccination of Ts65Dn mice resulted in a modest, but non-significant reduction in brain Aβ levels relative to vehicle-treated Ts65Dn mice, resulting in similar levels of Aβ as diploid (2N) mice. Importantly, vaccinated Ts65Dn mice showed resolution of memory deficits in the novel object recognition and contextual fear conditioning tests, as well as reduction of cholinergic neuron atrophy. No treatment adverse effects were observed; vaccine did not result in inflammation, cellular infiltration, or hemorrhage. These data are the first to show that an anti-Aβ immunotherapeutic approach may act to target Aβ-related pathology in a mouse model of DS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hoarding symptoms are associated with functional impairment, though investigation of disability among individuals with hoarding disorder has largely focused on clutter-related impairment to home ...management activities and difficulties using space because of clutter. This analysis assesses disability among individuals with hoarding symptoms in multiple domains of everyday functioning, including cognition, mobility, self-care, interpersonal and community-level interactions, and home management. The magnitude of the association between hoarding and disability was compared to that of medical and psychiatric disorders with documented high disability burden, including major depressive disorder (MDD), diabetes, and chronic pain.
Data were cross-sectionally collected from 16,312 adult participants enrolled in an internet-based research registry, the Brain Health Registry. Pearson's chi-square tests and multivariable logistic regression models were used to quantify the relationship between hoarding and functional ability relative to MDD, diabetes, and chronic pain.
More than one in ten participants endorsed clinical (5.7%) or subclinical (5.7%) hoarding symptoms (CHS and SCHS, respectively). After adjusting for participant demographic characteristics and psychiatric and medical comorbidity, CHS and SCHS were associated with increased odds of impairment in all domains of functioning. Moderate to extreme impairment was endorsed more frequently by those with CHS or SCHS compared to those with self-reported MDD, diabetes, and/or chronic pain in nearly all domains (e.g., difficulty with day-to-day work or school: CHS: 18.7% vs. MDD: 11.8%, p < 0.0001) except mobility and self-care. While those with current depressive symptoms endorsed higher rates of impairment than those with hoarding symptoms, disability was most prevalent among those endorsing both hoarding and comorbid depressive symptoms.
Hoarding symptoms are associated with profound disability in all domains of functioning. The burden of hoarding is comparable to that of other medical and psychiatric illnesses with known high rates of functional impairment. Future studies should examine the directionality and underlying causality of the observed associations, and possibly identify target interventions to minimize impairment associated with hoarding symptomatology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
INTRODUCTION
Alzheimer's‐focused participant recruitment registries are tools for accelerating enrollment into studies, however, registry members are primarily White women.
METHODS
We conducted a ...national online survey of 1501 adults ages 50–80, oversampling for Black and Hispanic/Latino respondents, assessing intention to join a generic “brain health” registry and to join a registry that required specific tasks.
RESULTS
Intention to join a registry was low (M 3.48, SD 1.77), and lower than intention to join a registry requiring specific tasks. Intention was greatest for registries requiring completing surveys (M 4.70, SD 1.77). Differences in intention were primarily between White women and Black women; differences between other groups were limited to specific tasks required.
DISCUSSION
The results indicate uncertainty about what a registry is, its purpose, and/or the concept of “brain health.” Using the Reasoned Action Approach (RAA) to develop evidence‐based outreach messages describing a registry and required tasks may increase diversity.
Introduction
Convenient, cost‐effective tests for amyloid beta (Aβ) are needed to identify those at higher risk for developing Alzheimer's disease (AD). This systematic review evaluates recent models ...that predict dichotomous Aβ. (PROSPERO: CRD42020144734).
Methods
We searched Embase and identified 73 studies from 29,581 for review. We assessed study quality using established tools, extracted information, and reported results narratively.
Results
We identified few high‐quality studies due to concerns about Aβ determination and analytical issues. The most promising convenient, inexpensive classifiers consist of age, apolipoprotein E genotype, cognitive measures, and/or plasma Aβ. Plasma Aβ may be sufficient if pre‐analytical variables are standardized and scalable assays developed. Some models lowered costs associated with clinical trial recruitment or clinical screening.
Discussion
Conclusions about models are difficult due to study heterogeneity and quality. Promising prediction models used demographic, cognitive/neuropsychological, imaging, and plasma Aβ measures. Further studies using standardized Aβ determination, and improved model validation are required.
The search for a convenient procedure to detect the earliest signs of Alzheimer's disease
Hoarding disorder often results in debilitating functional impairment and may also compromise health-related quality of life (QoL). This study investigated the association between hoarding behavior ...and QoL relative to six highly impairing medical and psychiatric disorders in a sample of 20,722 participants enrolled in the internet-based Brain Health Registry. Nearly 1 in 8 participants (12.2%) endorsed clinically relevant hoarding symptoms (CHS). In separate multivariable linear regression models, hoarding was more strongly associated with mental QoL than diabetes (Standardizedβ = −0.21, 95% CI: -0.22, −0.20 vs. −0.01 -0.02, 0.0), heart disease (−0.22 -0.23, −0.20 vs. 0.00 -0.02, 0.01), chronic pain (−0.18 -0.19, −0.16 vs. −0.12 -0.13, −0.10), post-traumatic stress disorder (PTSD; −0.20 -0.22, −0.19 vs. −0.07 -0.09, −0.06), and substance use disorder (SUD; −0.21 -0.23, −0.20 vs. −0.04 -0.05, −0.03). Similarly, CHS was more strongly negatively associated with physical QoL than diabetes (−0.11 -0.10, −0.12 vs. −0.08 -0.06, −0.09), major depressive disorder (−0.09 -0.10, −0.08 vs. −0.05 -0.06, 0.03), PTSD (−0.11 -0.12, −0.10 vs. −0.08 -0.09, −0.07), and SUD (−0.12 -0.13, −0.09 vs. −0.01 -0.02, 0.00). Higher hoarding severity was associated with reductions in both mental (Standardizedβ = −0.28, ΔR2 = 0.08, p < 0.0001) and physical (β = −0.12, ΔR2 = 0.02, p < 0.0001) QoL, though the strength of the relationship between hoarding symptoms and QoL varied with depression severity. Efforts to improve the overall QoL and well-being of those with CHS are needed.
•Self-reported QoL impairment increases with the severity of hoarding symptomatology.•Hoarding symptom severity is negatively associated with QoL even at low levels.•Hoarding is more associated with QoL than most health conditions assessed.•The association between hoarding and QoL varies with depression symptom severity.
Hoarding behaviors are positively associated with medical morbidity, however, current prevalence estimates and types of medical conditions associated with hoarding vary. This analysis aims to ...quantify the medical morbidity of hoarding disorder (HD). Cross-sectional data were collected online using the Brain Health Registry (BHR). Among 20,745 participants who completed the Hoarding and Clutter and Medical History thematic modules, 1348 had HD (6.5%), 1268 had subclinical HD (6.1%), and 18,829 did not meet hoarding criteria (87.4%). Individuals with HD were more likely to report a lifetime history of cardiovascular/metabolic conditions: diabetes (HD adjusted odds ratio (AOR):1.51, 95% confidence interval (CI):1.20, 1.91; subclinical HD AOR:1.24, 95% CI:0.95, 1.61), and hypercholesterolemia (HD AOR:1.24, 95% CI:1.06, 1.46; subclinical HD AOR:1.11, 95% CI:0.94, 1.31). Those with HD and subclinical HD were also more to report chronic pain (HD AOR: 1.69, 95% CI:1.44, 1.98; subclinical HD AOR: 1.44, 95% CI:1.22, 1.69), and sleep apnea (HD AOR: 1.58, 95% CI:1.31, 1.89; subclinical HD AOR:1.30, 95% CI:1.07, 1.58) than non-HD participants. For most conditions, likelihood of diagnosis did not differ between HD and subclinical HD. Structural equation modeling revealed that more severe hoarding symptomatology was independently associated with increased cardiovascular/metabolic vulnerability. The assessment and management of medical complications in individuals with HD is a fundamental component in improving quality of life, longevity, and overall physical health outcomes.
Introduction
Use of online registries to efficiently identify older adults with cognitive decline and Alzheimer's disease (AD) is an approach with growing evidence for feasibility and validity. ...Linked biomarker and registry data can facilitate AD clinical research.
Methods
We collected blood for plasma biomarker and genetic analysis from older adult Brain Health Registry (BHR) participants, evaluated feasibility, and estimated associations between demographic variables and study participation.
Results
Of 7150 participants invited to the study, 864 (12%) enrolled and 629 (73%) completed remote blood draws. Participants reported high study acceptability. Those from underrepresented ethnocultural and educational groups were less likely to participate.
Discussion
This study demonstrates the challenges of remote blood collection from a large representative sample of older adults. Remote blood collection from > 600 participants within a short timeframe demonstrates the feasibility of our approach, which can be expanded for efficient collection of plasma AD biomarker and genetic data.
Introduction
Assessment of functional status is associated with risk of cognitive decline and diagnosis of dementia, and can be assessed by participants and study partners (SPs).
Methods
In 770 older ...adults enrolled in the Imaging Dementia‐Evidence for Amyloid Scanning (IDEAS) study and the online Brain Health Registry (BHR), we estimated associations between online assessments and clinical variables related to Alzheimer's disease (AD) risk.
Results
Worse online learning scores and SP‐reported functional decline were associated with higher probability of AD dementia diagnosis and poor in‐clinic cognitive assessment, and with higher odds of amyloid beta (Aβ) positivity when combined with participants’ report of less decline. SP report of functional decline conferred predictive value independent of online cognitive assessments. Participants underreported decline compared to SPs.
Discussion
The results support the validity of online assessments and their greater utilization in healthcare and research settings. Online SP‐reported functional decline is an indicator of dementia and AD risk.
Remote, internet-based methods for recruitment, screening, and longitudinally assessing older adults have the potential to facilitate Alzheimer's disease (AD) clinical trials and observational ...studies.
The Brain Health Registry (BHR) is an online registry that includes longitudinal assessments including self- and study partner-report questionnaires and neuropsychological tests. New initiatives aim to increase inclusion and engagement of commonly underincluded communities using digital, community-engaged research strategies. New features include multilingual support and biofluid collection capabilities.
BHR includes > 100,000 participants. BHR has made over 259,000 referrals resulting in 25,997 participants enrolled in 30 aging and AD studies. In addition, 28,278 participants are coenrolled in BHR and other studies with data linkage among studies. Data have been shared with 28 investigators. Recent efforts have facilitated the enrollment and engagement of underincluded ethnocultural communities.
The major advantages of the BHR approach are scalability and accessibility. Challenges include compliance, retention, cohort diversity, and generalizability.
Brain Health Registry (BHR) is an online, longitudinal platform of > 100,000 members. BHR made > 259,000 referrals, which enrolled 25,997 participants in 32 studies. New efforts increased enrollment and engagement of underincluded communities in BHR. The major advantages of the BHR approach are scalability and accessibility. BHR provides a unique adjunct for clinical neuroscience research.
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