Convolutional Neural Networks for the segmentation of hippocampal structures in postmortem MRI scans.

Background: The hippocampus plays a crucial role in memory and is one of the first structures affected by Alzheimer's disease. Postmortem MRI offers a way to quantify the alterations by measuring the atrophy of the inner structures of the hippocampus. Unfortunately, the manual segmentation of hippocampal subregions required to carry out these measures is very time-consuming.

The African Initiative for Bioinformatics Online Training in Neurodegenerative Diseases (AI-BOND): Investing in the next generation of African neuroscientists.

Unlabelled: Neurodegenerative disorders, including Alzheimer's disease and AD-related dementias (AD/ADRD), pose significant challenges to health care systems globally, particularly in Africa. With the advances in medical technology and research capabilities, especially in next-generation sequencing and imaging, vast amounts of data have been generated from AD/ADRD research. Given that the greatest increase in AD/ADRD prevalence is expected to occur in Africa, it is critical to establish comprehensive bioinformatics training programs to help African scientists leverage existing data and collect additional information to untangle AD/ADRD heterogeneity in African populations.

MRI free water mediates the association between diffusion tensor image analysis along the perivascular space and executive function in four independent middle to aged cohorts.

Introduction: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was proposed for assessing glymphatic clearance function. This study evaluated DTI-ALPS as a biomarker for cerebral small vessel disease (cSVD) related vascular cognitive impairment and dementia (VCID).

Methods: Four independent cohorts were examined.

Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.

Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.

Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).

Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.

Unraveling the clinical-pathological correlations of subjects with isolated and mixed neurodegenerative processes in the National Alzheimer's Coordinating Center dataset.

Although Alzheimer disease neuropathologic change (ADNC) is the most common pathology underlying clinical dementia, the presence of multiple comorbid neuropathologies is increasingly being recognized as a major contributor to the worldwide dementia burden. We analyzed 1051 subjects with specific combinations of isolated and mixed pathologies and conducted multivariate logistic regression analysis on a cohort of 4624 cases with mixed pathologies to systematically explore the independent cognitive contributions of each pathology. Alzheimer disease neuropathologic change and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) were both associated with a primary clinical diagnosis of Alzheimer disease (AD) and were characterized by an amnestic dementia phenotype, while only ADNC associated with logopenic variant primary progressive aphasia (PPA).

Peripheral risk factors and their role in biomarker-based screening for dementia in the community.

Introduction: Peripheral risk factors (PRFs) may correlate with dementia plasma biomarkers, potentially reflecting peripheral rather than brain health. This study explores the associations between PRFs and plasma biomarkers glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and total-tau, and their role in predicting future dementia.

Methods: Data from the Age, Gene/Environment Susceptibility-Reykjavik Study (2002-2015) included 4353 participants mean age of 76.

Microglia internalize tau monomers and fibrils using distinct receptors but similar mechanisms.

Introduction: Alzheimer's disease (AD) and other tauopathies are characterized by intracellular aggregates of microtubule-associated protein tau that are actively released and promote proteopathic spread. Microglia engulf pathological proteins, but how they endocytose tau is unknown.

Methods: We measured endocytosis of different tau species by microglia after pharmacological modulation of macropinocytosis or clathrin-mediated endocytosis (CME) or antagonism/genetic depletion of known tau receptors heparan-sulfate proteoglycans (HSPGs) and low-density lipoprotein receptor-related protein 1 (LRP1).

Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.

Introduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized.

Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.

White matter free water mediates the associations between placental growth factor, white matter hyperintensities, and cognitive status.

Introduction: Placental growth factor (PlGF) may regulate cerebrovascular permeability. We hypothesized that white matter interstitial fluid accumulation, estimated via magnetic resonance imaging (MRI) free water (FW), would explain the associations between elevated PlGF, white matter hyperintensities (WMH), and cognitive impairment.

Methods: MarkVCID consortium participants ≥55 years old with plasma PlGF and brain MRI were included.

Caffeine intake during gestation and lactation causes long-term behavioral impairments in heterogenic mice offspring in a sex-dependent manner.

Growing evidence has indicated a potential association between maternal consumption of caffeine and impaired cognition and behavior in rodent offspring. However, potential sex differences, as well as caffeine-related effects in subsequent generations are still poorly investigated. We aimed to investigate the impact of pre-and/or neonatal exposition to caffeine on the neurodevelopment of male and female mice offspring.

Long Sleep Duration, Cognitive Performance, and the Moderating Role of Depression: A Cross-Sectional Analysis in the Framingham Heart Study.

Introduction: We investigated whether depression modified the associations between sleep duration and cognitive performance.

