The patient is an 87 year old man in good health, low-normal BMI, but not frail, not taking any meds and just a few supplements such as D, alpha-omega, magnesium, CoQ10, C. Not on rapamycin. Careful but not obsessive diet and exercise. Diagnosed with MCI. MoCA of 21 on two occasions. I daily life, there is obvious short term memory loss, but no other behavior changes or changes in ability to handle daily living. Could not tolerate donanemab or revistigme – GI distress.

APOE is 3/3 and no family history or genetic predisposition.

Recent MRI showed continuation of hippocampal loss. Lumbar puncture showed: "CSF biomarker for AD was inclonclusive. He has a normal p-tau 181/AB42 ration, normal absolute AB42 level, but abnormal p-tau and p-tau 181. With elevated p-tau it is possible that his is still a pathologically mld Alzheimers or it is possible his is elevated in relation to a primary taupathy. "

Patient was offered a PET scan as this would show conclusively whether there is elevated amyloid in the brain, and a definitive diagnosis of AD (or not). If amyloid is present, patient would be offered lecanemab.

Patient declined the PET scan for now and will be followed up in August. Currently does not want to take lecanemab because the risk/reward benefit does not seem compelling. Physician was fine with this and once it was clear that lecanemab was not of interest at present, she actually said that she was very impressed with the patient’s health and vigor, and that given his age and what we actually do know right now about his neuro status, she felt he was more likely to eventually succumb to an infection or accident than dementia!

So, other than continuing “lifestyle” and possibly adding some supplements, the patient is not medically treating.

What’s your view of this? What would you ask? What would you do?

Would really appreciate your thoughts as I have some major skin in this: the patient is my husband.

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FWIW:
I am nearly 84, so I am definitely in your husband’s age range.
Two meds that I had taken when I experienced brain fog several months ago were memantine and galantamine, both of which were obtained from India

Memantine: “Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe Alzheimer’s disease (AD). It works by regulating glutamate activity, which is thought to play a role in the pathophysiology of AD.
Improves cognitive function, activities of daily living, behavior, and mood ([2])
Benefits observed both as monotherapy and in combination with cholinesterase inhibitors ([1])
Combination of memantine with donepezil shows greater improvements in cognition, function, behavior, and global outcomes compared to donepezil alone in moderate to severe AD ([3])
Generally well-tolerated with a safety profile comparable to placebo ([2])”

Galantamine: “Galantamine is a medication primarily used in the treatment of Alzheimer’s disease (AD) and vascular dementia. It belongs to the class of drugs known as acetylcholinesterase inhibitors and has a unique dual mechanism of action ([1]).
Improves cognitive function ([2])
Enhances global function ([2])
Improves activities of daily living ([2])
Reduces behavioral symptoms ([2])
Adverse Effects:
Generally mild to moderate in severity
Transient and gastrointestinal in nature ([1])
Most common: nausea ([2])
Galantamine-memantine combination may be beneficial in AD treatment ([6])”

Since I took both, I am not sure which one, or maybe it was the combination. In any event, it cleared up my brain fog after a few weeks. When I felt back to normal, I stopped taking them.
I experienced no side effects other than vivid dreams, which is a common side effect of galantamine.

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Your husband is lucky to have you in his corner. You may find that we collectively give you too many ideas to investigate, discuss with your doctor, or actually implement.

In your shoes, I would consider adding serrapeptase/nattokinase, and low dose lithium, especially because these are both things you can get otc.

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Thanks Charles for your response. My husband dd try donepezil and the rivastigmine patch – these are acetylchoninesterase inhibitors, similar to galantamine. But he had so much GI distress that he had to stop.

I know from your other posts that you take supplements – are there any that you feel have been beneficial for cognitive function?

Thanks Nlo. I take these myself and will add them to my husband’s stack.

Gingko Biloba, Bacopa Monnieri, Vinpocetine, Huperzine A.

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I would look at:

  • Blood pressure: if not optimal, telmisartan (up to 80 mg if tolerated).
  • Glucose (HbA1c and HOMA-IR): if not optimal, dapagliflozin 10 mg or empagliflozin 25 mg
  • Lithium orotate (1 to 10 mg?).
  • Serum B12: if in the lower “normal”, methylcobalamin sublingual.
  • Theracurmin (high absorption curcumin).
  • If he has bladder issues due to prostate enlargement: terazosin 5 mg.
  • If ApoB > 100 mg/dL: ezetimibe 10 mg.
  • Vitamin K2 MK7 1,000 ug
  • If difficulties falling asleep: Melatonin 3 mg 3 hours before sleep (not “at bedtime”).
  • If waking up during the night: melatonin 3 mg (crashed and dissolved below the tongue) when waking up (to help fall back asleep).
  • Omega 3 (mostly EPA) might help as he’s not APOE4.
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