Decreased functional connectivity is associated with increased levels of Cerebral Spinal Fluid soluble-PDGFRβ, a marker of blood brain barrier breakdown, in older adults.

Resting-state functional connectivity (FC) is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. For instance, studies in pre-clinical AD subjects have shown increases of cerebral spinal fluid soluble platelet-derived growth factor receptor-β (CSF sPDGFRβ, a marker of BBB breakdown) but have not demonstrated if this vascular impairment affects neuronal dysfunction. It's possible that increased levels of sPDGFRβ in the CSF may correlate with impaired FC in metabolically demanding brain regions (i.

Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD.

Background: Cellular senescence is a hallmark of aging and has been implicated in Alzheimer's disease (AD) pathogenesis. Cholesterol accumulation drives cellular senescence; however, the underlying mechanisms are unclear. ATP-binding cassette transporter A1 (ABCA1) plays an important role in cholesterol homeostasis.

20-year depressive symptoms, dementia, and structural neuropathology in older women.

Introduction: The course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes.

Methods: Utilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study.

Assessment of arterial pulsatility of cerebral perforating arteries using 7T high-resolution dual-VENC phase-contrast MRI.

Purpose: Directly imaging the function of cerebral perforating arteries could provide valuable insight into the pathology of cerebral small vessel diseases (cSVD). Arterial pulsatility has been identified as a useful biomarker for assessing vascular dysfunction. In this study, we investigate the feasibility and reliability of using dual velocity encoding (VENC) phase-contrast MRI (PC-MRI) to measure the pulsatility of cerebral perforating arteries at 7 T.

Asian Cohort for Alzheimer's Disease (ACAD) pilot study on genetic and non-genetic risk factors for Alzheimer's disease among Asian Americans and Canadians.

Introduction: Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population.

Methods: The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites.

Association between late-life air pollution exposure and medial temporal lobe atrophy in older women.

Background: Ambient air pollution exposures increase risk for Alzheimer's disease (AD) and related dementias, possibly due to structural changes in the medial temporal lobe (MTL). However, existing MRI studies examining exposure effects on the MTL were cross-sectional and focused on the hippocampus, yielding mixed results.

Method: To determine whether air pollution exposures were associated with MTL atrophy over time, we conducted a longitudinal study including 653 cognitively unimpaired community-dwelling older women from the Women's Health Initiative Memory Study with two MRI brain scans (MRI-1: 2005-6; MRI-2: 2009-10; M at MRI-1=77.

Alzheimer's Related Neurodegeneration Mediates Air Pollution Effects on Medial Temporal Lobe Atrophy.

Exposure to ambient air pollution, especially particulate matter with aerodynamic diameter <2.5 μm (PM) and nitrogen dioxide (NO), are environmental risk factors for Alzheimer's disease and related dementia. The medial temporal lobe (MTL) is an important brain region subserving episodic memory that atrophies with age, during the Alzheimer's disease continuum, and is vulnerable to the effects of cerebrovascular disease.

Use of the Spanish English Neuropsychological Assessment Scale in older adult Latines and those at risk for autosomal dominant Alzheimer's disease.

Objective: The Spanish English Neuropsychological Assessment Scale (SENAS) is a cognitive battery with English and Spanish versions for use with persons for whom either language is predominant. Few studies have examined its utility outside the normative sample. The current study examined SENAS performance in samples of older adult Latines and Latines with or at risk for autosomal dominant Alzheimer's disease (ADAD) mutations.

Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease.

Importance: Increased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors.

Objective: To estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes.

Design, Setting, And Participants: This cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers-the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer's Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019).

Association Between Self- and Proxy-Reported Depression and Quality of Life in Mild-Moderate Alzheimer's Disease.

Objective: Prior studies have reported an association between depression and quality of life (QOL) in Alzheimer's disease (AD), but the effect of self- versus proxy rating of mood and QOL has not been described.

Design: In this secondary analysis of data from a cohort study, the authors used a linear mixed-effects model to determine if the association between depression and QOL is affected by whether both measures are assessed by the same member of the patient-caregiver dyad.

Setting: Participants and caregiver informants were recruited from 10 California Alzheimer Disease Centers.

White matter hyperintensity volume modifies the association between CSF vascular inflammatory biomarkers and regional FDG-PET along the Alzheimer's disease continuum.

