A steep decline in diastolic blood pressure over early to mid-life is associated with tau-PET burden in dementia-free adults.

BackgroundThe relationship between blood pressure (BP) trajectories across early (∼40 years) into mid-life (∼55 years) and preclinical dementia has not previously been well studied using positron emission tomography (PET) imaging outcomes.ObjectiveTo examine the association between BP trajectories across early mid-life into mid mid-life and amyloid- and tau-PET burden in adults without clinical dementia.MethodsThis prospective cohort study included dementia-free Framingham Heart Study 3 generation participants with data on remote BP (2002-2005) and recent BP (2016-2019) who participated in C-Pittsburgh Compound-B (PiB)-PET and/or F-Flortaucipir (FTP)-PET scans between 2016 to 2022.

Age-Related Changes in the Clinical Picture of Long COVID.

Background: This study evaluated the impact of aging on the frequency and prevalent symptoms of Long COVID, also termed post-acute sequelae of SARS-CoV-2, using a previously developed Long COVID research index (LCRI) of 41 self-reported symptoms in which those with 12 or more points were classified as likely to have Long COVID.

Methods: We analyzed community-dwelling participants ≥ 60 years old (2662 with prior infection, 461 controls) compared to participants 18-59 years (7549 infected, 728 controls) in the Researching COVID to Enhance Recovery adult (RECOVER-Adult) cohort ≥ 135 days post-onset.

Results: Compared to the Age 18-39 group, the adjusted odds of LCRI ≥ 12 were higher for the Age 40-49 group (odds ratio [OR] = 1.

Prevalent Cardiovascular Disease and Atrial Fibrillation in Relation to Cerebral Small Vessel Disease Burden.

Background/objectives: Cardiovascular disease (CVD) contributes to stroke and dementia. Individuals with CVD have high risk for adverse cognitive outcomes and stroke, possibly due to shared risk factors between CVD, stroke, and dementia, which may be attributed to cerebral small vessel disease (CSVD). We aim to determine the association between prevalent CVD and atrial fibrillation (AF) with CSVD.

Associations of Blood Pressure Level and Variability with Cortical Thickness: A Cross-Sectional Analysis from The Maracaibo Aging Study.

Background: Although high blood pressure (BP) level and variability are associated with Alzheimer's Disease (AD), their relationship with cortical thickness in brain regions that are associated with AD is unclear. Furthermore, the role of 24-hour BP has not been examined. We investigated the associations of office and ambulatory BP measures with cortical thickness in brain regions implicated in AD.

Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP): A global effort to identify genetic factors in Alzheimer's disease.

Introduction: Alzheimer's disease (AD) remains a major neurocognitive disorder of global health significance. Globalizing ancestral diversity in AD genetics is essential to identify causal variants, improve diagnosis, and enable equitable therapeutic interventions across populations. The Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP) initiative addresses this by including African ancestry and Hispanic/Latinx (HL) ancestry populations.

Multi-population Genome-Wide Association Study Identifies Multiple Novel Loci Associated with Asymptomatic Intracranial Large Artery Stenosis.

Introduction: Intracranial large artery stenosis (ILAS) is one of the most common causes of stroke worldwide and is associated with the risk for future vascular events. Asymptomatic ILAS is a frequent finding on neuroimaging and shares many risk factors with atherosclerotic vascular disease. Whether asymptomatic ILAS is driven by genetic variants is not well-understood.

Multi-marker cerebral small vessel disease score and risk of incident depression: The Framingham Heart Study.

Background: The vascular depression hypothesis postulates that cerebral small vessel disease (CSVD) contributes to the development of depression. This study examined the relationship between a multi-marker CSVD score derived from brain magnetic resonance imaging (MRI) with incident depression in community-dwelling individuals.

Methods: Framingham Heart Study (FHS) participants free of stroke, dementia, and depression with available data on CSVD MRI markers were included.

Signature White Matter Hyperintensity Locations Associated With Vascular Risk Factors Derived From 15 653 Individuals.

Background: White matter hyperintensities (WMHs) of presumed vascular origin are common in the elderly and are associated with vascular risk factors. There is evidence that vascular risk factors, in particular hypertension, are associated with WMH in particular locations of the white matter. However, it remains unclear whether this is true for all risk factors and whether signature WMH locations differ between risk factors.

