I think that the main reason that inhibited the adoption of the Kindle DX was its poor PDF support (not TOC, no annotations), and the slow speed of page turning.
I also think that they need to add the ability to open a few books simultaneously (in tabs), which might help research (if you want to compare two or more books at the same time).
As long as you have decent navigation (real page numbers, fixed page sizes, linkable TOC) I think that we can easily get by without parts of congnitive mapping.
So maybe you won't be able to remember where some page was in a book, but you'd still remember after (or before) which page it is located, and where a particular sentence or word was on the page.
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