TESTING FOR ALZHEIMER’S

One of the insidious aspects of Alzheimer’s is that most people are only motivated to undergo testing for the disease after they have begun experiencing clear symptoms of Alzheimer’s.

For both individuals with a higher risk of developing the disease as well as individuals with no known elevated risk factors, there are now several ways to detect Alzheimer’s even before symptoms become apparent.

According to the Alzheimer’s Association[1], these are several ways to diagnose the disease:

  1. Biomarkers
  2. Brain imaging
  3. Proteins in the cerebrospinal fluid (CSF)
  4. Proteins in the blood
  5. Genetic risk profiling
  6. Symptoms analysis

Biomarkers

Currently, there are four known[2] biomarkers that can be tested for that have been validated as indicative of the presence of Alzheimer’s disease.

Biomarkers are things that can be measured inside the body that indicate the presence of a disease, the same way that body temperature is a biomarker that indicates that an individual has a fever.

Together, the levels of the biomarkers in your blood are a very useful way for your doctor to identify the presence of Alzheimer’s as well as track its progress over time.

Brain Imaging

This refers to either a PET (positron emission tomography), CAT (computed tomography) or an MRI (magnetic resonance imaging) scan that creates a map of the interior of the brain.  As Alzheimer’s is a disease that causes physical changes inside the brain, advanced imaging tests can help locate the presence of characteristic symptoms of Alzheimer’s like large clumps of proteins, damage to the hippocampus, and shrinkage in certain areas of the brain.

PET scans work by injecting a special dye into your blood that has (mildly) radioactive tracers.  The PET scan then tracks the movement of the tracers, helping to build up a picture of how your tissues and organs (in particular, the brain) are working.  In 2012, the Food and Drug Administration (FRI) authorized a special tracer known as florbetapir F-18 (brand name Amyvid) for use in PET scans when diagnosing Alzheimer’s.  PET scans can reveal whether there are areas of the brain with reduced activity as well as the presence of amyloid beta proteins.

  • Brain imaging is just one tool used to help in determining a diagnosis of Alzheimer’s

A CAT scan (sometimes called CT scan)  uses X-rays to take many different “photographs” of the brain.  Later, a computer assembles these pictures together in order to get a three-dimensional image of the inside of the brain.  CAT scans can reveal key indicators of the presence of Alzheimer’s, such as the areas of the brain which have begun shrinking.

An MRI scan uses a magnetic field to “see inside” solid objects, including the brain.  By measuring minute changes in the magnetic alignment of hydrogen protons in the body, the MRI scan can create an extremely detailed image, including soft tissues like brain matter that are difficult to see with X-rays.

It’s important to note that brain imaging scans are not able to provide a conclusive diagnosis of Alzheimer’s.  Some people experience protein clumps and shrinkage in areas of their brain without ever experiencing the symptoms of mental decline associated with Alzheimer’s.  Instead, brain imaging is simply another tool for a doctor to use when diagnosing the presence or progression of Alzheimer’s.

Proteins in cerebrospinal fluid

The fluid circulating between the spinal cord and brain (CSF) is critically important for brain function. A procedure known as a spinal tap (sometimes called “lumbar puncture”) allows doctors to withdraw a sample of the CSF for further analysis.

Elevated levels of tau and phospho-tau, and reduced beta-amyloid 42, proteins in the CSF, are validated biomarkers of the presence of Alzheimer’s. The ATI (A-beta to tau index) is an established index providing strong evidence for or against Alzheimer’s disease, depending on the level of the index measured in your spinal fluid.

Proteins in the blood

Much like measuring the biomarkers tau and beta-amyloid in CSF, the presence of these same two proteins in the blood is also being researched to determine their efficacy in diagnosing Alzheimer’s. Recent evidence shows that measuring them in neural exosomes—tiny fragments in the blood that come from the brain—provides an accurate indication of the presence or absence of Alzheimer’s disease.

One of the most important biomarkers that has been validated to detect is the presence of the APOE-4 allele on chromosome 19. So far, this is the most conclusive genetic marker that has been shown to have a direct correlation to an increased risk of developing Alzheimer’s, a critically important step in early detection of risk for the disease.

Genetic risk profiling

There are three[3] known chromosomal variants associated with a person having an elevated risk of developing Alzheimer’s: mutations in the amyloid precursor protein (APP), two alleles of the PS (Presenilin) gene, and the Apolipoprotein E4 allele (APOE-4), the last of which is by far the most common connection to higher risk levels of developing Alzheimer’s. However, there are also many variants that are less common, but also associated with increased risk for Alzheimer’s, such as TREM2 and VDR, among many others. Most of these have more modest effects on risk than APOE-4 does.

A genetic risk profile is simply a way to measure a person’s risk of potentially developing Alzheimer’s, and is not a guarantee that the person will develop Alzheimer’s.  Many people with higher genetic risks of developing the disease never do, and conversely, a few with low risk will nevertheless develop Alzheimer’s.

Percentage of ApoE in the General Population

The combination we carry affects how our body processes food and reacts to the environment, creating unique risk profiles for different diseases. For example, while 25% of us have the 2/4, 3/4 or 4/4 combination, this carries a much higher chance of developing heart disease or Alzheimer’s – in the absence of a gene supportive environment.

Symptom analysis

Long before distinct symptoms of Alzheimer’s occur, doctors can use the presence of milder symptoms of cognitive decline as an additional tool in diagnosing the presence of the disease.  Mild impairment or degradation of cognitive function is common in many older people and does not automatically indicate that they are suffering from Alzheimer’s (or other related diseases like dementia).

Your doctor will interview you to get a detailed medical history in order to help determine whether any current symptoms of mental impairment could be indicative of the the presence of Alzheimer’s, including:

  • Having trouble remembering important information or data that they previously would have recalled easily.
  • Difficulty in making decisions, including how much time it takes to complete an action or mixing up the necessary steps to follow to complete a task.
  • Emotional changes, including struggles with depression and the sensation of feeling mentally “foggy”.

It is critically important to understand that it is the combined results from blood tests, brain scans, and symptoms analysis that will be used by your doctor when diagnosing the presence of Alzheimer’s.

[1] http://www.alz.org/research/science/earlier_alzheimers_diagnosis.asp

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467365/

[3] http://www.alz.org/research/science/alzheimers_disease_causes.asp#chromosomes