Cyrus Raji, MD, PhD

Brain Health and Imaging

Date Aired: December 1, 2017

Episode Description

Dr. Raji discusses the leading edge of quantitative neuroimaging volumetrics – the measurement of brain volumes from magnetic resonance images. Volume is a vital sign for the brain. When volumes are normal, this correlates to normal neuronal function. Reduction of brain volumes is seen with various neuropsychiatric disorders such as Alzheimer’s disease, depression, and traumatic brain injury. What Dr. Raji’s research has shown over the past 10 years is that brain volumes can actually change in relation to lifestyle choices from obesity to physical activity to dietary choices. This work has a tremendous impact on prevention of cognitive decline and preservation of brain health. His talk will overview these key points while presenting a framework for future growth of this new perspective in medicine. What Dr. Raji’s research has shown over the past 10 years is that brain volumes can actually change in relation to lifestyle choices from obesity to physical activity to dietary choices.

Preventive neuroradiology

  • Describes the application of imaging tools for identifying different causes of cognitive decline particularly the causes that are preventable or modifiable
  • Applied to brain imaging and cognitive decline
  • As people age, they have problems with memory, focus, attention
  • The concept that there are multiple possible mechanisms that contribute to cognitive decline
    • We can track these factors with neuroimaging with a series of functional tools with which we can measure.
    • We can identify these and treat them
    • You can find out whether vascular disease is a factor
    • Drug and alcohol
    • Study brain connections and connections of neurons
      • Connectomes are maps that describe the neuro-wiring of the brain
        • Changes occur early in disease TBI, AD
  • Positive life style factors correlated with larger grey matter: better neuronal health
  • Negative life style factors are correlated with reduced brain volume an increased risk of cognitive decline and AD

Life style Factors that impact the progression towards dementia

  • Epidemiological (Barnes and Jaffeein Lancet 2011)
  • In US 7 risk factors that influenced the risk of AD

In US                                                                      Globally

  • Physical inactivity Low education              Low education
  • Depression
  • Smoking
  • Midlife htn
  • Low education
  • Diabetes

Alzheimer’s Disease (AD) cognitive decline continues

  • Addressable (alcohol, hypertension) forms of cognitive decline can stop the progression if that risk factor is removed.
  • Will be able to track these for diagnosis and treatment



  • Obesity correlated to loss of grey matter in frontal lobes , temporal lobes
    • Adipose tissue releases inflammatory cytokines such as IL 6, TNf a
  • Increased physical activity ~ increased grey matter in frontal lobe, temporal lobes and hippocampus.

 Lack of Exercise

  • Especially aerobic increases BDNF
    • Axonal sprouting
    • Sprouts new connections in the brain
    • Dendrite formation
    • Improved neuronal structure
    • Neurogenesis in the hippocampus
  • Walking a mile per day increases grey volume in normal, mild MCI mci and mild dementia
    • Burn 500 calories per day have 5 % more grey volume
    • Dose response but effect plateaued
    • There is a minimum amount of exercise to get this effect
    • Preventative in cognitively normal
    • Slows progression of decline

Heavy metals

  • Are preventable cause of cognitive decline
  • Dr Dale Bredesen lists toxins as one cause of dementia


  • Affects cerebellum
  • Cerebellum has most number of neurons per volume
  • Coordination of movement
  • Integrate cognitive structure through the midline structure called the vermis
  • Don’t confuse with AD
  • Stopping alcohol will stop progression of cognitive decline


  • Dilantin related to cerebellar atrophy
  • Statins
    • Originally an important aspect of Alzheimer’s prevention by reducing the vascular effects
    • Aggressive statin therapy can lead to brain atrophy
    • Data is unclear as a confounder is that those with the worse vascular disease received aggressive statin therapy.
  • Antibiotics disrupt the microbiome
    • Can lead to inflammation and obesity
    • Obese persons are more likely to have a disrupted microbiome
    • Which comes first disrupted microbiome or obesity


  • Chronic use can lead to brain atrophy (grey matter)
  • Acute use results in toxicity in the white matter leading to acute cognitive decline.


