Association of Anxiety and Unspecified Emotional Distress Obtained from a Medical Records Linkage System with Incident Cognitive Outcomes in a Population-Based Setting.

Background: Studies that assess cognition prospectively and study in detail anxiety history in the participants' medical records within the context of brain aging and Alzheimer's disease are limited.

Objective: To examine the associations of anxiety and unspecified emotional distress (UED) acquired throughout a person's life with prospectively collected cognitive outcomes.

Methods: Mayo Clinic Study of Aging participants who were cognitively unimpaired at baseline were included.

CSF biomarkers of immune activation and Alzheimer's disease for predicting cognitive impairment risk in the elderly.

The immune system substantially influences age-related cognitive decline and Alzheimer's disease (AD) progression, affected by genetic and environmental factors. In a Mayo Clinic Study of Aging cohort, we examined how risk factors like APOE genotype, age, and sex affect inflammatory molecules and AD biomarkers in cerebrospinal fluid (CSF). Among cognitively unimpaired individuals over 65 ( = 298), we measured 365 CSF inflammatory molecules, finding age, sex, and diabetes status predominantly influencing their levels.

Association of Plasma Biomarkers of Alzheimer Disease With Cognition and Medical Comorbidities in a Biracial Cohort.

Background And Objectives: Recent advances in blood-based biomarkers offer the potential to revolutionize the diagnosis and management of Alzheimer disease (AD), but additional research in diverse populations is critical. We assessed the profiles of blood-based AD biomarkers and their relationships to cognition and common medical comorbidities in a biracial cohort.

Methods: Participants were evaluated through the Mayo Clinic Jacksonville Alzheimer Disease Research Center and matched on age, sex, and cognitive status.

Plasma-derived biomarkers of Alzheimer's disease and neuropsychiatric symptoms: A community-based study.

Introduction: We examined associations between plasma-derived biomarkers of Alzheimer's disease (AD) and neuropsychiatric symptoms (NPS) in community-dwelling older adults.

Methods: Cross-sectional study involving 1005 persons ≥50 years of age (mean 74 years, 564 male, 118 cognitively impaired), who completed plasma-derived biomarker (amyloid beta 42 [Aβ42]/Aβ40, phosphorylated tau 181 [p-tau181], p-tau217, total tau [t-tau], neurofilament light [NfL]), and NPS assessment.

Results: P-tau181 (odds ratio [OR] 2.

Plasma biomarkers for prediction of Alzheimer's disease neuropathologic change.

While plasma biomarkers for Alzheimer's disease (AD) are increasingly being evaluated for clinical diagnosis and prognosis, few population-based autopsy studies have evaluated their utility in the context of predicting neuropathological changes. Our goal was to investigate the utility of clinically available plasma markers in predicting Braak staging, neuritic plaque score, Thal phase, and overall AD neuropathological change (ADNC).We utilized a population-based prospective study of 350 participants with autopsy and antemortem plasma biomarker testing using clinically available antibody assay (Quanterix) consisting of Aβ42/40 ratio, p-tau181, GFAP, and NfL.

Interactions Between Neuropsychiatric Symptoms and Alzheimer's Disease Neuroimaging Biomarkers in Predicting Longitudinal Cognitive Decline.

Objective: To examine interactions between Neuropsychiatric symptoms (NPS) with Pittsburgh Compound B (PiB) and fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting cognitive trajectories.

Methods: We conducted a longitudinal study in the setting of the population-based Mayo Clinic Study of Aging in Olmsted County, MN, involving 1581 cognitively unimpaired (CU) persons aged ≥50 years (median age 71.83 years, 54.

Neuropsychiatric Symptoms and Commonly Used Biomarkers of Alzheimer's Disease: A Literature Review from a Machine Learning Perspective.

There is a growing interest in the application of machine learning (ML) in Alzheimer's disease (AD) research. However, neuropsychiatric symptoms (NPS), frequent in subjects with AD, mild cognitive impairment (MCI), and other related dementias have not been analyzed sufficiently using ML methods. To portray the landscape and potential of ML research in AD and NPS studies, we present a comprehensive literature review of existing ML approaches and commonly studied AD biomarkers.

Association between physical activity and longitudinal change in body mass index in middle-aged and older adults.

Background: In middle-aged and particularly older adults, body mass index (BMI) is associated with various health outcomes. We examined associations between physical activity (PA) and longitudinal BMI change in persons aged ≥ 50 years.

Methods: The sample included 5159 community-dwelling individuals aged ≥ 50 years (50.

Global neuropathologic severity of Alzheimer's disease and locus coeruleus vulnerability influences plasma phosphorylated tau levels.

