That's also a thing of the past. That is no longer relevant as Windows 10 not only has a much smaller pagefile, but the amount of paging is less than older OS'es especially if you have way more RAM that the OS needs. Besides, OP has most likely just upgraded to 10 and inherited all the problems, which is a bad idea in general.

I have an old 500GB 7200RPM that I use as a flash disk and no matter if I put it in USB 3 or directly on a SATA port, or using another filesystem it still is getting slower (at least slower than it used to be).

Main causes for slowdown/problems:
Programs, be it something in the foreground or in the background. Badly written/optimized.
Viruses/worms/root-kit
Badly configured software/hardware
OS itself (filesystem is one thing, but the OS itself, like Windows, becomes like a noodle soup chaos. In Linux you can in most cases fix problems with the software, but not on Windows, even as Admin/root)
Corruptions (software or hardware).
Damaged/old harddrive.
EDIT: Low space on RAM or HDD

NTFS isn't directly terrible, but not as good as others out there, so when it comes to defragmentation Windows uses a lot of metadata files which you can't normally defragment. Normal defrag tools doesn't defragment the indexes/metafiles, that is something one can do with the contig tool by Mark Russinovich (now a part of MS sysinternals).

SSD's do actually have faster slowdowns with NTFS compared to EXT4, and it's more noticeable the more files and folders you have. Using NTFS in network links is a nightmare because they can extend longer than 255 characters, which Windows is known for not handling well.

Like I wrote earlier, it's not worth it timewise to obsess too much on exactly what/where the problem is, the diagnosis here is clear: Buy a new harddrive (SSD) and install a clean Windows 10 (and then tweak it), or buy a new laptop (and then clean/tweak it).

A time ago i made a thread where in full text i give a basic tutorial to how disable all 4 telemetry's in windows 10(1909) they are the reason you get hard disk almost 100% of usage.

You can find it here: https://www.gog.com/forum/general/windows_tweaking

In my experience, slowdown seems to be exclusively a problem with laptops, every laptop i have ever used has done it, every laptop used by a friend or coworker has done it... i have always owned desktops as well, they never do it.

I've definitely seen it happen, but always on non-gaming desktops sold for cheap. I went through a long period where I didn't game much and had like a 6 year old CPU/GPU, and yeah it still ran pretty well for normal Windows tasks.

Do you play games on your laptop's keyboard …
… And looking at your laptop's screen?

most slow down due to old battery and then cpu is clocked down