  • Is correlation of abnormal microbiome and obesity
  • Disruption of microbiome leads to inflammation
  • Obese is more likely to have abnormal microbiome
  • Which is is first: disrupted microbiome or obesity?
  • Inflammation in gut and body has long term effect on the brain
  • They are trying to develop tracers to chart the course of the effects of brain inflammation


  • Role of Insulin degrading enzymes
    • Type 2 diabetes has overabundance of insulin due to malfunctioning of insulin receptors
    • Insulin is degraded by IDE (insulin degrading enzyme)
    • IDE also degrades amyloid which is involved in Alzheimer’s disease
    • IDE preferentially degrades insulin before degrading amyloid
    • Problems with this theory
      • Amyloid does not correlate with loss of neurons and synapses as does tau
      • The symptoms of cognitive decline in Alzheimer’s correlate with tau, not amyloid
      • Drugs that target amyloid have not been successful in helping Alzheimer’s patients
    • Body mass index accounts for all the effects attributed to diabetes
    • Each drop or increase in blood sugar provides an insult to the brain


  • With too little sleep the glymphatic system does not work as well as it is programmed on the circadianrhythms
    • Glymphatic system is the system in the brain that clean itself
    • Glymphatic system cleans out amyloid
    • We will probably be able to image the glymphatic system as well.
  • It is important to reach REM sleep to achieve the circadian rhythm
    • Sleep 6- 8 hours per night
    • Taking naps might be a feasible way to achieve this
  • Blue lights from computers can interfere with sleep by blocking melatonin which is needed for sleep
    • Orange light can help
  • One of challenge if for people who can not stay asleep
  • Sleep apnea is a preventable risk factor

Head Injuries

  • Motor vehicle injuries most common source
  • Blast exposure in veterans
  • Chronic Traumatic Encephalopathy (CTE)
  • 110 our of 111 deceased NFL players had this
  • For these players dementia can start as early as in the twenties
  • In movie Concussion with Will Smith
  • Is abnormal tau is in the brain stem (
    • Impact triangulates through and axis that involves the brain stem
  • The tau location in Alzheimer’s disease starts in the hippocampus
  • Soccer players who “head” the ball have more abnormal brain neural connections than players who do not “head” the ball
  • Protection from head injuries
    • The NCAA was established by President Teddy because in 1904, 100 players died from the traumatic effects
  • Recommendations for persons who suffer head traumas
    • Healthy diet
      • omega threes
    • Aerobic exercises
    • Cognitive brain games / rehabilitation
    • These can increase the size of the hippocampus

Multi infarct Dementia

  • Are white matter hyperintensitiesspots
    • These are abnormal white matter usually from chronic vascular matter
    • These correlate with grey matter atrophy
    • These originally present as silent strokes
      • Control blood pressure
        • Chronic necrosis of arteries going to white matter
      • Control sugars
      • Control cholesterol
        • Low cholesterol associated with increase risk of depression
      • E had 9 heart attacks inspite of a low fat diet
      • Cholesterol


  • Incorporates into cell membranes including neuronal cell membranes
  • Low cholesterol correlates with depression


 Magnetic Resonant imaging (MRI)

  • Usually does not have contrast
  • Can assess structure,
  • Volume
  • Connectomes (synapses connections

PET scans

  • Can image amyloid and tau
    • This is not approved by insurance
    • This is only beneficial if the scan is negative
    • Amyloid takes twenty years to cause symptoms so amyloid does not mean that people had Alzheimer’s disease
  • Glucose utilization (with FDG)
    • Nerves that don’t use glucose
  • Blood flow through out the brain
    • SPECT, PET scans


Weight Control

  • Keep body mass under 30
    • BMI > 30, greater rate of brain atrophy
    • BMI 25-29.9 have mild grey matter decline



  • Eat fish: baked or broiled salmon
    • Mercury is found in sword fish and mackerel (?)