Basic Science and Pathogenesis.

Background: Elevated iron in brain is a source of free radicals that causes oxidative stress which has been linked to neuropathologies and cognitive impairment among older adults. The aim of this study was to investigate the association of iron levels with transverse relaxation rate, R, and white matter hyperintensities (WMH), independent of the effects of other metals and age-related neuropathologies.

Method: Cerebral hemispheres from 437 older adults participating in the Rush Memory and Aging Project study (Table 1) were imaged ex-vivo using 3T MRI scanners.

Basic Science and Pathogenesis.

Background: The glymphatic system has been suggested as an important clearance mechanism for amyloid-β (Aβ) during sleep. Animal and cellular models have suggested this clearance mechanism involves the water-channel protein, Aquaporin-4 (encoded by the AQP4 gene), located primarily in the astrocytic end-feet. We have previously reported on the interaction between genetic variants within AQP4, sleep and cross-sectional cortical amyloid-β (Aβ) burden.

Basic Science and Pathogenesis.

Background: APOE is the major genetic risk factor for sporadic Alzheimer's disease (AD). Although APOE is well known to promote Aβ pathology, recent data also support an effect of APOE polymorphism on phosphorylated Tau (pTau) pathology.

Method: To elucidate this potential effect, the pTau interactome was analyzed across APOE genotypes in the frontal cortex of 10 advanced AD cases (n = 5 APOE and n = 5 APOE), using a combination of anti-pTau PHF1 (pS396/pS404) immunoprecipitation and mass spectrometry.

Basic Science and Pathogenesis.

Background: Prevalence of epilepsy is increased among Alzheimer's Disease (AD) patients and cognitive impairment is common among people with epilepsy, with seizures occurring in 10-22% of AD patients, subclinical epileptiform abnormalities in 22-54% of AD patients, and cognitive deficits in up to 80% of epilepsy patients. These shared pathophysiological changes remain poorly defined.

Methods: We aimed to identify protein differences associated with epilepsy and AD using published proteomics datasets, including our previous analysis in epilepsy hippocampus and from our searchable database of 38 AD proteomics studies (NeuroPro).

Basic Science and Pathogenesis.

Background: Recently, there has been substantial interest in investigating the role of short-chain fatty acids (SCFAs) and, medium chain fatty acids (MCFA) in the neuroinflammation associated with Alzheimer's disease (AD). Specifically, butyrate (SCFA) and lauric acid (MCFA) have demonstrated potential in alleviating neuroinflammation and reducing toxicity associated with amyloid proteins. Additionally, they have been found to enhance mitochondrial function and reduce neuronal hyperactivity.

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) have identified numerous genetic variants associated with Alzheimer's disease (AD) risk, but genetic variation in the onset and progression of AD pathology is less understood. Accumulation of amyloid-β (Aβ) in the brain is a key pathological hallmark of AD beginning 10 - 20 years prior to cognitive symptoms. We investigated the genetic basis of variation in age at onset (AAO) of brain Aβ by comparing the performance of polygenic scores (PGSs) based on AD risk and resilience with a Aβ-AAO trait-specific PGS.

Basic Science and Pathogenesis.

Background: Observational studies have suggested a co-occurring relationship between Alzheimer's disease (AD) and asthma. However, the aetiology and biological mechanisms underlying AD and its potential association with asthma, an autoimmune condition, remain unclear.

Method: We examine the genetic relationship between AD and asthma by analysing large-scale genome-wide association study (GWAS) summary data from international research consortia and groups.

Engaging family members in nutrition care during recovery from critical illness.

Purpose Of Review: The delivery of high-quality personalized nutrition care both during ICU and throughout post-ICU recovery is limited by multifactorial barriers. As families are often a present and consistent resource, family engagement may help to optimize nutrition support during hospitalization and after recovery from critical illness. In this review, we summarize the evidence base for family engagement in nutrition care and hypothesize future roles families may play, throughout the critical illness recovery trajectory.

Clinical Manifestations.

Background: Mild Behavioral Impairment (MBI) and functional ability are two non-cognitive markers of dementia. To date, little is known about the impact of functional ability on the clinical manifestation of MBI. Using data from the Australian population-based PATH Through Life Study we examined the impact of functional ability on MBI.

Clinical Manifestations.

Background: The Improving Interpreting for Dementia Assessments (MINDSET) study aimed to upskill interpreters through an online co-designed course in dementia and cognitive assessments.

Methods: A single-blinded randomized controlled digital trial conducted between June 2022 and November 2023. Interpreters were randomized to training or waitlist control conditions with 3- and 6-month follow-up.

Clinical Manifestations.

Background: Harmonization of neuropsychological assessment for vascular cognitive disorders (VCD) is important for ensuring the highest standards for diagnostic and post-diagnostic care. A battery jointly proposed by the NINDS-CSN has received much support. Considering significant developments in the field, and an urgent need for consensus on remote and computerised assessment methods, an international expert group was commissioned to develop an updated harmonized battery and associated assessment guidelines for VCD using the Delphi process.

Clinical Manifestations.

Background: In cognitively unimpaired (CU) older adults, the presence of a subjective cognitive decline (SCD) combined with evidence of abnormal b-amyloid (Ab) is proposed as stage 2 of Alzheimer's disease (AD) by the NIA-AA framework (Jack et al., 2018). However, the associations found between SCD and preclinical AD are inconsistent across studies, highlighting the importance of better understanding which specific SCD features are associated with either Ab or tau burden.