Background: Advances in ultrasensitive detection of phosphorylated tau (p-tau) in plasma has enabled the use of blood tests to measure Alzheimer's disease (AD) biomarker changes. Examination of postmortem brains of participants with antemortem plasma p-tau levels remains critical to understanding comorbid and AD-specific contribution to these biomarker changes.

Methods: We analyzed 35 population-based Mayo Clinic Study of Aging participants with plasma p-tau at threonine 181 and threonine 217 (p-tau181, p-tau217) available within 3 years of death.

Mid- and Late-Life Physical Activity and Neuropsychiatric Symptoms in Dementia-Free Older Adults: Mayo Clinic Study of Aging.

Objective: This study examined associations between physical activity (PA) and neuropsychiatric symptoms (NPS) in older adults free of dementia.

Methods: This cross-sectional study included 3,222 individuals ≥70 years of age (1,655 men; mean±SD age=79.2±5.

Association between CSF biomarkers of Alzheimer's disease and neuropsychiatric symptoms: Mayo Clinic Study of Aging.

Introduction: We examined the association between cerebrospinal fluid (CSF)-derived biomarkers of Alzheimer's disease and neuropsychiatric symptoms (NPS) in older non-demented adults.

Methods: We included 784 persons (699 cognitively unimpaired, 85 with mild cognitive impairment) aged ≥ 50 years who underwent CSF amyloid beta (Aβ42), hyperphosphorylated tau 181 (p-tau), and total tau (t-tau) as well as NPS assessment using Beck Depression and Anxiety Inventories (BDI-II, BAI), and Neuropsychiatric Inventory Questionnaire (NPI-Q).

Results: Lower CSF Aβ42, and higher t-tau/Aβ42 and p-tau/Aβ42 ratios were associated with BDI-II and BAI total scores, clinical depression (BDI-II ≥ 13), and clinical anxiety (BAI ≥ 10), as well as NPI-Q-assessed anxiety, apathy, and nighttime behavior.

Sex Differences in the Association Between Midlife Cardiovascular Conditions or Risk Factors With Midlife Cognitive Decline.

Background And Objectives: The prevalence of midlife cardiovascular conditions and risk factors is higher in men than women. Associations between midlife cardiovascular conditions or risk factors and midlife cognitive decline have been reported, but few studies have assessed sex differences in these associations.

Methods: We included 1,857 participants enrolled in the population-based Mayo Clinic Study of Aging who were 50 to 69 years of age at baseline.

Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes.

Background: Total tau protein (T-Tau) and neurofilament light chain (NfL) have emerged as candidate plasma biomarkers of neurodegeneration, but studies have not compared how these biomarkers cross-sectionally or longitudinally associate with cognitive and neuroimaging measures. We therefore compared plasma T-Tau and NfL as cross-sectional and longitudinal markers of (1) global and domain-specific cognitive decline and (2) neuroimaging markers of cortical thickness, hippocampal volume, white matter integrity, and white matter hyperintensity volume.

Methods: We included 995 participants without dementia who were enrolled in the Mayo Clinic Study of Aging cohort.

A longitudinal investigation of Aβ, anxiety, depression, and mild cognitive impairment.

Introduction: We investigated the longitudinal relationship between cortical amyloid deposition, anxiety, and depression and the risk of incident mild cognitive impairment (MCI).

Methods: We followed 1440 community-dwelling, cognitively unimpaired individuals aged ≥ 50 years for a median of 5.5 years.

Associations of amyloid and neurodegeneration plasma biomarkers with comorbidities.

Introduction: Blood-based biomarkers of amyloid pathology and neurodegeneration are entering clinical use. It is critical to understand what factors affect the levels of these markers.

Methods: Plasma markers (Aβ42, Aβ40, NfL, T-tau, Aβ42/40 ratio) were measured on the Quanterix Simoa HD-1 analyzer for 996 Mayo Clinic Study of Aging (MCSA) participants, aged 51 to 95 years.

P-tau/Aβ42 and Aβ42/40 ratios in CSF are equally predictive of amyloid PET status.

Introduction: Measurement of amyloid beta (Aβ40 and Aβ42) and tau (phosphorylated tau [p-tau] and total tau [t-tau]) in cerebrospinal fluid (CSF) can be utilized to differentiate clinical and preclinical Alzheimer's disease dementia (AD) from other neurodegenerative processes.

Methods: CSF biomarkers were measured in 150 participants from the Mayo Clinic Study of Aging and the Alzheimer's Disease Research Center. P-tau/Aβ42 (Roche Elecsys, Fujirebio LUMIPULSE) and Aβ42/40 (Fujirebio LUMIPULSE) ratios were compared to one another and to amyloid positron emission tomography (PET) classification.

