If you aren't changing the settings, what is there to persist? I'm still not quite sure what your problem is. If I create a setting called "MySetting" that is a string and has user scope with the value of "DefaultValue", the following code will display "DefaultValue" the first time I run the application and "Changed" the second time I run it:
Public Class Form1
Private Sub Form1_Load(ByVal sender As System.Object, _
ByVal e As System.EventArgs) Handles MyBase.Load
MsgBox(My.Settings.MySetting)
My.Settings.MySetting = "Changed"
My.Settings.Save()
End Sub
End Class