Biomarkers.

Background: Plasma tau phosphorylated at threonine 231 (p-tau231) is a promising novel biomarker of emerging Alzheimer's disease (AD) pathology. We aimed to characterize cross-sectional and longitudinal plasma p-tau231 measurements and estimated ages of biomarker onset in an exceptionally large number of presenilin (PSEN1) E280A (Glu280Ala) mutation carriers and age-matched non-carriers from the Colombian autosomal dominant Alzheimer's disease kindred.

Method: We included a cohort of 722 PSEN1 E280A mutation carriers (mean age 36.

Biomarkers.

Background: In the Systolic Blood Pressure Intervention Trial (SPRINT), intensive systolic blood pressure (SBP) lowering slowed progression of white matter injury (WMI) on MRI. We hypothesized that intensive lowering would be equally as effective and may confer greater benefits for brain health at younger ages compared to older ages. We tested whether the relative effects of intensive lowering on WMI differed by age using 2 MRI measures: white matter hyperintensity volume (WMHv) and peak-width skeletonized mean diffusivity (PSMD) in SPRINT.

Alzheimer's Imaging Consortium.

Background: In the Systolic Blood Pressure Intervention Trial (SPRINT), intensive systolic blood pressure (SBP) lowering slowed progression of white matter injury (WMI) on MRI. We hypothesized that intensive lowering would be equally as effective and may confer greater benefits for brain health at younger ages compared to older ages. We tested whether the relative effects of intensive lowering on WMI differed by age using 2 MRI measures: white matter hyperintensity volume (WMHv) and peak-width skeletonized mean diffusivity (PSMD) in SPRINT.

Relationships of Physical Activity and Type 2 Diabetes With Cognition in Mexican Americans and Non-Hispanic Whites.

Problem, Research Strategy, and Findings: Low physical activity (PA) and Type 2 diabetes are associated with cognitive aging and Alzheimer's disease, but the evidence is inconsistent and particularly limited by ethnicity. The purpose of this study was to examine the relationships of PA and Type 2 diabetes with cognition in Mexican Americans and non-Hispanic Whites. The study was a cross-sectional analysis of the Health and Aging Brain Study-Health Disparities (n = 1,982-2,000 after removing outliers).

Impact of APOE ε4 and ε2 on plasma neurofilament light chain and cognition in autosomal dominant Alzheimer's disease.

Background: Apolipoprotein E (APOE) genotypes have been suggested to influence cognitive impairment and clinical onset in presenilin-1 (PSEN1) E280A carriers for autosomal dominant Alzheimer's disease (ADAD). Less is known about their impact on the trajectory of biomarker changes. Neurofilament light chain (NfL), a marker of neurodegeneration, begins to accumulate in plasma about 20 years prior to the clinical onset of ADAD.

Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer's disease.

Vascular dysfunction is increasingly recognized as an important contributor to the pathogenesis of Alzheimer's disease. Alterations in vascular endothelial growth factor (VEGF) pathways have been implicated as potential mechanisms. However, the specific impact of VEGF proteins in preclinical Alzheimer's disease and their relationships with other Alzheimer's disease and vascular pathologies during this critical early period remain to be elucidated.

Understanding the role of psychiatrists in the diagnosis and management of mild cognitive impairment and mild Alzheimer's disease dementia: a cross-sectional survey.

Background: Alzheimer's disease (AD) is a progressive neurological disorder and the most common cause of dementia. The clinical continuum of AD ranges from asymptomatic disease to mild cognitive impairment (MCI), followed by AD dementia, categorized as mild, moderate, or severe. Almost one-third of patients suspected of having MCI or mild AD dementia are referred to specialists including psychiatrists.

Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimer's disease.

Autosomal dominant Alzheimer's disease (ADAD) is genetically determined, but variability in age of symptom onset suggests additional factors may influence cognitive trajectories. Although apolipoprotein E (APOE) genotype and educational attainment both influence dementia onset in sporadic AD, evidence for these effects in ADAD is limited. To investigate the effects of APOE and educational attainment on age-related cognitive trajectories in ADAD, we analyzed data from 675 Presenilin-1 E280A mutation carriers and 594 non-carriers.

Perspectives of patients, care partners, and primary care physicians on management of mild cognitive impairment and mild Alzheimer's disease dementia.

Objectives: Early diagnosis of mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) dementia is crucial for effective disease management and optimizing patient outcomes. We sought to better understand the MCI and mild AD dementia medical journey from the perspective of patients, care partners, and physicians.

Methods: We conducted online surveys in the United States among patients/care partners and physicians in 2021.

Medical Journey of Patients with Mild Cognitive Impairment and Mild Alzheimer's Disease Dementia: A Cross-sectional Survey of Patients, Care Partners, and Neurologists.

Background: Alzheimer's disease (AD) is a progressive, neurodegenerative disease presenting along a continuum ranging from asymptomatic disease to mild cognitive impairment (MCI), followed by dementia characterized as mild, moderate, or severe.

