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#236 Kellyann Niotis, M.D. – Neurodegenerative Disease: Pathology, Screening, And Prevention | The Drive With Peter Attia

Key Takeaways

  • Our brain needs sensory input and stimulation – if you don’t have it, neuronal circuits don’t get exercised and are more likely to atrophy; keep moving, keep diversifying cognitive experience
  • Parkinson’s disease is the fastest-growing neurodegenerative condition in the US
  • We’re intervening in neurodegenerative disease too late – the current approach is the equivalent of taking a woman with stage 4 metastatic breast cancer and doing a lumpectomy
    • Without biomarkers, we don’t know the stages of neurodegenerative disease and when to apply which interventions
  • “There’s probably no activity that you can participate in that will have a greater impact on your brain’s health than exercise.” – Dr. Peter Attia
  • Exercise has the most potential to move the needle on brain health and brain health prevention
  • Nothing stimulates BDNF more than exercise: BDNF helps grow and protect new brain cells in memory centers of the brain
  • Insights from continuous glucose monitors are profound, whether you wear it for a month or forever – it will change how you approach food and sleep more than other metrics like blood pressure which you measure at one point in time and don’t know in between


Kellyann Niotis, M.D. (@drkellyannniotis) is a neurologist specializing in risk reduction strategies for the prevention or slowing of neurodegenerative disorders. I currently lead the neurology program in Dr. Peter Attia’s medical practice, focused on the applied science of longevity.

In this episode of The Drive, Dr. Niotis provides an overview of various neurodegenerative diseases including Alzheimer’s disease, Lewy body dementia, and Parkinson’s disease. She highlights the importance of early screening, cognitive testing, proper steps to lower the risk of disease, and much more.

Host: Peter Attia (@PeterAttiaMD)


  • We don’t have effective treatments for most neurological disorders (except MS)
  • Neurodegeneration means the death of brain cells – understanding the region in which the cells are “dying” helps understand the symptoms
  • Neurodegeneration is the third leading cause of death behind heart disease and cancer – all of which combine to account for 70% of deaths
  • Some neurological diseases affect men and women at different rates
  • Diseases that fall under the umbrella of dementia: Alzheimer’s disease, vascular dementia, Lewy body dementia, frontal temporal dementia
    • Difficulty with depth perception, auditory processing difficulty, and movement disorder are distinct traits that separate Lewy body dementia and Alzheimer’s disease
    • Vascular dementia and Alzheimer’s dementia have more clinical overlap in presentation
  • Diseases under the broader category of neurodegeneration: Parkinson’s disease, ALS, Huntington’s disease, rarer diseases
    • ALS is rare, only about 18,000 people in the US have it versus Parkinson’s disease which is much more common (about 1 million people affected) and the fastest-growing neurological condition
    • There’s a connection between ALS and frontal temporal dementia – the C9orf gene puts people at risk for both
  • High apoB (high cholesterol) in patients often coincides with reduced processing speed and cognition as measured by cognitive assessment
    • Correcting apoB can improve processing speeds in as little as six months

Parkinson’s Disease

  • We aren’t very good at diagnosing Parkinson’s disease – the current standard is resting tremor, bradykinesia, stiffness of the muscles, unsteadiness on feet – but in reality, the disease is starting way before the symptoms present
  • Parkinson’s disease (PD): dopamine-producing cells in the brain reside in the center that control movement and in Parkinson’s disease, these cells die
    • Because of the vast effects of dopamine on the brain and body, patients with Parkinson’s disease often develop depression and anxiety as well
  • Mechanism: the immune system and inflammation play a role, but it seems more related to mitochondria and lysosome function and the inability to regulate cells through autophagy
    • Once the lysosome can’t get to substances to break them down appropriately, the mitochondria are negatively affected and set off a cascade of inflammatory cytokines
  • We don’t know what causes Parkinson’s disease but there is a correlation with pesticide exposure (specifically paraquat and rotenone),
    • Rotenone is not used in the US any longer but paraquat is; PD is clustered in those areas
  • Genetic landscape of disease: 10% has a clear genetic etiology (GBA, LRRK-2)
    • Note: 23andme tests both genes but only one variant of each so a negative result doesn’t actually mean much
    • GBA and LRRK-2 are like apoe4 where if you have one of these genes, they won’t necessarily result in Parkinson’s disease but you are at higher risk
  • Understanding of PD is at least 10 years behind Alzheimer’s disease
  • Melatonin signaling cycle is off in patients with PD, regulating could help improve sleep
  • REM sleep disturbance (kicking, punching, screaming, acting out dreams) has a positive predictive value of over 90% that you will go on to develop either Parkinson’s disease or Lewy body dementia
    • This usually happens 20-30 years before a physical symptom will onset
    • The gold standard for assessing REM sleep disturbance is polysomnography – but the bed partner can accurately identify with 80% sensitivity
    • Additional considerations: toxic exposures, water source, movement assessment (grounding through the non-dominant leg)
  • Sleep tracking & optimization is really important in PD and another neurodegenerative disease – REM sleep is critical for memory formation, emotional regulation (anxiety, depression)
  • “I can’t emphasize enough how important sleep is to speed of processing…you really have to be sleeping in order to process information.”– Dr. Kellyann Niotis
  • Early detection has been behind the ball but moving the needle at the right time could make a huge difference in slowing or stopping progress, we really don’t know

