Biomarkers.

Background: Biomarkers promise to significantly improve the differential diagnosis of Alzheimer's disease (AD). Plasma biomarkers, such as phosphorylated tau (p-tau), have shown potential in diagnosing AD with high accuracy. Unlike the widely-used [18 F]FDG-PET diagnostic biomarker in clinical practice, plasma p-tau is specific to AD and can provide an affordable and scalable diagnostic tool.

Biomarkers.

Background: Recently, the development of ultra-sensitive immunoassays has allowed for the detection, in blood, of proteins related to the pathophysiology of Alzheimer's disease (AD), with phosphorylated tau (p-tau) being the most promising. However, current methods are often limited by their ability to measure one analyte, lacking the potential for discovery and inclusion of additional biomarkers with supplemental value. In this pilot study, we explored proteomic changes using the novel NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) platform, focusing on patients with mild cognitive impairment (MCI).

Biomarkers.

Background: There is a critical need for minimally-invasive robust peripheral markers of neurodegenerative conditions. Peripheral RNA may be a powerful tool for in-depth tracking of biological processes in AD and related disorders. Here, we combine whole-blood microarray data from Alzheimer's Disease Neuroimaging Initiative (ADNI; N=743) and RNA-Seq from Translational Biomarkers in Aging and Dementia (TRIAD; N=77) and Montreal Neurological Institute (MNI; N=33) cohorts to predict cognitive performance across AD spectrum.

Biomarkers.

Background: We showed that plasma GFAP (a proxy of astrocyte reactivity) abnormality is key to unleashing Aβ effects on tau phosphorylation in preclinical AD. This suggests that selecting cognitively unimpaired(CU) individuals with both high Aβ and plasma GFAP could offer an early time window in the disease, but with an increased risk of developing tau pathology. Here, we tested the utility of plasma GFAP for population enrichment in clinical trials focusing on CU individuals.

Public Health.

Background: Social and health-related disparity factors are important predictors of brain health in low and middle-income countries (LMIC). Social predictors of cognition have a higher impact on brain health among LMICs than classic demographic factors, such as age and sex. This study aimed to evaluate the impact of modifiable and non-modifiable social and health-related factors on cognition in a Brazilian population-based cohort.

Public Health.

Background: Latin American Countries (LACs) have major health-related inequities due to historical, cultural, and social aspects. These factors have been suggested as important determinants of healthy aging in LACs. Here, we evaluated classic and socioeconomic risk factors for healthy brain aging across five large cohorts of LACs.

Public Health.

Background: Disease modifying therapies (DMTs) for Alzheimer's disease (AD) have been approved in some countries although these treatments will require substantial health resources for their implementation. Initial capacity planning to identify the resources required to support DMTs begins with estimating the number of people with dementia who may be eligible for DMTs. We estimated the potential number of individuals with dementia who are eligible for DMTs using population-based data in Alberta, Canada.

Public Health.

Background: This study describes the total healthcare costs integrating direct, indirect, and intangible or emotional cost components across the severity stages of Alzheimer's disease (AD) in US.

Method: Utilizing Health and Retirement Study (HRS) data (1994-2018), a bi-annual US national survey of older adults, we assessed out-of-pocket and indirect costs, including unpaid caregiving services, missed workdays, and early retirement. HRS, analyzed with sampling weights, provided a representative US national sample.

Public Health.

Background: Subjective Cognitive Decline (SCD) is characterized by cognitive complaints in cognitively unimpaired (CU) individuals. Its condition displays considerable heterogeneity etiologies, including neurodegenerative diseases. Our aim is to compare the memory complaints between patients with SCD and their informants in the BRASCODE cohort.

Public Health.

Background: The Better at Home Program (BHP) is a Brazilian government initiative to provide dehospitalization through homecare health access in primary care. The profile of modifiable risk factors of dementia in this vulnerable population may provide targets for public health policies, as it represents the majority of the Brazilian population. In this study, we aimed at investigating the profile of modifiable risk factors in primary care compared with a tertiary care clinic in Brazil.

Public Health.

Background: Higher education is often associated with reduced risk of cognitive decline. These findings fueled the conceptualization of cognitive reserve to explain individual variabilities in clinical trajectory. However, our understanding of the biological basis for this phenomenon is still not precise.

Biomarkers.

Background: White matter hyperintensities (WMHs) are age-related radiological abnormalities indicative of small vessel disease. It is unclear if WMHs in different regions represent similar pathophysiology and etiology. Here, we developed a framework to estimate WMH pathophysiology in vivo, which allowed us to precisely characterize spatial patterns of WMH tissue alterations associated with four disorders.

Biomarkers.

Background: Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Nevertheless, whether redox perturbations are associated with cognition and AD pathology in the preclinical AD stages, remains unclear. We examined associations of blood redox markers with AD biomarkers and cognitive performance in older adults without clinical dementia.

