Mild Cognitive Impairment Symposium: Diagnosis

At a 2003 international conference, researchers agreed that a person can be diagnosed with Mild Cognitive Impairment (MCI) if he:

• Is neither “normal” nor has dementia
• Complains about cognitive problems, and those problems have gotten worse over time
• Is still able to carry out daily activities.

These criteria, still in use today, weren’t very specific, because there wasn’t enough evidence to recommend specific tests or decide what scores on those tests should be the boundary between “normal” cognition and MCI. 

So for now, the diagnosis depends somewhat on doctors’ judgment.  But research on testing for MCI continues, and presenters at the 7th Annual Mild Cognitive Impairment Symposium gave updates on neuropsychological tests and brain scans. 

Neuropsychological Tests

Neuropsychological tests are designed to measure and categorize problems with memory and thinking.  The Mini-Mental Status Exam, or MMSE, often used to screen for dementia, may not be sensitive enough to detect mild memory loss. Another test, called Montreal Cognitive Assessment (MoCA), may be better at screening for MCI, but is not widely used.

Dr. David Loewenstein, Director of Research and Neuropsychology at the Wien Center for Alzheimer’s Disease and Memory Disorders and Professor of Psychiatry and Behavioral Sciences at the University of Miami, gave a presentation on detecting mild memory loss at last month’s MCI Symposium.  He said that the neuropsychological tests typically used to detect mild memory loss don’t work very well because:

1. they compare a person’s performance with that of a control group of people the same age.  Dr. Loewenstein questions whether people in the control group are “normal” for their age.   A person’s test results would be more valid if they could be compared with his own performance on the same tests at an earlier point in time, but that’s not usually possible for someone with mild memory loss.
2. test results can be affected by education, primary language, gender, cultural or other factors which are not related to problems with memory and thinking
3. tests do not usually parallel the real world, where people must “remember to remember”
4. people with mild memory loss tend to have good days and bad days, so they might do very well on standard tests on a “good” day.

If we are to detect mild memory loss (perhaps even a stage that might precede MCI), then we need to take a new approach to neuropsychological testing, Dr. Loewenstein said.    One such approach may be “semantic interference” tests, which he and his colleagues have found to be much more sensitive to mild memory loss than other more commonly used tests.  Semantic interference is the disruption of learning due to the presence of information similar to the information being learned.

Dr. Loewenstein and colleagues have developed one such test, the Florida Brief Memory Scale (FBMS), in which the person being tested is given a list of 15 objects that fall into three categories.  Then he is given a second list of 15 objects that fall into the same three categories as the first list.  Finally, he is asked to remember the items on the first list.  The “interference” of the second list causes terrible problems for people with Amnestic MCI, Dr. Loewenstein said.

The initial FBMS screen takes only three minutes (the interference portion takes an additional ten minutes), and is not affected by factors such as education, gender, age or language.

While FBMS is promising for detecting Amnestic MCI, more research is needed, particularly on tests to detect Non-Amnestic MCI.  In an email conversation after the Symposium, Dr. Loewenstein said he and his colleagues plan to team up with researchers at Albert Einstein College of Medicine to continue to study this and other methods of detecting early cognitive problems.

Brain Scans

Jennifer Whitwell, Ph.D.

Jennifer Whitwell, Assistant Professor of Radiology at Mayo Clinic, gave a presentation on brain scans, or neuroimaging, at the MCI Symposium.  While there’s not enough evidence to make a diagnosis of MCI based on a brain scan, results of these tests can provide information on changes in the brain over time, as well as hints about what might be causing a person’s problems with memory and thinking.  They may also suggest whether those problems are likely to get worse over time (I’ll write about this in a later report).

Characteristics of the brain that may help with a diagnosis of MCI and can be seen on brain scans include:

•    Shrinkage, or atrophy, in various regions of the brain (seen on MRIs)
•    Metabolite levels (seen using Magnetic Resonance Spectroscopy or MRS)
•    Abnormal amyloid protein deposits (seen on PET scans using PIB “tracers”)
•    Metabolism patterns (seen on PET Scans).

Dr. Whitwell focused her talk on the first three characteristics above.

Atrophy

Atrophy of the brain, especially of the medial temporal lobe, is associated with Amnestic Mild Cognitive Impairment.  There’s no agreement on which structures in the medial temporal lobe might be the best indicators of MCI.  Researchers at Kupio University in Finland found that atrophy of an area called the entorhinal cortex is the best sign of early memory problems, while Mayo Clinic researchers found that atrophy of the hippocampus is an equally good indicator.  Along with his colleagues, Dr. Ranjan Duara, who organized the MCI Symposium, has concluded a specific method of measuring atrophy in the entorhinal cortex is best for distinguishing MCI from normal memory and thinking.

The association of atrophy and Non-Amnestic MCI is less clear, although the medial temporal lobe does not appear to be the focus of atrophy in Non-Amnestic MCI, said Dr. Whitwell.

Metabolism and Metabolites

The term metabolism generally refers to the processes in the body that break down nutrients to create energy.  Brain cells use oxygen and glucose (sugar) to create energy, and the use of these nutrients can be seen on PET scans.  Areas of the brain where there is reduced use of these nutrients may not be functioning well.

Metabolites are chemicals left behind by metabolism, and can show what processes are taking place in cells.  Research at Mayo suggests that the patterns of certain metabolites in people with Amnestic MCI are similar to those in people with Alzheimer’s.  Chinese researchers have also found metabolites to be useful in diagnosing MCI.

Additional research at Mayo has shown that these metabolite patterns are not present in people with Non-Amnestic MCI, perhaps because cognitive problems are caused by neurodegenerative diseases other than Alzheimer’s, or by vascular disease.

PiB

Imaging using Pittsburgh Compound B (PiB) can show the amount and distribution of the amyloid deposits in the brain associated with Alzheimer’s.  Dr. Whitwell said that Mayo researchers have found the amount of amyloid for someone with Amnestic MCI can be similar to that of people with Alzheimer’s or similar to people with “normal” memory and thinking, with the average value lying between that of people with Alzheimer’s and that of people with “normal” memory and thinking.  For both cognitively normal people and people with Amnestic MCI, though, the level of amyloid shown with PiB didn’t seem to make much difference in learning and memory. 

So far, imaging with PiB cannot be used to make a definitive diagnosis of Mild Cognitive Impairment.   A study by Australian scientists suggests that only 60% of people with MCI have Alzheimer’s-like amyloid deposits as shown by PiB (the remaining 40% were normal).  Of course, detecting amyloid deposits may not be as useful if diseases other than Alzheimer’s are causing or contributing to impairment. 

Research at Mayo also suggests that imaging with PiB is not useful for diagnosing Non-Amnestic MCI.

Comments

[Gail Rae Hudson]

Got a question regarding the various types of brain scans. Maybe the answer was implied in the article but flew by me. Here's my question (it's a triad but essentially the same question): What is considered a baseline for determining atrophy, lowered metabolic activity and amounts of amyloid? Are these baselines objectively established, i.e., based on scans of what we consider healthy brains, or are they established based on individual patient history? Is there any discussion anywhere about the efficacy of objective baselines versus personal baselines, considering that there probably isn't enough data on most people to establish a personal brain scan baseline of any type?
Are my questions making sense? Are they, indeed, the same question? (Grinning here...)