Functional connectivity changes in advanced Alzheimer’s disease (AD) are similar whether the patient has autosomal dominant AD (ADAD) or late-onset AD (LOAD), according to a study published in the September issue of JAMA Neurology.
The findings reinforce emerging biomarker data demonstrating the similarity between the two types of AD, and support the use of ADAD as a model of LOAD, according to Beau M. Ances, MD, PhD, of the Department of Neurology at Washington University in St Louis, and colleagues.
“Both ADAD and LOAD manifest similar functional connectivity changes with respect to [clinical dementia rating],” they wrote. “Moreover, regression models constructed in one cohort distinguished [clinical dementia rating] stages in the other.”
ADAD is caused by rare mutations in three specific genes, while LOAD has a more polygenetic risk profile, explained Ances and colleagues.
To analyze the functional connectivity in multiple brain resting state networks, the authors recruited a cross-sectional cohort featuring 79 participants in an ADAD group and 444 in a LOAD group. For those with ADAD, 54 were mutation positive and 25 were mutation negative, while the LOAD group was divided between those with mild AD dementia, very mild AD dementia and cognitively normal older adults. All participants underwent resting-state functional MRI and dementia severity was measured by the Clinical Dementia Rating Scale.
Results showed a decrease in functional connectivity along with increasing clinical dementia ratings with similar patterns for both LOAD and ADAD in multiple resting state networks. This suggests that resting-state functional connectivity MRI may be a useful end point for LOAD and ADAD therapy trials, according to the authors.
Ances and colleagues did not some differences in functional connectivity between the AD types, with a modestly greater effect of disease severity being present for ADAD compared with LOAD.
“The available data suggest that ADAD may serve as an effective model to study LOAD pathophysiology, albeit with some reservations,” wrote the authors.
Evan joined TriMed in 2011, writing primarily for Health Imaging. Prior to diving into medical journalism, Evan worked for the Nine Network of Public Media in St. Louis. He also has worked in public relations and education. Evan studied journalism at the University of Missouri, with an emphasis on broadcast media.