CHAPTER 3

WHAT TROUBLE LOOKS LIKE

HOW BRAIN IMAGING CHANGES EVERYTHING

Take away the brain, you take away the person.

MARIAN DIAMOND, PHD, UC BERKELEY

If you knew a train was going to hit you, would you get out of the way? A news story described the plight of two women trapped on an 80-foot-high railroad bridge in Indiana as a freight train barreled toward them. There was no way they could get out of its path! Ultimately, the women survived by lying down flat in the middle of the tracks, but what were they doing on an active railroad bridge with no escape route? I often include this story when I lecture because it reminds me of how blind most people are to the health of their brains. Like the women on the tracks, they are heading down a potentially deadly path. If you knew brain problems were coming for you, would you start making better decisions today to get out of the way?

All of us need a baseline brain health assessment to find out if our brains are in trouble. Unfortunately, this is rarely done. When I turned 50, my doctor wanted me to have a colonoscopy. I asked him why he didn’t want to look at my brain. “Isn’t the other end of my body just as important?” I asked. From colonoscopies and cardiac stress tests to mammograms and pap smears, baseline testing and preventive screening are done for most organs except the most important one —the organ that runs your life. That is just plain wrong when illnesses like Alzheimer’s disease that rob people’s very souls are expected to skyrocket in the coming decades.

This chapter will explore the early warning signs of trouble, a simple computerized test that can help you evaluate your cognitive abilities, and the brain imaging tests we use at Amen Clinics. Even if you never get a brain scan, the lessons they have taught us provide the foundation for Memory Rescue.

At Amen Clinics, the first thing we do when we meet a new patient is take a very detailed history. Understanding the story of a person’s life is critical to getting the right diagnosis and developing an effective treatment plan. Since problems in the brain typically start years before people have any symptoms, it is essential to understand the early warning signs.

It’s like the boiling frog analogy: If a frog is put suddenly into boiling water, it will jump out; but if the frog is put in cold water that is very gradually brought to a boil, it will not perceive the danger and will be cooked to death. We and our family members tend either to miss or discount the small, incremental changes that taken together can add up to significant problems.

A simple way to avoid making this mistake is to take a self-assessment regularly, beginning now and then every year hereafter. It highlights the most significant early warning signs of memory problems.

AMEN CLINICS’ EARLY WARNING SIGNS QUESTIONNAIRE

Rate each question on a scale of 0–4, from Never (0) to Very Frequently (4).

• 0: Never
• 1: Rarely
• 2: Occasionally
• 3: Frequently
• 4: Very Frequently

Memory issues

1. 1. ___ Tend to be forgetful?
2. 2. ___ Notice that your memory, which has never been good, is getting worse?
3. 3. ___ Misplace your keys or wallet?
4. 4. ___ Wonder why you came into a room?
5. 5. ___ Have trouble remembering names?
6. 6. ___ Feel embarrassed by forgetting appointments?
7. 7. ___ Read a book or an article, but don’t remember much of it?
8. 8. ___ Have trouble remembering things that happened recently?
9. 9. ___ Struggle with brain fog?
10. 10. ___ Have trouble remembering to consistently take medications or supplements?
11. 11. ___ Rely more and more on memory aids or reminders on your phone?
12. 12. ___ Know something one day but forget it the next?
13. 13. ___ Forget what you’re going to say right in the middle of saying it?
14. 14. ___ Have trouble following directions that have more than one or two steps?
15. 15. ___ Suspect that your memory is worse than it was 10 years ago?
16. 16. ___ Lose track of the conversation?
17. 17. ___ Find things in unusual places, like your keys in the refrigerator?
18. 18. ___ Get mad at others, thinking they took your things, only to find out later you misplaced them?

Trouble planning and problem solving

1. 19. ___ Have trouble making plans and sticking to them?
2. 20. ___ Find it harder to follow a recipe or directions on how to put something together?
3. 21. ___ Find it hard to focus on more complex tasks, especially those that involve math? For example, are you struggling with managing your bills or balancing your checkbook?

Confusion with times and places

1. 22. ___ Have trouble driving to locations that had been familiar to you?
2. 23. ___ Get easily confused or out of sorts?
3. 24. ___ Get lost more easily or have to rely on GPS more than before?

