Medical Doctors and Dementia: A Longitudinal Study.

Objective: To examine the association between being a medical doctor (MD) and the risk of incident dementia.

Design: Cohort study.

Setting: Olmsted County, Minnesota.

Association of Dual Decline in Memory and Gait Speed With Risk for Dementia Among Adults Older Than 60 Years: A Multicohort Individual-Level Meta-analysis.

Importance: Dual decline in both memory and gait speed may characterize a group of older individuals at high risk for future dementia.

Objective: To assess the risk of dementia in older persons who experience parallel declines in memory and gait speed compared with those who experience no decline or decline in either memory or gait speed only.

Design, Setting, And Participants: A multicohort meta-analysis was performed of 6 prospective cohort studies conducted between 1997 and 2018 in the United States and Europe.

Longitudinal Comparison of in Clinic and at Home Administration of the Cogstate Brief Battery and Demonstrated Practice Effects in the Mayo Clinic Study of Aging.

Background: The Cogstate Brief Battery (CBB) is a computerized cognitive assessment that can be completed in clinic or at home. Design/Objective: This retrospective study investigated whether practice effects / performance trajectories of the CBB differ by location of administration.

Participants/setting: Participants included 1439 cognitively unimpaired individuals age 50-75 at baseline participating in the Mayo Clinic Study of Aging (MCSA), a population-based study of cognitive aging.

Relationship Between Risk Factors and Brain Reserve in Late Middle Age: Implications for Cognitive Aging.

Background: Brain reserve can be defined as the individual variation in the brain structural characteristics that later in life are likely to modulate cognitive performance. Late midlife represents a point in aging where some structural brain imaging changes have become manifest but the effects of cognitive aging are minimal, and thus may represent an ideal opportunity to determine the relationship between risk factors and brain imaging biomarkers of reserve.

Objective: We aimed to assess neuroimaging measures from multiple modalities to broaden our understanding of brain reserve, and the late midlife risk factors that may make the brain vulnerable to age related cognitive disorders.

Traumatic brain injury preceding clinically diagnosed α-synucleinopathies: A case-control study.

Objective: To determine the association between traumatic brain injury (TBI) and any clinically diagnosed α-synucleinopathy including Parkinson disease (PD), dementia with Lewy bodies (DLB), PD dementia (PDD), and multiple system atrophy (MSA).

Methods: Using the medical records-linkage system of the Rochester Epidemiology Project, we identified incident cases of α-synucleinopathies in Olmsted County, Minnesota, from 1991 to 2010, matching by age (±1 year) at symptom onset and sex to controls. We reviewed records of cases and controls to detect TBI prior to clinical-motor onset of any α-synucleinopathies.

Imaging Biomarkers of Alzheimer Disease in Multiple Sclerosis.

Objective: To investigate β-amyloid and tau depositions using Pittsburgh compound B (PiB) positron emission tomography (PET) and AV1451 tau PET imaging in aging multiple sclerosis (MS) patients.

Methods: Patients with MS (n = 16) and controls (n = 80) matched for age, sex, and APOE ε4 status from the population-based Mayo Clinic Study of Aging who underwent PiB PET imaging were studied. Of these individuals, 12 patients with MS and 60 matching controls also underwent AV1451 tau PET.

Better stress coping associated with lower tau in amyloid-positive cognitively unimpaired older adults.

Objective: Research in animals has shown that chronic stress exacerbates tau pathology. In humans, psychological stress has been associated with higher risk of Alzheimer disease clinical syndrome. The objective of this cross-sectional study was to assess the hypothesis that stress coping ability (assessed via the Brief Resilience Scale [BRS]) is associated with tau burden and to evaluate whether these associations differed by sex and amyloid status (A+/A-) in cognitively unimpaired (CU) older adults.

Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and cognitive training (ACT) in amnestic mild cognitive impairment: the blood biomarkers study protocol of a randomized controlled trial (the ACT Trial).

Background: Alzheimer's disease (AD) is an epidemic with tremendous public health impacts because there are currently no disease-modifying therapeutics. Randomized controlled trials (RCTs) for prevention of AD dementia often use clinical endpoints that take years to manifest (e.g.

Identifying incident Parkinson's disease using administrative diagnostic codes: a validation study.

Background: Administrative databases that capture diagnostic codes are increasingly being used worldwide for research because they can save time and reduce costs. However, assessing validity is necessary before defining diseases using only diagnostic codes in research applications.