Biomarkers.

Background: Anti-amyloid therapy appears to have an increased effect on reducing cognitive decline in amyloid- and tau-positive individuals. However, clinical trials inclusion criteria require solely amyloid positivity. Herein, we developed a machine-learning prediction model to identify tau positivity in amyloid-positive individuals using clinical variables.

Biomarkers.

Background: Recent evidence indicated that cognitive impairment is more closely associated with the spatial extent of tauopathy (SEOT) than with tau load. It remains unclear whether this is also true for other markers of Alzheimer's disease (AD) severity, such as fluid levels of phosphorylated tau (pTau). Here, we compared the link between fluid pTau and the SEOT and tau load in the brain, as assessed by PET.

Biomarkers.

Background: Synaptic dysfunction is a central pathologic feature of Alzheimer's disease (AD), with synaptic loss even preceding neuronal loss in specific brain regions. In healthy individuals, synaptic function and plasticity are orchestrated through the complex integration of signaling inputs generated by cell surface receptors.

Methods: In this study, we investigate the role of one such receptor, protein tyrosine phosphatase receptor sigma (PTPRS), in the context of Alzheimer's disease.

Biomarkers.

Background: Wearable sensor technology shows promise for neuropsychiatric symptoms (NPS) identification/monitoring in persons living with dementia (PLWD). Accelerometry measures acceleration of body segments and physical activity. This study explores the diagnostic test accuracy (DTA) of accelerometry to identify the following 6 NPS associated with motor activity: aberrant motor behavior (AMB), aggression, agitation, anxiety, apathy, and wandering.

Biomarkers.

Background: Synapse loss in Alzheimer's disease (AD) is correlates closely with cognitive impairment. Recent evidence suggests that synapse loss is promoted by amyloid-beta, leading in turn to the spread of tau pathology. We sought to assess: 1) the association in positron emission tomography (PET) between several cerebrospinal fluid (CSF) synaptic biomarkers and amyloid and tau burden, as well as their annual change; and 2) the potential clinical utility of these synaptic biomarkers in preclinical AD.

Biomarkers.

Background: The association between medial temporal and neocortical SUVR depends on availability of cortical tau. However, tracer differences in affinity and off-target binding might interfere in these associations. Here, we examined the association between medial temporal and neocortical SUVR using voxel-based approach.

Biomarkers.

Background: Predicting Alzheimer's disease (AD) and frontotemporal dementia (FTD) using polygenic risk scores (PRS) for late-onset forms holds promise, but its accuracy might be influenced by social determinants of health (SDOH). This study explores how considering SDOH alongside genes can improve prediction, focusing on potential differences for each disease.

Methods: Employing logistic regression in 677 individuals (287 AD, 102 FTD, and 288 controls) aged 40-80 from the ReDLat study across six Latin American countries, we investigated the potential for SDOH to modify the association between PRS and susceptibility to AD and FTD.

Biomarkers.

Background: Tau aggregates in Alzheimer's disease (AD) induce loss of synapses and neurons, leading to cognitive impairment. Predicting tau and neurodegeneration temporal evolution could be used for prognostication and for assessing results of therapeutic trials. Tau PET and MRI volumetry are reliable markers of disease stage, but cost and radiation protection considerations limit research measurement frequency, lowering the accuracy of disease progression modeling.

Biomarkers.

Background: Alzheimer's disease (AD) disproportionately impacts females, who exhibit a higher tau load compared to males. Existing literature suggests that biological sex may alter the impact of APOE on tau pathology in AD. Nevertheless, the genetic factors contributing to sex differences in AD tau pathology, beyond the influence of APOE, have been minimally investigated.

Biomarkers.

Background: Epigenetics plays a crucial role in regulating genetic transcription and responding to environmental and lifestyle changes without altering the DNA sequence. Their dysregulation is associated with AD, presenting potential as blood biomarkers. However, no study has evaluated whether peripheral blood (PB) epigenetic biomarkers are associated with brain metabolism, indexed by FDG-PET, a classic Imaging AD biomarker.

Biomarkers.

Background: Long-COVID is characterized by persistent symptoms post-infection with SARS-CoV-2. This condition includes neurological manifestations and has been proposed as a potential risk factor for the development of dementia. Individuals presenting with dementia due to Alzheimer's disease have dysfunctional brain metabolism, including metabolic brain network (MBN) hypoconnectivity.

Biomarkers.

Background: Compared to men, insulin-resistant women have more brain atrophy, cognitive impairment, and higher dementia risk, but the mechanisms for this sex difference are unknown. We examined sex differences in how blood insulin relates to cortical thickness in cognitively intact older adults. Gaining a better understanding of the relationship between insulin and brain health could help inform the development of insulin-targeting treatments and reduce the risk of dementia associated with insulin resistance.