Struggle with words

1. 25. ___ Have more trouble finding the right word?
2. 26. ___ Call things by the wrong name?
3. 27. ___ Limit conversation with people, rather than join in?
4. 28. ___ Have trouble following along in conversations?
5. 29. ___ Keep repeating yourself?

Worsening judgment

1. 30. ___ Struggle with making more bad decisions?
2. 31. ___ Make mistakes with your finances?

Social withdrawal

1. 32. ___ Feel more isolated from friends?
2. 33. ___ Feel like cutting back at work because you just don’t care as much?
3. 34. ___ Feel less interested in activities you usually find fun?
4. 35. ___ Take less care of your physical appearance?

Scoring:

Add up the number of questions that you answered 3 (Frequently) or 4 (Very Frequently).

• 0     low risk of significant memory issues

• 1–2   mild risk of significant memory issues
• 3–5   moderate risk of significant memory issues
• 6+     high risk of significant memory issues

Of course, everyone should take brain health and our BRIGHT MINDS approach seriously; the higher you score, the more serious you should be. If you are at moderate to high risk, it is important to get a thorough medical evaluation.

A RELIABLE COGNITIVE TEST

Several online cognitive tests can give you a sense of how well your brain is functioning compared to an age-matched group. At Amen Clinics, we use a comprehensive online test called Brain Fit WebNeuro that measures a wide range of cognitive and emotional functions. It takes about 35 minutes to complete and provides an objective assessment of how your brain works in 17 specific areas, scoring each one on a scale of 1 to 10. The test also generates an overall brain health score. Specifically, it measures:

1. Motor coordination
2. Processing speed (how quickly you process information)
3. Sustained attention (ability to maintain focus)
4. Controlled attention (ability to stop reactions when needed)
5. Flexibility (shifting attention)
6. Inhibition (self-control)
7. Working memory (ability to hold information for short periods)
8. Recall memory (ability to remember information)
9. Executive function (ability to plan and organize information)
10. Identifying emotions (reading faces)
11. Emotion bias (impact of emotions on decision making)
12. Stress level
13. Anxiety level
14. Depressed mood
15. Positivity-negativity bias (tendency to notice positive or negative emotions)
16. Resilience (coping during times of trial)
17. Social capacity (building and keeping relationships)

You can take this test through our online Brain Fit Life program (www.mybrainfitlife.com). It will provide you with a baseline score and, with retesting, a way to find out over time if your brain function is getting better or worse. Based on your scores, our program recommends targeted exercises in the form of fun brain games to strengthen vulnerable areas.

Determining the health of your brain with baseline testing is a critical strategy to keeping it strong over the long run. Studies have found that adding a brief objective assessment tool can improve early detection of trouble by more than nine times![15] New research shows that it is possible to detect the seeds of Alzheimer’s disease in lower memory and thinking scores obtained up to 18 years in advance of a diagnosis,[16] when it is more likely that something can be done about it.

If you are at moderate or high risk for memory problems, consider taking the Brain Fit WebNeuro test every few months to chart your progress. I also recommend everyone 40 or older take this test annually to spot issues early. Baseline testing and regular checkups can also help you uncover problems when they first appear.

EXAMPLE OF WEBNEURO RESULTS

Be concerned about any individual scores below 5. In this example, there are issues with working memory and executive function (judgment). Emotion bias, stress, anxiety, depression, negativity, low resilience, and social isolation also seem to be issues, which can weaken memory.

AMEN CLINICS’ BRAIN IMAGING TOOLS

There are several ways to look at your brain if you are concerned about your memory. Most physicians will order an imaging study, such as an MRI or CT scan, which looks at the structural integrity of the brain. Most of these studies are read as normal, or as “mild atrophy (shrinkage) consistent with aging.”

In my experience, functional brain imaging studies, like SPECT, PET (positron-emission tomography), or QEEG (quantitative electroencephalogram) are more useful, because functional problems almost always precede structural ones. These studies typically show problems before symptoms occur, which is when treatment is likely to be most helpful.

Functional studies are leading indicators of problems, meaning they show evidence of the disease process years before people show signs of it. Anatomical studies, such as CT and MRI, are lagging indicators. They show problems later in the course of the illness, when interventions tend to be less effective.

At Amen Clinics, we find two functional brain imaging studies particularly helpful.