Objective: Our objective was to assess the validity of using diagnostic codes to identify incident Parkinson's disease (PD) cases in Olmsted County, Minnesota using an established standard for comparison (1976-2005).

An Update on Blood-Based Markers of Alzheimer's Disease Using the SiMoA Platform.

The development of blood-based biomarkers of Alzheimer's disease (AD) pathology as tools for screening the general population, and as the first step in a multistep process to determine which non-demented individuals are at greatest risk of developing AD dementia, is essential. Proteins that are reflective of AD pathology, such as amyloid beta 42 (Aβ), tau proteins [total tau (T-tau) and phosphorylated tau (P-tau)], and neurofilament light chain (NfL), are detectable in the blood. However, a major challenge in measuring these blood-based proteins is that their concentrations are much lower in plasma or serum than in the cerebrospinal fluid.

REM sleep atonia loss distinguishes synucleinopathy in older adults with cognitive impairment.

Objective: To determine whether quantitative polysomnographic REM sleep without atonia (RSWA) distinguishes between cognitive impairment phenotypes.

Background: Neurodegenerative cognitive impairment in older adults predominantly correlates with tauopathy or synucleinopathy. Accurate antemortem phenotypic diagnosis has important prognostic and treatment implications; additional clinical tools might distinguish between dementia syndromes.

Prostate Cancer, Use of Androgen Deprivation Therapy, and Cognitive Impairment: A Population-based Study.

Introduction: The association of prostate cancer and androgen deprivation therapy (ADT) use with the odds of developing mild cognitive impairment (MCI) was determined in men from the population-based Mayo Clinic Study of Aging (MCSA).

Methods: The study included 2513 men (mean age of 73.1 y) enrolled in the MCSA.

Consideration of Sex Differences in the Measurement and Interpretation of Alzheimer Disease-Related Biofluid-Based Biomarkers.

Background: The development of cerebrospinal fluid and blood-based biomarkers for Alzheimer disease (AD) and related disorders is rapidly progressing. Such biomarkers may be used clinically to screen the population, to enhance diagnosis, or to help determine prognosis. Although the use of precision medicine methods has contributed to enhanced understanding of the AD pathophysiological changes and development of assays, one aspect not commonly considered is sex differences.

Cerebral microbleed incidence, relationship to amyloid burden: The Mayo Clinic Study of Aging.

Objective: To determine the incidence of cerebral microbleeds (CMBs) and the association of amyloid PET burden with incident CMBs.

Methods: A total of 651 participants, age ≥50 years (55% male), underwent 3T MRI scans with ≥2 separate T2*-weighted gradient recalled echo sequences from October 2011 to August 2017. Eighty-seven percent underwent C Pittsburgh compound B (PiB) PET scans.

Association of non-exercise physical activity in mid- and late-life with cognitive trajectories and the impact of APOE ε4 genotype status: the Mayo Clinic Study of Aging.

In this study derived from the population-based Mayo Clinic Study of Aging, we investigated whether non-exercise physical activity (PA) was associated with global and domain-specific cognitive trajectories (memory, language, visuospatial skills, attention) and whether the association differed by apolipoprotein E (APOE) ε4 genotype status. We included 2061 community-dwelling individuals aged ≥ 70 years (50.5% males, 26.

Incidence of frontotemporal disorders in Olmsted County: A population-based study.

Introduction: Frontotemporal dementia disorders (FTDs) are heterogeneous phenotypical behavioral and language disorders usually associated with frontal and/or temporal lobe degeneration. We investigated their incidence in a population-based cohort.

Methods: Using a records-linkage system, we identified all patients with a diagnostic code for dementia in Olmsted County, MN, 1995-2010, and confirmed the diagnosis of FTD.

Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition.

Objective: To determine the frequency of high-convexity tight sulci (HCTS) in a population-based sample and whether the presence of HCTS and related features influenced participants' cognitive status and classification within the new Alzheimer-biomarker framework.

Methods: We analyzed 684 participants ≥50 years of age who were enrolled in the prospective population-based Mayo Clinic Study of Aging and underwent structural MRI, amyloid PET imaging, and tau PET imaging. A fully automated machine-learning algorithm that had been developed previously in house was used to detect neuroimaging features of HCTS.

Practical algorithms for amyloid β probability in subjective or mild cognitive impairment.

Introduction: Practical algorithms predicting the probability of amyloid pathology among patients with subjective cognitive decline or mild cognitive impairment may help clinical decisions regarding confirmatory biomarker testing for Alzheimer's disease.

