Brain Imaging Can Advance Alzheimer’s Disease Research

“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, USA). “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 contains both reviews of the basic concepts of neuroimaging in the context of AD, the latest developments in imaging, and insights into: pathology and pathophysiologic bases of AD; structural and cerebral blood flow imaging; metabolism, amyloid plaques, and neurofibrillary tangles in vascular comorbidity and AD; current advances in functional magnetic resonance imaging for detecting AD; electromagnetic brain mapping; diffusion tensor imaging; magnetic resonance (MR) spectroscopy; and longitudinal neuroimaging measures.

Investigators have utilized brain imaging to track some of the earliest changes associated with the predisposition to AD. In their article, a group of scientists proposes to evaluate research treatments in healthy individuals 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,” said lead author Eric M. Raiman, of the Banner Alzheimer’s Institute (Phoenix, AZ, USA) and the University of Arizona (Tucson, USA). The project will use brain imaging studies, cerebrospinal fluid biomarkers, and cognitive measures to assess AD-modifying treatments earlier than is otherwise possible and to determine the degree to which the treatment’s brain imaging and other biomarker effects predict a clinical benefit, among other outcomes.

Dr. Ashford commented, “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 provide fascinating insights into the association between cortical thinning and AD. In another study, researchers from the department of Veterans Affairs Medical Center, San Francisco, the University of California (UCSF) and the Hospital of the University of Pennsylvania (Philadelphia, USA) examined the relationship 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 discovered that these biomarkers were tied to 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,” stated lead author Dr. Duygu Tosun.

It is well 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 another study, researchers examined whether the brain cortex thinning is the result of the disease, or a preexisting endophenotype. Drawing on imaging data from a large US sample, the study examined the influence of ApoE on regional brain thickness and structure. The presence of the e4+ revealed considerably thinner cortex in the frontal areas, and may clarify susceptibility to AD. The presence of the e2 allele was related to thicker cortex, suggesting a protective role.

In all, 31 articles discussed the developments in numerous imaging methodologies that are being used to increase our understanding of the pathophysiologic basis of AD and drive physicians toward new therapies for this complicated 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,” noted George Perry, PhD, editor-in-chief, Journal of Alzheimer’s Disease, and dean and professor, College of Sciences, University of Texas at San Antonio (SA).

Related Links:
Stanford/VA Alzheimer Center
Banner Alzheimer’s Institute
Veterans Affairs Medical Center, San Francisco, the University of California