Exploring the art and science of impactful management of cognitive decline (CD), Ampiro and Metagenics recently hosted an event with guest speaker Dr Mark Menolascino (Medical Director of the Meno Clinic – Center for Functional Medicine in the US)

The most effective approach to cognitive decline is one based on personalised precision medicine

Dr Menolascino focused on the reversal of CD defining Alzheimer’s as a neuro inflammatory disease involving the innate immune system as opposed to the Adaptive neuro inflammatory diseases like MS and encephalitis. “Patients with the ApoE4 allele have a more active innate immune system and are thus more prone to developing AD (Alzheimer’s disease),” said Dr Menolascino. The ApoE4 allele used to be considered the wild type, the development of Apo E2 is a more recent occurrence in the last 2 000 years. Our ancestors required vigilant innate immune systems back then, we have come to rely more on our adaptive immune responses.

The sad state of affairs 

  • Patients fail to seek medical care because they are told there is nothing that can be done; they fear loss of functionality and independence, the stigma of diagnosis and ultimately fear placement in a nursing home.
  • They often decide to seek treatment late in the process. The more advanced the disease process the harder it is to treat.
  • Single drug therapy is still the mainstay of treatment. Monotherapy does not work. Why? Because CD is not caused by a singular defect of deficiency.
  • Tacrine drug trials show no clinical change in patients with AD, however if they stop drug therapy they drop down or worsen. They have to stay on it once they start. When the patient presents with AD, you have many ‘holes in the roof’ that need to be fixed. Fixing one hole very well does not stop the ‘roof leak’. You have to fill all the holes.
  • However, fix the first ten and the rest will tend to slam shut.
  • The most effective approach to CD is one based on personalised precision medicine.
  • Ask ‘where does my patient fit on the bell curve, where do they feel their best?. Patients are not ok just because they fit within a reference range. Often a reference range can be a deterrent for therapy initiation as the practitioner waits for the patient to regress to the point that they are no longer within reference range. Therapy is initiated in the progressive or later stage rather than early onset or disease progression.
  • Current evaluation of AD patients does not include nutrition, genetics, inflammatory markers, hormonal evaluation, or toxic burden. Why not?

7 Keys for personalised medicine

1. Optimum nutrition

2. Balance hormones

3. Reduce inflammation

4. Fix digestion

5. Enhance detoxification

6. Boost energy

7. Help patient experience a calm mind

There is hope, according to Dr Menolascino: “AD is easily reversible but patients have to stay on the programme. If they stop it they become worse and often cannot be brought back up to normal functionality.”

The subtypes at a glance:

1. Hot/Inflamed Patient

2. Trophic/Cold/Non-Inflammatory

3. Toxic/Vile

4. Vascular/Pale

5. Traumatic/Dazed

Patients are always a combination of the above. “These patients all have elevated Cortisol which contributes to their recorded risk for developing AD,” said Dr Menolascino. He recommends you consider: “What sort of patient has the disease vs. what disease does the patient have?” He also notes that when treating a patient with AD, it is important to treat the caregiver too. It’s interesting to note that family history does not play a big role and is not an important factor when considering CD in a patient. Rather epigenetic factors are the most important clues in a patient’s history.

Concepts in evaluation and intervention

Current evaluation consists of complete blood count (CBC), chemistry, thyroid-stimulating hormone (TSH), rapid plasma reagin (RPR). Dr Mark Menolascino recommends looking at the following:

  • The patient’s microbiome: dysbiosis is one of the two most important causes of loss of tight junction functioning. The resultant increased permeability contributes to systemic inflammation and insulin resistance. Once dysbiosis sets in, studies show that a probiotic becomes mandatory. Simply changing the patient’s diet and adding prebiotics will not correct dysbiosis.
  • Gut health: increased gut permeability results in systemic inflammation. The three most important drugs associated with increased permeability are: antibiotics, NSAIDS, and prednisone.
  • Nutrient deficiency: particularly Vitamin D3, aim for 80ng/dl
  • Toxicity: most toxins are fat soluble and can cross the BBB. The brain is the most vulnerable organ to toxic burden. Reducing toxic burden and improving detoxification improves cognitive function in patients with impaired cognition.
  • Hormone imbalance
  • SNPS, ApoE allele
  • Methylation: keep Homocysteine under 7. Homocysteine is an amino acid that is formed as an intermediate in the metabolism of methionine and cysteine. It is an important marker of overall health and methylation status. If it is elevated, gene testing may show you how to modulate it.
  • Diet: ketogenic diet packed with phytonutrients
  • Exercise: the number one way to increase Brain-Derived Neutrophic Factor (BDNF) is through exercise.
  • Sleep: test every patient with AD for sleep apnoea. If patients experience hypoxia at night it has to be addressed.

A novel diagnostic method

Retinal scan for AD – here a curcumin stain for the eye can pick up amyloid deposits in the eye before AD sets in. Note however that not all AD patients have amyloid accumulation.

Key aspects of intervention:

  • Initiate therapy early. This means that you have to screen patients for CD when there are signs of the above subtypes.
  • Patients must never stop the programme once they start.
  • When you reverse CD, you reverse heart disease and diabetes. It is all the same thing. Evaluate insulin when you suspect CD in a patient.
  • A ketogenic diet packed with phytonutrients are the two lifestyle factors that have the biggest positive impact on the brain.
  • Cortisol is the most toxic chemical in the hippocampus. Always consider the patient has had excessive exposure to cortisol as in prolonged stress. Salivary cortisol is the gold standard in testing and allows for quantification of cortisol as well as diurnal assessment.
  • For raised cortisol at night give Phosphatidyl serine.
  • Neuro-psych test remains one of the best tests to evaluate AD but can take up to two days and leave.


Author: Nicky Belseck