1. Brain SPECT imaging: This scan looks at blood flow and activity patterns and shows us areas of the brain that are functionally healthy, underactive, or overactive.
2. QEEG testing: This scan shows the electrical activity in the brain.

Due to cost, PET scans are not commonly used, though they are sometimes used to detect plaques in the brain associated with Alzheimer’s disease (see “What about Amyloid Imaging with PET Scans?” on page 38).

Brain SPECT imaging: seeing is believing

I became hooked on functional imaging, and SPECT in particular, because it made me a better doctor. In 1991, I went to my first lecture on brain SPECT imaging given by Jack Paldi, MD, a forward-thinking nuclear medicine physician. Dr. Paldi told us that SPECT could give us more information to help our patients. In fact, the scan results of eight of the first ten patients for which I ordered SPECT led me to change what I did for them. When it came to memory problems, the story of one woman remains deeply embedded in my own memory. In fact, I talk about her often because her case helped convince me of how invaluable SPECT can be.

Dementia: Not Just Alzheimer’s

Alzheimer’s is the most common type of dementia —estimated to account for 60 to 80 percent of cases. Widespread damage occurs in the brain as neurons die after they stop functioning and connecting with other neurons. However, other forms of dementia also create serious problems. They include:

• Vascular dementia, the second most common type of dementia, typically occurs as a result of one or more strokes that have created blockages to the brain’s blood vessels.
• Lewy body dementia refers to both Parkinson’s disease and dementia with Lewy bodies, abnormal protein deposits that disrupt the brain’s normal functioning.
• Frontotemporal lobe dementia is caused by progressive nerve cell loss in the frontal or temporal lobes, stemming from various uncommon disorders that cause the affected lobes to atrophy.

Margaret: was it really Alzheimer’s?

Margaret, 68, had been diagnosed with Alzheimer’s disease by her family physician. She wanted to continue living independently, but her five daughters were afraid for her and wanted her to move into a supervised senior living facility. After Margaret left something burning on the stove —nearly burning down her home as a result —she was admitted to the hospital. Her family wanted her evaluated one more time before seeking a legal custody order to force her into supervised living.

When I first evaluated Margaret in the early 1990s, she appeared to have Alzheimer’s disease. She was seriously forgetful, neglecting her appearance, and frequently getting lost driving. However, when I studied her SPECT scan, I realized that her brain did not look like one affected by Alzheimer’s disease. The scientific literature in the late 1980s had described Alzheimer’s as decreased blood flow in the parietal and temporal lobes. Those areas of Margaret’s brain looked fine. But she had marked increases in blood flow in the emotional part of her brain.

Based on her scan, I suspected Margaret had something called pseudodementia, which is depression that results in dementia-like symptoms. I prescribed the stimulating antidepressant Wellbutrin (bupropion), hoping for the best. Within three weeks, Margaret had dramatically improved. She was much more talkative, took better care of her appearance, and even led cooking classes in the hospital. I have never forgotten her amazing transformation. She lived independently for another 15 years.

MARGARET’S BRAIN SPECT SCAN

Full, even, symmetrical activity not typical of Alzheimer’s

Increased activity in the emotional brain

Normal active scan: In a healthy SPECT scan, the most active areas are in the back part of the brain in the cerebellum.

Brain SPECT imaging has taught me that there are many treatable causes of memory problems. But if you never look at how the brain functions, you will never know how to address them. Too many people diagnosed with Alzheimer’s disease or other forms of dementia have potentially treatable problems —and may not even have a true form of dementia. A 2017 study from the University of California at San Francisco using PET imaging drives this point home: When the researchers scanned 4,000 patients with mild cognitive impairment or dementia for the amyloid plaques that can be a sign of Alzheimer’s, they discovered that just 54.3 percent of those with MCI and 70.5 percent of dementia patients had the plaques. Those who tested negative for the plaques —including some who’d been diagnosed with Alzheimer’s —definitely did not have AD. Doctors altered the treatment for two-thirds of the enrolled patients as a result of the imaging.[17]

I learned early on that SPECT imaging can also be a useful tool when trying to distinguish Alzheimer’s from other forms of dementia. That brings me to another case that was key to my understanding of SPECT imaging’s potential.

