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Review
. 2022 Jan;18(1):159-177.
doi: 10.1002/alz.12372. Epub 2021 May 27.

State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer's disease

Harald Hampel  1 , Leslie M Shaw  2 , Paul Aisen  3 , Christopher Chen  4 , Alberto Lleó  5   6 , Takeshi Iwatsubo  7 , Atsushi Iwata  8 , Masahito Yamada  9 , Takeshi Ikeuchi  10 , Jianping Jia  11 , Huali Wang  12 , Charlotte E Teunissen  13 , Elaine Peskind  14 , Kaj Blennow  15   16 , Jeffrey Cummings  17 , Andrea Vergallo  1
Affiliations
Review

State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer's disease

Harald Hampel et al. Alzheimers Dement. 2022 Jan.

Abstract

Recent advances in developing disease-modifying therapies (DMT) for Alzheimer's disease (AD), and the recognition that AD pathophysiology emerges decades before clinical symptoms, necessitate a paradigm shift of health-care systems toward biomarker-guided early detection, diagnosis, and therapeutic decision-making. Appropriate incorporation of cerebrospinal fluid biomarker analysis in clinical practice is an essential step toward system readiness for accommodating the demand of AD diagnosis and proper use of DMTs-once they become available. However, the use of lumbar puncture (LP) in individuals with suspected neurodegenerative diseases such as AD is inconsistent, and the perception of its utility and safety differs considerably among medical specialties as well as among regions and countries. This review describes the state-of-the-art evidence concerning the safety profile of LP in older adults, discusses the risk factors for LP-associated adverse events, and provides recommendations and an outlook for optimized use and global implementation of LP in individuals with suspected AD.

Keywords: Alzheimer's disease; biomarker; cerebrospinal fluid; diagnosis; evidence-based guidelines; lumbar puncture; system readiness.

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Conflict of interest statement

H. Hampel is an employee of Eisai Inc. and serves as Senior Associate Editor for the journal Alzheimer's & Dementia. He has not received any fees or honoraria since May 2019. Before May 2019, he was a consultant for, and had received lecture fees from, Servier, Biogen, and Roche; research grants from Pfizer Inc., Avid, and MSD Avenir (paid to the institution); travel funding from Eisai Inc., Functional Neuromodulation, Axovant, Eli Lilly and Company, Takeda and Zinfandel, GE Healthcare, and Oryzon Genomics; consultancy fees from Qynapse, Jung Diagnostics, Cytox Ltd., Axovant, Anavex, Takeda and Zinfandel, GE Healthcare, Oryzon Genomics, and Functional Neuromodulation; and participated in the scientific advisory boards of Functional Neuromodulation, Axovant, Eisai Inc., Eli Lilly and Company, Cytox Ltd., GE Healthcare, Takeda and Zinfandel, Oryzon Genomics, and Roche Diagnostics.

He is co‐inventor in the following patents as a scientific expert and has received no royalties:

  1. In Vitro Multiparameter Determination Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders. Patent Number: 8916388

  2. In Vitro Procedure for Diagnosis and Early Diagnosis of Neurodegenerative Diseases. Patent Number: 8298784

  3. Neurodegenerative Markers for Psychiatric Conditions. Publication Number: 20120196300

  4. In Vitro Multiparameter Determination Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders. Publication Number: 20100062463

  5. In Vitro Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders. Publication Number: 20100035286

  6. In Vitro Procedure for Diagnosis and Early Diagnosis of Neurodegenerative Diseases. Publication Number: 20090263822

  7. In Vitro Method for The Diagnosis of Neurodegenerative Diseases. Patent Number: 7547553

  8. CSF Diagnostic in Vitro Method for Diagnosis of Dementias and Neuroinflammatory Diseases. Publication Number: 20080206797

