Biomarkers.

Background: Uniform manifold approximation and projection (UMAP) is a technique for dimension reduction and visualization of high-dimensional (HD) data. Here, we apply UMAP to represent in two dimensions, data from members of the Wake Forest School of Medicine Alzheimer's Disease Research Center (WFUSM-ADRC) clinical cohort.

Methods: We examined baseline data from 542 WFUSM-ADRC participants with mean age 70.

Biomarkers.

Background: Early autonomic function changes in Alzheimer's disease (AD) may represent a biomarker for early affective changes in prodromal disease. We report preliminary differences in metrics of heart rate variability (HRV) before and during routine cognitive testing.

Method: We enrolled 50 participants from the Wake Forest Alzheimer's Disease Research Center to wear continuous ECG devices during their visit to assess time and frequency domain based metrics of HRV over 5 minutes at rest and during cognitive testing.

Public Health.

Background: Adverse social exposome (indexed by national Area Deprivation Index [ADI] 80-100 or 'high ADI') is linked to structural inequities and increased risk of Alzheimer's disease neuropathology. Twenty percent of the US population resides within high ADI areas, predominantly in inner cities, tribal reservations and rural areas. The percentage of brain donors from high ADI areas within the Alzheimer's Disease Research Center (ADRC) brain bank system is unknown.

Biomarkers.

Background: Cardiometabolic disorders are emerging risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). There is currently insufficient understanding of how different cardiometabolic profiles and blood biomarkers impact different AD-related brain pathology regionally. This project uses data-driven approaches and explainable artificial intelligence methods to determine the cardiometabolic and fluid contributions toward AD-related pathophysiologic patterns in the brain.

Developing Topics.

Background: Adverse social exposome (indexed by high national Area Deprivation Index [ADI]) is linked to structural inequities and increased risk of clinical dementia diagnosis, yet linkage to ADRD neuropathology remains largely unknown. Early work from single site brain banks suggests a relationship, but assessment in large national cohorts is needed to increase generalizability and depth, particularly for rarer neuropathology findings.

Objective: Determine the association between adverse social exposome by ADI and ADRD neuropathology for brain donors from 21 Alzheimer's Disease Research Center (ADRC) brain banks as part of the on-going Neighborhoods Study.

Developing Topics.

Introduction: Over 9 million Americans are projected to have dementia by 2030, and adults with mild cognitive impairment (MCI), a potential pre-cursor to dementia, will also rise. With recent and emerging clinical trial evidence for interventions to slow the progression of MCI to dementia, identification of persons in primary care with undiagnosed early-stage cognitive impairment may provide opportunity for preventive intervention.

Methods: A Machine Learning (ML)-based prediction model trained using data from the electronic health record was applied to patients without formal diagnoses of cognitive impairment who were currently seen in selected primary care practices.

Alzheimer's Imaging Consortium.

Background: Cardiometabolic disorders are emerging risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). There is currently insufficient understanding of how different cardiometabolic profiles and blood biomarkers impact different AD-related brain pathology regionally. This project uses data-driven approaches and explainable artificial intelligence methods to determine the cardiometabolic and fluid contributions toward AD-related pathophysiologic patterns in the brain.

Alzheimer's Imaging Consortium.

Background: Neuropsychiatric symptoms (NPS) in the Alzheimer's Disease (AD) clinical spectrum are common, yet the pathological underpinnings are unclear. Prior research has been inconsistent, attributed in part to concomitant co-pathologies. Additionally, prior modeling approaches have disregarded the distributional properties of right-skewed NPS data and utilized predominantly racially homogenous cohorts.

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.

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.

The protean presentations of XK disease (McLeod syndrome): a case series with new observations and updates on previously reported families.

XK disease is a very rare, multi-system disease, which can present with a wide spectrum of symptoms. This disorder can also be identified pre-symptomatically with the incidental detection of serological abnormalities when typing erythrocytes in peripheral blood, or on other routine laboratory testing. Increasing awareness of this disorder and improved access to genetic testing are resulting in increasing identification of affected patients and families.

Depressive Symptoms Affect Cognitive Functioning from Middle to Late Adulthood: Ethnoracial Minorities Experience Greater Repercussions.

Cognitive deficits, a diagnostic criterion for depressive disorders, may precede or follow the development of depressive symptoms and major depressive disorder. However, an individual can report an increase in depressive symptoms without any change in cognitive functioning. While ethnoracial minority group differences exist, little is known to date about how the relationship between depressive symptoms and cognitive function may differ by ethnoracial minority status.

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).

Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand.

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.

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).

Biopsychosocial contexts influence adult cognitive function concurrently and longitudinally.

Background: Cognitive aging is a complex process that impacts human behavior. Identifying the factors that preserve cognitive functioning is a public health priority, given that 20% of the US population will be at least 65 years old in the next decade. Biopsychosocial determinants of cognitive decline across the lifespan are often examined as ecological factors that independently moderate cognitive aging, despite the known complexity surrounding these relationships.

Feasibility of Remote Administration of the Uniform Data Set-Version 3 for Assessment of Older Adults With Mild Cognitive Impairment and Alzheimer's Disease.

Objective: Assess the feasibility and concurrent validity of a modified Uniform Data Set version 3 (UDSv3) for remote administration for individuals with normal cognition (NC), mild cognitive impairment (MCI), and early dementia.

Method: Participants (N = 93) (age: 72.8 [8.

Network Localization of Spontaneous Confabulation.

Objective: Spontaneous confabulation is a symptom in which false memories are conveyed by the patient as true. The purpose of the study was to identify the neuroanatomical substrate of this complex symptom and evaluate the relationship to related symptoms, such as delusions and amnesia.

Methods: Twenty-five lesion locations associated with spontaneous confabulation were identified in a systematic literature search.

Social genomics, cognition, and well-being during the COVID-19 pandemic.

Introduction: Adverse psychosocial exposure is associated with increased proinflammatory gene expression and reduced type-1 interferon gene expression, a profile known as the conserved transcriptional response to adversity (CTRA). Little is known about CTRA activity in the context of cognitive impairment, although chronic inflammatory activation has been posited as one mechanism contributing to late-life cognitive decline.

Methods: We studied 171 community-dwelling older adults from the Wake Forest Alzheimer's Disease Research Center who answered questions via a telephone questionnaire battery about their perceived stress, loneliness, well-being, and impact of COVID-19 on their life, and who provided a self-collected dried blood spot sample.