Objectives: To better understand the medical journey of patients with all-cause MCI or mild AD dementia from the perspective of patients, care partners, and physicians.

Design: Cross-sectional study.

A public resource of baseline data from the Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease Trial.

Introduction: The Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease (API ADAD) Trial evaluated the anti-oligomeric amyloid beta (Aβ) antibody therapy crenezumab in cognitively unimpaired members of the Colombian presenilin 1 (PSEN1) E280A kindred. We report availability, methods employed to protect confidentiality and anonymity of participants, and process for requesting and accessing baseline data.

Methods: We developed mechanisms to share baseline data from the API ADAD Trial in consultation with experts and other groups sharing data from Alzheimer's disease (AD) prevention trials, balancing the need to protect anonymity and trial integrity with making data broadly available to accelerate progress in the field.

Physical activity is associated with increased resting-state functional connectivity in networks predictive of cognitive decline in clinically unimpaired older adults.

Introduction: Physical activity (PA) promotes resilience with respect to cognitive decline, although the underlying mechanisms are not well understood. We examined the associations between objectively measured PA and resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) across seven anatomically distributed neural networks.

Methods: rs-fcMRI, amyloid beta (Aβ) positron emission tomography (PET), PA (steps/day × 1 week), and longitudinal cognitive (Preclinical Alzheimer's Cognitive Composite) data from 167 cognitively unimpaired adults (ages 63 to 90) were used.

Association of β-Amyloid and Vascular Risk on Longitudinal Patterns of Brain Atrophy.

Background And Objectives: Vascular risk factors and elevated β-amyloid (Aβ) are commonly observed together among older adults. Here, we examined the interactive vs independent effects of systemic vascular risk and Aβ burden on longitudinal gray matter atrophy and how their co-occurrence may be related to cognitive decline in a cohort of clinically normal adults. A secondary goal was to examine whether vascular risk influences gray matter atrophy independently from markers of white matter injury.

Plasma IL-12/IFN-γ axis predicts cognitive trajectories in cognitively unimpaired older adults.

Introduction: Immune dysregulation is implicated in neurodegeneration and altered cytokine levels are seen in people with dementia. However, whether cytokine levels are predictive of cognitive decline in cognitively unimpaired (CU) elderly, especially in the setting of elevated amyloid beta (Aβ), remains unclear.

Methods: We measured nine cytokines in the baseline plasma of 298 longitudinally followed CU elderly and assessed whether these measures were associated with cognitive decline, alone or synergistically with Aβ.

Amyloid-beta burden predicts prospective decline in body mass index in clinically normal adults.

In the present study, we tested the hypothesis that higher amyloid-beta (Aβ) burden at baseline is associated with greater longitudinal decline in body mass index (BMI) in clinically normal adults. Participants from the Harvard Aging Brain Study (n = 312) and the Alzheimer's Disease Neuroimaging Initiative (n = 336) underwent Aβ positron emission tomography at baseline. BMI was assessed longitudinally over a median of >4 years.

Cerebral amyloid angiopathy and Alzheimer disease - one peptide, two pathways.

The shared role of amyloid-β (Aβ) deposition in cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD) is arguably the clearest instance of crosstalk between neurodegenerative and cerebrovascular processes. The pathogenic pathways of CAA and AD intersect at the levels of Aβ generation, its circulation within the interstitial fluid and perivascular drainage pathways and its brain clearance, but diverge in their mechanisms of brain injury and disease presentation. Here, we review the evidence for and the pathogenic implications of interactions between CAA and AD.

Associations of Physical Activity and β-Amyloid With Longitudinal Cognition and Neurodegeneration in Clinically Normal Older Adults.

Importance: In the absence of disease-modifying therapies for Alzheimer disease, there is a critical need to identify modifiable risk factors that may delay the progression of Alzheimer disease.

Objective: To examine whether physical activity moderates the association of β-amyloid (Aβ) burden with longitudinal cognitive decline and neurodegeneration in clinically normal individuals and to examine whether these associations are independent of vascular risk.

Design, Setting, And Participants: This longitudinal observational study included clinically normal participants from the Harvard Aging Brain Study.

Memory complaints, dementia, and neuropathology in older blacks and whites.

Objective: To determine relationships of memory complaints to cognitive function and decline, incident dementia, and neurodegenerative and other neuropathologies, as well as the population-attributable risk for dementia in older black and white persons.

Methods: A total of 4,015 community-based persons (28% black; 74% women; mean baseline age = 78 years) were enrolled in 1 of 4 longitudinal cohort studies, and another 2,937 in a population-based cohort. Memory scores, assessed using 2 questions (5-point Likert scales) were categorized as complaints present or absent.

Review: Relationship of type 2 diabetes to human brain pathology.

Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both highly prevalent diseases worldwide, and each is associated with high-morbidity and high-mortality. Numerous clinical studies have consistently shown that T2D confers a two-fold increased risk for a dementia, including dementia attributable to AD. Yet, the mechanisms underlying this relationship, especially nonvascular mechanisms, remain debated.