Factors Influencing Successful Lumbar Puncture in Alzheimer Research

Abstract

Objective Lumbar puncture (LP) is increasingly common in Alzheimer disease research; however, agreement to undergo LP varies. We sought to determine factors influencing LP consent at Alzheimer’s Disease Centers (ADCs) in the United States. Methods A three-part survey was distributed to each ADC: 1) ADC LP Experience; 2) LP Requestor Experience; and 3) Patient LP Experience (both Initial and Follow-up). 64 LP Requestor, 579 Patient/Initial, and 404 Patient/Follow-up surveys were collected. Logistic regression analyses with generalized estimating equations were used to assess factors associated with LP agreement and post-LP complications. Results Asians and those viewing LP negatively were less likely to agree to LP. Three hundred and fifty-two participants had an LP; LP headache occurred in 11.9% (blood patch required in 1.4%) and 9.9% reported other complications. Younger individuals, women, those diagnosed with mild cognitive impairment, use of a Quincke needle, ≤20mL cerebrospinal fluid drawn, and hemorrhage during LP were associated with LP headache. Use of gravity flow during LP was associated with fewer other complications (nausea, dizziness, vasovagal response, back pain, neck stiffness, and/or nerve root pain). Conclusions LP in AD research is generally safe and well-tolerated. Factors influencing LP agreement potentially could be studied to advance participant acceptance of the procedure.

New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer’s disease

“…Most fluid biomarkers that have proven valuable for the diagnosis or monitoring of AD have been measured in CSF. Lumbar puncture, which is necessary to obtain CSF, is generally safe and well tolerated; however, it is time consuming and sometimes results in postpuncture headache and other side effects 97 . There are increasing efforts to develop easily assessable fluid biomarkers (e.g., from peripheral sources).…”

CSF Pressure, Volume, and Post‐Dural Puncture Headache: A Case‐Control Study and Systematic Review

“…Among studies evaluating V, a significant association with PDPH was identified by 4/14 (28.5%) . An increased volume of CSF withdrawal was associated with either reduced PDPH risk by 2/4 (50%), or increased PDPH risk in 1 study . Finally, Monserrate demonstrated an increased risk with either high or low volume removal, depending on the timing of the outcome .…”

“…Manual review of abstracts and/or full texts identified 22 unique references evaluating the relationship between CSF volume and/or pressure measurements and PDPH incidence (Fig. ) . The references included analysis of V (n = 14), OP (n = 11) and/or CP (n = 4) (Table ).…”

“…Chan et al documented an adjusted OR (95% CI) of 0.17 (0.04‐0.79) in comparing 20 mL vs 10 mL volume removal for any headache occurring within 3 days of the LP . Moulder et al evaluated a prospective cohort utilizing ICHD‐2 criteria, reporting an adjusted OR (95% CI) of 0.52 (0.31‐0.87) comparing volume removal >20 mL to ≤20 mL as a reference . Hammond et al reported an adjusted OR (95% CI) of 1.47 (1.01‐2.14) for every additional 5 mL as compared to 0‐5 mL removal, based on prospective data at post‐procedural day 2‐5 .…”

“…The data concerning V appears to be more nuanced, with the majority of studies not documenting an association. Instances of documented association are notable for inclusion of cases with high‐volume removal (>20 mL, >30 mL), and/or dissection of the interaction between timing of headache and volume removal . Accordingly, high‐volume loss may predispose to immediate headache, but subsequently facilitate earlier dural closure, as higher volumes are associated with 24 hour headache risk reduction .…”