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New Diagnostic Biomarkers Offer Ray of Hope for Alzheimer’s Disease

State-of-the-Art Imaging Technology for Biomarker Development Explored in a Supplement to Journal of Alzheimer’s Disease

August 30, 2012
Alzheimer’s disease (AD) is one of the most common brain disorders, with an estimated 35 million people affected worldwide. In the last decade, research has advanced our understanding of how AD affects the brain. However, diagnosis continues to rely primarily on neuropsychological tests which can only detect the disease after clinical symptoms begin. In a supplement to the Journal of Alzheimer’s Disease, investigators report on the development of imaging-based biomarkers that will have an impact on diagnosis before the disease process is set in motion.

“There is an urgent need for the development of reliable diagnostic biomarkers that can detect AD pathology at an incipient phase,” says Guest Editor Dr. Pravat Mandal, Adjunct Associate Professor of the Department of Radiology, Johns Hopkins Medicine, Baltimore, MD and Additional Professor, National Brain Research Center, India.  “This special issue focuses on the latest strides made in identifying diagnostic biomarkers using state-of-the-art imaging modalities.”

The issue looks at the application of various magnetic resonance imaging (MRI) technologies for diagnosing AD and monitoring the progression of the disease.  For example, Brian T. Gold and colleagues report on the use of diffusion tension imaging (DTI) to identify changes in the white matter of patients with amnestic mild cognitive impairment (MCI), an early symptom of AD.  Charles D. Smith and colleagues describe MRI-based detection of key structural alterations in cognitively normal subjects that can serve as a predictor of memory impairment. 

While MRI provides information about the anatomy of the brain, functional MRI (fMRI) provides crucial information about the regions involved during specific tasks.  The issue explores how fMRI can detect changes in functional activation and connectivity in AD patients.  Monitoring alterations in functional brain activity related to visual processing deficits in AD has immense potential as an early diagnostic biomarker, according to a review by Dr. Mandal and colleagues.  By using fMRI to study normal older individuals, patients with MCI, and those with AD as they perform cognitive tasks and at rest, Jasmeer P. Chhatwal and Reisa Sperling reveal the functional alterations associated with healthy aging as well as MCI and AD. 

Magnetic resonance spectroscopy (MRS) is a powerful non-invasive imaging technique that can provide crucial information about neurochemical changes in AD.  Dr. Mandal and colleagues report that the identification of neurochemical changes in the brains of MCI and AD patients may provide a “signature” of early AD pathology, and may aid in diagnosing patients who are moving from MCI to more advanced AD. 

Imaging is also used to examine the molecular and therapeutic effects of potential AD treatments.  Liam Zaidel and colleagues found that patients treated with donepezil for mild cognitive symptoms had a significant increase in interhemispheric functional connectivity of the left and right dorsolateral prefrontal cortices.  Giulia Liberati and colleagues describe a non-invasive brain-computer interface that can detect a patient’s emotional and cognitive state.  It could provide vital information on the effect of clinical drugs on brain function and cognition in patients with AD. 

The issue also includes a thought-provoking argument from Edo Richard and colleagues calling for a paradigm shift in dementia research and biomarker development.  Current biomarker research focuses on correlates of plaques and tangles, which are poor markers in older dementia subjects.  The authors suggest that the acknowledgement that dementia in older subjects is different from dementia at a young age will lead to new approaches in biomarker development and research. 

“Research is needed to understand which molecular, structural, and functional changes are causally related to the onset of AD,” says Dr. Mandal.  “This special issue aims to conceptualize more effective and reliable biomarkers for AD.” 

George Perry, PhD, Editor-in-Chief, Journal of Alzheimer’s Disease, and Dean and Professor, College of Sciences, University of Texas at San Antonio, says, “The development of biomarkers to aid in early detection of the onset of AD is critical.  This special issue will spur research into multi-model imaging based biomarker development for AD.”    

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“Biomarkers for Alzheimer’s Disease Using Multi-Model Imaging Research,” Guest Edited by Pravat K. Mandal.  Journal of Alzheimer’s Disease, Volume 31 (2012), Supplement 3.  Published by IOS Press.

Full text of the articles in the Supplement is available to credentialed journalists upon request. Contact Daphne Watrin, IOS Press at +31 20 688 3355,  to obtain a copies or to request an interview with the authors.