Methods: Algorithm feature selection was conducted with Alzheimer's Disease Neuroimaging Initiative and Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing data. Probability algorithms were developed in Alzheimer's Disease Neuroimaging Initiative using nested cross-validation accompanied by stratified subsampling to obtain 1000 internally validated decision trees.

Comparison of variables associated with cerebrospinal fluid neurofilament, total-tau, and neurogranin.

Introduction: Three cerebrospinal fluid (CSF) markers of neurodegeneration (N) (neurofilament light [NfL], total-tau [T-tau], and neurogranin [Ng]) have been proposed under the AT(N) scheme of the National Institute on Aging-Alzheimer's Association Research Framework.

Methods: We examined, in a community-based population (N = 777, aged 50-95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T-tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in-house enzyme-linked immunosorbent assays.

Incidence of Convexal Subarachnoid Hemorrhage in the Elderly: The Mayo Clinic Study of Aging.

Objectives: Nontraumatic convexal subarachnoid hemorrhages in the elderly can be a manifestation of cerebral amyloid angiopathy associated with a high risk of future intracerebral hemorrhage. The incidence in the elderly population is unknown. Our objectives were to: 1) determine the incidence of convexal subarachnoid hemorrhage in a population-based study, and, 2) to compare apopolipoprotein-E genotype and amyloid positron emission tomographic (PET) imaging for those with versus without hemorrhage.

Anesthesia With and Without Nitrous Oxide and Long-term Cognitive Trajectories in Older Adults.

Background: We evaluated the hypothesis that the rate of postoperative decline in global cognition is greater in older adults exposed to general anesthesia with nitrous oxide (N2O) compared to general anesthesia without N2O.

Methods: Longitudinal measures of cognitive function were analyzed in nondemented adults, 70-91 years of age, enrolled in the Mayo Clinic Study of Aging. Linear mixed-effects models with time-varying covariates assessed the relationship between exposure to surgery with general anesthesia (surgery/GA) with or without N2O and the rate of long-term cognitive changes.

Association of Apolipoprotein E ɛ4, Educational Level, and Sex With Tau Deposition and Tau-Mediated Metabolic Dysfunction in Older Adults.

Importance: While amyloidosis is an early event in the Alzheimer disease (AD) biomarker cascade, a complex interplay among the apolipoprotein E (APOE) ɛ4 allele, educational levels, and sex may be associated with an individual's resilience to dementia.

Objective: To assess whether APOE ɛ4, educational levels, and sex are associated with regional tau deposition and tau-mediated metabolic dysfunction in older adults.

Design, Setting, And Participants: Population-based cohort study of individuals aged 65 years and older enrolled between January 1, 2004, and May 1, 2018, in the Mayo Clinic Study of Aging, a prospective longitudinal study of cognitive aging in Olmsted County, Minnesota.

Sex-specific norms for verbal memory tests may improve diagnostic accuracy of amnestic MCI.

Objective: To examine whether the use of sex-specific norms and cut scores to identify memory impairment improves diagnostic accuracy of amnestic mild cognitive impairment (aMCI) compared to non-sex-specific (typical) norms/cut scores given the female advantage in verbal memory.

Methods: We calculated sex-specific and typical norms/cut scores (age and education specific) for impairment on the Rey Auditory Verbal Learning Test in the Mayo Clinic Study of Aging. Norms/cut scores were applied to 453 women and 532 men from the Alzheimer's Disease Neuroimaging Initiative.

Incidence and Trends of Progressive Supranuclear Palsy and Corticobasal Syndrome: A Population-Based Study.

Background: Few studies have investigated the incidence of PSP and CBS in the population.

Objective: To examine the incidence of and trends in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in a population-based cohort of residents of Olmsted County, MN.

Methods: We used the 1991-2005 population-based, Olmsted County Parkinsonism-cohort study, defined via the Rochester Epidemiology Project.

Exposure to surgery under general anaesthesia and brain magnetic resonance imaging changes in older adults.

Background: Preclinical studies suggest that exposure to general anaesthesia (GA) could cause neurodegeneration consistent with Alzheimer's disease (AD) pathology. Brain magnetic resonance imaging (MRI) is useful to study structural brain changes. We tested the hypothesis that exposure to surgery with GA (surgery/GA) is associated with greater cortical thinning and increased frequency of white matter lesions.