Alzheimer’s Disease Pathology & Diagnosis

  • Toxic proteins in Alzheimer’s disease (AD): amyloid can be misfolded and can cause neurodegeneration; tau accumulates as neurofibrillary tangles
    • Once these proteins develop, the inflammatory cascade that drives neurodegeneration is triggered
  • PET scan shows areas of less glucose signaling which identifies regions of neurodegeneration but doesn’t tell you about protein deposition
  • Amyloid PETs look at tracer tagging amyloid deposition in the brain and scoring diffusion – this can be helpful in AD diagnosis but amyloid deposition also takes place in “normal” people (for example, with sleep deprivation)
    • Everyone has amyloid proteins but in healthy brains, they’re being cleared, especially during sleep
    • New amyloid biomarker: amyloid beta 40/42 gives amyloid probability scored based on apoe status – offers about 80% accuracy
  • Debate about which markers to follow: is it a matter of amyloid deposition or cognitive function?
  • Tau scans exist but are not covered by insurance so very expensive and have very high radiation exposure (not something to do for the heck of it)
    • Pros of tau scan: positive tau does have a stronger tie to the likelihood of developing cognitive impairment
    • New tau biomarker (available for research, not clinically): tau-217 looks at ratios of phosphorylated to non-phosphorylated p-tau with an accuracy of about 90%
  • Serum tests may be better at detecting very early AD better than scans
  • We need to do a better job at identifying what stage someone is in the disease and intervene earlier
  • AD affects women twice as often as men – possibly in part because of the hormone shifts later in life
    • As a note, men get PD and Lewy body twice as often as women

Genes Involved In Alzheimer’s Disease

  • There are three isoforms for the apoe gene – apoe1, apoe2, apoe3, apoe4 (we each have two copies)
  • The normal isoform is a 3-3 combo
  • The high-risk isoform is the 4 – but, it’s also a “devil you know” scenario – you know the impact on the body, role in cholesterol, ability to metabolize carbohydrates
    • If you have someone with strong family history and 3-3, you don’t know the pathogenic mechanism
  • The lowest risk isoform is the 2
  • “Your genes are not your destiny.” – Dr. Kellyann Niotis
  • Most people will also inherit a harmful copy of TOM40 if they have apoe4
  • Klotho gene offers a protective role against apoe4 and reduces the rate of cognitive decline
    • But there’s no fast, cheap, or easy way to identify klotho at the moment – it’s a key thing holding us back
    • The goal is to teach AI how to do this but you have to understand a person’s risk factors
  • Importance of knowing haplotype of mitochondria: helpful in understanding risk for apoe4 and other neurodegenerative diseases
    • Certain haplotypes put you at higher risk for both AD and PD
    • To increase mitochondrial function, turn up zone 2

Cognitive Testing For Early Detection

  • The art of the assessments is in watching someone take them
  • Olfactory test: 9 things you smell; the idea is that cranial nerve 1 is the olfactory nerve – smell feeds directly into memory so it’s one of the first parts to degenerate in disease
  • Reading, registering, auditory, and visual memory function tests – for example, when you read something, do you remember it? When you hear something, do you remember it? etc.
  • Additional cognitive exercises: attention tasks, speed of processing tasks, episodic memory (what order you saw something), visuospatial processing, verbal learning
  • Distraction is a huge confounder of memory – if you’re not focused on something, you’re not going to remember it
  • Ideal test conditions: in the morning after a good night of sleep
  • The forms are changed so learning the test is unlikely; apoe4 is also resistant to learning so it’s a non-issue
  • Many people who have trouble forgetting will still ace the tests so you have to look deeper – is it a distraction problem? Trouble keeping attention? Etc.

The Importance Of Exercise

  • “There’s probably no activity that you can participate in that will have a greater impact on your brain’s health than exercise.” – Dr. Peter Attia
  • Caveat: if you’re not sleeping, you’ll do more damage than exercise can repair
  • Think of exercise in 4 categories: (1) coordination/proprioception; (2) zone 2 for improved energy efficiency; (3) strength training; (4) high intensity
    • People overlook the benefit of dance – you need to process visual information and make your body do that thing while raising your heart rate
  • Nothing stimulates BDNF more than exercise: BDNF helps grow and protect new brain cells in memory centers of the brain

Relationship Between Hearing & Dementia

  • There’s an association between hearing loss and dementia
  • Some schools of thought theorize that there’s a causative relationship between hearing loss and dementia: this means that by intervening and treating hearing loss early, you’re staving off dementia
    • Rationale: when you can’t hear you’re increasing cognitive load which is taking bandwidth from other areas and diverting resources from the memory function
    • Our brains need sensory input, when you aren’t getting it you lose it
  • Similarly, if you can’t see properly, you are expending a lot of resources to be able to see instead of memory

Oral Health

  • The health of gums and teeth are strong predictors of your overall health
  • Certain microbes (gram-negative bacteria) are associated with amyloid and tau depositions
  • Focusing on oral health in high-risk patients is critical – there is autopsy evidence that bacteria can go to the brain and/or inflammation can trigger damage
  • If you use a retainer or mouthguard of any kind, be vigilant about cleaning it!
  • Try a water pick or something with a brush that scrapes away the bacteria

Approaching Blood Pressure And Glucose Monitoring

  • Blood pressure control is better for cognitive control over time
  • Need to check blood pressure first thing in the morning or at night using an arm cuff – the wrist measurements are inaccurate
  • Insights from continuous glucose monitors are profound, whether you wear it for a month or forever – it will change how you approach food and sleep
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Notes By Maryann

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