Ed: the sign of the lobster

Ed, 72, came to Amen Clinics because his daughter Candace was concerned about his forgetfulness. His mood and judgment were poor, and when Candace looked at his finances, she discovered he had paid some bills twice and forgotten others. The local neurologist diagnosed Ed with Alzheimer’s disease. Candace had read about SPECT imaging in my book Change Your Brain, Change Your Life and was unhappy that the doctor had made that diagnosis without ordering a scan. She then brought Ed to see us.

ED’S BRAIN SPECT SCAN

The image shows slices from the top to the bottom of the brain. Slices 15 and 16 show the “lobster sign,” which suggested that Ed was suffering from a condition other than Alzheimer’s.

Ed’s SPECT scan revealed very large ventricles, or fluid-filled cavities, in his brain. I have labeled this pattern the “lobster sign” because it looks like an upside-down lobster in the brain slice images on page 36. The scan also revealed low activity in Ed’s cerebellum (base of his brain). Ed definitely did not have the typical Alzheimer’s pattern.

NORMAL BRAIN SPECT SCAN

Full, even, symmetrical activity

ED’S BRAIN SPECT SCAN

Not typical Alzheimer’s pattern, but large ventricles (middle hole) and small cerebellum (bottom)

The reason finding the large ventricles was so important was that it is a classic sign of normal pressure hydrocephalus, or NPH. In this condition, the normal drainage of cerebrospinal fluid is gradually blocked. As a result, excessive fluid builds up slowly, over time. This disorder is often, but not always, accompanied by urinary incontinence and trouble walking. Because Ed did not have those other symptoms, his neurologist never suspected NPH. Subsequently, Ed’s brain continued to deteriorate. Upon seeing his scan, I recommended Ed have an immediate neurosurgical consultation. The neurosurgeon agreed with me and placed a shunt in Ed’s brain. Within three weeks, Ed’s memory came back. How do you know unless you look?

Not one thing

As I have written about in several of my previous books, one of the biggest lessons from our brain imaging work at Amen Clinics is that all psychiatric illnesses, including ADHD, anxiety, depression, and addictions, are not single or simple disorders in the brain; they all have multiple types that need their own unique treatments.

SPECT has taught us that memory problems are similar. Just as there are many roads to depression, so, too, are there many roads to losing your memory. As we will see throughout the rest of the book, SPECT can help in the diagnosis of different types of memory problems. Not only can it help diagnose Alzheimer’s disease and other forms of dementia, it can also suggest mild cognitive impairment stemming from such causes as head trauma, infections, toxins, and depression.

What About Amyloid Imaging with PET Scans?

Many scientists believe that Alzheimer’s disease is caused by the accumulation of toxic beta-amyloid plaques, sticky clumps of proteins that cause short circuits in the brain, as well as the formation of tangles inside neurons from inflamed tau proteins. The plaques and tau proteins begin forming before Alzheimer’s symptoms become obvious.

AUTOPSY MICROSCOPIC BRAIN TISSUE

Healthy neurons: no amyloid plaques

Unhealthy neurons: loaded with amyloid plaques

Based on the assumption that early detection of these processes would lead to earlier detection —and possibly better outcomes —for Alzheimer’s patients, several companies developed amyloid imaging agents for the brain, and they are currently working on tau imaging tools. Unfortunately, amyloid scans can tell only one thing: whether or not a person has classic Alzheimer’s caused by amyloid. Plus, all the drugs that target the cleanup of these two toxic proteins have failed in clinical trials. Eliminating the amyloid plaques and tau proteins after they have caused damage has not been helpful. This suggests targeting Alzheimer’s is more complicated than finding a one-size-fits-all solution.

SPECT imaging, on the other hand, potentially gives information on 10 different causes of memory loss, consistent with the BRIGHT MINDS risk factors. (See table below for a summary of the types of memory loss and dementia with the SPECT findings.) When evaluated with other presenting issues, it allows us to address the specific causes of memory loss.

