No abstract

Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated

Importance-It is unclear if female carriers of the Apolipoprotein E (APOE) ε4 allele are at greater risk of developing Alzheimer's disease (AD) than men, and the sex-dependent association of mild cognitive impairment (MCI) and APOE has not been established.Objective-To determine how sex and APOE genotype affect the risks for developing MCI and AD.Data Sources-Twenty-seven independent research studies in the Global Alzheimer's Association Interactive Network with data on nearly 58,000 subjects.Neu et al.

Neurovascular dysfunction, including blood–brain barrier (BBB) breakdown and cerebral blood flow (CBF) dysregulation and reduction, are increasingly recognized to contribute to Alzheimer’s disease (AD). The spatial and temporal relationships between different pathophysiological events during preclinical stages of AD, including cerebrovascular dysfunction and pathology, amyloid and tau pathology, and brain structural and functional changes remain, however, still unclear. Recent advances in neuroimaging techniques, i.e., magnetic resonance imaging (MRI) and positron emission tomography (PET), offer new possibilities to understand how the human brain works in health and disease. This includes methods to detect subtle regional changes in the cerebrovascular system integrity. Here, we focus on the neurovascular imaging techniques to evaluate regional BBB permeability (dynamic contrast-enhanced MRI), regional CBF changes (arterial spin labeling- and functional-MRI), vascular pathology (structural MRI), and cerebral metabolism (PET) in the living human brain, and examine how they can inform about neurovascular dysfunction and vascular pathophysiology in dementia and AD. Altogether, these neuroimaging approaches will continue to elucidate the spatio-temporal progression of vascular and neurodegenerative processes in dementia and AD and how they relate to each other.

Objective-Subgroups of mild cognitive impairment (MCI) have been proposed, but few studies have investigated the non-amnestic, single-domain subgroup of MCI. The goal of the study was to compare clinical and neuroimaging characteristics of two single domain MCI subgroups: amnestic MCI (aMCI) and dysexecutive MCI (dMCI).Methods-We compared the cognitive, functional, behavioral and brain imaging characteristics of patients with aMCI (n=26), dMCI (n=32) and age-and education-matched controls (n=36) using analysis of variance and chi-squared tests. We used voxel-based morphometry (VBM) to examine group differences in brain MRI atrophy patterns.Results-Patients with dMCI had significantly lower scores on the majority of executive function tests, increased behavioral symptoms, and left prefrontal cortex atrophy on MRI when compared to controls. In contrast, patients with aMCI had significantly lower scores on tests of memory and a pattern of atrophy including bilateral hippocampi and entorhinal cortex, right inferior parietal cortex, and posterior cingulate gyrus when compared to controls.Interpretation-Overall, the clinical and neuroimaging findings provide support for two distinct single-domain subgroups of MCI, one involving executive function and the other involving memory. The brain imaging differences suggest that the two MCI subgroups have distinct patterns of brain atrophy.