We have had three circumstances where a President was unable to handle the job due to health issues, but refused to step aside.
Woodrow Wilson suffered a stroke in the fall of 1919, and was basically incapacitated for the remaining year and a half of his Presidency, but refused to resign, and his wife conducted cabinet meetings.
Franklin D. Roosevelt had congestive heart failure in 1944, and should not have run for a fourth term, but did anyway.,
Ronald Reagan had clear cut dementia, noticed by 1986-1987, but his wife Nancy and his top advisers covered for him in his last years in office.
Also, Donald Trump clearly has signs of mental deterioration for anyone who wishes to be honest.
And now, Joe Biden has what some people think are early signs of dementia, but not clear cut at this point.
We are likely to face a situation where either Donald Trump or Joe Biden will likely be President in the next term, but might not be able to finish the term.
It is sad but reality that Donald Trump would never resign if he was incapable of doing his job, but Joe Biden needs to be willing to step aside if his early signs become more evident during a future Presidency.
Some would say we have the 25th Amendment to allow for the Vice President to be “Acting President”, but that is more useful for physical ailments than mental ailments.
Looking back, Reagan was the first President under the 25th Amendment situation, and now Trump, both of them the oldest Presidents in office.
Joe Biden, or even Bernie Sanders, would be easily the most advanced in age, and while the 25th Amendment could be used, it does not seem adeqate if mental deterioration is present.
If anything, this situation that we are now presented with is an argument for Joe Biden to pick the best possible Vice President, who could be fully ready to take the oath of office if Biden, at some point, could not handle the job of President.