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Advances in Brain Imaging Can Expedite Research and Diagnosis in Alzheimer’s Disease

October 11, 2011
Alzheimer’s disease (AD) is a common problem that is becoming progressively burdensome throughout the world. A new supplement to the Journal of Alzheimer’s Disease, Imaging the Alzheimer Brain, clearly shows that multiple imaging systems are now available to help understand, diagnose, and treat the disease.

“Alzheimer’s disease is now seen as a continuum that is influenced by factors early in life, including genetics and education,” according to Guest Editor J. Wesson Ashford, MD, PhD, Clinical Professor and Senior Research Scientist at the Stanford/VA Alzheimer Center, Palo Alto, CA.  “Conceptualizing the continuum of AD with advanced imaging technology will provide a greater understanding of the disease, and help advance diagnosis and the quest for prevention and treatment.”

The supplement features both reviews of the basic concepts of neuroimaging in the context of AD, the latest developments in imaging, and various discussions and perspectives of the problems of the field and promising directions. It provides in-depth insights into: pathology and pathophysiological bases of AD; structural and cerebral blood flow imaging; metabolism, amyloid plaques, and neurofibrillary tangles in vascular co-morbidity and AD; current advances in functional magnetic resonance imaging for detecting AD; electromagnetic brain mapping; diffusion tensor imaging; magnetic resonance spectroscopy; and longitudinal neuroimaging measures.

Investigators have used brain imaging to track some of the earliest changes associated with the predisposition to AD.  In their paper, “Alzheimer’s Prevention Initiative:  A Plan to Accelerate the Evaluation of Presymptomatic Treatments,” a group of scientists proposes to evaluate investigational treatments in healthy people who, based on their age and genetic background, are at the highest imminent risk of developing symptomatic AD.  “It currently takes too many average healthy people, too much money, and too many years to evaluate the range of promising presymptomatic treatments using clinical endpoints,” says lead author Eric M. Raiman, of the Banner Alzheimer’s Institute and theUniversityofArizona. The project will use brain imaging studies, cerebrospinal fluid biomarkers, and cognitive measures to evaluate AD-modifying treatments earlier than is otherwise possible and to determine the extent to which the treatment’s brain imaging and other biomarker effects predict a clinical benefit, among other outcomes.   

Dr. Ashford comments that “even when imaging data are not applied to the management of individual patients, these data have the potential to assist in evaluating other components of care and diagnosis. To the extent that imaging can more sensitively measure brain integrity than existing techniques, novel treatments may be discovered because beneficial effects of treatments are not detectable with other methods.”

Two articles in the supplement offer intriguing insights into the relationship between cortical thinning and AD.  In “Relationship Between CSF Biomarkers of Alzheimer’s Disease and Rates of Regional Cortical Thinning in ADNI Data,” investigators from the Department of Veterans Affairs Medical Center,San Francisco, theUniversityofCaliforniaand the Hospital of theUniversityofPennsylvaniatested the association between rates of regional brain cortex thinning and reduced amyloid (Ab1-42) and higher tau concentrations.  Using data from the Alzheimer’s Disease Neuroimaging Initiative, they found that these biomarkers were associated with increased rates of brain tissue loss, and that the patterns varied across the healthy elderly and the mildly cognitively impaired.  “The finding of faster progression of brain atrophy in the presence of lower Ab1-42 levels and higher p-tau levels supports the hypothesis that they are measures of early AD pathology,” says lead author Duygu Tosun. 

It’s known that the presence of an ApoE e4 (e4+) allele increases the risk of developing AD. There is an adverse relationship between e4+ status and brain structure and function in mild cognitive impairment; the presence of an e2 allele may be protective.  In “Presence of ApoE e4 Allele Associated with Thinner Frontal Cortex in Middle Age,” investigators examined whether the brain cortex thinning is the result of the disease, or a pre-existing endophenotype.  Drawing on imaging data from a large national sample, the study examined the influence of ApoE on regional brain thickness and structure.  The presence of the e4+ demonstrated significantly thinner cortex in the frontal areas, and may explain susceptibility to AD.  The presence of the e2 allele was related to thicker cortex, suggesting a protective role.

In all, 31 papers discuss the advances in numerous imaging methodologies that are being used to increase our understanding of the pathophysiological basis of AD and drive us toward new therapies for this complex brain disorder.  “Ultimately, the prospects for neuroimaging to enhance clinical care in Alzheimer’s disease are bright as researchers collaborate and clinicians become informed about innovations and advances,” says George Perry, PhD, Editor-in-Chief, Journal of Alzheimer’s Disease, and Dean and Professor, College of Sciences, University of Texas at San Antonio.