Developing biobanking processes for Alzheimer's disease and related dementia research in Africa: Experience from the Recruitment and Retention for Alzheimer's Disease Diversity in the Alzheimer's Disease Sequencing Project (READD-ADSP).

The Recruitment and Retention for Alzheimer's Disease Diversity in the Alzheimer's Disease Sequencing Project (READD-ADSP) aims to recruit 5000 African participants (Alzheimer's disease [AD] and cognitively unimpaired controls) to generate genomic and biomarker data to better characterize AD neurobiology in Africa from countries that constitute the African Dementia Consortium (AfDC). Blood samples from study participants are separated into fractions and transported to the African Coordinating Centre (ACC: Ibadan, Nigeria), where DNA extraction and long-term biospecimen storage are carried out. Plasma and DNA aliquots are shipped to the John P.

Cross-tissue omics-guided drug repurposing triangulates novel targetable mechanisms for Alzheimer's disease and candidate genetic biomarkers for treatment stratification.

White matter hyperintensities (WMH) are covert magnetic resonance imaging (MRI) - markers of microvascular dysfunction and are primary vascular contributors to dementia, emphasizing its importance in prevention strategies. Here, we integrate gene expression and protein levels measured across plasma, cerebrospinal fluid (CSF), brain and multiple other tissues from population-based and biobank-scale data to triangulate druggable genes influencing WMH-burden and Alzheimer's disease (AD) and to map their spatial localization specifically in brain-cell types. Lowering the expression levels of and shows putative causal associations with reduced WMH-burden, and AD risk.

Altered Gut Microbiota Mediates the Association between APOE Genotype and Amyloid-β Accumulation in Middle-Aged Adults.

Importance: The apolipoprotein E ( ) ε4 allele is the strongest genetic risk factor for Alzheimer's disease (AD), yet the mechanisms linking to amyloid-β (Aβ) pathology remain incompletely understood. Emerging evidence suggests that the gut microbiome may modulate neurodegeneration; however, its role as a mediator in the APOE-Aβ relationship remains unclear.

Objective: To evaluate whether specific microbial taxa mediate APOE-related effects on brain Aβ burden in an established population-based study of middle-aged adults.

The role of community advisory boards in enhancing recruitment and retention in Alzheimer's disease and related dementia research in Africa: Experience from the READD-ADSP study.

Introduction:  The Recruitment and Retention of Alzheimer's Disease Diversity Genetic Cohorts in the Alzheimer's Disease Sequencing Project (READD-ADSP) was established to bridge the gap in Alzheimer's disease and related dementias (ADRD) research in Africa. We examined the role of Community Advisory Boards (CABs) in improving participant recruitment and retention in ADRD research in Africa, by exploring how culturally sensitive engagement, community trust-building, and stakeholder involvement influence research participation.

Methods:  A multi-site, multi-phased qualitative study approach that involved establishment of CABs, initial planning meetings and community engagement cum recruitment activities.

Advancing Fair and Explainable Machine Learning for Neuroimaging Dementia Pattern Classification in Multi-Ethnic Populations.

Dementia, a degenerative disease affecting millions globally, is projected to triple by 2050. Early and precise diagnosis is essential for effective treatment and improved quality of life. However, current diagnostic approaches frequently demonstrate inconsistent precision and impartiality, particularly among diverse cultural groups.

Long-Term Incidence of Dementia Following Transient Ischemic Attack: A Longitudinal Cohort Study.

Background: The association between transient ischemic attack (TIA) and dementia is incompletely characterized. Determining the cognitive sequalae of TIA is important as it can function as an early warning sign or additional risk factor for dementia. We sought to determine the long-term incidence of post-TIA dementia and examined whether TIA prompts changes in vascular risk factors.

COVID-19 and Cognitive Change in a Community-Based Cohort.

Importance: SARS-CoV-2 infection has been linked to neurotoxic effects and cognitive deficits.

Objective: To determine whether decreases in cognitive function were accelerated after SARS-CoV-2 infection compared with individuals not infected.

Design, Setting, And Participants: Multicenter, prospective cohort study from 2016 to 2022 among 3525 participants alive on March 1, 2020, and enrolled in The Atherosclerosis Risk in Communities (ARIC) study and the Collaborative Cohort of Cohorts for COVID-19 Research study who completed a prepandemic cognitive assessment and a pandemic-era assessment of SARS-CoV-2 infection.

