Default mode network integrity associated with spinal fluid markers in preclinical AD

Amyloid beta and tau pathologies appear to be associated with default mode network (DMN) integrity before clinical onset of Alzheimer’s disease (AD), according to a study published online Aug. 19 in JAMA Neurology. The study offers further evidence of the association between functional connectivity in the DMN and cerebrospinal fluid biomarker abnormalities.

“Resting-state functional connectivity magnetic resonance imaging has great potential for characterizing pathophysiological changes during the preclinical phase of Alzheimer disease,” wrote Liang Wang, MD, and colleagues at Washington University in St. Louis.

Amyloid beta and tau proteins begin accumulating years before the clinical onset of AD. To better understand the progression of these pathologies, the authors conducted a cross-sectional cohort study of 207 older adults with normal cognition. Resting-state functional MRI was used to examine the relationship between DMN integrity and the cerebrospinal fluid biomarkers of AD.

Results showed that amyloid beta-42 and phosphorylated tau-181 were independently associated with reduced DMN integrity, reported Wang and colleagues. The most prominent decreases in functional connectivity were between the posterior cingulate and medial temporal regions.

“Observed reductions in functional connectivity were unattributable to age or structural atrophy in the posterior cingulate and medial temporal areas,” wrote the authors.

Similar findings related to the cerebrospinal fluid biomarkers were obtained using region-of-interest analyses and voxel-wise correlation mapping, added Wang and colleagues.

They called for future studies that used more rigorous approaches to control for the effects of structural brain changes, and for examinations of resting-state networks other than the DMN.