A neurologist’s perspective on serum neurofilament light in the memory clinic: a prospective implementation study

Abstract Background Neurofilament light in serum (sNfL) is a biomarker for axonal damage with elevated levels in many neurological disorders, including neurodegenerative dementias. Since within-group variation of sNfL is large and concentrations increase with aging, sNfL’s clinical use in memory clinic practice remains to be established. The objective of the current study was to evaluate the clinical use of serum neurofilament light (sNfL), a cross-disease biomarker for axonal damage, in a tertiary memory clinic cohort. Methods Six neurologists completed questionnaires regarding the usefulness of sNfL (n = 5–42 questionnaires/neurologist). Patients that visited the Alzheimer Center Amsterdam for the first time between May and October 2019 (n = 109) were prospectively included in this single-center implementation study. SNfL levels were analyzed on Simoa and reported together with normal values in relation to age, as part of routine diagnostic work-up and in addition to cerebrospinal fluid (CSF) biomarker analysis. Results SNfL was perceived as useful in 53% (n = 58) of the cases. SNfL was more often perceived as useful in patients < 62 years (29/48, 60%, p = 0.05) and males (41/65, 63%, p < 0.01). Availability of CSF biomarker results at time of result discussion had no influence. We observed non-significant trends for increased perceived usefulness of sNfL for patients with the diagnosis subjective cognitive decline (64%), psychiatric disorder (71%), or uncertain diagnosis (67%). SNfL was mostly helpful to neurologists in confirming or excluding neurodegeneration. Whether sNfL was regarded as useful strongly depended on which neurologist filled out the questionnaire (ranging from 0 to 73% of useful cases/neurologist). Discussion Regardless of the availability of CSF biomarker results, sNfL was perceived as a useful tool in more than half of the evaluated cases in a tertiary memory clinic practice. Based on our results, we recommend the analysis of the biomarker sNfL to confirm or exclude neurodegeneration in patients below 62 years old and in males.

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Serum neurofilament light in memory clinic practice

Alzheimer s & Dementia ◽

10.1002/alz.045155 ◽

2020 ◽

Vol 16 (S5) ◽

Author(s):

Eline A.J. Willemse ◽

Charlotte E. Teunissen ◽

Philip Scheltens ◽

Everard Vijverberg

Keyword(s):

Memory Clinic ◽

Neurofilament Light ◽

Clinic Practice

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Use of Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Risk in Mild Cognitive Impairment and Subjective Cognitive Decline in Routine Clinical Care in Germany

Journal of Alzheimer s Disease ◽

10.3233/jad-200794 ◽

2020 ◽

Vol 78 (3) ◽

pp. 1137-1148

Author(s):

Claudia Bartels ◽

Anna Kögel ◽

Mark Schweda ◽

Jens Wiltfang ◽

Michael Pentzek ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Clinical Care ◽

Subjective Cognitive Decline ◽

Csf Biomarkers ◽

Routine Clinical Care ◽

Biomarker Analysis ◽

Csf Biomarker

Background: The National Institute of Aging and Alzheimer’s Association’s diagnostic recommendations for preclinical Alzheimer’s disease (AD) and mild cognitive impairment (MCI) define AD by pathological processes which can be detected by biomarkers. These criteria were established as part of a research framework intended for research purposes but progressively enter the clinical practice. Objective: We investigated the availability, frequency of use, interpretation, and therapeutic implications of biomarkers for the etiologic diagnosis and prognosis in MCI and subjective cognitive decline (SCD) in routine clinical care. Methods: We conducted a cross-sectional questionnaire survey among 215 expert dementia centers (hospitals and memory clinics) in Germany. Results: From the 98 centers (45.6% of contacted centers) included, two-thirds reported use of the cerebrospinal fluid (CSF) biomarkers Aβ42, tau, and phospho-tau in the diagnostic workup of MCI and one third in SCD. CSF biomarker analysis was more often employed by neurological (MCI 84%; SCD 42%) compared to psychiatric institutions (MCI 61%; SCD 33%; p≤0.001). Although dementia experts disagreed on the risk of progression associated with different CSF biomarker constellations, CSF biomarker results guided therapeutic decisions: ∼40% of responders reported to initiate cholinesterase inhibitor therapy in MCI and 18% in SCD (p = 0.006), given that all CSF biomarkers were in the pathological range. Conclusion: Considering the vast heterogeneity among dementia expert centers in use of CSF biomarker analysis, interpretation of results, and therapeutic consequences, a standardization of biomarker-based diagnosis practice in pre-dementia stages is needed.

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Serum markers glial fibrillary acidic protein and neurofilament light for prognosis and monitoring in cognitively normal older people: a prospective memory clinic-based cohort study

The Lancet Healthy Longevity ◽

10.1016/s2666-7568(20)30061-1 ◽

2021 ◽

Vol 2 (2) ◽

pp. e87-e95

Author(s):

Inge M W Verberk ◽

Malika B Laarhuis ◽

Karlijn A van den Bosch ◽

Jarith L Ebenau ◽

Mardou van Leeuwenstijn ◽

...