The Ethnic/Racial Variations of Intracerebral Hemorrhage Genetics (ERICH-GENE) Study Protocol.

Background: Spontaneous, non-traumatic intracranial hemorrhage (ICH) is highly heritable disease. However, the identification of the genetic risk factors driving this high genetic predisposition has been limited by small sample sizes and underrepresentation of non-European populations. The ERICH-GENE study will gather and harmonize clinical, neuroimaging and genomic data on the largest and more diverse collection of ICH cases assembled to date.

Whole genome sequence association analysis of brain structural volume measures in the NHLBI TOPMed Program highlights novel loci in diverse participants.

Brain structural volumes are highly heritable and are linked to multiple neuropsychological outcomes, including Alzheimer's disease (AD). Genome-wide association studies have successfully identified genetic variants associated with intracranial volume (ICV), total brain volume (TBV), hippocampal volume (HV), and lateral ventricular volume (LVV). However, these studies mostly focused on common genetic variants with minor allele frequencies (MAF) > 1%, and individuals included in most of these studies were of predominantly European ancestry.

Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations.

A polygenic score (PGS) for Alzheimer's disease (AD) was derived recently from data on genome-wide significant loci in European ancestry populations. We applied this PGS to populations in 17 European countries and observed a consistent association with the AD risk, age at onset and cerebrospinal fluid levels of AD biomarkers, independently of apolipoprotein E locus (APOE). This PGS was also associated with the AD risk in many other populations of diverse ancestries.

Midlife Steroid-Binding Globulin Levels and In Vivo Neuroimaging Measures of Tau in Older Men and Women.

Objective: In men and women, sex steroid hormones have been associated with increased risk of Alzheimer's disease (AD) dementia. We aimed to investigate the influence of midlife testosterone and sex hormone binding globulin (SHBG) levels on later-life in vivo markers of β-amyloid (Aβ) and tau deposition in clinically healthy older men.

Methods: This time-lagged study includes participants enrolled in the Framingham Heart Study (FHS) Third Generation cohort.

Assessing the Global Impact of Brain Small Vessel Disease on Cognition: The Multi-Ethnic Study of Atherosclerosis.

Introduction: We aimed to examine the global impact of brain small vessel disease (SVD) on cognitive performance.

Methods: In 892 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), we derived perivascular spaces (PVS), white matter hyperintensities (WMH), microbleeds (MB), and white matter fractional anisotropy (FA) and trace (TR). Cognitive function was assessed with a comprehensive neuropsychological battery.

Association of MRI visible Perivascular Spaces with Early White Matter Injury.

Background And Purpose: MRI Visible Perivascular Spaces (PVS) are considered markers of cerebral small vessel disease (CSVD) and may reflect dysfunction of brain perivascular drainage. White matter integrity assessed with Diffusion Tensor Imaging (DTI) provides a sensitive assessment of early brain injury, related vascular risk factors and risk of stroke and dementia. We investigated the relation between PVS and white matter integrity in community-dwelling participants.

Interocular Asymmetry of OCT Retinal Nerve Fiber Layer Values in a Normative Population: The Framingham Heart Study.

Purpose: To explore interocular asymmetry in retinal nerve fiber layer (RNFL) thickness using optical coherence tomography (OCT), assess factors that predict this asymmetry, and quantify the 95% central range for OCT-defined average cup-disc ratio (CDR).

Methods: Participants from the Framingham Heart Study were included. Interocular differences in OCT parameters were calculated by subtracting left eye values from the right eye.

Association of Blood Lipoprotein Levels With Incident Alzheimer Disease in Community-Dwelling Individuals: The Framingham Heart Study.

Background And Objectives: Cardiovascular risk factors are important contributors to the risk of Alzheimer disease (AD). To further explore the physiologic links between cardiovascular health and AD risk, we studied the associations between various blood lipoprotein levels and AD risk in community-dwelling older adults.

Methods: This longitudinal analysis included participants aged 60 years or older without prevalent dementia and with available cognitive follow-up and lipoprotein marker data from the Framingham Heart Study.

Rapamycin treatment for Alzheimer's disease and related dementias: a pilot phase 1 clinical trial.

Background: Rapamycin has been shown to extend lifespan and acts on pathologies underlying Alzheimer's disease and related dementias in animal models. However, rapamycin's clinical application remains underexplored.

Methods: We conducted a single-site open-label phase 1 clinical trial (ClinicalTrials.