In older adults with abnormal levels of Alzheimer's disease neuropathology, lower cerebrospinal fluid (CSF) vascular endothelial growth factor (VEGF) levels are associated with lower [¹⁸F]-fluorodeoxyglucose positron emission tomography (FDG-PET) signal, but whether this association is (1) specific to VEGF or broadly driven by vascular inflammation, or (2) modified by vascular risk (e.g., white matter hyperintensities [WMHs]) remains unknown.

Proteomics of brain, CSF, and plasma identifies molecular signatures for distinguishing sporadic and genetic Alzheimer's disease.

Proteomic studies for Alzheimer's disease (AD) are instrumental in identifying AD pathways but often focus on single tissues and sporadic AD cases. Here, we present a proteomic study analyzing 1305 proteins in brain tissue, cerebrospinal fluid (CSF), and plasma from patients with sporadic AD, risk variant carriers, patients with autosomal dominant AD (ADAD), and healthy individuals. We identified 8 brain, 40 CSF, and 9 plasma proteins that were altered in individuals with sporadic AD, and we replicated these findings in several external datasets.

The relationship of history of psychiatric and substance use disorders on risk of dementia among racial and ethnic groups in the United States.

Introduction: Dementia is characterized by significant declines in cognitive, physical, social, and behavioral functioning, and includes multiple subtypes that differ in etiology. There is limited evidence of the influence of psychiatric and substance use history on the risk of dementia subtypes among older underrepresented racial/ethnic minorities in the United States. Our study explored the role of psychiatric and substance use history on the risk of etiology-specific dementias: Alzheimer's disease (AD) and vascular dementia (VaD), in the context of a racially and ethnically diverse sample based on national data.

The association between white matter hyperintensities and amyloid and tau deposition.

White matter hyperintensities (WMHs) frequently occur in Alzheimer's Disease (AD) and have a contribution from ischemia, though their relationship with β-amyloid and cardiovascular risk factors (CVRFs) is not completely understood. We used AT classification to categorize individuals based on their β-amyloid and tau pathologies, then assessed the effects of β-amyloid and tau on WMH volume and number. We then determined regions in which β-amyloid and WMH accumulation were related.

Decreased functional connectivity is associated with increased levels of Cerebral Spinal Fluid soluble-PDGFRβ, a marker of blood brain barrier breakdown, in older adults.

Resting-state functional connectivity (FC) is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. For instance, studies in pre-clinical AD subjects have shown increases of cerebral spinal fluid soluble platelet-derived growth factor receptor-β (CSF sPDGFRβ, a marker of BBB breakdown) but have not demonstrated if this vascular impairment affects neuronal dysfunction. It's possible that increased levels of sPDGFRβ in the CSF may correlate with impaired FC in metabolically demanding brain regions (i.

Microstructural mapping of dentate gyrus pathology in Alzheimer's disease: A 16.4 Tesla MRI study.

The dentate gyrus (DG) is an integral portion of the hippocampal formation, and it is composed of three layers. Quantitative magnetic resonance (MR) imaging has the capability to map brain tissue microstructural properties which can be exploited to investigate neurodegeneration in Alzheimer's disease (AD). However, assessing subtle pathological changes within layers requires high resolution imaging and histological validation.

Metabolomic and lipidomic signatures in autosomal dominant and late-onset Alzheimer's disease brains.

Introduction: The identification of multiple genetic risk factors for Alzheimer's disease (AD) suggests that many pathways contribute to AD onset and progression. However, the metabolomic and lipidomic profiles in carriers of distinct genetic risk factors are not fully understood. The metabolome can provide a direct image of dysregulated pathways in the brain.

White matter degradation near cerebral microbleeds is associated with cognitive change after mild traumatic brain injury.

To explore how cerebral microbleeds (CMBs) accompanying mild traumatic brain injury (mTBI) reflect white matter (WM) degradation and cognitive decline, magnetic resonance images were acquired from 62 mTBI adults (imaged ∼7 days and ∼6 months post-injury) and 203 matched healthy controls. On average, mTBI participants had a count of 2.7 ± 2.

Brain age estimation reveals older adults' accelerated senescence after traumatic brain injury.

Adults aged 60 and over are most vulnerable to mild traumatic brain injury (mTBI). Nevertheless, the extent to which chronological age (CA) at injury affects TBI-related brain aging is unknown. This study applies Gaussian process regression to T-weighted magnetic resonance images (MRIs) acquired within [Formula: see text]7 days and again [Formula: see text]6 months after a single mTBI sustained by 133 participants aged 20-83 (CA [Formula: see text] = 42.