Thought this was interesting, in terms of target levels. The mouse study suggests quite a high dose of the best “lysophosphatidylcholine” form of DHA: 452mg. Or double that for the next best phospholipid form (phosphatidylserine) and 7 to 17x for the non-phospholipid form - triacylglycerol DHA (TAG).
If eating sardines that would require at least 2 tins a day?
“Using the allometric scaling [50], we calculate that the human equivalent daily dose of LPC-DHA for efficient brain enrichment is about 452 mg DHA for a 70 kg person, whereas the dosage using TAG-DHA, based on the previous studies, is about 3.4 g to 8.9 g of DHA per day.”
This metabolic pathway diagram is quite neat. But it suggests that the phospholipid-bound dha in Krill oil, containing being sn2 form won’t help DHA brain levels.
“Based on the results presented here, we conclude that the most commonly used carriers of DHA, namely TAG-DHA (as in fish oil), sn-2 DHA PC (as in krill oil) or ethyl esters (as in Lovaza®, Omacor®) do not enrich brain DHA, because they are absorbed as TAG, which is not efficiently converted to LPC-DHA in the liver”
Lithium orotate, not galantamine hydrochloride, memantine, or rivastigmine, is the only medication that I know of that addresses prevention, symptoms, and possible reversal of dementia progression.
back on my hobby horse topic : “how much phospholipid-bound DHA is enough?”… this association (only) study I posted elsewhere suggests 4 portions of fish a week is better than 3 (the % relates to vascular brain disease in 75 year olds and is rather terrifyingly high!)
“Researchers found that among people who ate no fish, 31% had markers of severe underlying vascular brain disease, compared to 23% of those who ate three servings a week, and 18% of those who ate four or more servings of fish per week. This association between lower fish consumption and greater severity of markers of vascular brain disease was independent of any differences in brain volumes and other variables like age and sex.”
I’ll get round to it some time. Very busy time in the clinic + ER these days. Come the New Year will have a bit more time.
I think statins are a wonderful choice as it looks solid in regard to decreasing risk of AD, the longer you are on them the better. The recent Mendelian Randomization study saw >70% reduction, and with ezetimibe like mutations >80% reduction in AD. However, this would be the effect of using them lifelong.
Then over the short term, a well done trial looked like 60% rate reduction I believe (from memory) for ApoE4 carriers who went on a statin - albeit this was a short study.
I’d say skip the pterostilbene as if it has benefit, it’ll be small … treat the LDL / ApoB with a combination of Ezetimibe and a Statin would be my take on it.
As usual, consult your physician … but two drugs that hit your LDL, each of which decreases risk of AD … if worried about AD … I’d jump on that plan.
Rapamycin enhances neurovascular, peripheral metabolic, and immune function in cognitively normal, middle-aged APOE4 Carriers: genotype-dependent effects compared to non-carriers
“Impaired kidney function has been linked to altered concentrations of blood biomarkers of Alzheimer disease (AD), but the underlying mechanisms and its potential role in dementia development remain poorly understood. We explored the associations between estimated glomerular filtration rate (eGFR), blood-based biomarkers of AD, and dementia development.”
“The aims of this study were (1) to explore the cross-sectional association between estimated glomerular filtration rate (eGFR) and a comprehensive panel of AD blood biomarkers; (2) to quantify the hazard of dementia across different eGFR values over a 16-year period; and (3) to investigate the potential modifying effect of kidney function in the association between AD blood biomarkers and dementia.”
“The possible mechanisms by which kidney dysfunction alters the circulating levels of AD blood biomarkers are not yet fully understood—and include peripheral mechanisms, direct effects on neuropathology, or both. Indeed, it is plausible to hypothesize that reduced GFR impairs the peripheral clearance of these molecules, subsequently leading to an increase in their blood levels.35 Nonetheless, it is also plausible that a decline in kidney function is directly implicated in neuropathology,16,18 and that biomarker levels increase as a mere consequence of it. In fact, both the accumulation of uremic toxins and the release of neuroinflammatory cytokines that accompany CKD have been associated with neurotoxicity and nonspecific brain damage,17,36,37 which could contribute to dementia development. Of note, the older age and the higher comorbidity burden among participants with impaired kidney function might indicate the presence of underlying mixed brain pathology, which could also partially account for the elevated levels of biomarkers—especially NfL—observed in this subgroup.”
