Confirm you reopen the same edition and copy stored in Applications. App Store, direct, and beta copies can maintain separate settings.
Change one preference, quit normally, and reopen. A force quit during a write can prevent persistence.
Remember that thresholds and ignore rules affect new scans, not an already open result.
An organization profile or read-only environment can enforce settings. Contact the administrator for a managed Mac.
If the issue continues, record the exact setting, before-and-after values, edition, version, and whether all preferences or only one are affected.