Trajectory of clinical symptoms in relation to amyloid chronicity.

Introduction: While it is generally appreciated that amyloid precedes symptomatic Alzheimer's disease (AD) by decades, a greater understanding of this timeline may increase prognostic accuracy, planning, and care of persons who are on the AD continuum.

Methods: We examined trajectories of Clinical Dementia Rating-Sum of Boxes (CDR-SB) relative to estimated years of amyloid positivity (A+) in  = 123 participants who were all A+ based on [C-11]Pittsburgh compound B positron emission tomography.

Results: The average amyloid chronicity at CDR-SB of 2.

Validity Evidence for the Research Category, "Cognitively Unimpaired - Declining," as a Risk Marker for Mild Cognitive Impairment and Alzheimer's Disease.

While clinically significant cognitive impairment is the key feature of the symptomatic stages of the Alzheimer's disease (AD) continuum, subtle cognitive decline is now known to occur years before a clinical diagnosis of mild cognitive impairment (MCI) or dementia due to AD is made. The primary aim of this study was to examine criterion validity evidence for an operational definition of "cognitively unimpaired-declining" (CU-D) in the Wisconsin Registry for Alzheimer's Prevention (WRAP), a longitudinal cohort study following cognition and risk factors from mid-life and on. Cognitive status was determined for each visit using a consensus review process that incorporated internal norms and published norms; a multi-disciplinary panel reviewed cases first to determine whether MCI or dementia was present, and subsequently whether CU-D was present, The CU-D group differed from CU-stable (CU-S) and MCI on concurrent measures of cognition, demonstrating concurrent validity.

Metabolic syndrome components moderate the association between executive function and functional connectivity in the default mode network.

Middle aged individuals with Metabolic Syndrome are at high risk for cognitive decline. Dyssynchrony in the resting state Default Mode Network is one early indicator of brain vulnerability. We set out to explore the relationship between default mode resting state functional connectivity and cognitive performance in both memory and executive domains at midlife in the presence of Metabolic Syndrome components.

Phenotypic heterogeneity of obesity-related brain vulnerability: one-size interventions will not fit all.

Intact memory and problem solving are key to functional independence and quality of life in older age. Considering the unprecedented demographic shift toward a greater number of older adults than children in the United States in the next few decades, it is critically important for older adults to maintain work productivity and functional independence for as long as possible. Implementing early interventions focused on modifiable risk factors for cognitive decline at midlife is a strategy with the highest chance of success at present, bearing in mind the current lack of dementia cures.

Associations of carotid arterial compliance and white matter diffusion metrics during midlife: modulation by sex.

Sex differences in cerebral white matter (WM) aging have been debated extensively over the past 2 decades without unequivocal resolution. We aimed to determine if the effects of age and arterial stiffness on WM microstructure differ between sexes. Artery elasticity via carotid artery compliance (CAC) and WM diffusion metrics via diffusion tensor image-derived fractional anisotropy (FA) and mean diffusivity (MD) were measured in 155 (87 females) middle-aged (40-62 years) adults.