This post covers work of Daniel Amen. .. ir just a very small bit of a large amount. Dr Amens has become a celebrity over promoting SPECT imaging, “blood Flow” through various regions of the brain, and of course brain directed nutrients to restore “blood flow” to normal. Purists may associate “flow” with a unit volume per unit time such as mL per minute. Mayo Clinic breaks down single-photon emission computerized tomography (SPECT) imaging in simple steps: (1) inject patient with γ radiation emitting compound. (2) The patient allows the compound to partition from blood to tissues of the body for 20 minutes or more. (3) The image is acquired. (4) The patient is asked to drink plenty of fluids to encourage the compound to partition back into the blood where it can be eliminated in the urine.
What am I looking at?
Technetium (99mTc) exametazime is very simply a radioactive agent that emits a photon of the gamma radiation wavelength. It is used to measure blood distribution in tissue. It should not be confused with Fluorodeoxyglucose (18F) used in positron emission tomography PET. The latter measures uptake of glucose assumed to be related to the metabolic activity of a tissue. The active rendering of blood flow is petty straight forward. One just needs to be constantly aware of the color code.
The surface rendering is difficult for many to conceptualize. The colors themselves seem to have little bearing on the flow. Pure green, cyan, orange, and red are all the same flow going down into the brain. Gray shades of the colors indicate <45% of the average perfusion. [1]
You are looking at different renderings to make statements
On an anxiety page the Amen group makes a point that there is high relative blood flow in the cerebellum of normal and in individuals with anxiety. Basal ganglia blood flow in the person with anxiety is high compared to the normal control. The activity rendering is an excellent way to locate the region of increased blood flow and gives the patient peace of mind that there is indeed something tangible out of order in their brain. It gives the psychiatrist some insight on possible medications. Interestingly, the sight on anxiety is linked to a sight on marijuana, a plant based medicine used to treat anxiety.
The surface rendered healthy brain has some grayish dips indicating somewhat lower blood flow in regions below the surface. The cerebellum is bright and shiny smooth in this surface rendering of a healthy brain. The marijuana user’s brain is full of pot holes indicating substantial regions of decreased blood flow. We were not told how much THC was in the system of the patient at the time of the scan. Was this patient self medicating with mmj and just missed the mark by decreasing more than the intended brain activity? The “Swiss cheese” surface rendering of the mmj patient’s brain would make a more powerful statement than a nice, calm, mostly blue activity rendering. Finding surface abd activity plots of habitual coffee drinkers before and after the morning cup is a bit more difficult.
Excess body weight and brain blood flow
Blood flow was compared among the following group of patients: underweight (BMI < 18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25–29.9), obese (BMI≥30), morbidly obese (BMI≥40). [2] All subjects received intravenous administration of an age- and weight-appropriate dose of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) for brain SPECT imaging. Each subject received a resting, or baseline, scan and a task. [2] What was not clear was if 99mTc-HMPAO partitioned into adipose tissue. If so, it would not be enough to simply assume that morbidly obese patients have more blood than their underweight counterparts.
The authors reported a pattern across virtually all brain regions in which a decline in cerebral perfusion inversely correlated with BMI. Flow was best in the under weight and wose in the morbidly obese. [2] The authors reported no regions that showed elevated perfusion in relation to higher BMI. [2] To have a small region of hyper perfusion (arrow) suggests that decreased flow as BMI increases is not an artifact of the detector partitioning into adipose tissue.
The Brain Directed Nutrients (BDN) Clinical Trial
The Goal was to determine whether supplementation with BDNs improved cerebral blood flow CBF and neuropsychological function in healthy individuals. The participants were randomized to receive the BDN or a placebo for two months. [3] Neither the investigators nor the participants knew whether they were receiving the placebo or BDN. At the end of two months the groups crossed over. The placebo group got the BDN and the BDN group crossed over to receiving the placebo. [3] This study was conducted at the Amen Clinic in Newport Beach, CA. The participants included 30 locals, 15 of which were men and the other 15 women. Five participants failed to complete the study for reasons unrelated to the study. In a cross over design participants were given a baseline brain scan and then a placebo or brain directed nutrients for two months. At the end f this time they were given another brain scan and the same tests. Then the participants crossed over: the placebo group got the BDN and the BDN group got the placebo for two months. At the end of four months the participants were given a third brain scan and the same tests.
The treatments
- fish oil, 2.8 g per day
- multivitamins and minerals that include 1mg copper glycinate and 30 mg nicotinamide
- A mixture of small molecule anti oxidants and hormone modulators that included huperzine A, Ginkgo biloba, and N-acetyl cysteine and sodium/copper chlorophyllin
- some digestive enzymes, which are technically large molecules, were also included
In the placebo treatment rice flour to replace all BND components except the fish oil. A mixture of undisclosed vegetable oils was used to replace the fish oil.
Outcome measures, results
Let’s take a look at a table reporting significant changes in well defined regions of the brain. Some images of major blood vessels in the brain are included to make a point that changes in blood flow depend on smooth muscle in the major vessels as well as smaller arterioles and venules.
As one might expect, cognitive test scores improve the more times the test is taken.
when BDNs are given first compared to a quadratic response when BDNs are given second, regressing from baseline to treatment to placebo[3]
Significant improvements were observed for the BDNs
- MicroCog—reasoning, P = .008
- memory, P = .014
- information processing accuracy, P = .027
- WebNeuro—executive function, P = .002
- information processing efficiency, P = .015
- depressed mood, P = .017
- emotional identification, P = .041
- BSI—positive symptom total, P = .024
A reduction in the hostility score was seen. P = .018. Adjusting for the effect of order was required to reach significance. [3]
Conclusions… sort of
It is fairly easy to see why Dr Daniel Amen has achieved celebrity status with his mixture of psychiatry and SPECT imaging. He sells peace of mind of seeing proof that something no so good is going on in a person’s brain in a non insurance funded sort of way. Proper presentation of the data can encourage and/or guide healthy living. In true MD fashion, the BDN are “everything but the kitchen sink” to reduce oxidative stress that might be causing reduced blood flow, excitotoxicity, and so on. This latter was not a study to establish a mechanism. The trial did offer convincing evidence that the Amen group is on the right tack.
References
- Amen D. Brain SPECT imaging in clinical practice. Am J Psychiatry. 2010 Sep;167(9):1125; author reply 1125-6.
- Amen, D. G., Wu, J., George, N., & Newberg, A. (2020). Patterns of Regional Cerebral Blood Flow as a Function of Obesity in Adults. Journal of Alzheimer’s disease : JAD, 77(3), 1331–1337. PMC free article
- Amen DG, Taylor DV, Ojala K, Kaur J, Willeumier K. (2013) Effects of brain-directed nutrients on cerebral blood flow and neuropsychological testing: a randomized, double-blind, placebo-controlled, crossover trial. Adv Mind Body Med. 2013 Spring;27(2):24-33.
Cuprous niacin 