Spring 2017 4

Alzheimer’s and Dementia Testing for Earlier Diagnosis

Current diagnosis of Alzheimer’s relies largely on documenting mental decline. We now know that Alzheimer’s has already caused severe brain damage in individuals by the time they are diagnosed. But what if Alzheimer’s disease could be diagnosed before symptoms started? The hope is, future treatments could then target the disease in its earliest stages, before irreversible brain damage or mental decline has occurred. Research on new strategies for earlier diagnosis is among the most active areas in Alzheimer’s science. Here are some areas of early detection possibilities currently being investigated by researchers:

Biomarkers: Experts believe that biomarkers (short for “biological markers”) offer one of the most promising paths. A biomarker is something that can be measured to accurately and reliably indicate the presence of disease. An example of a biomarker is fasting blood glucose (blood sugar) level, which indicates the presence of diabetes if it is 126 mg/dL or higher. Recent research suggests that these indicators may change at different stages of the disease process. There are currently no validated biomarkers for Alzheimer’s disease, but researchers are investigating several promising candidates, including brain imaging, proteins in cerebrospinal fluid, proteins in blood and genetic risk profiling.

Brain imaging/neuroimaging: Neuroimaging is among the most promising areas of research focused on early detection. Today, a standard workup for Alzheimer’s disease often includes structural imaging with magnetic resonance imaging (MRI) or computed tomography (CT). These tests are currently used chiefly to rule out other conditions that may cause symptoms similar to Alzheimer’s but require different treatment. Structural imaging can reveal tumors, evidence of small or large strokes, damage from severe head trauma or a buildup of fluid in the brain.
Functional imaging research with positron emission tomography (PET) and other methods suggests that those with Alzheimer’s typically have reduced brain cell activity in certain regions. For example, studies with fluorodeoxyglucose (FDG)-PET indicate that Alzheimer’s disease is often associated with reduced use of glucose (sugar) in brain areas important in memory, learning and problem solving. However, as with the shrinkage detected by structural imaging, there is not yet enough information to translate these general patterns of reduced activity into diagnostic information about individuals.
Molecular imaging technologies are among the most active areas of research aimed at finding new approaches to diagnose Alzheimer’s in its earliest stages. Molecular strategies may detect biological clues indicating Alzheimer’s is under way before the disease changes the brain’s structure or function, or takes an irreversible toll on memory, thinking and reasoning. Molecular imaging also may offer a new strategy to monitor disease progression and assess the effectiveness of next-generation, disease-modifying treatments.

Cerebrospinal fluid (CSF) proteins: CSF is a clear fluid that bathes and cushions the brain and spinal cord. Adults have about 1 pint of CSF, which physicians can sample through a minimally invasive procedure called a lumbar puncture, or spinal tap. Research suggests that Alzheimer’s disease in early stages may cause changes in CSF levels of tau and beta-amyloid, two proteins that form abnormal brain deposits strongly linked to the disease. One challenge researchers face is that analysis of protein levels in the same sample often varies significantly from institution to institution. Achieving consistent measurement is a barrier that has been overcome in other medical conditions by using a standard procedure protocol and comparing results from the same sample at multiple sites designated as reference laboratories.

Proteins in blood or other parts of the body: Researchers are also investigating whether presymptomatic Alzheimer’s disease causes consistent, measurable changes in urine or blood levels of tau, beta-amyloid or other biomarkers. In addition, scientists are exploring whether early Alzheimer’s leads to detectable changes elsewhere in the body.

Genetic risk profiling: Scientists have identified three genes with rare variations that cause Alzheimer’s and several genes that increase risk but don’t guarantee that a person will develop the disease. Investigators worldwide are working to find additional risk genes. As more effective treatments are developed, genetic profiling may become a valuable risk assessment tool for wider use. Genetic testing for APOE-e4, the strongest risk gene, is included in some clinical trials to identify participants at high risk for the disease. APOE-e4 testing is not currently recommended outside research settings because there are no treatments yet available that can change the course of Alzheimer’s.

For more information on Alzheimer’s testing and videos on the topics described above, visit http://www.alz.org/research/science/earlier_alzheimers_diagnosis.asp

Source: Alzheimer’s Association www.alz.org