Prevalence and risk factors of cerebral microhemorrhages and superficial siderosis in cognitively unimpaired older adults: analysis from the CHARIOT-PRO SubStudy.

Introduction: Cerebral microhemorrhages (CMHs) and superficial siderosis (SS) are relatively common side effects of anti-amyloid immunotherapies, termed amyloid-related imaging abnormalities (ARIA-H). They are also observed in treatment-naïve older adults. This study explored relationships with modifiable and non-modifiable risk factors.

Early detection of Alzheimer's disease using small RNAs. Results from the EPAD cohort.

Background: Alzheimer's disease (AD) is the most common form of dementia, and early diagnosis is crucial to enable effective interventions. Currently, Alzheimer's disease is diagnosed through cognitive assessments, brain imaging and fluid biomarkers focused on determining amyloid (A) and, tau (T) protein levels as well as neurodegeneration (N) in the AT(N) framework. Prognostic biomarkers for predicting cognitive decline within the amyloid positive (Aβ+) individuals would further strengthen the framework.

The impact of mild cognitive impairment on healthcare utilization and costs: A UK Biobank study.

Introduction: Mild cognitive impairment (MCI) is common in older adults, but the burden on patients and health systems is not well understood. We aimed to estimate the impact of MCI on healthcare utilization and costs.

Methods: This was a matched cohort study in UK Biobank comparing healthcare costs and Alzheimer's disease (AD) dementia incidence rates in participants with MCI to propensity score-matched participants without MCI.

Intimate partner violence, traumatic brain injury and long-term mental health outcomes in midlife: the Drake IPV study.

Background: Approximately 30% of women experience intimate partner violence (IPV) in their lifetime, often with traumatic brain injury (TBI) exposure. Nevertheless, there has been limited research exploring lifelong brain health outcomes following IPV with TBI. To address this, we investigated the relationship between IPV, TBI and midlife mental health outcomes within an observational cohort study.

Exploring the potential of digital biomarkers as a measure of brain health 'capital'.

Neurological conditions, including dementia, pose a major public health challenge, contributing to a significant and growing clinical, economic, and societal burden. Traditionally, research and clinical practice have focused on diseases like dementia in isolation. However, in an ageing, multimorbid population, this approach is becoming increasingly inadequate.

GWAS meta-analysis of CSF Alzheimer's disease biomarkers 18,948 individuals reveal novel loci and genes regulating lipid metabolism, brain volume and autophagy.

Cerebrospinal fluid (CSF) amyloid beta (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau181) are well accepted markers of Alzheimer's disease. We performed a GWAS meta-analysis including 18,948 individuals of European and 416 non-European ancestry. We identified 12 genome-wide significant loci across all three biomarkers, eight of them novel.

Hypothalamic volume, sleep, and APOE genotype in cognitively healthy adults.

Introduction: Sleep dysfunction in those at higher risk of dementia may be associated with early structural changes to the hypothalamus.

Methods: We used multivariate regression to analyze self-reported sleep (Pittsburgh Sleep Quality Index [PSQI]) from cognitively healthy participants in the PREVENT Dementia and Alzheimer's and Families (ALFA) studies (n = 1939), stratified by apolipoprotein E (APOE) genotype as homozygotes, heterozygotes, and non-carriers. FreeSurfer was used to extract hypothalamic subunit volumes from T1-weighted magnetic resonance images.

Accrual of Alzheimer's disease pathology as a function of proximity to parental dementia onset.

Introduction: Whether temporal proximity to parental onset of dementia (PPO) can be used to estimate timing of the preclinical stage of sporadic Alzheimer's disease (AD) remains uncertain.

Methods: We investigated cross-sectionally adults aged > 50 without dementia included in the European Prevention of Alzheimer's Dementia (EPAD) study. PPO was tested as a predictor of quantitative levels of cerebrospinal fluid (CSF) β-amyloid (1-42) (Aβ1-42) in those with a parental history of dementia ( = 688) and of phosphorylated tau (p-tau) and EPAD neuropsychological examination (ENE) subscores in an amyloid positive subgroup ( = 226).

