Biomarkers.

Background: Neuritic plaques with fibrillar beta-amyloid (Aβ) peptides and tau-protein neurofibrillary tangles, hallmark features of Alzheimer's disease (AD) pathology, have been concomitantly associated with white matter (WM) integrity loss, while a unique effect of each pathology on WM integrity in a more demographically diverse population remains unknown.

Method: To examine the degree to which each pathology affects WM integrity in a more diverse non-demented cohort, Aβ and tau PET, diffusion-weighted imaging (DWI), and cognition (memory and executive function composites) were examined from the U.S.

Alzheimer's Imaging Consortium.

Background: Neuritic plaques with fibrillar beta-amyloid (Aß) peptides and tau-protein neurofibrillary tangles, hallmark features of Alzheimer's disease (AD) pathology, have been concomitantly associated with white matter (WM) integrity loss, while a unique effect of each pathology on WM integrity in a more demographically diverse population remains unknown.

Method: To examine the degree to which each pathology affects WM integrity in a more diverse non-demented cohort, Aß and tau PET, diffusion-weighted imaging (DWI), and cognition (memory and executive function composites) were examined from the U.S.

APOE4-related differences in cortical thickness are modulated by sex in middle age.

Apolipoprotein E (APOE) ε4, the strongest genetic risk for late-onset Alzheimer's disease (AD), confers greater risk in females than males. While APOE4-related modulation of structural brain integrity in AD is well documented, extant literature on sex-APOE interactions has focused on older adults. The understanding of the healthy brain as a part of the normal aging process and as distinct from explicit disease or pathology is essential before comparison can be made with pathological states.

BDNF and KIBRA Polymorphisms Are Related to Altered Resting State Network Connectivity in Middle Age.

Background: Disease-modifying treatments for Alzheimer's disease (AD) may be more successful if interventions occur early, prior to significant neurodegeneration and subsequent to the onset of clinical symptoms, potentially during middle age. Polymorphisms within BDNF, COMT, and KIBRA have been implicated in AD and relate to episodic memory and executive functioning, two domains that decline early in AD.

Objective: The purpose of the current study was to use an endophenotype approach to examine in healthy, non-demented middle-aged adults the association between polymorphisms in BDNF, COMT, and KIBRA and functional connectivity within networks related to episodic memory and executive function (i.

Brain-behavior investigation of potential cognitive markers of Alzheimer's disease in middle age: a multi-modal imaging study.

Early detection of Alzheimer's disease remains a challenge, and the development and validation of novel cognitive markers of Alzheimer's disease is critical to earlier disease detection. The goal of the present study is to examine brain-behavior relationships of translational cognitive paradigms dependent on the medial temporal lobes and prefrontal cortices, regions that are first to undergo Alzheimer's-associated changes. We employed multi-modal structural and functional MRI to examine brain-behavior relationships in a healthy, middle-aged sample (N = 133; 40-60 years).

Single Nucleotide Polymorphisms in Alzheimer's Disease Risk Genes Are Associated with Intrinsic Connectivity in Middle Age.

Background: It is critical to identify individuals at risk for Alzheimer's disease (AD) earlier in the disease time course, such as middle age and preferably well prior to the onset of clinical symptoms, when intervention efforts may be more successful. Genome-wide association and candidate gene studies have identified single nucleotide polymorphisms (SNPs) in APOE, CLU, CR1, PICALM, and SORL1 that confer increased risk of AD.

Objective: In the current study, we investigated the associations between SNPs in these genes and resting-state functional connectivity within the default mode network (DMN), frontoparietal network (FPN), and executive control network (ECN) in healthy, non-demented middle-aged adults (age 40 -60; N = 123; 74 females).