The Independent and Interactive Effects of Economic Stability and Health Care Access on 10-Year Cognitive Trajectories of Black/African American and White Older Adults from the ACTIVE Study.

Objectives: Social and structural determinants of health (SSDoH) have been linked to racial disparities in Alzheimer's disease and related dementias (ADRD). Research has established that living in an environment with greater economic stability (ES) or health care access (HCA) is associated with better baseline cognition, but the interactive effects between these distinct SSDoH on cognition over time have not been studied. Therefore, the present study examined the independent and interactive effects of ES and HCA on 10-year change in cognitive functioning within a large sample of racially diverse community-dwelling older adults.

Self- and study partner-reported cognitive decline in older adults without dementia: The role of α-synuclein and amyloid biomarkers in the Alzheimer's Disease Neuroimaging Initiative.

Introduction: Subjective cognitive decline (SCD) may be an early marker of Alzheimer's disease (AD) pathology. Until recently, it was impossible to measure biomarkers specific for α-synuclein pathology; therefore, its association with subjective reports of cognitive decline is unknown.

Methods: Alzheimer's Disease Neuroimaging Initiative participants without dementia (n = 918) were classified as positive or negative for amyloid beta (Aβ+ or Aβ-) and α-synuclein (α-syn+ or α-syn-) biomarkers.

PTSD moderates the association between subjective cognitive decline and Alzheimer's disease biomarkers in older veterans.

Objectives: Post-traumatic stress disorder (PTSD) and subjective cognitive decline (SCD) are independent risk factors for Alzheimer's disease (AD) and dementia, but the association of their interaction on AD biomarkers have yet to be characterized. This study aimed to examine the impact of PTSD on the association between SCD and tau and amyloid positron emission tomography (PET) as well as global cognition in older Veterans.

Method: This study included 87 Vietnam-Era Veterans without dementia (42 with PTSD; 45 without PTSD) from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative.

Cognition and Amyloid-β in Older Veterans: Characterization and Longitudinal Outcomes of Data-Derived Phenotypes.

Background: Within older Veterans, multiple factors may contribute to cognitive difficulties. Beyond Alzheimer's disease (AD), psychiatric (e.g.

Pulse pressure and APOE ε4 dose interact to affect cerebral blood flow in older adults without dementia.

This study assessed whether the effect of vascular risk on cerebral blood flow (CBF) varies by gene dose of apolipoprotein (APOE) ε4 alleles. 144 older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative underwent arterial spin labeling and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure (BP) assessment. Vascular risk was assessed using pulse pressure (systolic BP - diastolic BP).

Type 2 Diabetes Moderates the Association Between Amyloid and 1-Year Change in Everyday Functioning in Older Veterans.

Background: Type 2 diabetes mellitus (T2DM) affects ∼25% of Veterans, a prevalence rate double that of the general population. T2DM is associated with greater dementia risk and has been shown to exacerbate the impact of Alzheimer's disease (AD) risk factors on declines in daily functioning; however, there are few studies that investigate these patterns in older Veterans.

Objective: This study sought to determine whether T2DM moderates the association between amyloid-β (Aβ) positron emission tomography (PET) and 1-year change in everyday functioning in older Veterans.

White Matter Hyperintensity Volume and Amyloid-PET Synergistically Impact Memory Independent of Tau-PET in Older Adults Without Dementia.

Background: Alzheimer's disease (AD) and cerebrovascular disease are common, co-existing pathologies in older adults. Whether the effects of cerebrovascular disease and AD biomarkers on cognition are additive or synergistic remains unclear.

Objective: To examine whether white matter hyperintensity (WMH) volume moderates the independent association between each AD biomarker and cognition.

Brain Derived Neurotrophic Factor Interacts with White Matter Hyperintensities to Influence Processing Speed and Hippocampal Volume in Older Adults.

Background: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in regulating synaptic activity and plasticity.

Objective: Given that type-2 diabetes (T2DM) increases the risk of cognitive decline, and studies have suggested lower BDNF levels may be a risk factor of diabetic neurovascular complications, we sought to investigate total white matter hyperintensities (WMH) as a moderator of the effect of BDNF on hippocampal volume and cognition.

Methods: Older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative (N = 454 including 49 with T2DM and 405 without diabetes) underwent neuropsychological evaluation, magnetic resonance imaging to quantify hippocampal and WMH volumes, and blood draw to assess BDNF.

Perceived Discrimination in Health Care for LGBTQIA+ People Living With Parkinson's Disease.

Objectives: People who identify as lesbian, gay, bisexual, transgender, queer/questioning, intersex, asexual, other non-cisgender, and non-heterosexual identities (LGBTQIA+) experience discrimination when accessing health care. We investigated specific experiences of LGBTQIA+ people with Parkinson's disease (PwP) as they are less known.

Methods: Data were obtained from Fox Insight for PwP identifying as LGBTQIA+ (n = 210), cisgender, heterosexual women (n = 2,373) or cisgender, heterosexual men (n = 2,453).

Cognitive reserve moderates the association between cerebral blood flow and language performance in older adults with mild cognitive impairment.

Higher cognitive reserve (CR) may offer protection from cognitive changes associated with reduced cerebral blood flow (CBF). We investigated CR as a moderator of the effect of CBF on cognition in older adults with mild cognitive impairment (MCI; N = 46) and those who are cognitively unimpaired (CU; N = 101). Participants underwent arterial spin labeling MRI, which was used to quantify CBF in 4 a priori regions.

Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART.

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD.

Associations between social determinants of health and 10-year change in everyday functioning within Black/African American and White older adults enrolled in ACTIVE.

Introduction: Given prior work showing racial differences on baseline social determinants of health (SDoH) and 10-year trajectories of everyday functioning, we examined associations between SDoH and longitudinal everyday functioning performance in Black/African American and White older adults.

Methods: Participants were 2505 older adults (M = 73.5; 28% Black/African American) without dementia.

Comprehensive characterization of elevated tau PET signal in the absence of amyloid-beta.

Recently proposed biomarker-only diagnostic frameworks propose that amyloid-beta is necessary for placement on the Alzheimer's disease continuum, whereas tau in the absence of amyloid-beta is considered to be a non-Alzheimer's disease pathologic change. Similarly, the pathologic designation of tau in the absence of amyloid-beta is characterized as primary age-related tauopathy and separable from Alzheimer's disease. Our study sought to identify an early-to-moderate tau stage with minimal amyloid-beta using PET imaging and characterize these individuals in terms of clinical, cognitive and biological features.

Cerebral blood flow, tau imaging, and memory associations in cognitively unimpaired older adults.

Objective: Cerebral blood flow (CBF) has been independently linked to cognitive impairment and traditional Alzheimer's disease (AD) pathology (e.g., amyloid-beta [Aβ], tau) in older adults.

Cognitive Heterogeneity and Risk of Progression in Data-Driven Subtle Cognitive Decline Phenotypes.

Background: There is increasing recognition of cognitive and pathological heterogeneity in early-stage Alzheimer's disease and other dementias. Data-driven approaches have demonstrated cognitive heterogeneity in those with mild cognitive impairment (MCI), but few studies have examined this heterogeneity and its association with progression to MCI/dementia in cognitively unimpaired (CU) older adults.

Objective: We identified cluster-derived subgroups of CU participants based on comprehensive neuropsychological data and compared baseline characteristics and rates of progression to MCI/dementia or a Dementia Rating Scale (DRS) of ≤129 across subgroups.

Interactive Effects of Pulse Pressure and Tau Imaging on Longitudinal Cognition.

Background: Studies have demonstrated that both tau and cardiovascular risk are associated with cognitive decline, but the possible synergistic effects of these pathologic markers remain unclear.

Objective: To explore the interaction of AD biomarkers with a specific vascular risk marker (pulse pressure) on longitudinal cognition.

Methods: Participants included 139 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

What's the cut-point?: a systematic investigation of tau PET thresholding methods.

Background: Tau positron emission tomography (PET) is increasing in popularity for biomarker characterization of Alzheimer's disease (AD), and recent frameworks rely on tau PET cut-points to stage individuals along the AD continuum. Given the lack of standardization in tau PET thresholding methods, this study sought to systematically canvass and characterize existing studies that have derived tau PET cut-points and then directly assess different methods of tau PET thresholding in terms of their concurrent validity.

Methods: First, a literature search was conducted in PubMed to identify studies of AD and related clinical phenotypes that used the Flortaucipir (AV-1451) tau PET tracer to derive a binary cut-point for tau positivity.

Diffusion MRI tractography of the locus coeruleus-transentorhinal cortex connections using GO-ESP.

Purpose: The locus coeruleus (LC) is implicated as an early site of protein pathogenesis in Alzheimer's disease (AD). Tau pathology is hypothesized to propagate in a prion-like manner along the LC-transentorhinal cortex (TEC) white matter (WM) pathway, leading to atrophy of the entorhinal cortex and adjacent cortical regions in a progressive and stereotypical manner. However, WM damage along the LC-TEC pathway may be an earlier observable change that can improve detection of preclinical AD.

Arterial Stiffening Moderates the Relationship Between Type-2 Diabetes Mellitus and White Matter Hyperintensity Burden in Older Adults With Mild Cognitive Impairment.

Cerebrovascular dysfunction has been proposed as a possible mechanism underlying cognitive impairment in the context of type 2 diabetes mellitus (DM). Although magnetic resonance imaging (MRI) evidence of cerebrovascular disease, such as white matter hyperintensities (WMH), is often observed in DM, the vascular dynamics underlying this pathology remain unclear. Thus, we assessed the independent and combined effects of DM status and different vascular hemodynamic measures (i.

Higher cerebrospinal fluid tau is associated with history of traumatic brain injury and reduced processing speed in Vietnam-era veterans: A Department of Defense Alzheimer's Disease Neuroimaging Initiative (DOD-ADNI) study.

Introduction:  Our goal was to determine whether cognitive and cerebrospinal fluid (CSF) markers of tau and amyloid beta 1-42 (Aβ) differ between Vietnam-era veterans with and without history of traumatic brain injury (TBI) and whether TBI moderates the association between CSF markers and neurocognitive functioning.

Methods:  A total of 102 male participants (52 TBI, 50 military controls [MCs]; mean age = 68) were included. Levels of CSF Aβ, tau phosphorylated at the threonine 181 position (p-tau), and total tau (t-tau) were quantified.

Objective subtle cognitive decline and plasma phosphorylated tau181: Early markers of Alzheimer's disease-related declines.

Introduction: Objectively-defined subtle cognitive decline (Obj-SCD) and plasma phosphorylated-tau181 (p-tau181) are promising early Alzheimer's disease (AD) markers. However, associations between Obj-SCD and p-tau181, and their combined prognostic potential, are unknown.

Methods: Baseline and 4-year longitudinal p-tau181 changes were compared across cognitively unimpaired (CU;  = 402), Obj-SCD ( = 199), and mild cognitive impairment (MCI;  = 346) groups.