Keyword(s):

Cohort Study ◽

Glial Fibrillary Acidic Protein ◽

Older People ◽

Prospective Memory ◽

Serum Markers ◽

Acidic Protein ◽

Memory Clinic ◽

Neurofilament Light ◽

Cognitively Normal

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Monitoring concussion in a knocked-out boxer by CSF biomarker analysis

Knee Surgery Sports Traumatology Arthroscopy ◽

10.1007/s00167-014-3066-6 ◽

2014 ◽

Vol 23 (9) ◽

pp. 2536-2539 ◽

Cited By ~ 15

Author(s):

Sanna Neselius ◽

Helena Brisby ◽

Fredrik Granholm ◽

Henrik Zetterberg ◽

Kaj Blennow

Keyword(s):

Biomarker Analysis ◽

Csf Biomarker

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Heterogeneity of Amyloid Binding in Cognitively Impaired Patients Consecutively Recruited from a Memory Clinic: Evaluating the Utility of Quantitative 18F-Flutemetamol PET-CT in Discrimination of Mild Cognitive Impairment from Alzheimer’s Disease and Other Dementias

Journal of Alzheimer s Disease ◽

10.3233/jad-200890 ◽

2020 ◽

pp. 1-14

Author(s):

Yi-Wen Bao ◽

Anson C.M. Chau ◽

Patrick Ka-Chun Chiu ◽

Yat Fung Shea ◽

Joseph S.K. Kwan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Amyloid Β ◽

Standardized Uptake Value ◽

Subjective Cognitive Decline ◽

Cognitively Impaired ◽

Memory Clinic ◽

Pet Ct

Background: With the more widespread use of 18F-radioligand-based amyloid-β (Aβ) PET-CT imaging, we evaluated Aβ binding and the utility of neocortical 18F-Flutemetamol standardized uptake value ratio (SUVR) as a biomarker. Objective: 18F-Flutemetamol SUVR was used to differentiate 1) mild cognitive impairment (MCI) from Alzheimer’s disease (AD), and 2) MCI from other non-AD dementias (OD). Methods: 109 patients consecutively recruited from a University memory clinic underwent clinical evaluation, neuropsychological test, MRI and 18F-Flutemetamol PET-CT. The diagnosis was made by consensus of a panel consisting of 1 neuroradiologist and 2 geriatricians. The final cohort included 13 subjective cognitive decline (SCD), 22 AD, 39 MCI, and 35 OD. Quantitative analysis of 16 region-of-interests made by Cortex ID software (GE Healthcare). Results: The global mean 18F-Flutemetamol SUVR in SCD, MCI, AD, and OD were 0.50 (SD-0.08), 0.53 (SD-0.16), 0.76 (SD-0.10), and 0.56 (SD-0.16), respectively, with SUVR in SCD and MCI and OD being significantly lower than AD. Aβ binding in SCD, MCI, and OD was heterogeneous, being 23%, 38.5%, and 42.9% respectively, as compared to 100% amyloid positivity in AD. Using global SUVR, ROC analysis showed AUC of 0.868 and 0.588 in differentiating MCI from AD and MCI from OD respectively. Conclusion: 18F-Flutemetamol SUVR differentiated MCI from AD with high efficacy (high negative predictive value), but much lower efficacy from OD. The major benefit of the test was to differentiate cognitively impaired patients (either SCD, MCI, or OD) without AD-related-amyloid-pathology from AD in the clinical setting, which was under-emphasized in the current guidelines proposed by Amyloid Imaging Task Force.

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Evaluation of Cerebrospinal Fluid Neurofilament Light Chain as a Routine Biomarker in a Memory Clinic

The Journals of Gerontology Series A ◽

10.1093/gerona/gly179 ◽

2018 ◽

Vol 74 (4) ◽

pp. 442-445 ◽

Cited By ~ 7

Author(s):

Matías Niikado ◽

Patricio Chrem-Méndez ◽

Tatiana Itzcovich ◽

Micaela Barbieri-Kennedy ◽

Ismael Calandri ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Light Chain ◽

Memory Clinic ◽

Neurofilament Light Chain ◽

Neurofilament Light

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Differences in quantitative methods for measuring subjective cognitive decline – results from a prospective memory clinic study

International Psychogeriatrics ◽

10.1017/s1041610216000272 ◽

2016 ◽

Vol 28 (9) ◽

pp. 1513-1520 ◽

Cited By ~ 16

Author(s):

Asmus Vogel ◽

Lise Cronberg Salem ◽

Birgitte Bo Andersen ◽

Gunhild Waldemar

Keyword(s):

Depressive Symptoms ◽

Cognitive Decline ◽

Quantitative Methods ◽

Cognitive Status ◽

Cognitive Test ◽

Subjective Cognitive Decline ◽

Linear Regression Models ◽

Memory Clinic ◽

Subjective Memory ◽

Wide Range

ABSTRACTBackground:Cognitive complaints occur frequently in elderly people and may be a risk factor for dementia and cognitive decline. Results from studies on subjective cognitive decline are difficult to compare due to variability in assessment methods, and little is known about how different methods influence reports of cognitive decline.Methods:The Subjective Memory Complaints Scale (SMC) and The Memory Complaint Questionnaire (MAC-Q) were applied in 121 mixed memory clinic patients with mild cognitive symptoms (mean MMSE = 26.8, SD 2.7). The scales were applied independently and raters were blinded to results from the other scale. Scales were not used for diagnostic classification. Cognitive performances and depressive symptoms were also rated. We studied the association between the two measures and investigated the scales’ relation to depressive symptoms, age, and cognitive status.Results:SMC and MAC-Q were significantly associated (r = 0.44, N = 121, p = 0.015) and both scales had a wide range of scores. In this mixed cohort of patients, younger age was associated with higher SMC scores. There were no significant correlations between cognitive test performances and scales measuring subjective decline. Depression scores were significantly correlated to both scales measuring subjective decline. Linear regression models showed that age did not have a significant contribution to the variance in subjective memory beyond that of depressive symptoms.Conclusions:Measures for subjective cognitive decline are not interchangeable when used in memory clinics and the application of different scales in previous studies is an important factor as to why studies show variability in the association between subjective cognitive decline and background data and/or clinical results. Careful consideration should be taken as to which questions are relevant and have validity when operationalizing subjective cognitive decline.

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