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Earlier Diagnosis

What if we could diagnose Alzheimer's disease 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, and funding from the Alzheimer's Association has spurred significant advances and steady progress.

Biomarkers for earlier detection

Current diagnosis of Alzheimer's disease relies largely on documenting mental decline, at which point, Alzheimer's has already caused severe brain damage. Researchers hope to discover an easy and accurate way to detect Alzheimer's before these devastating symptoms begin.

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, such as fasting blood glucose (blood sugar) level, which indicates the presence of diabetes if it is 126 mg/dL or higher.

Several potential biomarkers are being studied for their ability to indicate early stages of Alzheimer's disease. Examples being studied include beta-amyloid and tau levels in cerebrospinal fluid (CSF) and brain changes detectable by imaging. Recent research suggests that these indicators may change at different stages of the disease process.

Before a biomarker can be used in medical clinics, it must be validated, in which multiple studies in large groups of people establish that it accurately and reliably indicates the presence of disease. Furthermore, the laboratory methods used to measure the biomarker must be shown to be stable and reliable.

There are currently no validated biomarkers for Alzheimer's disease, but researchers are investigating several promising candidates, including brain imaging, proteins in CSF, blood and urine tests, and genetic risk profiling.

Brain imaging/neuroimaging

Neuroimaging is among the most promising areas of research focused on early detection of Alzheimer's disease.

Structural imaging

Having shown that the brains of people with Alzheimer's shrink significantly as the disease progresses, structural imaging research also has shown that shrinkage in specific brain regions such as the hippocampus may be an early sign of Alzheimer's. However, scientists have not yet agreed upon standardized values for brain volume that would establish the significance of a specific amount of shrinkage for any individual person at a single point in time.

Today, a standard workup for Alzheimer's disease often includes structural imaging, and these tests are currently used 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

Functional imaging research 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 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

These 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. Several molecular imaging compounds are being studied, and three have been approved for clinical use:

Florbetaben (Neuraceq®), Florbetapir (Amyvid®) and Flutemetamol (Vizamyl®) have been approved for detection of beta-amyloid in the brain.

Even though amyloid plaques in the brain are a characteristic feature of Alzheimer's disease, their presence cannot be used to diagnose the disease. Many people have amyloid plaques in the brain but have no symptoms of cognitive decline or Alzheimer's. Because amyloid plaques cannot be used to diagnose Alzheimer's, amyloid imaging is not recommended for routine use in patients suspected of having the disease.

In addition, clinical trials are underway testing radiotracers for the protein tau, which is present in abnormally large quantities in the brains of people with Alzheimer’s.

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