Table of Contents:

Introduction, Pravat K. Mandal

Magnetic Resonance Imaging Based Clinical Research in Alzheimer’s Disease, Nicolás Fayed, Pedro J Modrego, Gulillermo Rojas Salinas, José Gazulla

Multimodal Imaging Evidence for Axonal and Myelin Deterioration in Amnestic Mild Cognitive Impairment, Brian T. Gold, Yang Jiang, David K. Powell, Charles D. Smith

Anatomical MRI and DTI in the Diagnosis of Alzheimer’s Disease: A European Multicenter Study, Stefan J. Teipel, Martin Wegrzyn, Thomas Meindl, Giovanni Frisoni, Arun L.W. Bokde, Andreas Fellgiebel, Massimo Filippi, Harald Hampel, Stefan Klöppel, Karlheinz Hauenstein, Michael Ewers, and the EDSD study group

Structural Brain Alterations before Mild Cognitive Impairment in ADNI: Validation of Volume Loss in a Predefined Antero-Temporal Region, Charles D. Smith, Anders H. Andersen, Brian T. Gold for the Alzheimer’s Disease Neuroimaging Initiative

Assessment of Alzheimer’s Disease Risk with Functional Magnetic Resonance Imaging: An Arterial Spin Labeling Study, Katherine J. Bangen, Khaled Restom, Thomas T. Liu, Christina E. Wierenga, Amy J. Jak, David P. Salmon, Mark W. Bondi

Mapping of Hippocampal pH and Neurochemicals from in vivo Multi-voxel 31P Experiments in Healthy Normal Young Male/Female, Mild Cognitive Impairment, and Alzheimer’s Patients, Pravat K. Mandal, Himanshu Akolkar, Manjari Tripathi

Proton and Phosphorus Magnetic Resonance Spectroscopy of a Mouse Model of Alzheimer’s Disease, Vladimír Mlynárik, Matthias Cacquevel, Lili Sun-Reimer, Sharon Janssens, Cristina Cudalbu, Hongxia Lei, Bernard L. Schneider, Patrick Aebischer, Rolf Gruetter

Handling Macromolecule Signals in the Quantification of the Neurochemical Profile, Cristina Cudalbu, Vladimir Mlynárik, Rolf Gruetter

Visuospatial Perception: An Emerging Biomarker for Alzheimer’s Disease, Pravat K Mandal, Jitesh Joshi, Sumiti Saharan

Relevance of in vivo Neurophysiological Biomarkers for Mild Cognitive Impairment and Alzheimer’s Disease, Takao Yamasaki, Shizuka Horie, Hiroyuki Muranaka, Yumiko Kaseda, Yasuyo Mimori, Shozo Tobimatsu

Functional MRI of Mnemonic Networks Across the Spectrum of Normal Aging, Mild Cognitive Impairment, and Alzheimer’s Disease, Jasmeer P. Chhatwal, Reisa A. Sperling

Structural Brain Atlases: Design, Rationale, and Applications in Normal and Pathological Cohorts, Pravat K Mandal, Rashima Mahajan, Ivo D. Dinov

Analysis of Regional Cerebral Blood Flow Data to Discriminate among Alzheimer’s Disease, Frontotemporal Dementia, and Elderly Controls: A Multi-Block Barycentric Discriminant Analysis (MUBADA) Methodology, Hervé Abdi, Lynne J. Williams, Derek Beaton, Mette T. Posamentier, Thomas S. Harris, Anjali Krishnan, Michael D. Devous, Sr.

The Alzheimer Myth and Biomarker Research in Dementia, Edo Richard, Ben Schmand, Piet Eikelenboom, Rudi G. Westendorp, Willem A. Van Gool

Toward a Brain-Computer Interface for Alzheimer’s Disease Patients by Combining Classical Conditioning and Brain State Classification, Giulia Liberati, Josué Luiz Dalboni da Rocha, Linda van der Heiden Antonino Raffone, Niels Birbaumer, Marta Olivetti Belardinelli, Ranganatha Sitaram

Donepezil Effects on Hippocampal and Prefrontal Functional Connectivity in Alzheimer’s Disease: Preliminary Report, Liam Zaidel, Greg Allen, C. Munro Cullum, Richard W. Briggs, Linda S. Hynan, Myron F. Weiner, Roderick McColl, Kaundinya S. Gopinath, Elizabeth McDonald, Craig D. Rubin


The Journal of Alzheimer’s Disease ( is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer’s disease. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer’s Disease has an Impact Factor of 3.745 according to Thomson Reuters’ 2011 Journal Citation Reports, 2012. It is ranked #19 on the Index Copernicus Top 100 Journal List. The Journal is published by IOS Press.


Commencing its publishing activities in 1987, IOS Press ( serves the information needs of scientific and medical communities worldwide. IOS Press now (co-)publishes over 100 international journals and about 130 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.

IOS Press continues its rapid growth, embracing new technologies for the timely dissemination of information. All journals are available electronically and an e-book platform was launched in 2005.

Headquartered in Amsterdam with satellite offices in the USA, Germany, India and China, IOS Press has established several strategic co-publishing initiatives. Notable acquisitions included Delft University Press in 2005 and Millpress Science Publishers in 2008.

George Perry, PhD
Editor-in-Chief, Journal of Alzheimer’s Disease
Dean and Professor of Biology, The University of Texas at San Antonio
Tel: +1 210 458 4450
Fax:+1 210 458 4445

Daphne Watrin
IOS Press
Tel: +31 20 688 3355
Fax: +31 20 687 0019