Basic Science and Pathogenesis.

Background: Inflammation is central to Alzheimer Disease (AD), as astrocyte reactivity accompanies the appearance of Aβ and phosphorylated tau (Bellaver et al., 2023). As expected, therefore, AD patients have elevated levels of CSF inflammatory cytokines (Onyango et al.

Basic Science and Pathogenesis.

Background: Clusterin is a major cholesterol transporter in the central nervous system (CNS) and different SNPs in the CLU gene have been associated with Alzheimer's disease (AD) risk. The rs11136000_T variant in the CLU gene has been shown to decrease the risk of AD. In this work, we investigate the role of the CLU rs11136000_T protective variant and of the clusterin protein throughout different phases of the AD spectrum.

Modeling the progression of neuropsychiatric symptoms in Alzheimer's disease with PET-based Braak staging.

In Alzheimer's disease (AD), neuropsychiatric symptoms (NPS) correlate with tau deposition in the brain. Here, we investigated the association of PET-based Braak stages with NPS and assessed whether they predict annual changes in NPS. We evaluated 231 individuals in the aging and AD continuum.

Studying the context of psychoses to improve outcomes in Ethiopia (SCOPE): Protocol paper.

Background: Global evidence on psychosis is dominated by studies conducted in Western, high-income countries. The objectives of the Study of Context Of Psychoses to improve outcomes in Ethiopia (SCOPE) are (1) to generate rigorous evidence of psychosis experience, epidemiology and impacts in Ethiopia that will illuminate aetiological understanding and (2) inform development and testing of interventions for earlier identification and improved first contact care that are scalable, inclusive of difficult-to-reach populations and optimise recovery.

Methods: The setting is sub-cities of Addis Ababa and rural districts in south-central Ethiopia covering 1.

Neurobehavioral Mechanisms Influencing the Association Between Generativity, the Desire to Promote Well-Being of Younger Generations, and Purpose in Life in Older Adults at Risk for Alzheimer's Disease.

Objectives: Generativity, the desire and action to improve the well-being of younger generations, is associated with purpose in life among older adults. However, the neurobehavioral factors supporting the relationship between generativity and purpose in life remain unknown. This study aims to identify the functional neuroanatomy of generativity and mechanisms linking generativity with purpose in life in at-risk older adults.

Predicting functional decline in aging and Alzheimer's disease with PET-based Braak staging.

The progression of PET-based Braak stages correlates with cognitive deterioration in aging and Alzheimer's disease. Here, we investigate the association between PET-based Braak stages and functional impairment and assess whether PET-based Braak staging predicts a longitudinal decline in the performance of activities of daily living. In this cohort study, we evaluated cognitively unimpaired individuals and individuals with mild cognitive impairment or Alzheimer's disease dementia.

Iron Deposition and Distribution Across the Hippocampus Is Associated with Pattern Separation and Pattern Completion in Older Adults at Risk for Alzheimer's Disease.

Elevated iron deposition in the brain has been observed in older adult humans and persons with Alzheimer's disease (AD), and has been associated with lower cognitive performance. We investigated the impact of iron deposition, and its topographical distribution across hippocampal subfields and segments (anterior, posterior) measured along its longitudinal axis, on episodic memory in a sample of cognitively unimpaired older adults at elevated familial risk for AD ( = 172, 120 females, 52 males; mean age = 68.8 ± 5.

Psychiatric Comorbidities of Inflammatory Bowel Disease: It Is a Matter of Microglia's Gut Feeling.

Inflammatory bowel disease (IBD), a common term for Crohn's disease and ulcerative colitis, is a chronic, relapse-remitting condition of the gastrointestinal tract that is increasing worldwide. Psychiatric comorbidities, including depression and anxiety, are more prevalent in IBD patients than in healthy individuals. Evidence suggests that varying levels of neuroinflammation might underlie these states in IBD patients.

A prognostic risk score for development and spread of chronic pain.

Chronic pain is a complex condition influenced by a combination of biological, psychological and social factors. Using data from the UK Biobank (n = 493,211), we showed that pain spreads from proximal to distal sites and developed a biopsychosocial model that predicted the number of coexisting pain sites. This data-driven model was used to identify a risk score that classified various chronic pain conditions (area under the curve (AUC) 0.

Plasma and CSF concentrations of N-terminal tau fragments associate with in vivo neurofibrillary tangle burden.

Introduction: Fluid biomarkers capable of specifically tracking tau tangle pathology in vivo are greatly needed.

Methods: We measured cerebrospinal fluid (CSF) and plasma concentrations of N-terminal tau fragments (NTA-tau), using a novel immunoassay (NTA) in the TRIAD cohort, consisting of 272 individuals assessed with amyloid beta (Aβ) positron emission tomography (PET), tau PET, magnetic resonance imaging (MRI) and cognitive assessments.

Results: CSF and plasma NTA-tau concentrations were specifically increased in cognitively impaired Aβ-positive groups.

Biomarker modeling of Alzheimer's disease using PET-based Braak staging.

