Plasma biomarkers identify older adults at risk of Alzheimer's disease and related dementias in a real-world population-based cohort

Introduction: Plasma biomarkers—cost effective, non-invasive indicators of Alzheimer's disease (AD) and related disorders (ADRD)—have largely been studied in clinical research settings. Here, we examined plasma biomarker profiles and their associated factors in a population-based cohort to determine whether they could identify an at-risk group, independently of brain and cerebrospinal fluid biomarkers. Methods: We measured plasma phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta (Aβ)42/40 ratio in 847 participants from a population-based cohort in southwestern Pennsylvania. Results: K-medoids clustering identified two distinct plasma Aβ42/40 modes, further categorizable into three biomarker profile groups: normal, uncertain, and abnormal. In different groups, plasma p-tau181, NfL, and GFAP were inversely correlated with Aβ42/40, Clinical Dementia Rating, and memory composite score, with the strongest associations in the abnormal group. Discussion: Abnormal plasma Aβ42/40 ratio identified older adult groups with lower memory scores, higher dementia risks, and higher ADRD biomarker levels, with potential implications for population screening. Highlights: Population-based plasma biomarker studies are lacking, particularly in cohorts without cerebrospinal fluid or neuroimaging data. In the Monongahela-Youghiogheny Healthy Aging Team study (n = 847), plasma biomarkers associated with worse memory and Clinical Dementia Rating (CDR), apolipoprotein E ε4, and greater age. Plasma amyloid beta (Aβ)42/40 ratio levels allowed clustering participants into abnormal, uncertain, and normal groups. Plasma Aβ42/40 correlated differently with neurofilament light chain, glial fibrillary acidic protein, phosphorylated tau181, memory composite, and CDR in each group. Plasma biomarkers can enable relatively affordable and non-invasive community screening for evidence of Alzheimer's disease and related disorders pathophysiology

Central Coherence in Eating Disorders: A Synthesis of Studies Using the Rey Osterrieth Complex Figure Test

Background: Large variability in tests and differences in scoring systems used to study central coherence in eating disorders may lead to different interpretations, inconsistent findings and between study discrepancies. This study aimed to address inconsistencies by collating data from several studies from the same research group that used the Rey Osterrieth Complex Figure Test (Rey Figure) in order to produce norms to provide benchmark data for future studies. Method: Data was collated from 984 participants in total. Anorexia Nervosa, Bulimia Nervosa, recovered Anorexia Nervosa, unaffected family members and healthy controls were compared using the Rey Figure. Results: Poor global processing was observed across all current eating disorder sub-groups and in unaffected relatives. There was no difference in performance between recovered AN and HC groups. Conclusions: This is the largest dataset reported in the literature and supports previous studies implicating poor global processing across eating disorders using the Rey Figure. It provides robust normative data useful for future studies

An olfactory self-test effectively screens for COVID-19

International audienceAbstract Background Key to curtailing the COVID-19 pandemic are wide-scale screening strategies. An ideal screen is one that would not rely on transporting, distributing, and collecting physical specimens. Given the olfactory impairment associated with COVID-19, we developed a perceptual measure of olfaction that relies on smelling household odorants and rating them online. Methods Each participant was instructed to select 5 household items, and rate their perceived odor pleasantness and intensity using an online visual analogue scale. We used this data to assign an olfactory perceptual fingerprint, a value that reflects the perceived difference between odorants. We tested the performance of this real-time tool in a total of 13,484 participants (462 COVID-19 positive) from 134 countries who provided 178,820 perceptual ratings of 60 different household odorants. Results We observe that olfactory ratings are indicative of COVID-19 status in a country, significantly correlating with national infection rates over time. More importantly, we observe indicative power at the individual level (79% sensitivity and 87% specificity). Critically, this olfactory screen remains effective in participants with COVID-19 but without symptoms, and in participants with symptoms but without COVID-19. Conclusions The current odorant-based olfactory screen adds a component to online symptom-checkers, to potentially provide an added first line of defense that can help fight disease progression at the population level. The data derived from this tool may allow better understanding of the link between COVID-19 and olfaction

Minor Physical Anomalies in Patients with Schizophrenia, Unaffected First-Degree Relatives, and Healthy Controls: A Meta-Analysis

Background: Minor physical anomalies (MPAs) have been found to be more prevalent in schizophrenia than control participants in numerous studies and may index a potential endophenotype for schizophrenia.</p

The Shine-Through Masking Paradigm Is a Potential Endophenotype of Schizophrenia

BACKGROUND: To understand the genetics of schizophrenia, a hunt for so-called intermediate phenotypes or endophenotypes is ongoing. Visual masking has been proposed to be such an endophenotype. However, no systematic study has been conducted yet to prove this claim. Here, we present the first study showing that masking meets the most important criteria for an endophenotype. METHODOLOGY/PRINCIPAL FINDINGS: We tested 62 schizophrenic patients, 39 non-affected first-degree relatives, and 38 healthy controls in the shine-through masking paradigm and, in addition, in the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST). Most importantly, masking performance of relatives was significantly in between the one of patients and controls in the shine-through paradigm. Moreover, deficits were stable throughout one year. Using receiver operating characteristics (ROC) methods, we show that the shine-through paradigm distinguishes with high sensitivity and specificity between schizophrenic patients, first-order relatives and healthy controls. CONCLUSIONS/SIGNIFICANCE: The shine-through paradigm is a potential endophenotype

Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study

<p>Abstract</p> <p>Background</p> <p>A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.</p> <p>Methods</p> <p>In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals.</p> <p>Results</p> <p>ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation.</p> <p>Conclusions</p> <p>Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.</p

Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease

An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of Aβ with tau phosphorylation in CU individuals. We found that Aβ was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast+). Cross-sectional and longitudinal tau-positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of Aβ only in CU Ast+ individuals. Our findings suggest astrocyte reactivity as an important upstream event linking Aβ with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials

Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies

Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844-852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures- approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcome