The Relationship of Alzheimer's Disease and Related Dementias Blood-Based Biomarkers and Informant-Reported Neuropsychiatric Symptoms Differs by Informant Type in Older Adults Without Dementia.

Objectives: In a sample of community-dwelling older adults, we examined the association of Alzheimer's Disease and Related Dementias (AD/ADRD) blood-based biomarkers (BBMs) and neuropsychiatric symptoms (NPS) and whether informant type (i.e., spouse vs.

The differential relationship between white matter cerebrovascular perfusion and microstructure between normal cognition and mild cognitive impairment.

BackgroundMild cognitive impairment (MCI) has been related to impairment in cerebrovascular perfusion and microstructural magnetic resonance imaging (MRI) parameters. However, the relationship between cerebrovascular perfusion and microstructure remains understudied, especially within normal-appearing white matter (NAWM).ObjectiveThis study aimed to investigate the differential relationship between white matter cerebrovascular perfusion and microstructure between normal cognition (NC) and MCI using multiple MRI measurements within NAWM.

Performance change while learning novel cognitive tasks as a potential identifier of preclinical Alzheimer's disease.

Background: In healthy older adults (OA), the effects of amyloid-β (Aβ) deposition on cognitive functions involved in learning are unclear.

Objective: This study aimed to determine how age, practice, and neuropsychological test performance are associated with performance change during the learning of three cognitive tasks, and if Aβ deposition impacts performance change in OA.

Methods: Fifty-five OA and 28 young adults completed neuropsychological tests, and Aβ deposition was assessed in OA.

Evaluation of plasma p-tau217 for detecting amyloid pathology in a heterogeneous community-based cohort.

Introduction: Studies suggest excellent performance of plasma phosphorylated tau 217 (p-tau217) for detecting amyloid pathology, though studies in more representative populations are needed to validate previously determined cutpoints.

Methods: Plasma p-tau217 utility for detecting amyloid pathology (Aβ) via amyloid positron emission tomography (PET) was assessed in a heterogeneous, community-based cohort in the Wake Forest Alzheimer's Disease Research Center (WFADRC). Participants with baseline plasma data (n = 598) were 21% Black; 313 cognitive unimpaired (CU), 214 mild cognitive impairment (MCI), and 64 dementia (DEM); 49% prediabetic, 44% hypertensive, 29% overweight/obese; and 64% had mild-to-moderate kidney disease.

Effects of Diminished Cerebrospinal Fluid Flow in the Spinal Canal on Amyloid Pathophysiology in Vervet Monkeys.

Background: Translational models using nonhuman primates provide valuable insights into the pathological changes associated with human brain aging. This study investigates the vervet monkey () as a model for age-related Alzheimer's disease (AD)-like amyloid clearance impairment. The cerebrospinal fluid (CSF) plays a crucial role as a transport medium for waste clearance from the brain's interstitial space to lymphatic vessels.

Total and Structural Carotid Artery Stiffness Are Associated With Cognitive Decline and Structural Brain Abnormalities Related to Alzheimer Disease and Alzheimer Disease-Related Dementias Pathology: The Multi-Ethnic Study of Atherosclerosis.

Background: Arterial stiffness is associated with pathological changes underlying Alzheimer disease and related dementias. Total pulse wave velocity can be subdivided into 2 main mechanisms: structural arterial stiffness (S-PWV) due to intrinsic remodeling of the artery wall and load-dependent arterial stiffness due to increased blood pressure.

Methods And Results: In this prospective cohort study, MESA (Multi-Ethnic Study of Atherosclerosis) participants completed B-mode carotid ultrasounds from which carotid total pulse wave velocity was calculated.

Plasma and neuroimaging biomarkers of small vessel disease and Alzheimer's disease in a diverse cohort: MESA.

Introduction: Little is known about how Alzheimer's disease (AD) plasma biomarkers relate to cerebral small vessel disease (cSVD) neuroimaging biomarkers.

Methods: The study involved 251 Wake Forest Multi-Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD biomarkers, MRI, amyloid PET, and adjudicated cognitive status. Multivariable models examined cross-sectional relationships between plasma and neuroimaging biomarkers, considering comorbidities.

Evaluation of plasma p-tau217 for detecting amyloid pathology in a diverse and heterogeneous community-based cohort.

Introduction: Studies suggest excellent performance of plasma p-tau217 for detecting amyloid pathology, though studies in more diverse populations are needed to validate previously determined cutpoints.

Methods: Plasma p-tau217 utility for detecting amyloid pathology (Aβ) via amyloid PET (=598) and/or cerebrospinal fluid (CSF; =154) was assessed in a heterogeneous, community-based cohort in the Wake Forest Alzheimer's Disease Research Center (WFADRC). Participants (=598) were 21% Black; 313 cognitive unimpaired (CU), 214 mild cognitive impairment (MCI), and 64 dementia (DEM); 49% prediabetic, 44% hypertensive; 29% overweight/obese; and 64% with mild-to-moderate kidney disease.

Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

Impact of neighborhood disadvantage on cardiometabolic health and cognition in a community-dwelling cohort.

Introduction: Neighborhood disadvantage may be an important determinant of cardiometabolic health and cognitive aging. However, less is known about relationships among individuals with mild cognitive impairment (MCI).

Methods: The objective of this study is to investigate the relationship between neighborhood disadvantage measured by national Area Deprivation Index (ADI) rank with measures of cardiometabolic health and cognition among Wake Forest (WF) Alzheimer's Disease Research Center (ADRC) participants, with and without MCI.

The POINTER Imaging baseline cohort: Associations between multimodal neuroimaging biomarkers, cardiovascular health, and cognition.

Introduction: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.

Social support may buffer the effect of ε4 allele on cognition in older adults.

Apolipoprotein E () ε4 is a genetic risk factor for Alzheimer's disease (AD). Social support may confer protection against cognitive decline even in the presence of ε4. We examined the relationship among ε4 allele(s) carrier status, social support (overall and sub-sources), and cognition in 115 older adults (72.

Associations Between Deficit Accumulation Frailty and Baseline Markers of Lifestyle in the U.S. POINTER Trial.

Background: Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index developed by the U.S.

Heterogeneity of factors associated with cognitive decline and cortical atrophy in early- versus late-onset Alzheimer's disease.

The objectives of this study were to investigate the variable factors associated with cognitive function and cortical atrophy and estimated variable importance of those factors in affecting cognitive function and cortical atrophy in patients with EOAD and LOAD. Patients with EOAD (n = 40), LOAD (n = 34), and healthy volunteers with normal cognition were included (n = 65). All of them performed 3T MRI, [F]THK5351 PET (THK), [F]flutemetamol PET (FLUTE), and detailed neuropsychological tests.

Exploring microtubule dynamics in Alzheimer's disease: Longitudinal assessment using [C]MPC-6827 PET imaging in rodent models of Alzheimer's-related pathology.

Introduction: Microtubule (MT) stability is crucial for proper neuronal function. Understanding MT dysregulation is critical for connecting amyloid beta (Aβ) and tau-based degenerative events and early changes in presymptomatic Alzheimer's disease (AD). Herein we present positron emission tomography (PET) imaging properties of our MT-PET radiotracer, [C]MPC-6827, in multiple established AD mouse models.

Amyloid-β Deposition Predicts Grocery Shopping Performance in Older Adults Without Cognitive Impairment.

Background: A screening tool sensitive to Alzheimer's disease (AD) risk factors, such as amyloid-β (Aβ) deposition, and subtle cognitive changes, best elicited by complex everyday tasks, is needed.

Objective: To determine if grocery shopping performance could differentiate older adults at elevated risk of developing AD (OAer), older adults at low risk of developing AD (OAlr), and young adults (YA), and if amount of Aβ deposition could predict grocery shopping performance in older adults (OA).

Methods: Twenty-one OAer (78±5 years), 33 OAlr (78±5 years), and 28 YA (31±3 years) performed four grocery shopping trials, with the best and worst performances analyzed.

Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities in a community-dwelling cohort.

Introduction: We evaluated associations between plasma and neuroimaging-derived biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities.

Methods: We examined plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid beta [Aβ] 42/40, phosphorylated tau 181) and neuroimaging measures of amyloid deposition (Aβ-positron emission tomography [PET]), total brain volume, white matter hyperintensity volume, diffusion-weighted fractional anisotropy, and neurite orientation dispersion and density imaging free water. Participants were adjudicated as cognitively unimpaired (CU; N = 299), mild cognitive impairment (MCI; N = 192), or dementia (DEM; N = 65).

When prion disease Isn't suspected: prion disease as the cause of terminal decline in chronic mixed dementia.

Alzheimer's Disease (AD) is the most common cause of dementia, although multiple pathologies are found in nearly half of the cases with clinically diagnosed AD. Prion diseases, such as Creutzfeldt-Jakob disease (CJD), are rare causes of dementia and typically manifest as a rapidly progressive dementia, where symptom onset to dementia most often occurs over the course of months. In this brief report, we describe a patient's typically progressive dementia with a precipitous decline at the end of their life who, on neuropathological evaluation, was found to have multiple neurodegenerative proteinopathies as well as spongiform encephalopathy due to CJD.

Examining a Preclinical Alzheimer's Cognitive Composite for Telehealth Administration for Reliability Between In-Person and Remote Cognitive Testing with Neuroimaging Biomarkers.

Background: The preclinical Alzheimer's cognitive composite (PACC) was developed for in-person administration to capture subtle cognitive decline. At the outset of the COVID-19 pandemic, cognitive testing was increasingly performed remotely by telephone or video administration. It is desirable to have a harmonized composite measurement derived from both in-person and remote assessments for identifying cognitive changes and to examine its relationship with common neuroimaging biomarkers.

Mediterranean diet protects against a neuroinflammatory cortical transcriptome: Associations with brain volumetrics, peripheral inflammation, social isolation, and anxiety in nonhuman primates (Macaca fascicularis).

Mediterranean diets may be neuroprotective and prevent cognitive decline relative to Western diets; however, the underlying biology is poorly understood. We assessed the effects of Western versus Mediterranean-like diets on RNAseq-generated transcriptional profiles in lateral temporal cortex and their relationships with longitudinal changes in neuroanatomy, circulating monocyte gene expression, and observations of social isolation and anxiety in 38 socially-housed, middle-aged female cynomolgus macaques (Macaca fascicularis). Diet resulted in differential expression of seven transcripts (FDR < 0.

Differential diagnosis of frontotemporal dementia subtypes with explainable deep learning on structural MRI.

Background: Frontotemporal dementia (FTD) represents a collection of neurobehavioral and neurocognitive syndromes that are associated with a significant degree of clinical, pathological, and genetic heterogeneity. Such heterogeneity hinders the identification of effective biomarkers, preventing effective targeted recruitment of participants in clinical trials for developing potential interventions and treatments. In the present study, we aim to automatically differentiate patients with three clinical phenotypes of FTD, behavioral-variant FTD (bvFTD), semantic variant PPA (svPPA), and nonfluent variant PPA (nfvPPA), based on their structural MRI by training a deep neural network (DNN).

Age and beta amyloid deposition impact gait speed, stride length, and gait smoothness while transitioning from an even to an uneven walking surface in older adults.

Background: Capturing a measure of movement quality during a complex walking task may indicate the earliest signs of detrimental changes to the brain due to beta amyloid (Aβ) deposition and be a potential differentiator of older adults at elevated and low risk of developing Alzheimer's disease. This study aimed to determine: 1) age-related differences in gait speed, stride length, and gait smoothness while transitioning from an even to an uneven walking surface, by comparing young adults (YA) and older adults (OA), and 2) if gait speed, stride length, and gait smoothness in OA while transitioning from an even to an uneven walking surface is influenced by the amount of Aβ deposition present in an OA's brain.

Methods: Participants included 56 OA (>70 years of age) and 29 YA (25-35 years of age).