BRIGHT MINDS: CLINICAL ISSUES AND SPECT FINDINGS

RISK FACTOR	CLINICAL ISSUES	SPECT FINDINGS
Blood Flow	Memory loss tends to go down in a stepwise manner, rather than a consistently progressive decline	Overall low blood flow; larger strokes seen on SPECT
Retirement/Aging	Progressive memory loss with age	Overall low blood flow, especially in the parietal and temporal lobes
Inflammation	Progressive memory loss, also associated with depression and pain	Overall low blood flow, seen in all areas of the brain
Genetics	Progressive memory loss, direction sense, and thinking skills	Decreased blood flow in parietal and temporal lobes
Head Trauma	History of repetitive head trauma	Focal damage, especially affecting the frontal and temporal lobes
Toxins	History of toxic exposure or excessive alcohol intake	Overall decreased blood flow in a scalloped pattern
Mental Health	History of depression in self or family members	Increased limbic activity; less decreased activity than other types
Immunity/Infectious Issues	History of autoimmune or untreated infections, such as Lyme disease or syphilis	Overall decreased blood flow in a scalloped pattern
Neurohormone Deficiencies	Low thyroid, testosterone, estrogen, progesterone	Overall low blood flow
Diabesity	High BMI and blood glucose levels	Overall low blood flow
Sleep Issues	Sleep apnea, chronic insomnia	Decreased blood flow, especially in the parietal lobes

SPECT examples

HEALTHY

Overall full, even, symmetrical blood flow

CLASSIC ALZHEIMER’S DISEASE

Parietal/temporal lobe decreases

FRONTOTEMPORAL LOBE DEMENTIA

Frontotemporal lobe decreases

VASCULAR DEMENTIA

Due to blood vessel changes or one large stroke or multiple small strokes

LEWY BODY DEMENTIA, ASSOCIATED WITH PARKINSON’S

Occipital lobe decreases

NORMAL PRESSURE HYDROCEPHALUS

Large ventricles, with lobster pattern seen on brain slices

ALCOHOLISM

Overall decreased blood flow

INFECTION (LYME DISEASE)

Overall decreased blood flow

TOXIN (MOLD EXPOSURE)

Overall decreased blood flow

TRAUMATIC BRAIN INJURY

Decreases in areas hurt

DEPRESSION

Outside surface often healthier

DEPRESSION

Increased activity in limbic structures

Quantitative electroencephalogram (QEEG)

QEEG is a tool we use for patients who are pregnant or are concerned about radiation exposure for any other reason. We may use it in combination with a SPECT scan if we need more information on the underlying cause of symptoms. With a QEEG, powerful computer programs take electrical signals from the brain and break them into five distinct brain wave patterns, showing how much of each is present compared to an age- and gender-matched healthy group. There are literally thousands of studies on QEEG for a wide variety of clinical indications, including memory problems, anxiety, depression, traumatic brain injury, and ADHD.

The five commonly discussed types of brain wave patterns, from the slowest to the fastest:

• delta waves (1–4 cycles per second): very slow brain waves, seen mostly during sleep
• theta waves (5–7 cycles per second): slow brain waves, seen during daydreaming and twilight states
• alpha waves (8–12 cycles per second): brain waves seen during relaxed states
• beta waves (13–20 cycles per second): fast brain waves seen during concentration or mental work states
• high beta waves (21–40 cycles per second): fast brain waves seen during intense concentration or anxiety

Memory issues typically show up as too much delta or theta activity, and QEEG helps us determine whether neurofeedback could be a helpful part of a patient’s treatment plan.

QEEG EXAMPLES

No color represents normal limits. The deeper the gray color, the higher the activity in each band.

HEALTHY (ALL BANDS WITHIN NORMAL LIMITS)

HIGH ALPHA IN EXPERIENCED MEDITATOR

VERY HIGH THETA IN DEMENTIA PATIENT

Throughout the course of my career I have often said, “A picture is worth a thousand words, but a map is worth a thousand pictures. A map tells you where you are and gives you directions on how to get to where you want to go.”

Without a map, you are lost. Not knowing the proper routes to get you back on track can cost you precious time in getting the help you need. At Amen Clinics we think of SPECT and QEEG as maps to help guide people to better brains and better lives.

MEMORY RESCUE: BRIGHT MINDS TAKEAWAYS

Now that you know how to begin assessing the health of your brain, consider how you will use this information:

1. Do you have early warning symptoms? Which ones?
2. When will you test your brain?
3. Would you look at your brain, given the chance? I recommend people be screened at the age of 50, or as early as 40 if there is a history of dementia in their families.