Clinical Manifestations.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative condition, with considerable variation in disease progression from the mild cognitive impairment (MCI) stage. Predicting disease progression will support prognostic decisions and patient management. Here we designed a machine learning (ML) stack model, where a classifier was used to differentiate MCI progressors from non-progressors (i.

Clinical Manifestations.

Background: Anxiety and stress have been identified as potential risk factors of cognitive impairment, but research examining this association in midlife has been limited.

Method: The current study examined the associations between anxiety and stress symptoms, and cognition in middle-aged cognitively unimpaired adults (n = 2,463) enrolled in the Healthy Brain Project. Exploratory factor analysis was conducted on items in the Anxiety Subscale of the Hospital Anxiety and Depression Scale, Anxiety and Stress Subscales of the Depression, Anxiety and Stress Scale, and Perceived Stress Scale.

Clinical Manifestations.

Background: Recent studies suggest learning deficits are the earliest cognitive abnormality to emerge in Alzheimer's disease (AD). Using the Online Repeatable Cognitive Assessment-Language Learning Test (ORCA-LLT), cognitively unimpaired (CU) Aβ+ older adults showed a substantial (d∼2) learning deficit compared to Aβ- controls. This deficit was six times greater than that observed from reduced practice effects after 9+ years of assessment with conventional neuropsychological memory tests (d∼0.

Clinical Manifestations.

Background: Cognitive dysfunction is central to clinicopathological models of Alzheimer's disease (AD). While AD prospective studies assess similar cognitive domains, the neuropsychological tests used vary between studies, limiting potential for aggregation. We examined a machine learning (ML) data harmonisation method for neuropsychological test data to develop a harmonised PACC score for the Alzheimer's Dementia Onset and Progression in International Cohorts (ADOPIC) consortium.

Basic Science and Pathogenesis.

Background: For large genomic studies of middle-aged individuals, the prevalence of Alzheimer's disease (AD) is extremely low, making it difficult to conduct genomic analysis of the condition. To enable genome-wide association studies of AD in such datasets, an approach called Genome-wide association by proxy (GWAX) uses family history of disease as a proxy for disease status. Borrowing from the machine learning (ML) literature, we treat the development of proxy phenotypes as a pseudo-labelling task, where an ideal proxy label accurately predicts the lifetime risk of AD.

Clinical Manifestations.

Background: Language and cultural factors are known to influence cognitive performance on neuropsychological measures used to assess cognitive impairment and dementia. A new measure, the Characterising Language Experience and Acculturation Questionnaire (CLEAr-Q) was developed to address the gap in access to a brief measure of these factors in the Australian context. The aim is to validate and further develop the CLEAr-Q as a tool to capture linguistic and acculturation variables to improve measurement of cognition in older adults from Culturally and Linguistically Diverse (CALD) backgrounds.

Clinical Manifestations.

Background: In cognitively unimpaired (CU) individuals, the PACC is widely used as a cognitive outcome measure and endpoint in observational studies and clinical trials. However, it has drawn criticism for being heavily weighted towards memory. Increasing evidence indicates a decline spanning multiple cognitive domains in CU individuals.

Clinical Manifestations.

Background: Recent research has highlighted the importance of sleep on cognitive processes. However, conflicting evidence exists regarding optimal sleep duration and the impact of other co-occurring conditions, such as depression. A diagnosis of depression in mid-life may increase the risk of developing dementia.

Clinical Manifestations.

Background: Transcultural adaptations of brief cognitive screening tools (BCTs) involve the development of alternate versions that are psychometrically equivalent to the original, while being linguistically and culturally adapted to a new sociodemographic context. The RUDAS (Rowland Universal Dementia Assessment Scale) is less affected by culture, language, and education compared with other BCTs. However, several studies have reported an effect of education on RUDAS scores.

Clinical Manifestations.

Background: Intracerebral hemorrhage (ICH) is the most severe and disabling stroke, accounting for up to 50% of the cases in low-to-middle-income countries. High rates of cognitive decline and dementia follow acute ICH, due to the common underlying vasculopathy of cerebral small vessel disease (CSVD). The international clinical trial, TRIDENT (Triple therapy prevention of Recurrent Intracerebral Disease EveNts Trial), aims to determine the effectiveness of the fixed low-dose Triple Pill combination of blood pressure-lowering agents (telmisartan 20 mg, indapamide 1.

Clinical Manifestations.

Background: Several sets of diagnostic criteria have been published for vascular cognitive disorders (VCD) since the 1960s. The International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) working group published a comprehensive and operationalized criteria set in 2014. Considering the significant developments in the field in the last decade, an international expert group was commissioned to revise these criteria using the Delphi process.

Clinical Manifestations.

Background: Sporadic bvFTD is often misdiagnosed as a primary psychiatric disorder (PPD) due to overlapping clinical features and lack of reliable biomarkers. The multi-centre study DIPPA-FTD aims to develop diagnostic- and prognostic-algorithms that can distinguish sporadic bvFTD from late-onset PPD. The aim of the retrospective DIPPA-FTD study was to identify the strongest clinical discriminators.

Missing data and long-term outcomes from nutrition research in the critically ill.

Purpose Of Review: The use of functional outcomes in critical care nutrition research is increasingly advocated; however, this inevitably gives rise to missing data. Consequently there is a need to adopt modern approaches to the foreseeable problem of missing functional and survival outcomes in research trials.

Recent Findings: Analyses that ignore unobserved or missing data will often return biased effect estimates.