Resting-State fcMRI Useful Endpoint for Alzheimer's Outcomes

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Resting-state functional connectivity magnetic resonance imaging was accurate in measuring progression of Alzheimer's disease severity in both autosomal dominant and late-onset forms of the disease and may play an important role in future trials to assess potential therapies for the disease, study findings suggest.

In a cross-sectional cohort of participants with autosomal dominant Alzheimer's disease (ADAD; n=79) and late-onset Alzheimer's disease (LOAD; n=444), Beau M. Ances, MD, PhD, of Massachusetts General Hospital in Boston, and colleagues analyzed functional connectivity changes using resting-state functional connectivity magnetic resonance imaging (fcMRI) to see if it correlated with dementia severity progression.

In the JAMA Neurology study, the researchers measured dementia severity using the Clinical Dementia Rating Scale for all subjects, and qualitatively compared functional connectivity changes among multiple resting state networks (RSNs) in ADAD and LOAD patients with respect to estimated years from onset of symptoms.

Decreasing functional connectivity correlated with increasing Clinical Dementia Rating scores in patients with both LOAD and ADAD across multiple RSNs, the researchers found.

"Ordinal logistic regression models constructed in one type of Alzheimer disease accurately predicted clinical dementia rating scores in the other, further demonstrating the similarity of functional connectivity loss in each disease type," the researchers wrote.

The study highlights the need for direct comparisons between biomarkers for the two forms of Alzhiemer's disease, despite differences in genetic risk profiles, Adam S. Fleisher, MD, MAS, of Banner Alzheimer's Institue in Pheonix, Arizona, wrote in an accompanying editorial.

The study findings are "a key example of how biomarker changes in ADAD may be similar to those manifested in [LOAD] will facilitate an understanding of phenotypic similarities and incongruences and bidirectionally inform the use of biomarkers in clinical trials of both forms of AD," Fleisher wrote.

Similarly, the researchers concluded the disease process of ADAD may be an effective model for the LOAD disease process and that resting-state fcMRI may be a useful end point to assess AD therapy efficacy in future trials. 

MRI, PET, and CSF Biomarkers Up Prediction of Alzheimer's
Resting-State fcMRI Changes Similar Across Alzheimer's Types

This study looks at the similarities and differences in functional connectivity changes in late-onset Alzheimer's disease (LOAD), which is caused by rare genetic mutations in three specific genes, and autosomal dominant Alzheimer's disease (ADAD), which has a more polygenetic risk profile.

Beau M. Ances, MD, PhD, of the Department of Neurology, Martinos Center for Biomedical Imaging, at the Massachusetts General Hospital and Harvard Medical School, in Boston, and colleagues, assessed the similarities and differences in functional connectivity changes owing to ADAD and LOAD in multiple brain resting state networks (RSNs) using resting-state functional connectivity magnetic resonance imaging at multiple international academic sites.

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