What an Alzheimer’s Prevention Clinic Director Recommends to Cut Your Risk

February 3rd marks the anniversary of my Dad passing from dementia at age 80. We were lucky in a way that the gap between when he showed severe symptoms to his passing was relatively short at 2-2.5 years. As I've mentioned before - I hold one of the genetic markers for late on-set Alzheimer's (I have one ApoE4 gene inherited from my father), which gives me a slightly elevated risk. This has led me to research ways to limit my risks via diet and lifestyle changes and to communicate what I learn in the hope that it can impact your life too. It's also the reason why Lean Caffeine was born as a company - as one of the best things you can do to keep your body and mind in tip top shape is to practice intermittent fasting. I listened to a very good podcast on The Drive hosted by Peter Attia MD and featuring insights from Dr Richard Isaacson MD (Director of the Alzheimer's Prevention Clinic in the US and advisor to 23 and me), and one of his star patients Lauren Miller Rogen. Lauren is Seth Rogen's wife and holds two copies of the ApoE4 gene, giving her a very elevated risk of developing late on-set Alzheimer's. https://peterattiamd.com/laurenmillerrogen-richardisaacson/ The podcast really struck home with me as Lauren also comes from a family where she saw her parent (mum) develop Alzheimer's early on in her 50's and rapidly decline. Lauren also saw the same fate for her uncle later in his life. Dr Isaacson's interventions have had measurable success in reducing Lauren's risk of getting Alzheimer's based on cognitive tests carried out during her treatment. Dr Isaacson & Dr Attia had some very interesting observations and recommendations in the podcast. I've summarised the most important points below:

• Dr Isaacson considers high-intensity interval training to be the most important factor in Alzheimer’s prevention. Lauren's uncle was a fit cyclist and her mother very sedentary. “High intensity interval training is probably the only thing that can move the needle in terms of certain aspects of cognitive function in people with the APOE4 variant.” — Richard Isaacson
• There is a greater Alzheimer's risk amongst women. Perimenopause transition is a huge unrealized risk factor for progression to dementia in an Alzheimer’s susceptible woman. Lauren’s mother had a hysterectomy which was likely a contributing factor in her progression
• Women with an enlarged waist circumference have a 39% increase in dementia risk!
• People with 2 copies of the ApoE4 gene don’t absorb omega-3 fats from eating fatty fish very well. Therefore they should be supplementing with omega-3 from an early age to protect the brain (especially DHA).
• Head trauma may be more of a concern in individuals with the ApoE4 variant. Dr Attia believes knowing the child’s ApoE status would be an important factor in choosing to play contact sports like Rugby (Union and League), Ice Hockey, or American Football (and even Football/Soccer - if they regularly header the ball). On a side note - there have been a statistically large number of cases of Dementia in older rugby players in Australia (both rugby union and rugby league players).
• The gene for TNF-α (an inflammatory cytokine), is another factor that can increase the risk associated with the ApoE4 variant. Lauren has a variant of the gene for TNF-α that increases her risk (Lauren’s mother had this variant, but interestingly her uncle did not).
• Dr Isaacson mentions the “ABCs” of Alzheimer’s prevention. All of his patients are assessed every 6 months — and the protocol is fine-tuned each time based on results:
  • A is for anthropometrics, mainly body composition
  • B is for blood biomarkers, primarily related to cholesterol, inflammation, metabolism, nutrition, and genetics
  • C is for cognitive function
• The specific recommendation's from Dr Isaacson research and treatment protocol that Lauren has been following are as follows:
  1. Exercise is extremely important and especially High Intensity Interval Tarining (HIIT). Lauren has been prioritising her exercise.
  2. Lauren takes a purified fish oil supplement containing approximately 2000mg of DHA.
  3. To lower inflammation (due to her TNF-a gene variant) - Lauren takes a purified form of Cocoa Flavanols (like this UK one I've ordered and will start taking) and a nanoparticle version of Curcumin called Theracurmin. I would dare say a reputable liposomal Curcumin would work just as well. The company that manufactures our liposomal multivitamin had their liposomal curcumin measured versus a standard tablet and it was 38 x more absorbed (32.75 micrograms/L versus 0.86 micrograms/L).
  4. To lower her Homocysteine (a common amino acid in blood - mostly from eating meat) - Lauren takes a B-vitamin complex (which has B12, B6, and folic acid, etc.). High homocysteine is associated with increased brain atrophy resulting in impaired memory function. The B-complex combined with sufficient levels of Omega-3s can slow brain shrinkage, brain atrophy, and improve memory.
  5. To increase her vitamin D levels (Lauren's was measured at less than 20 ng/ml) - Lauren consumes vitamin D supplements with a meal containing fat and aims to get at least 10-15 minutes of sun exposure between 11am and 1pm. Based on a study in the European Journal of Nutrition, people with ApoE4/4 “better have good vitamin D levels… at 50 or more”. I've personally started taking over 2000 IU per day (especially due to the observational studies linking low levels to higher risk of catching COVID and having serious complications afterwards).
  6. Dr Attia is a big fan of magnesium L-threonate as L-threonate helps the magnesium enter the brain more easily. A small study has shown magnesium L-threonate to improve cognitive function in people with mild to moderate dementia. I take 1 of these capsules along with my Better You Magnesium spray before bed.
  7. Further advice from Dr Attia:
     1. Tobacco use has more of a negative effect in ApoE4 carriers.
     2. ApoE4 carriers should maybe be more conservative with alcohol consumption, with there potentially being more benefit from completely abstaining (which contradicts the normal moderate consumption offering protection advice).
     3. Cognitive engagement may be more important for ApoE4 carriers, but the data is unclear here.
     4. A trial is underway to determine the influence of saturated fat and a high-glycemic diet on ApoE4 carriers. The theory is that both of these things may be highly detrimental to those carrying the ApoE4 gene.
     5. Dr Attia is also in favour of using MCT oil, but he’s more careful prescribing MCT for those with an ApoE4 variant — “a tricky topic worthy of a separate discussion”!
     6. Dr Attia is open minded about CBD and THC, but considers this a difficult topic! He thinks the benefit is dependent on the ratio of CBD to THC. Consuming as an edible form makes more sense to him than smoking it. Dr Attia is “not anti-CBD,” but is “not pro” THC (he says he’s “in the middle”). It depends on the patient, and the situation should be objectively measured by tracking things like sleep and cognitive function.
     7. Loss of smell and inability to identify certain smells can and also be “a harbinger of Alzheimer’s disease”. Be aware of any changes!
     8. In a 2020 report of the Lancet Commission, hearing loss was identified as one of the strongest modifiable risk factors for dementia — one’s reaction to the study could be that “a huge number of cases of dementia could be potentially reduced if a person gets early recognition of hearing impairment and gets it addressed.”