Soluble Aβ pathology predicts neurodegeneration and cognitive decline independently on p-tau in the earliest Alzheimer's continuum: Evidence across two independent cohorts.

Introduction: Identifying the link between early Alzheimer's disease (AD) pathological changes and neurodegeneration in asymptomatic individuals may lead to the discovery of preventive strategies. We assessed longitudinal brain atrophy and cognitive decline as a function of cerebrospinal fluid (CSF) AD biomarkers in two independent cohorts of cognitively unimpaired (CU) individuals.

Methods: We used longitudinal voxel-based morphometry (VBM) in combination with hippocampal subfield segmentation.

Association between choroidal microvasculature in the eye and Alzheimer's disease risk in cognitively healthy mid-life adults: A pilot study.

Introduction: We explored associations between measurements of the ocular choroid microvasculature and Alzheimer's disease (AD) risk.

Methods: We measured the choroidal vasculature appearing in optical coherence tomography (OCT) scans of 69 healthy, mid-life individuals in the PREVENT Dementia cohort. The cohort was prospectively split into low-, medium-, and high-risk groups based on the presence of known risk factors (apolipoprotein E [] ε4 genotype and family history of dementia [FH]).

Cerebral perfusion alterations in healthy young adults due to two genetic risk factors of Alzheimer's disease: APOE and MAPT.

Functional brain changes such as altered cerebral blood flow occur long before the onset of clinical symptoms in Alzheimer's disease (AD) and other neurodegenerative disorders. While cerebral hypoperfusion occurs in established AD, middle-aged carriers of genetic risk factors for AD, including APOE ε4, display regional hyperperfusion due to hypothesised pleiotropic or compensatory effects, representing a possible early biomarker of AD and facilitating earlier AD diagnosis. However, it is not clear whether hyperperfusion already exists even earlier in life.

The pivotal role of sleep in mediating the effects of life stressors and healthy habits on allostatic load in mid-life adults.

Objectives: We assessed the modulation of allostatic load (AL) by engagement in healthy habits and life stressors, mediated through resilience and the perceived influence of the stressors. Sleep was included as third mediator given extensive evidence associating to all the analysed factors.

Methods: Structural equation models to assess the modulation of AL by either traumatic or psychosocial stressors and healthy habits were generated with data from 620 mid-life adults (age 51.

The effects of two Alzheimer's disease related genes and in healthy young adults: An attentional blink study.

Background: Genetic risk factors start to affect the brain and behavior in Alzheimer's disease (AD) before clinical symptoms occur. Although AD is mainly associated with memory deficits, attention and executive dysfunctions can present at the early presymptomatic stages in middle age for those with non-modifiable risks.

Objective: Here, we investigated whether known risk genes for AD already affected attention in young adulthood.

Associations between sex and lifestyle activities with cognitive reserve in mid-life adults with genetic risk for Alzheimer's disease.

Background: Females have a higher age-adjusted incidence of Alzheimer's Disease (AD) than males, even when accounting for longer lifespan and, therefore, stand to benefit the most from dementia prevention efforts. As exposure to many modifiable risk factors for dementia begins in mid-life, interventions must be implemented from middle-age. Building cognitive reserve, particularly through stimulating avocational activities and occupational attainment presents a crucial, underexplored, dementia prevention approach for mid-life.

Cardiovascular risk of dementia is associated with brain-behaviour changes in cognitively healthy, middle-aged individuals.

Alzheimer's Disease (AD) neuropathology start decades before clinical manifestations, but whether risk factors are associated with early cognitive and brain changes in midlife remains poorly understood. We examined whether AD risk factors were associated with cognition and functional connectivity (FC) between the Locus Coeruleus (LC) and hippocampus - two key brain structures in AD neuropathology - cross-sectionally and longitudinally in cognitively healthy midlife individuals. Neuropsychological assessments and functional Magnetic Resonance Imaging were obtained at baseline (N=210), and two-years follow-up (N=188).

Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia.

Background And Objectives: Vascular risk factors (VRFs) and cerebral small vessel disease (cSVD) are common in patients with Alzheimer disease (AD). It remains unclear whether this coexistence reflects shared risk factors or a mechanistic relationship and whether vascular and amyloid pathologies have independent or synergistic influence on subsequent AD pathophysiology in preclinical stages. We investigated links between VRFs, cSVD, and amyloid levels (Aβ) and their combined effect on downstream AD biomarkers, that is, CSF hyperphosphorylated tau (P-tau), atrophy, and cognition.

Differences in Grey Matter Concentrations and Functional Connectivity between Young Carriers and Non-Carriers of the APOE ε4 Genotype.

: The pathophysiology of Alzheimer's disease (AD) may begin developing years or even decades prior to the manifestation of its first symptoms. The APOE ε4 genotype is a prominent genetic risk for AD that has been found to be associated with brain changes across the lifespan since early adulthood. Thus, studying brain changes that may occur in young adults with an APOE ε4 status is highly relevant.

The association between selenium status and global and attention-specific cognition in very old adults in the Newcastle 85+ Study: cross-sectional and longitudinal analyses.

Background: Selenium has potential safeguarding properties against cognitive decline, because of its role in protecting DNA, proteins, and lipids in the brain from oxidative damage. However, acute and chronic overexposure to selenium can be neurotoxic.

Objective: The aim of this analysis was to explore the association between selenium status [serum selenium and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity] and cognitive function in 85-y olds living in Northeast England at baseline and ≤5 y of follow-up.

Neuroimaging and Clinical Findings in Healthy Middle-Aged Adults With Mild Traumatic Brain Injury in the PREVENT Dementia Study.

Importance: Traumatic brain injuries (TBI) represent an important, potentially modifiable risk factor for dementia. Despite frequently observed vascular imaging changes in individuals with TBI, the relationships between TBI-associated changes in brain imaging and clinical outcomes have largely been overlooked in community cases of TBI.

Objective: To assess whether TBI are associated with and interact with midlife changes in neuroimaging and clinical features in otherwise healthy individuals.

Association of optic disc pallor and RNFL thickness with cerebral small vessel disease in the PREVENT-Dementia study.

Introduction: We tested associations between two retinal measures (optic disc pallor, peripapillary retinal nerve fiber layer [pRNFL] thickness) and four magnetic resonance imaging markers of cerebral small vessel disease (SVD; lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces [ePVSs]).

Methods: We used PallorMetrics to quantify optic disc pallor from fundus photographs, and pRNFL thickness from optical coherence tomography scans. Linear and logistic regression assessed relationships between retinal measures and SVD markers.

Remote data collection speech analysis in people at risk for Alzheimer's disease dementia: usability and acceptability results.

Introduction: Digital cognitive assessments are gathering importance for the decentralized remote clinical trials of the future. Before including such assessments in clinical trials, they must be tested to confirm feasibility and acceptability with the intended participant group. This study presents usability and acceptability data from the Speech on the Phone Assessment (SPeAk) study.

Texture-based morphometry in relation to apolipoprotein ε4 genotype, ageing and sex in a midlife population.

Brain atrophy and cortical thinning are typically observed in people with Alzheimer's disease (AD) and, to a lesser extent, in those with mild cognitive impairment. In asymptomatic middle-aged apolipoprotein ε4 (ΑPOE4) carriers, who are at higher risk of future AD, study reports are discordant with limited evidence of brain structural differences between carriers and non-carriers of the ε4 allele. Alternative imaging markers with higher sensitivity at the presymptomatic stage, ideally quantified using typically acquired structural MRI scans, would thus be of great benefit for the detection of early disease, disease monitoring and subject stratification.