Evaluation and Tracking of Alzheimer's Disease Severity Using Resting-State Magnetoencephalography

Issue title: Imaging the Alzheimer Brain

Guest editors: J. Wesson Ashford, Allyson Rosen, Maheen Adamson, Peter Bayley, Osama Sabri, Ansgar Furst, Sandra E. Black and Michael Weiner

Article type: Research Article

Authors: Verdoorn, Todd A.^{a; *} | McCarten, J. Riley^b | Arciniegas, David B.^c | Golden, Richard^d | Moldauer, Leslie^e | Georgopoulos, Apostolos^b | Lewis, Scott^b | Cassano, Michael^a | Hemmy, Laura^b | Orr, William^f | Rojas, Donald C.^c

Affiliations: [a] Orasi Medical, Inc., Minneapolis, MN, USA | [b] Geriatric Research and Education Clinic and Brain Sciences Center, Minneapolis VA Medical Center, Minneapolis, MN, USA | [c] Neurobehavioral Disorders Program, Department of Psychiatry, University of Colorado School of Medicine, Denver, CO, USA | [d] Noran Neurology Clinic, Minneapolis, MN, USA | [e] Radiant Research, Denver, CO, USA | [f] Orr and Associates Memory and Geriatric Behavioral Clinic, Mendota Heights, MN, USA

Correspondence: [*] Correspondence to: Todd A. Verdoorn, Chief Scientific Officer, Orasi Medical, Inc., 6465 Wayzata Blvd, Suite 810, Minneapolis, MN 55426, USA. Tel.: +763 405 2210; E-mail: [email protected].

Abstract: We have conducted multicenter clinical studies in which brain function was evaluated with brief, resting-state magnetoencephalography (MEG) scans. A study cohort of 117 AD patients and 123 elderly cognitively normal volunteers was recruited from community neurology clinics in Denver, Colorado and Minneapolis, Minnesota. Each subject was evaluated through neurological examination, medical history, and a modest battery of standard neuropsychological tests. Brain function was measured by a one-minute, resting-state, eyes-open MEG scan. Cross-sectional analysis of MEG scans revealed global changes in the distribution of relative spectral power (centroid frequency of healthy subjects = 8.24 ± 0.2 Hz and AD patients = 6.78 ± 0.25 Hz) indicative of generalized slowing of brain signaling. Functional connectivity patterns were measured using the synchronous neural interactions (SNI) test, which showed a global increase in the strength of functional connectivity (cO2 value of healthy subjects = 0.059 ± 0.0007 versus AD patients = 0.066 ± 0.001) associated with AD. The largest magnitude disease-associated changes were localized to sensors near posterior and lateral cortical regions. Part of the cohort (31 AD and 46 cognitively normal) was evaluated in an identical fashion approximately 10 months after the first assessments. Follow-up scans revealed multiple MEG scan features that correlated significantly with changes in neuropsychological test scores. Linear combinations of these MEG scan features generated an accurate multivariate model of disease progression over 10 months. Our results demonstrate the utility of brief resting-state tests based on MEG. The non-invasive, rapid and convenient nature of these scans offers a new tool for translational AD research and early phase development of novel treatments for AD.

Keywords: Alzheimer's disease, magnetoencephalography, electrophysiology, biomarkers

DOI: 10.3233/JAD-2011-0056

Journal: Journal of Alzheimer's Disease, vol. 26, no. s3, pp. 239-255, 2011