Gold-standard diagnosis of Alzheimer's disease (AD) relies on histopathological staging systems. Using the topographical information from [F]MK6240 tau positron-emission tomography (PET), we applied the Braak tau staging system to 324 living individuals. We used PET-based Braak stage to model the trajectories of amyloid-β, phosphorylated tau (pTau) in cerebrospinal fluid (pTau, pTau, pTau and pTau) and plasma (pTau and pTau), neurodegeneration and cognitive symptoms.

The influence of generativity on purpose in life is mediated by social support and moderated by prefrontal functional connectivity in at-risk older adults.

Objectives: Generativity, the desire and action to improve the well-being of younger generations, is positively associated with purpose in life among older adults. However, the neural basis of generativity and the neurobehavioral factors supporting the relationship between generativity and purpose in life remain unknown. This study aims to identify the functional neuroanatomy of generativity and mechanisms linking generativity with purpose in life in at-risk older adults.

Social isolation is linked to classical risk factors of Alzheimer's disease-related dementias.

Alzheimer's disease and related dementias is a major public health burden-compounding over upcoming years due to longevity. Recently, clinical evidence hinted at the experience of social isolation in expediting dementia onset. In 502,506 UK Biobank participants and 30,097 participants from the Canadian Longitudinal Study of Aging, we revisited traditional risk factors for developing dementia in the context of loneliness and lacking social support.

APOE alleles are associated with sex-specific structural differences in brain regions affected in Alzheimer's disease and related dementia.

Alzheimer's disease is marked by intracellular tau aggregates in the medial temporal lobe (MTL) and extracellular amyloid aggregates in the default network (DN). Here, we examined codependent structural variations between the MTL's most vulnerable structure, the hippocampus (HC), and the DN at subregion resolution in individuals with Alzheimer's disease and related dementia (ADRD). By leveraging the power of the approximately 40,000 participants of the UK Biobank cohort, we assessed impacts from the protective APOE ɛ2 and the deleterious APOE ɛ4 Alzheimer's disease alleles on these structural relationships.

The Association of Age-Related and Off-Target Retention with Longitudinal Quantification of [F]MK6240 Tau PET in Target Regions.

6-(fluoro-F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([F]MK6240) tau PET tracer quantifies the brain tau neurofibrillary tangle load in Alzheimer disease. The aims of our study were to test the stability of common reference region estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and off-target retention on the longitudinal quantification of [F]MK6240 in target regions. We assessed reference, target, age-related, and off-target regions in 125 individuals across the aging and Alzheimer disease spectrum with longitudinal [F]MK6240 SUVs and SUV ratios (SUVRs) (mean ± SD, 2.

Mindfulness-based cognitive therapy vs. a health enhancement program for the treatment of late-life depression: Study protocol for a multi-site randomized controlled trial.

Background: Late-life depression (LLD) affects up to 18% of older adults and has been linked to elevated dementia risk. Mindfulness-based cognitive therapy (MBCT) holds promise for treating symptoms of depression and ameliorating cognitive deficits in older adults. While preliminary findings are promising, a definitive RCT investigating its effects on late life depression and cognition have not yet been conducted.

DARQ: Deep learning of quality control for stereotaxic registration of human brain MRI to the T1w MNI-ICBM 152 template.

Linear registration to stereotaxic space is a common first step in many automated image-processing tools for analysis of human brain MRI scans. This step is crucial for the success of the subsequent image-processing steps. Several well-established algorithms are commonly used in the field of neuroimaging for this task, but none have a 100% success rate.

Climate change and Indigenous mental health in the Circumpolar North: A systematic review to inform clinical practice.

Climate change is disproportionally impacting the Circumpolar North, with particular impacts among Indigenous populations. Environmental changes are felt in many aspects of daily life of Northern communities, including both physical and mental health. Thus, health institutions from around the Arctic must meet emerging needs, while the phenomenon remains marginal to their southern counterparts.

Mu opioid receptors on hippocampal GABAergic interneurons are critical for the antidepressant effects of tianeptine.

Tianeptine is an atypical antidepressant used in Europe to treat patients who respond poorly to selective serotonin reuptake inhibitors (SSRIs). The recent discovery that tianeptine is a mu opioid receptor (MOR) agonist has provided a potential avenue for expanding our understanding of antidepressant treatment beyond the monoamine hypothesis. Thus, our studies aim to understand the neural circuits underlying tianeptine's antidepressant effects.

Combined polygenic risk scores of different psychiatric traits predict general and specific psychopathology in childhood.

Background: Polygenic risk scores (PRSs) operationalize genetic propensity toward a particular mental disorder and hold promise as early predictors of psychopathology, but before a PRS can be used clinically, explanatory power must be increased and the specificity for a psychiatric domain established. To enable early detection, it is crucial to study these psychometric properties in childhood. We examined whether PRSs associate more with general or with specific psychopathology in school-aged children.

Next-generation gene panel testing in adolescents and adults in a medical neuropsychiatric genetics clinic.

Intellectual disability (ID) encompasses a clinically and genetically heterogeneous group of neurodevelopmental disorders that may present with psychiatric illness in up to 40% of cases. Despite the evidence for clinical utility of genetic panels in pediatrics, there are no published studies in adolescents/adults with ID or autism spectrum disorder (ASD). This study was approved by our institutional research ethics board.