The stability of resting state networks in aging: Relevance for early memory dysfunction

Abstract

in the preclinical stages of AD. Identifying brain biomarkers of AD risk in this group could help promote preclinical diagnosis of AD and early intervention and prevention strategies. OBJECTIVE: To characterize the relationship between relative cerebral blood flow (rCBF), CSF biomarkers, and age in asymptomatic middle-aged adults with a parental history of AD. Methods: CSF biomarkers were measured in 96 non-demented, middle-aged adult children of persons with AD (mean6SD; age1⁄453.568.0yrs; n1⁄466 [69%] women; n1⁄435 [36%] apolipoprotein E e4 allele carriers [APOE4+]). Among this group, 42 participants (age1⁄453.866.9yrs; n1⁄430 [71%] women; n1⁄414 [33%] APOE4+) underwent 1.5T-DSC perfusionweighted MRI scans which were used to estimate measures of rCBF. CSF b-amyloid1-42 (Ab1-42), total-tau (T-tau) and phosphorylated tau (P-tau 181) were analyzed using the INNO-BIA AlzBio3 (xMAP) assay. CSF Abx-38, Abx-40 and Abx-42 were measured using Meso Scale Discovery (MSD ) electrochemiluminescence. Results: A semi-partial regression model controlling for systolic blood pressure (SBP) and APOE4 status revealed that age was a) negatively associated with rCBF within a region of left parahippocampal gyrus (PHG) (Figure) and b) positively associated with seven CSF measures: Abx-38, Abx-40, Abx-42, T-tau, P-tau 181, the ratio (T-tau)/(Ab42), and the ratio (P-tau 181)/(Ab42). CBF within left PHG, however, was not associated with any of the CSF measures when controlling for age. Conclusions: In asymptomatic adult children of persons with AD, CBF and CSF biomarkers are significantly associated with increasing age but appear to be independent of each other in the preclinical stages of the disease. Whereas cerebrovascular dysfunction and Ab dysregulation likely interact and accelerate neurodegeneration later in the disease course, these processes may not interact with each other as strongly during this asymptomatic stage. The temporal point at which CBF and Ab processes significantly affect each other requires further longitudinal investigation.