Supplementation is going to be most effective when taken at the earliest stage, and there is currently insufficient evidence to answer whether higher doses are needed to provide benefit at later stages. Although mechanistically this would make sense it will be confounded by genotype etc., especially APOE. As regards the optimal dose, the available evidence suggests that higher doses (e.g., DHA/EPA above 1 g/day) appear generally more effective, and many multinutrient supplements which contain a combination of phospholipids, DHA/EPA, and B vitamins typically contain very low levels of nutrients, especially of DHA/EPA and B vitamins (where they are much lower than the doses shown to be effective in the trials). It may therefore be better to take a variety of supplements to achieve the greatest benefits.  

The short answer is that no, we’re not at the point in time where we can get certain images of the brain, pinpoint certain exercises, and then reliably see changes afterwards. Part of the problem is a lack of large population data and standardised imaging to benchmark against. We have it for MRI volumetrics but you really want DTI as well to look at white matter tracts, plus EEG to look at network function. A targeted training approach has been suggested a few times in the literature (see Fig 2 in Turrini et al. attached for an example, though I don’t think their prescriptions are precise enough). And we do know that strength training improves white matter structure, cardio/HIIT improves hippocampal structure/function (but you could also use olfactory stimulation or meditation depending on the individual), and processing speed training improves attention networks etc. We also know that complex creative skills bolster a number of networks that are susceptible to aging. However, nobody has tested a targeted approach where people are randomised/stratified based on imaging to different training types. I would also perhaps argue that there may be downsides to doing that. An ideal approach would almost certainly be a balance of exercise modalities in addition to learning a complex skill, and I would recommend that regardless of what a brain scan shows. So for now, anybody selling targeted interventions based on brain imaging is probably a bit ahead of the evidence.

That is a really great question!! And throughout ALL time individual variation is wide, but why is our average menopausal age 52 when it used to be 40?!  I think it’s unknown but would suspect it’s overall better nutrition, less infectious disease.  And now puberty and perimenopause likely EARLIER than 20 years ago because of environmental endocrine disruptors: ubiquitous and mostly unknown!

Several changes from early 20th century:  YES higher allostatic load for all of us… I kind of think there was a sweet spot of advances in our nutrition immune health 1950-2000, lots of open spaces,  pollution more limited to industrial sites…  and now many disadvantaged people have more opportunities but tension are rising, too, as are hidden pollutants: microplastics? and 24/7 plugged-in culture is stressful in and of itself and of course affects our sleep, our hormones, and more!

Sorry I wasn’t clear: CONVENTIONAL wisdom is start HRT at menopause and think of stopping around the age of 60.

MY opinion is start as early as you can, but TODAY is a good day if you’ve missed your “as early as you can” possibility… and CONTINUE for as long as you can.  (Heading for 78, I’ve been happily on BHRT for… 26 years?). Reasons to discontinue may arise (other stressors in life or health) but there is no automatic reason to discontinue at any given age.

The lymphatic system does indeed clear Abeta from the brain, but it probably does not clear all species of Abeta equally. Monomers and small oligomers will be handled easily, but larger aggregates (plaques for example) are too large to pass. Also, Abeta can catch a ride out of the brain on the ApoE lipid carrier. That pathway is different from the lymphatic system but also clears brain Abeta.

The “efficiency” of Abeta or tau production is hard to gauge directly. It will depend on the age of the brain in question for sure. The other point of note that this question brings up is that neurons are not the only brain cell type that produce Abeta. All cells in the brain make APP and there is direct experimental evidence that oligodendrocytes can make Abeta and (at least in mouse) this oligo-generated Abeta is part of the plaque pathology. And just to make life even more complicated, Abeta produced in liver can produce neurodegenerative events in brain so the central/peripheral question is also important