Predicting Survival Rate by Plasma Biomarkers and Clinical Variables in Syndromes Associated with Frontotemporal Lobar Degeneration

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2025 Feb 12

PMID 39936177

Authors

Maria Sofia Cotelli

Barbara Tarantino

Kubra Tan

Hanna Huber

Valentina Cantoni

Valeria Bracca

Roberto Gasparotti

Enrico Premi

Giancarlo Logroscino

Andrea L Benedet

Kaj Blennow

Henrik Zetterberg

Mario Grassi

Nicholas J Ashton

Barbara Borroni

Affiliations

Soon will be listed here.

Abstract

Introduction: Modeling the survival rate in syndromes associated with frontotemporal lobar degeneration (FTLD) is essential to assess disease trajectories.

Methods: In 262 patients with FTLD, we considered plasma neurofilament light chain (NfL), glial fibrillary acidic protein, brain-derived tau, phosphorylated tau217 and amyloid beta (Aβ42/Aβ40). The FTLD Survival Score (FTLD-SS) was calculated by the β coefficients of the variables independently associated with survival rate.

Results: Increased plasma NfL levels (p < 0.001), older age at evaluation (p = 0.002), positive family history (p = 0.04), and motor phenotypes (p < 0.001) were associated with reduced survival. The predictive validity of FTLD-SS was 0.75 (95% confidence interval, 0.59-0.91) at 1 year.

Discussion: Survival rate in FTLD is shaped by intensity of neurodegeneration (using plasma NfL as proxy) together with certain clinical variables. The FTLD-SS may serve as a simple tool for survival rate estimation and for patient stratification in clinical trials.

Highlights: Plasma neurofilament light chain and clinical variables can predict survival in frontotemporal lobar degeneration (FTLD)-associated syndromes. FTLD Survival Score (FTLD-SS), computed with survival predictors, may serve as a simple tool for patient stratification. FTLD-SS is associated with greater atrophy in frontal and putamen areas.

Citing Articles

Predicting survival rate by plasma biomarkers and clinical variables in syndromes associated with frontotemporal lobar degeneration.

Cotelli M, Tarantino B, Tan K, Huber H, Cantoni V, Bracca V Alzheimers Dement. 2025; 21(2):e14558.

PMID: 39936177 PMC: 11815202. DOI: 10.1002/alz.14558.

References

Varela R, Gonzalez-Ortiz F, Dias A, Knuth N, Fonte J, Pinto B . Plasma Brain-Derived Tau in Prognosis of Large Vessel Occlusion Ischemic Stroke. Stroke. 2024; 55(9):2353-2358. DOI: 10.1161/STROKEAHA.123.046117. View

Solje E, Benussi A, Buratti E, Remes A, Haapasalo A, Borroni B . State-of-the-Art Methods and Emerging Fluid Biomarkers in the Diagnostics of Dementia-A Short Review and Diagnostic Algorithm. Diagnostics (Basel). 2021; 11(5). PMC: 8145467. DOI: 10.3390/diagnostics11050788. View

Malpetti M, Swann P, Tsvetanov K, Chouliaras L, Strauss A, Chikaura T . Blood inflammation relates to neuroinflammation and survival in frontotemporal lobar degeneration. Brain. 2024; 148(2):493-505. PMC: 7617268. DOI: 10.1093/brain/awae269. View

Benussi A, Ashton N, Karikari T, Gazzina S, Premi E, Benussi L . Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration. J Alzheimers Dis. 2020; 77(3):1129-1141. DOI: 10.3233/JAD-200608. View

El-Wahsh S, Finger E, Piguet O, Mok V, Rohrer J, Kiernan M . Predictors of survival in frontotemporal lobar degeneration syndromes. J Neurol Neurosurg Psychiatry. 2021; . DOI: 10.1136/jnnp-2020-324349. View

Murley A, Rouse M, Coyle-Gilchrist I, Jones P, Li W, Wiggins J . Predicting loss of independence and mortality in frontotemporal lobar degeneration syndromes. J Neurol Neurosurg Psychiatry. 2021; 92(7):737-744. PMC: 8223632. DOI: 10.1136/jnnp-2020-324903. View