Full text of contributions is available to credentialed journalists upon request. To obtain copies contact Daphne Watrin, IOS Press, Tel: +31 20 688 3355, To request an interview with any of the authors contact Dr. J. Wesson Ashford at  

 Imaging the Alzheimer Brain

Guest Edited by J.W. Ashford, A. Rosen, M. Adamson, P. Bayley, O. Sabri, A. Furst and S.E. Black and M. Weiner

Journal of Alzheimer’s Disease, 26 (Supplement 3)


Introduction: Imaging the Alzheimer’s Brain
J. Wesson Ashford et al.                                                                                                                       

Hippocampal Network Alterations in Alzheimer’s Disease and Down Syndrome: From Structure to Therapy 29
Martha Millan Sanchez et al.

Presence of ApoE e4 Allele Associated with Thinner Frontal Cortex in Middle Age
Christine Fennema-Notestine et al.

Survey of Protocols for the Manual Segmentation of the Hippocampus: Preparatory Steps Towards a Joint EADC-ADNI Harmonized Protocol
Marina Boccardi et al. 

Relationship Between CSF Biomarkers of Alzheimer’s Disease and Rates of Regional Cortical Thinning in ADNI Data
Duygu Tosun et al.

Ultra-High Field 7T MRI: A New Tool for Studying Alzheimer’s Disease  
Geoffrey A. Kerchner

Nuclear Medicine Diagnostic Techniques in the Era of Pathophysiology-Based CSF Biomarkers for Alzheimer’s Disease
Markus Weih et al.

Amyloid-ß and Glucose Metabolism in Alzheimer’s Disease
Ansgar J. Furst and Rayhan A. Lal

Florbetaben to Trace Amyloid-ß in the Alzheimer Brain by Means of PET
Henryk Barthel and Osama Sabri

Effects of Hypoperfusion in Alzheimer’s Disease
Benjamin P. Austin et al.

The Merits of FDDNP-PET Imaging in Alzheimer’s Disease
Jonghan Shin et al.

Research Towards Tau Imaging
Jordan R. Jensen et al.

Disease Tracking Markers for Alzheimer’s Disease at the Prodromal (MCI) Stage
Valeria Drago et al

Resting State Cortical Rhythms in Mild Cognitive Impairment and Alzheimer’s Disease: Electroencephalographic Evidence
Claudio Babiloni et al.

Cognitive Event-Related Potentials: Biomarkers of Synaptic Dysfunction Across the Stages of Alzheimer’s Disease
John M. Olichney et al.

P300 Energy Loss in Aging and Alzheimer’s Disease
J. Wesson Ashford et al.

Evaluation and Tracking of Alzheimer’s Disease Severity Using Resting-State Magnetoencephalography
Todd A. Verdoorn et al.

Diffusion Tensor Imaging of the Hippocampus in MCI and Early Alzheimer’s Disease
Andreas Fellgiebel and Igor Yakushev

Mapping the Structural Brain Changes in Alzheimer’s Disease: The Independent Contribution of Two Imaging Modalities
Elisa Canu et al.

Multiple Diffusion Indices Reveals White Matter Degeneration in Alzheimer’s Disease and Mild Cognitive Impairment: A Tract-Based Spatial Statistics Study
Ni Shu, Zhiqun Wang et al.

DTI Analyses and Clinical Applications in Alzheimer’s Disease
Kenichi Oishi et al. 

Searching for Novel Biomarkers Using High Resolution Diffusion Tensor Imaging
Michael A. Yassa

Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy for Detection of Early Alzheimer’s Disease
Eric Westman et al.

Alzheimer’s Prevention Initiative: A Plan to Accelerate the Evaluation of Presymptomatic Treatments
Eric M. Reiman et al.

MR Spectroscopy for Assessment of Memantine Treatment in Mild to Moderate Alzheimer Dementia
J. Wesson Ashford et al.

Effects of a 6-Month Cognitive Intervention on Brain Metabolism in Patients with Amnestic MCI and Mild Alzheimer’s Disease
Stefan Förster et al.

Cognitive Training Changes Hippocampal Function in Mild Cognitive Impairment: A Pilot Study Review
Allyson C. Rosen et al.

An MRI Brain Atrophy and Lesion Index to Assess the Progression of Structural Changes in Alzheimer’s Disease, Mild Cognitive Impairment, and Normal Aging: A Follow-Up Study
Ningnannan Zhang et al.

Power Calculations for Clinical Trials in Alzheimer’s Disease
M. Colin Ard and Steven D. Edland

Complexity of MRI White Matter Hyperintensity Assessments in Relation to Cognition in Aging and Dementia from the Sunnybrook Dementia Study
Fu-qiang Gao et al.

Principles of Classification Analyses in Mild Cognitive Impairment (MCI) and Alzheimer Disease
Sven Haller, Karl O. Lovblad and Panteleimon Giannakopoulos

Combinatorial Markers of Mild Cognitive Impairment Conversion to Alzheimer’s Disease – Cytokines and MRI Measures Together Predict Disease Progression
Simon J. Furney et al.


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. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. 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 4.261 according to Thomson Reuters’ 2011 edition of Journal Citation Reports. 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
Tel: +1 210 458 4450
Fax:+1 210 458 4445

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