WASHINGTON – Imaging techniques designed to enable identification of preclinical Alzheimer's disease were showcased in numerous presentations at an international conference sponsored by the Alzheimer's Association.
Preclinical Biochemical Changes
Using magnetic resonance spectroscopy (MRS), researchers in the United Kingdom identified biochemical changes in the posterior cingulate in a group of symptom-free subjects genetically destined to develop Alzheimer's disease (AD).
The researchers imaged seven volunteers with familial AD, who carry presenilin 1 and amyloid precursor protein gene mutations and have an almost 100% chance of developing AD, according to Alison Godbolt, M.B., of the Dementia Research Centre at University College, London.
At the time of the study, these individuals had normal memory. Six healthy volunteers without familial AD were also recruited to serve as controls.
MRS provides information about select chemicals in a specific area of the brain that are involved in metabolism. MRS is performed using the same scanners as magnetic resonance imaging (MRI) and takes about 45 minutes.
The researchers looked at a single voxel along the midline of the posterior cingulate, a region that is known to be involved in AD. They measured the ratio of n-acetylaspartate to creatine and the ratio of myo-inositol to creatine.
Subjects with the genetic mutation had n-acetylaspartate/creatine ratios that were 10% lower and myo-inositol/creatine ratios that were 20% greater than those of the control group. The difference in the myo-inositol/creatine ratios between the two groups did not reach statistical significance. “Interestingly, other researchers have found the same changes in people who already have the disease,” Dr. Godbolt said.
Reduced levels of n-acetylaspartate are thought to be due to nerve cell dysfunction and loss; increased myo-inositol levels are thought to be due to increased inflammation. In addition, the volunteers with the gene mutation who were closest to their predicted age of onset had the most abnormal levels of these two chemicals, “suggesting a gradual buildup of changes over the several years before symptoms begin,” she said.
Screening via Hippocampal Size
Reduced hippocampal volume on MRI, combined with the results of the Mini Mental State Examination (MMSE), appears to do a better job of identifying patients with mild cognitive impairment (MCI) and AD than MMSE alone, according to a poster presented by Claire K. Sandstrom, who is a medical student at Duke University in Durham, N.C., and her colleagues.
Several recent studies have shown that individuals with MCI have smaller hippocampal volumes on MRI, compared with healthy controls. This is especially true for those subgroups of individuals with MCI, who later convert to AD.
The researchers evaluated 18 volunteers (11 men) with MCI and 17 volunteers (8 men) with normal cognition with the MMSE and MRI. Those with MCI were age 74 years on average and had a mean MMSE score of 27, while the control group was age 70 years on average and had a mean score of 28, Ms. Sandstrom told this newspaper.
Hippocampal atrophy was greater in the volunteers with MCI than in the controls. Left hippocampal volume was significantly smaller than on the right only in people with MCI.
The researchers developed receiver operating characteristic curves to evaluate the ability of left hippocampal volume, right hippocampal volume, MMSE score, and the combination of left hippocampal volume and MMSE score to accurately identify patients with AD and MCI. After analyzing these curves, the researchers concluded that left hippocampal volume was superior to MMSE alone in identifying patients with AD and MCI. “Left hippocampal volume added significantly to the discriminatory capacity of the MMSE scores for differentiating between cognitively normal individuals and those with MCI,” the authors wrote.
DTI Reveals Brain Changes in MCI
Researchers have identified changes in the left and right anterior hippocampus and amygdala in patients with MCI and in those with mild cognitive complaints but not in cognitively normal subjects, using diffusion-tensor imaging (DTI).
The researchers imaged 27 individuals with MCI (mean age 74 years), 25 individuals with cognitive complaints (mean age 73 years), and 33 healthy controls (mean age 72 years), according to a poster presented by John D. West of the Brain Imaging Lab at Dartmouth College in Hanover, N.H., and his colleagues.
The participants were drawn from the ongoing Dartmouth Memory and Aging Study. The groups were balanced for age, education, and sex. They also were assessed using the California Verbal Learning Test.
DTI reveals disruptions of the white matter tracts that are not visible on MRI. Within white matter, water moves parallel to tracts. Conventional MRI can distinguish white from gray matter but can provide very little detail about the white matter; MRI cannot observe or quantify specific fiber tract directions.