PET Measurements of the Hippocampus May Improve Alzheimer's Diagnosis

New evidence reveals that declines in regional cerebral glucose metabolism (rCMglc) in the brain as measured with positron emission tomography (PET) imaging have been demonstrated to correlate to the progression of Alzheimer's disease (AD), and to distinguish between dementias.

Recent studies have shown that the accuracy of Alzheimer's diagnosis may be improved by including measurement of rCMglc in the hippocampus (HIP), area of the brain that is critical to the formation of new memories. However, according to researchers, HIP rCMglc cannot be accurately and effectively sampled in broad populations using traditional techniques. This is because the hippocampus has an irregular shape and undergoes varying degrees of shrinkage during aging and when affected by disease, such as AD. Conventional analysis techniques rely on the ability to align images of each patient's brain to a template brain map, and there is loss of sensitivity and precision due to the difficulty of aligning this irregular shape.

Lisa Mosconi, Ph.D., and colleagues in the Center for Brain Health at New York University (NYU) School of Medicine (New York, NY, USA), directed by Mony de Leon, Ph.D., developed and evaluated an automated method that achieves accurate, rapid sampling of many brain regions, including the hippocampus. Dr. Matthews and her team collaborated with NYU to apply the automated method to 250 participants from the U.S. National Institute on Aging's (NIA) Alzheimer's Disease Neuroimaging Initiative (ADNI) database (78 female, 172 male, aged 59-88; 79 healthy, 111 with mild cognitive impairment (MCI), 60 with Alzheimer's). Using the automated approach, rCMglc was measured by PET in 32 brain regions. Participants were divided into seven subgroups across normal, MCI, and AD categories, based upon their initial diagnosis and results of subsequent memory and thinking tests up to three years after the scan.

The researchers observed a significant correlation between rCMglc in several brain regions and the progression from "stable normal” to "normal with subsequent clinical decline,” to subcategories of MCI and AD. They also found that HIP rCMglc was a sensitive predictor of decline and discriminator between disease stages. As compared to people considered "stable normal,” HIP rCMglc was reduced by 5% in "normal with subsequent clinical decline,” 12% in "stable MCI,” 14% in "MCI with subsequent clinical decline” (p < 0.05), and 24% in Alzheimer's (p < 0.001).

"We found that glucose metabolism levels were highest in the healthy participants who did not decline to MCI, lower in healthy people who later declined, and progressively lower in people with MCI who remained MCI, lower in MCI patients who declined to AD, and lowest in those with Alzheimer's,” Dr. Matthews said. "These results demonstrate the feasibility of achieving highly specific diagnosis by incorporating glucose metabolism measurements from the hippocampus.”

The ADNI is a US$60 million, five-year, public-private partnership developed to evaluate whether imaging technologies (such as MRI and PET), other biomarkers, and clinical and neuropsychologic assessment can be combined to measure progression toward AD.

The study's findings were reported July 14, 2009, at the Alzheimer's Association 2009 International Conference on Alzheimer's Disease (ICAD 2009) in Vienna, Austria. The main funding for the study came from Abiant, Inc. (Deerfield, IL, USA).

Related Links:
New York University School of Medicine