Neuropsychiatric symptoms and the outcome of cognitive trajectories in older adults free of dementia: The Mayo Clinic Study of Aging.

Objective: Neuropsychiatric symptoms (NPS) are associated with the risk of incident mild cognitive impairment (MCI) and dementia. We examined associations between NPS and the outcomes of global and domain-specific cognitive trajectories.

Methods: In this longitudinal study conducted in the setting of the population-based Mayo Clinic Study of Aging, 5081 community-dwelling, nondemented individuals aged ≥50 years (51% males) underwent NPS assessment using Neuropsychiatric Inventory Questionnaire (NPI-Q), and Beck Depression and Anxiety Inventories (BDI-II, BAI).

Physical Activity and Trajectory of Cognitive Change in Older Persons: Mayo Clinic Study of Aging.

Background: Little is known about the association between physical activity (PA) and cognitive trajectories in older adults.

Objective: To examine the association between PA and change in memory, language, attention, visuospatial skills, and global cognition, and a potential impact of sex or Apolipoprotein E (APOE) ɛ4 status.

Methods: Longitudinal study derived from the population-based Mayo Clinic Study of Aging, including 2,060 cognitively unimpaired males and females aged ≥70 years.

Association of Cortical and Subcortical β-Amyloid With Standardized Measures of Depressive and Anxiety Symptoms in Adults Without Dementia.

Objective: The purpose of this study was to test the hypothesis that subcortical β-amyloid (Aβ) deposition was associated with elevated scores on standardized measures of depressive and anxiety symptoms when compared with cortical (Aβ) deposition in persons without dementia.

Methods: The authors performed a cross-sectional study, derived from the population-based Mayo Clinic Study of Aging, comprising participants aged ≥70 years (N=1,022; 55% males; 28% apolipoprotein E [APOE] ε4 carriers; without cognitive impairment, N=842; mild cognitive impairment; N=180). To assess Aβ deposition in cortical and subcortical (the amygdala, striatum, and thalamus) regions, participants underwent Pittsburgh Compound B positron emission tomography (PiB-PET) and completed the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI).

Association Between Neuropsychiatric Symptoms and Functional Change in Older Non-Demented Adults: Mayo Clinic Study of Aging.

We examined the associations between baseline neuropsychiatric symptoms (NPS) and longitudinal changes in functional performance among 5,394 non-demented individuals aged ≥50 years (2,729 males; median age 74.2 years; 4,716 cognitively unimpaired, 678 mild cognitive impairment). After adjusting for age, sex, education, and medical comorbidities, NPS assessed by the Neuropsychiatric Inventory Questionnaire, clinical depression (Beck Depression Inventory score ≥13) and anxiety (Beck Anxiety Inventory score ≥10) were significantly associated with an increase in the Functional Activities Questionnaire score, indicating functional decline over time.

Associations Between Plasma Ceramides and Cerebral Microbleeds or Lacunes.

Objective: High plasma ceramide levels and ratios are associated with poor outcomes in individuals with cardiovascular disease; less is known about their relation to cerebral small vessel disease. We examined whether high plasma ceramide levels or ratios were associated with cerebral microbleeds (CMBs) and lacunes and whether associations differ by sex. Approach and Results: We included 548 participants enrolled in the MCSA (Mayo Clinic Study of Aging) with concurrent plasma ceramide assays and magnetic resonance imaging.

Quality of life and caregiver burden in familial frontotemporal lobar degeneration: Analyses of symptomatic and asymptomatic individuals within the LEFFTDS cohort.

Objective: The Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects evaluates familial frontotemporal lobar degeneration (FTLD) kindreds with MAPT, GRN, or C9orf72 mutations. Objectives were to examine whether health-related quality of life (HRQoL) correlates with clinical symptoms and caregiver burden, and whether self-rated and informant-rated HRQoL would correlate with each other.

Methods: Individuals were classified using the Clinical Dementia Rating (CDR ) Scale plus National Alzheimer's Coordinating Center (NACC) FTLD.

Brain Regional Glucose Metabolism, Neuropsychiatric Symptoms, and the Risk of Incident Mild Cognitive Impairment: The Mayo Clinic Study of Aging.

Objective: The authors conducted a prospective cohort study to examine the risk of incident mild cognitive impairment (MCI) as predicted by baseline neuropsychiatric symptoms (NPS) and brain regional glucose metabolic dysfunction.

Methods: About 1,363 cognitively unimpaired individuals (52.8% males) aged ≥50 years were followed for a median of 4.