  9. In Vitro Method for The Diagnosis of Neurodegenerative Diseases. Publication Number: 20080199966

  10. Neurodegenerative Markers for Psychiatric Conditions. Publication Number: 20080131921

P. Aisen reports grants from Janssen, Eisai Inc., National Institute on Aging, Foundation for the National Institutes of Health, and the Alzheimer's Association; and consulting fees from Merck, Biogen, Roche, Lundbeck, and Immunobrain Checkpoint. C. Chen has provided consultation to Cerecin, Danone, Eisai Inc., Lundbeck, Moleac, and Senescence. A. Lleó has served as a consultant or on advisory boards for Fujirebio‐Europe, Roche, Biogen, and Nutricia. Dr. Lleó has received funding from the Fondo de Investigaciones Sanitario (FIS), Instituto de Salud Carlos III (AC19/00103), and the CIBERNED program (Program 1, Alzheimer Disease) partially funded by Fondo Europeo de Desarrollo Regional, Unión Europea, Una manera de hacer Europa. In addition, Dr. Lleó has patent WO2019175379 A1 Markers of synaptopathy in neurodegenerative disease. A. Iwata has received lecture and consultant fees from Eisai Inc. M. Yamada has received research grants from the Japan Society for the Promotion of Science (JSPS); the Ministry of Health, Labour and Welfare, Japan (MHLW); and the Japan Agency for Medical Research and Development (AMED). He has received scholarship grants from Astellas Pharma Inc.; Eisai Co., Ltd.; Otsuka Pharmaceutical Co., Ltd.; Kyowa Kirin Co., Ltd.; Shionogi Co., Ltd.; Daiichi Sankyo Healthcare Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Tsumura & Co.; Teijin Pharma, Ltd.; Nihon Medi‐Physics Co., Ltd.; Fujifilm Co.; Pfizer Japan Inc.; and Ricoh Co., Ltd. He received honoraria for sponsored lectures from Alnylam Japan K.K.; Alexion Pharma GK; Eisai Co., Ltd.; FP Pharmaceutical Co.; Otsuka Pharmaceutical Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Sumitomo Dainippon Pharma Co., Ltd.; Daiichi Sankyo Healthcare Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Tsumura & Co.; Teijin Pharma, Ltd.; Nippon Chemiphar Co., Ltd.; Nihon Medi‐Physics Co., Ltd.; Nihon Pharmaceutical Co., Ltd.; Biogen Japan Ltd.; Fujifilm Co.; and Janssen Pharmaceutical K.K. T. Ikeuchi has provided consultation to Eisai Inc., Takeda, Janssen, Chugai, and Ono, and received lecture honoraria from Eisai Inc., Daiichi Sankyo, Novartis, Janssen, Takeda, Roche, and FUJIFILM RI Pharma. J. Jia has provided consultation to Eisai Inc., Novartis, Green Valley, Eli Lilly and Company, AstraZeneca, and CSPC‐NBP. H. Wang has provided consultation to Eisai Inc., Lundbeck, Roche, and Signant Health pharmaceutical and assessment companies. Dr. Wang owns the copyright of the individualized management system of neuropsychiatric symptoms (NPSIMS). C.E. Teunissen has a collaboration contract with ADx Neurosciences and Quanterix, and performed contract research for or received grants from Axon Neurosciences, Biogen, Boehringer Ingelheim, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai inc., Janssen Prevention Center, Roche, Toyama, and Vivoryon. K. Blennow has served as a consultant, on advisory boards, or data monitoring committees for Abcam, Axon Neurosciences, Biogen, JOMDD/Shimadzu, Julius Clinical, Eli Lilly and Company, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is part of the GU Ventures Incubator Program. J. Cummings has provided consultation to Acadia, Actinogen, Alkahest, Alzheon, Annovis, Avanir, Axsome, Biogen, Cassava, Cerecin, Cerevel, Cortexyme, Cytox, EIP Pharma, Eisai inc., Foresight, GemVax, Genentech, Green Valley, Grifols, Karuna, Merck, Novo Nordisk, Otsuka, Resverlogix, Roche, Samumed, Samus, Signant Health, Suven, and United Neuroscience pharmaceutical and assessment companies. Dr. Cummings has stock options in ADAMAS, AnnovisBio, MedAvante, and BiOasis. Dr. Cummings owns the copyright of the Neuropsychiatric Inventory. A. Vergallo is an employee of Eisai Inc. He has not received any fees or honoraria since November 2019. Before November 2019, he had received lecture honoraria from Roche, MagQu LLC, and Servier. E. Peskind has provided consultation to Acadia, Avanir, Eli Lilly and Company, and Takeda.

Figures

FIGURE 1
FIGURE 1
Estimated growth in dementia relative to the size of the aged 60+ population by region. Global incidence and projected growth in numbers of people living with dementia
FIGURE 2
FIGURE 2
Guidance for a safe lumbar puncture. Expert consensus recommendations for reducing the risk of adverse events after lumbar puncture in patients with neurological diseases,
FIGURE 3
FIGURE 3
Current barriers to widespread use of lumbar puncture (LP) in Alzheimer's disease (AD) diagnosis. Factors negatively influencing the widespread use of LP in AD diagnosis include patient‐related, physician‐related, and health system infrastructure‐related barriers., , , , CSF, cerebrospinal fluid
See this image and copyright information in PMC

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