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213Identifying Prodromal Alzheimer’s Disease - Clinical Incorporation of CSF Biomarkers into the Diagnostic Paradigm in a Memory Clinic Setting

Background: Updated diagnostic guidelines for Alzheimer’s disease (AD) recommend utilisation of biomarkers including cerebrospinal fluid (CSF) to support diagnosis. Individuals with Amnestic Mild Cognitive Impairment (aMCI) with positive AD biomarkers are at considerably higher risk of converting to AD within three years and diagnosed as Mild Cognitive Impairment Alzheimer-Type (MCI-AD). The aim of this study was to evaluate the feasibility of integrating CSF biomarker testing within a memory clinic setting, and to investigate if testing refined the diagnosis in aMCI. Methods: Diagnosis of aMCI was based on standard clinical assessment, neuroimaging, and detailed multi-domain neuropsychological testing, followed by discussion at consultant-led multidisciplinary meeting. Newly diagnosed aMCI individuals were offered further testing for CSF Amyloid, Phosphorylated Tau (P-Tau) and Tau levels. Lumbar puncture was performed within the memory clinic and CSF was analysed in a nationally-accredited laboratory. Amyloid values ≤135 pg/ml, in conjunction with p-tau levels ≥64 pg/ml, and/or Tau values ≥345 pg/ml were consistent with Alzheimer’s type pathology. Results: Testing was performed in 15 patients with aMCI. Mean age was 72 years and 53% (8/15) were male. Two thirds (10/15) had CSF biomarkers consistent with Alzheimer-type pathology and their diagnosis was refined to Mild Cognitive Impairment Alzheimer-Type (MCI-AD). 5 (33%) patients did not meet criteria for AD pathology and therefore had Suspected NonAlzheimer’s pathology (SNAP). There were no significant differences between the MCI-AD and SNAP groups in scores on cognitive domains of immediate and delayed memory, language, attention and visuospatial and constructional ability. Conclusions: This study demonstrates that it is feasible to incorporate CSF testing for AD biomarkers within a memory clinic and that it led to diagnostic refinement in two thirds of patients with aMCI. Identification of such high-risk groups is important from a future preventative perspective, especially with regards to risk factor and lifestyle modification.