Methods: Multivariable linear regression models examined the associations between sleep duration and cognition in 1,853 dementia- and stroke-free participants from the Framingham Heart Study. Participants were categorized in four groups: no depressive symptoms, no antidepressants; depressive symptoms without antidepressants use; antidepressant use without depressive symptoms; both depressive symptoms and antidepressant use.

Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects.

Background: Quantification of Amyloid beta (Aβ) oligomers in plasma enables early diagnosis of Alzheimer's Disease (AD) and improves our understanding of underlying pathologies. However, quantification necessitates an extremely sensitive and selective technology because of very low Aβ oligomer concentrations and possible interference from matrix components.

Methods: In this report, we developed and validated a surface-based fluorescence distribution analysis (sFIDA) assay for quantification of Aβ oligomers in plasma.

Deep learning reveals pathology-confirmed neuroimaging signatures in Alzheimer's, vascular and Lewy body dementias.

Concurrent neurodegenerative and vascular pathologies pose a diagnostic challenge in the clinical setting, with histopathology remaining the definitive modality for dementia-type diagnosis. To address this clinical challenge, we introduce a neuropathology-based, data-driven, multi-label deep learning framework to identify and quantify in-vivo biomarkers for Alzheimer's disease (AD), vascular dementia (VD), and Lewy body dementia (LBD) using antemortem T1-weighted MRI scans of 423 demented and 361 control participants from NACC and ADNI datasets. Based on the best-performing deep learning model, explainable heatmaps are extracted to visualize disease patterns, and the novel Deep Signature of Pathology Atrophy REcognition (DeepSPARE) indices are developed, where a higher DeepSPARE score indicates more brain alterations associated with that specific pathology.

Association between dietary inflammatory index score and incident dementia.

Introduction: We evaluated whether higher Dietary Inflammatory Index (DII) scores were associated with increased incidence of all-cause dementia and Alzheimer's disease (AD) dementia over 22.3 years of follow-up in the community-based Framingham Heart Study Offspring cohort.

Methods: One thousand four hundred eighty-seven participants (mean ± standard deviation, age in years 69 ± 6) completed food frequency questionnaires (FFQs) and had incident all-cause dementia and AD surveillance data available.

Associations of plasma SMOC1 and soluble IL6RA levels with the progression from mild cognitive impairment to dementia.

Despite the central role attributed to neuroinflammation in the etiology and pathobiology of Alzheimer's disease (AD), the direct link between levels of inflammatory mediators in blood and cerebrospinal fluid (CSF) compartments, as well as their potential implications for AD diagnosis and progression, remains inconclusive. Moreover, there is debate on whether inflammation has a protective or detrimental effect on disease onset and progression. Indeed, distinct immunological mechanisms may govern protective and damaging effects at early and late stages, respectively.

Utilization and perceived usefulness of monitoring technology for family caregivers of people living with Alzheimer's disease and related dementias.

Background: Caregivers of people living with dementia (PLWD) often experience burden based on their care recipients' symptoms of wandering, disorientation, and agitation.

Objective: To examine the utilization and perceived value of technology-based solutions for caregiving among caregivers of PLWD.

Methods: In collaboration with three Texas sites, PLWD and family caregiver dyads were recruited from clinical and community sites to assess the feasibility of a caregiving technology.

mHealth Apps for Dementia Caregivers: Systematic Examination of Mobile Apps.

Background: Informal caregivers of persons living with dementia are increasingly using mobile health (mHealth) apps to obtain care information. mHealth apps are seen as promising tools to better support caregivers' complex and evolving information needs. Yet, little is known about the types and quality of dementia care information that these apps provide.

Urinary Metal Levels, Cognitive Test Performance, and Dementia in the Multi-Ethnic Study of Atherosclerosis.

Importance: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited.

Objective: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4).

Design, Setting, And Participants: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018.

Alzheimer's disease-specific transcriptomic and epigenomic changes in the tryptophan catabolic pathway.

Background: Neurodegenerative disorders, including Alzheimer's disease (AD), have been linked to alterations in tryptophan (TRP) metabolism. However, no studies to date have systematically explored changes in the TRP pathway at both transcriptional and epigenetic levels. This study aimed to investigate transcriptomic, DNA methylomic (5mC) and hydroxymethylomic (5hmC) changes within genes involved in the TRP and nicotinamide adenine dinucleotide (NAD) pathways in AD, using three independent cohorts.

Diets to promote healthy brain ageing.

Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best, small effects on cognitive outcomes.

Biological validation of peak-width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium.

Background: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

Methods: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567).