Gonzalez-Ortiz F, Dulewicz M, Ashton N, Kac P, Zetterberg H, Andersson E . Association of Serum Brain-Derived Tau With Clinical Outcome and Longitudinal Change in Patients With Severe Traumatic Brain Injury. JAMA Netw Open. 2023; 6(7):e2321554. PMC: 10318474. DOI: 10.1001/jamanetworkopen.2023.21554. View

Cotelli M, Tarantino B, Tan K, Huber H, Cantoni V, Bracca V . Predicting survival rate by plasma biomarkers and clinical variables in syndromes associated with frontotemporal lobar degeneration. Alzheimers Dement. 2025; 21(2):e14558. PMC: 11815202. DOI: 10.1002/alz.14558. View

Kurth F, Gaser C, Luders E . A 12-step user guide for analyzing voxel-wise gray matter asymmetries in statistical parametric mapping (SPM). Nat Protoc. 2015; 10(2):293-304. DOI: 10.1038/nprot.2015.014. View

10.

Kansal K, Mareddy M, Sloane K, Minc A, Rabins P, McGready J . Survival in Frontotemporal Dementia Phenotypes: A Meta-Analysis. Dement Geriatr Cogn Disord. 2016; 41(1-2):109-22. DOI: 10.1159/000443205. View

11.

Hoglinger G, Respondek G, Stamelou M, Kurz C, Josephs K, Lang A . Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord. 2017; 32(6):853-864. PMC: 5516529. DOI: 10.1002/mds.26987. View

12.

Agarwal S, Ahmed R, DMello M, Foxe D, Kaizik C, Kiernan M . Predictors of survival and progression in behavioural variant frontotemporal dementia. Eur J Neurol. 2018; 26(5):774-779. DOI: 10.1111/ene.13887. View

13.

Farokhian F, Beheshti I, Sone D, Matsuda H . Comparing CAT12 and VBM8 for Detecting Brain Morphological Abnormalities in Temporal Lobe Epilepsy. Front Neurol. 2017; 8:428. PMC: 5573734. DOI: 10.3389/fneur.2017.00428. View

14.

Chelban V, Nikram E, Perez-Soriano A, Wilke C, Foubert-Samier A, Vijiaratnam N . Neurofilament light levels predict clinical progression and death in multiple system atrophy. Brain. 2022; 145(12):4398-4408. PMC: 9762941. DOI: 10.1093/brain/awac253. View

15.

Bennett D, Brayne C, Feigin V, Barker-Collo S, Brainin M, Davis D . Development of the standards of reporting of neurological disorders (STROND) checklist: a guideline for the reporting of incidence and prevalence studies in neuroepidemiology. Eur J Epidemiol. 2015; 30(7):569-76. DOI: 10.1007/s10654-015-0034-5. View

16.

Goldman J, Farmer J, Wood E, Johnson J, Boxer A, Neuhaus J . Comparison of family histories in FTLD subtypes and related tauopathies. Neurology. 2005; 65(11):1817-9. DOI: 10.1212/01.wnl.0000187068.92184.63. View

17.

Rascovsky K, Hodges J, Knopman D, Mendez M, Kramer J, Neuhaus J . Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011; 134(Pt 9):2456-77. PMC: 3170532. DOI: 10.1093/brain/awr179. View

18.

Strong M, Abrahams S, Goldstein L, Woolley S, McLaughlin P, Snowden J . Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria. Amyotroph Lateral Scler Frontotemporal Degener. 2017; 18(3-4):153-174. PMC: 7409990. DOI: 10.1080/21678421.2016.1267768. View

19.

Caswell C, McMillan C, Xie S, Van Deerlin V, Suh E, Lee E . Genetic predictors of survival in behavioral variant frontotemporal degeneration. Neurology. 2019; 93(18):e1707-e1714. PMC: 6946477. DOI: 10.1212/WNL.0000000000008387. View

20.

Borroni B, Urso D, Zecca C, Binetti G, Fostinelli S, Benussi L . Survival in Incident Cases with Frontotemporal Lobar Degeneration: A Registry-Based Study. J Alzheimers Dis. 2023; 96(3):1019-1024. DOI: 10.3233/JAD-230676. View