Background: Despite an extensive evaluation program, patients may remain diagnostically unresolved with regard to the etiology of their cognitive dysfunction. Cerebrospinal fluid neuroinflammation and Alzheimer disease (AD) biomarkers may act as indicators of neurodegenerative disorders in diagnostically unresolved patients. Methods: Data on 348 patients were retrospectively evaluated. All participants had a standardized diagnostic workup and follow-up in a memory clinic. Results: Aβ42 levels and Aβ42/p-tau ratios were reduced and levels of t-tau and p-tau as well as the t-tau × p-tau/Aβ42 ratio were elevated in diagnostically unresolved patients who clinically progressed, compared to a stable group. No differences in neuroinflammatory parameters were found. Conclusion: AD biomarkers-in particular the Aβ42/p-tau ratio, but not neuroinflammatory parameters-predicted clinical progression, regardless of etiology.