In their report that will appear in the journal Brain and has been released online, the MGH/Martinos team show how their software program can accurately differentiate patients with mild cognitive impairment or Alzheimer's disease from normal elderly individuals based on anatomic differences in brain structures known to be affected by the disease.
"Traditionally Alzheimer's has been diagnosed based on a combination of factors – such as a neurologic exam, detailed medical history and written tests of cognitive functioning – with neuroimaging used primarily to rule out other diseases such as stroke or a brain tumor," says Rahul Desikan MD, PhD, of the Martinos Center and Boston University School of Medicine, lead author of the Brain paper. "Our findings show the feasibility and importance of using automated, MRI-based neuroanatomic measures as a diagnostic marker for Alzheimer's disease."
The researchers note that mild cognitive impairment occurs in about 20 percent of elderly individuals – as many as 40 percent of those over 85 – 80 percent of whom develop Alzheimer's within five or six years. Since drugs that may slow the progression of Alzheimer's are in development, the ability to treat patients in the earliest stages of the disease may significantly delay progression to dementia. To investigate whether MR imaging can produce diagnostic markers for mild cognitive impairment and Alzheimer's disease, the research team used FreeSurfer – an openly available imaging software package developed at the Martinos Center and the University of California at San Diego – to examine a number of neuroanatomic regions across a range of normal individuals and patients with mild cognitive impairment and Alzheimer's disease.
In the first phase of the study, the investigators examined MR images of 97 elderly individuals, some who had been determined to have mild cognitive impairment and others who were cognitively normal. Analyzing those images identified three regions of the brain where structural differences distinguished the normal controls from participants with mild cognitive impairment with an accuracy of 91 percent. Earlier pathological and imaging studies have found evidence of early Alzheimer's disease in these three areas – the hippocampus, entorhinal cortex and the supramarginal gyrus.
To validate the accuracy and assess the reliability of the first-phase observations, the investigators analyzed imaging data from 216 individuals in the Alzheimer's Disease Neuroimaging Database – 94 of whom were normal, 58 who had mild cognitive impairment at the time of imaging and went on to develop dementia, and 65 who had probable Alzheimer's based on their clinical symptoms. These participants also had a series of neuropsychological tests, and samples of cerebrospinal fluid were available for many of them.
Automated MRI measures of the same three areas identified in the first phase – entorhinal cortex, hippocampus, and supramarginal gyrus – discriminated individuals with mild cognitive impairment from normal elderly controls with 95 percent accuracy, and patients with Alzheimer's were discriminated from normal controls with 100 percent accuracy. The MRI measures also were significantly correlated with clinical and cognitive tests of dementia, particularly memory decline, and with biomarkers of cellular pathology such as the Alzheimer's-associated forms of the tau and amyloid proteins.
"Our results indicate that these automated MRI measures are one effective way of identifying individuals in the earliest stages of Alzheimer's disease, but before this technology can be used clinically, several follow-up studies need to be done," says Desikan. "Those include determining whether these automated MRI measures can accurately predict which individuals with mild cognitive impairment will progress to Alzheimer's; seeing if they can differentiate Alzheimer's from other neurodegenerative diseases; assessing how these measures do at early diagnosis, compared to other measures such as cellular biomarkers; and then validating all of these findings against the gold standard for diagnosis, postmortem examination of brain tissue."
Bruce Fischl, PhD, of the Martinos Center is the senior author of the Brain study. Additional co-authors are Nicholas Schmansky, Douglas Greve and David Salat of the Martinos Center; Howard Cabral, Boston University School of Public Health; Christopher Hess, William Dillon, Christine Glastonbury and Michael Weiner, University of California, San Francisco; and Randy Buckner, Harvard University and Howard Hughes Medical Institute. Support for the study came from the American Federation for Aging Research, the National Center for Research Resources, the National Institute for Biomedical Imaging and Bioengineering, the Mental Illness and Neuroscience Discovery Institute, the National Institute on Aging, the National Institute for Neurologic Disorders and Stroke and several other organizations.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.
Sue McGreevey | EurekAlert!
Further reports about: > Alzheimer > Alzheimer's Disease > Brain > Hippocampus > MGH > MRI > MRI-based neuroanatomic measures > Medical Wellness > amyloid proteins > brain aging > brain structure > cellular pathology > dementia > diagnostic marker > entorhinal cortex > mild cognitive impairment > neurodegenerative disease > neurodegenerative diseases > neurologic exam > supramarginal gyrus
Novel PET imaging agent could help guide therapy for brain diseases
03.04.2018 | Society of Nuclear Medicine and Molecular Imaging
New Computer Architecture: Time Lapse for Dementia Research
29.03.2018 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy