We focused on the diagnostic value of Cerebrospinal Fluid (CSF) biomarker assays in older patients. Literature data on this topic are very scarce. CSF biomarkers now constitute an additional body of evidence in the diagnosis of Alzheimer Disease, along with clinical observations, neuropsychological data and imaging findings. We present data obtained in a geriatric memory clinic (Lille, France) over 10 years. We included solely patients having undergone Lumbar Puncture (LP) with diagnostic intent, i.e., when the clinical, neuropsychological and imaging data had not enabled the clinic’s physicians to establish a certain diagnosis. A total of 3,236 patients attended our memory clinics; 37 of them underwent LP. The application of CSF biomarker assays enabled rectification of the clinical diagnosis in 35.1% of cases. The diagnosis of cognitive disorders must always be based on a personalized approach.