Use of Alzheimer’s Disease Cerebrospinal Fluid Biomarkers in A Tertiary Care Memory Clinic

Abstract

Introduction: Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers are promising tools to help identify the underlying pathology of neurocognitive disorders. In this manuscript, we report our experience with AD CSF biomarkers in 262 consecutive patients in a tertiary care memory clinic. Methods: We retrospectively reviewed 262 consecutive patients who underwent lumbar puncture (LP) and CSF measurement of AD biomarkers (Aβ1–42, total tau or t-tau, and p-tau181). We studied the safety of the procedure and its impact on patient’s diagnosis and management. Results: The LP allowed to identify underlying AD pathology in 72 of the 121 patients (59%) with early onset amnestic mild cognitive impairment (aMCI) with a high probability of progression to AD; to distinguish the behavioral/dysexecutive variant of AD from the behavioral variant of frontotemporal dementia (bvFTD) in 25 of the 45 patients (55%) with an atypical neurobehavioral profile; to identify AD as the underlying pathology in 15 of the 27 patients (55%) with atypical or unclassifiable primary progressive aphasia (PPA); and to distinguish AD from other disorders in 9 of the 29 patients (31%) with psychiatric differential diagnoses and 19 of the 40 patients (47%) with lesional differential diagnoses (normal pressure hydrocephalus, encephalitis, prion disease, etc.). No major complications occurred following the LP. Interpretation: Our results suggest that CSF analysis is a safe and effective diagnostic tool in select patients with neurocognitive disorders. We advocate for a wider use of this biomarker in tertiary care memory clinics in Canada.

Clinical utility of fluid biomarkers in the evaluation of cognitive impairment: a systematic review and meta-analysis

“…Five studies, comprising 918 patients, evaluated the impact on CSF biomarkers on patient management 29,30,35,36,43 . The overall proportion of patients whose management changed after availability of fluid biomarkers ranged between 13-47%, and the overall pooled proportion of patients whose management changed was 31% (95% CI 12–50) with substantial heterogeneity (I 2 : 97%, p < 0.001) (Fig.…”

“…Most (13 of 18, 72%) of the included studies were prospective observational studies [27][28][29][30][31][32][33][34][35][36][37][38] . ,…”

“…Outcome measures are described in Table 2. The majority (14 of 18, 78%) of studies required the clinician to complete a pre-and post-CSF results questionnaire, listing initial and final diagnoses respectively [27][28][29][30][31][33][34][35][36][37][38]43,44 . Of these studies, eight examined how CSF biomarker results changed diagnostic confidence [29][30][31][32][33]38,43,44 , and seven assessed their impact on patient management, defined as the initiation or discontinuation of dementia medications such as cholinesterase inhibitors, the ability to enrol in clinical trials, and/or length of follow-up [29][30][31]34,36,43,44 .…”

From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer’s Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients

“…They have been proven useful in cases with primary progressive aphasia [51], corticobasal syndrome [57], and cases of AD mixed with Lewy body pathology [58] or cerebrovascular disease [14,59]. They can identify the concomitant presence of AD in cases with normal pressure hydrocephalus [60,61], and possibly predict a worse neurosurgical prognosis [62], although recent data suggest that they may predict the opposite [16].…”

Logogenic Primary Progressive Aphasia or Alzheimer Disease: Contribution of Acoustic Markers in Early Differential Diagnosis

“…An inequality of accessibility depending on place of residence and the expensive cost have been raised as obstructions to early diagnosis [ 29 , 35 ]. Nonetheless, CSF biomarkers, associated with clinical and neuroimage analyses, remain the most sensitive and specific diagnostic tool to discriminate AD at initial phases from other neurodegenerative pathologies [ 37 ].…”