There is no definitive clinical test to diagnose dementing illnesses. The words probable or possible are usually attached to their clinical diagnosis.
Absolute diagnosis requires tissue examination on biopsy or at autopsy. Yet, as with any disease, early detection is critical to management. Differing forms of dementia must be distinguished from each other and from other neurologic conditions:
Knowing the type and severity of the patient's dementia aids prognosis, family counseling, and therapeutic intervention.
Current medical therapies treat symptoms, but the goal of dementia research is targeted, disease-altering drugs that could halt disease progression. Their development rests on understanding the mechanisms of the various dementias, on accurate diagnosis, and on noninvasive ways of monitoring outcomes in clinical trails. The eventual success of experimental therapies rests on early detection.
Neuroimaging is providing crucial information in all these areas and is benefiting ongoing patient care. Mayo Clinic has long been a world leader in imaging science. Using state-of-the-art equipment, researchers in the Mayo Clinic Imaging Research Center, housed in the new Opus Building on the Rochester, Minnesota, campus, are generating new algorithms and methods of interpreting neuroimages. They work closely with clinical specialists in dementia and with researchers in Mayo's Alzheimer's Disease Research Center (ADRC), funded by the National Institutes of Health.
Neuroimaging for the dementias includes various magnetic resonance (MR) and nuclear medicine techniques. The glossary summarizes imaging techniques applicable to dementia.
As Clifford R. Jack Jr, M.D., the radiologist who directs Mayo's neuroimaging research, notes, "Each imaging technique measures something different about what happens to the brain in the face of pathologic changes associated with a dementing syndrome. Each can provide information about severity, the type of dementia, and specific brain regions involved."
An image is only as good as its interpretation. Dr. Jack, Val Lowe, M.D., whose focus is nuclear medicine imaging, and their colleagues are developing new analytic tools or algorithms to refine and transform images into ever more precise and useful information. For example, they are currently updating ways to quantify MRI FLAIR sequencing and to make MR perfusion techniques increasingly applicable to dementia.
Mayo scientists are investigating the latest techniques to identify type and severity of dementia:
Dr. Jack and Ronald C. Petersen, M.D., Ph.D., head of Mayo's ADRC, agree that amyloid imaging could revolutionize diagnosis and management. Of particular note is its ability to distinguish AD from FTD and its potential use as an outcome measure in clinical trials aimed at reducing amyloid deposition.
DAT is a SPECT tracer that binds to dopamine receptors in the basal ganglia. It is not yet used in the United States, but is being considered for research studies at Mayo Clinic to identify DLB.
In MR perfusion studies, ASL is a noninvasive way to measure brain perfusion that is similar to the physiologic information obtained from FDG PET.
This type of fMRI indirectly measures the degree to which different brain regions are functionally connected but does not require the patient to perform a task. When combined with amyloid imaging, areas active during the resting state in patients with AD mirror areas that are susceptible to amyloid deposits.
Equally important, resting state functional connectivity appears to measure the strength of functional (vs anatomic) connectivity, demonstrating differing patterns of functional loss relative to severity and dementia type.
Future goals for the field include developing a tau protein tracer and one specific to the abnormal protein aggregates associated with DLB and (AD).
Dr. Petersen was the lead investigator in the identification of MCI, a memory disorder considered a precursor to dementia. It begins with abnormalities in the hippocampus which are visible on structural MRI and critical for early detection. Even now, early detection and differential diagnosis through imaging help determine therapy type. "For example," Dr. Petersen states, "one wouldn't give a cholinesterase inhibitor that might work in AD to a patient with FTD. Similarly, one wouldn't give a patient with DLB a dopamine blocker."
Patients have been actively recruited into ADRC studies. A major goal of imaging research and the ADRC is to identify patterns of disease, work that is being led by Mayo researcher Prashanthi Vemuri, Ph.D. Many patients with dementia have combined pathologies (eg, a combination of Lewy bodies, vascular disease, and amyloid deposition).
Identifying the predominant pathology and lesser ones will permit specifically tailored drug combinations. Advances in neuroimaging are critical to achieving this and other intervention goals.
A measure of gross brain anatomy used to detect the presence or absence of atrophy in areas specific to AD, including mesial-temporal lobe structures such as the hippocampus. With disease progression, areas of abnormal atrophy can include the basotemporal lobes, the posterior cingulate, paralimbic cortex, and, eventually, the temporoparietal association areas.
FLAIR imaging helps determine if cognitive changes reflect cerebrovascular disease.
This technique measures the concentration of specific metabolites relevant to AD and other dementias, including N-acetylaspatate (NAA) and myo-inositol. Decrease in NAA is thought to reflect neuron loss in AD. Serial MRS has been used to measure outcomes in clinical trials.
Both techniques measure microscopic diffusion of water molecules in biologic tissue. It is thought that AD disrupts cell membranes, thus increasing the diffusion coefficient of water and decreasing the coherence of directional water diffusion due to loss of neuronal track integrity. Brain maps made from DTI images can illuminate regions of connectivity and loss of connectivity among brain structures.
This MRI technique measures regional cerebral perfusion. In AD it shows a bilateral temporal-parietal decrease in blood flow, consistent with perfusion patterns in single-photon emission computed tomography (SPECT) studies and with decreased cerebral glucose metabolism on fluorodeoxyglucose positron emission tomography (FDG PET) studies.
This is an MRI-based measure of cerebral blood flow volume in activated brain regions during functional tasks. Because it requires that the subject perform a directed cognitive task while in the MRI magnet, it is not particularly effective in patients with moderate to severe dementia. However, it has been used to help diagnose MCI and to study patients thought to be at risk. To date, at-risk patients and those with forms of MCI show both increased and decreased activation relative to controls.
A nuclear medicine-based method of labeling amyloid plaques. The most common binding compound used in Pittsburgh compound B (PiB). Positive PiB uptake occurs in brain regions known to be areas of plaque distribution in AD (eg, frontal lobes, posterior cingulate gyrus, and temporal parietal association cortex).