Mendeley HiDPI manifest (copy this to C:\Program Files (x86)\Mendeley Desktop\)

MendeleyDesktop.exe.manifest

<?xml version="1.0" encoding="UTF-8" standalone="yes"?>

<assembly xmlns="urn:schemas-microsoft-com:asm.v1" manifestVersion="1.0" xmlns:asmv3="urn:schemas-microsoft-com:asm.v3">

<dependency>
  <dependentAssembly>
    <assemblyIdentity
      type="win32"
      name="Microsoft.Windows.Common-Controls"
      version="6.0.0.0" processorArchitecture="*"
      publicKeyToken="6595b64144ccf1df"
      language="*">
    </assemblyIdentity>
  </dependentAssembly>
</dependency>

<dependency>
  <dependentAssembly>
    <assemblyIdentity
      type="win32"
      name="Microsoft.VC90.CRT"
      version="9.0.21022.8"
      processorArchitecture="amd64"
      publicKeyToken="1fc8b3b9a1e18e3b">
    </assemblyIdentity>
  </dependentAssembly>
</dependency>

<trustInfo xmlns="urn:schemas-microsoft-com:asm.v3">
  <security>
    <requestedPrivileges>
      <requestedExecutionLevel
        level="asInvoker"
        uiAccess="false"/>
    </requestedPrivileges>
  </security>
</trustInfo>

<asmv3:application>
  <asmv3:windowsSettings xmlns="http://schemas.microsoft.com/SMI/2005/WindowsSettings">
    <ms_windowsSettings:dpiAware xmlns:ms_windowsSettings="http://schemas.microsoft.com/SMI/2005/WindowsSettings">false</ms_windowsSettings:dpiAware>
  </asmv3:windowsSettings>
</asmv3:application>

</assembly>

I think the system enhanced settings of high dpi display for mendeley is not perfect. You will get a blurred image

And I tried to add the registry manifest once but failed to yield reasonable result. I will try again this time.

Update: this time it works but yielded the same result as setting the high dpi display option.

In fact I found that another option which may be helpful:
Mendeley is written using QT, and QT program reads a universal environment variable, QT_AUTO_SCREEN_SCALE_FACTOR, to determine the scaling factor. set QT_AUTO_SCREEN_SCALE_FACTOR to 1, you will get a perfect ui(normal size, not blurring), BUT A MALFUNCTIONAL PDF READING INTERFACE. (like this)

I used the approach described above by @patrickmdnet except I checked the top box in the menu, rather than the over-ride box.

It seems to be working well for both the UI and the pdf reader.

Thank you @evanmascitti, your solution is superior and does not scale down the resolution of the icons.

Thank you, @evanmascitti. I was baffled at why my Mendeley was suddenly TINY, but this fixed it and it looks like it did before my last Windows update.

Thank you, @evanmascitti. I was baffled at why my Mendeley was suddenly TINY, but this fixed it and it looks like it did before my last Windows update.

Glad that you found it useful!