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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Systematic Review Article

Clinical, Genetic, and Pathological Features of very Early Onset Frontotemporal Lobe Degeneration: A Systematic Review

Author(s): Min Chu, Liyong Wu*, Li Liu, Haitian Nan, Deming Jiang, Yihao Wang and Pedro Rosa-Neto

Volume 19, Issue 13, 2022

Published on: 17 January, 2023

Page: [870 - 877] Pages: 8

DOI: 10.2174/1567205020666221226122557

Price: $65

Abstract

Background: In most patients with frontotemporal lobe degeneration (FTLD), the degenerative process begins between the ages 45 and 65 years; onset younger than 45 years is relatively rare and considered very early onset FTLD (VEO-FTLD).

Objective: To delineate the clinical, genetic, and pathological features of VEO-FTLD.

Methods: A systematic literature review was carried out in PubMed and Embase from inception to September 2021. Patients diagnosed with definite FTLD with onset before age 45 years were included. Patients lacking detailed clinical data or both genetic and neuropathological data were excluded. Phenotypic, genotypic, and pathological data were extracted for further analyses.

Results: Data from 110 patients with VEO-FTLD, reported in a cumulative 70 publications, were included. Age of onset was 35.09 ± 7.04 (14-44) years. Sixty-seven patients were reported age at death of 42.12 ± 7.26 (24–58) years, with a disease course lasting 8.13 ± 4.69 (1–20) years. Behavioural variant frontotemporal dementia (104/110, 94.5%) was the most common clinical subtype, often manifesting as disinhibition (81.8%) and apathy (80.9%), and frequently accompanied by a cognitive deficit (90.9%) and parkinsonism (37.3%). Frequency of familial aggregation was high (familial vs. sporadic, 73/37, 66.4%); most patients carried MAPT gene mutations (72.9% in familial, 40% in sporadic), followed by C9 (18.8% in familial, 10% in sporadic), TARDBP (2.1% in familial), and VCP (2.1% in familial). The most common neuropathology subtype was tau (43.5%), followed by ubiquitin- positive (24.6%), FUS (20.3%), and TDP 43 (2.9%).

Conclusion: VEO-FTLD may have unique clinical, genetic, and neuropathological markers and should be considered in young patients with psycho-behavioral symptoms.

[1]
Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134(9): 2456-77.
[http://dx.doi.org/10.1093/brain/awr179] [PMID: 21810890]
[2]
Khan I, De Jesus O. Frontotemporal Lobe Dementia. StatPearlsPublishing Copyright © 2022, StatPearls Publishing LLC.; Treasure Island (FL): StatPearls 2022.
[3]
Moore KM, Nicholas J, Grossman M, et al. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study. Lancet Neurol 2020; 19(2): 145-56.
[http://dx.doi.org/10.1016/S1474-4422(19)30394-1] [PMID: 31810826]
[4]
Shinagawa S, Toyota Y, Ishikawa T, et al. Cognitive function and psychiatric symptoms in early- and late-onset frontotemporal dementia. Dement Geriatr Cogn Disord 2008; 25(5): 439-44.
[http://dx.doi.org/10.1159/000124751] [PMID: 18401172]
[5]
Seo SW, Thibodeau MP, Perry DC, et al. Early vs. late age at onset frontotemporal dementia and frontotemporal lobar degeneration. Neurology 2018; 90(12): e1047-56.
[http://dx.doi.org/10.1212/WNL.0000000000005163] [PMID: 29453245]
[6]
Ye BS, Choi SH, Han SH, et al. Clinical and neuropsychological comparisons of early-onset versus late-onset frontotemporal dementia: A CREDOS-FTD Study. J Alzheimers Dis 2015; 45(2): 599-608.
[http://dx.doi.org/10.3233/JAD-141044] [PMID: 25589724]
[7]
Borroni B, Agosti C, Bellelli G, Padovani A. Is early-onset clinically different from late-onset frontotemporal dementia? Eur J Neurol 2008; 15(12): 1412-5.
[http://dx.doi.org/10.1111/j.1468-1331.2008.02338.x] [PMID: 19049564]
[8]
Ando K, Ferlini L, Suain V, et al. de novo MAPT mutation G335A causes severe brain atrophy, 3R and 4R PHF-tau pathology and early onset frontotemporal dementia. Acta Neuropathol Commun 2020; 8(1): 94.
[http://dx.doi.org/10.1186/s40478-020-00977-8] [PMID: 32600421]
[9]
Silverman H, Ake J, Manoochehri M, Appleby B, Brushaber D, Devick K. The contribution of behavioral features to caregiver burden in FTLD spectrum disorders. Alzheimers Dement 2022; 18(9): 1635-49.
[PMID: 34854532]
[10]
Chemali Z, Withall A, Daffner KR. The plight of caring for young patients with frontotemporal dementia. Am J Alzheimers Dis Other Demen 2010; 25(2): 109-15.
[http://dx.doi.org/10.1177/1533317509352335] [PMID: 20107238]
[11]
Sirkis DW, Geier EG, Bonham LW, Karch CM, Yokoyama JS. Recent advances in the genetics of frontotemporal dementia. Curr Genet Med Rep 2019; 7(1): 41-52.
[http://dx.doi.org/10.1007/s40142-019-0160-6] [PMID: 31687268]
[12]
Seeley WW. Behavioral variant frontotemporal dementia. Continuum 2019; 25(1): 76-100.
[http://dx.doi.org/10.1212/CON.0000000000000698] [PMID: 30707188]
[13]
Padovani A, Agosti C, Premi E, Bellelli G, Borroni B. Extrapyramidal symptoms in Frontotemporal Dementia: Prevalence and clinical correlations. Neurosci Lett 2007; 422(1): 39-42.
[http://dx.doi.org/10.1016/j.neulet.2007.05.049] [PMID: 17574750]
[14]
Boeve BF, Boxer AL, Kumfor F, Pijnenburg Y, Rohrer JD. Advances and controversies in frontotemporal dementia: diagnosis, biomarkers, and therapeutic considerations. Lancet Neurol 2022; 21(3): 258-72.
[http://dx.doi.org/10.1016/S1474-4422(21)00341-0] [PMID: 35182511]
[15]
Liu L, Cui B, Chu M, et al. The frequency of genetic mutations associated with behavioral variant frontotemporal dementia in chinese han patients. Front Aging Neurosci 2021; 13: 699836.
[http://dx.doi.org/10.3389/fnagi.2021.699836] [PMID: 34305575]
[16]
Greaves CV, Rohrer JD. An update on genetic frontotemporal dementia. J Neurol 2019; 266(8): 2075-86.
[http://dx.doi.org/10.1007/s00415-019-09363-4] [PMID: 31119452]
[17]
Haass C, Neumann M. Frontotemporal dementia: from molecular mechanisms to therapy. J Neurochem 2016; 138 (Suppl. 1): 3-5.
[http://dx.doi.org/10.1111/jnc.13619] [PMID: 27502123]
[18]
Roeber S, Mackenzie IRA, Kretzschmar HA, Neumann M. TDP-43-negative FTLD-U is a significant new clinico-pathological subtype of FTLD. Acta Neuropathol 2008; 116(2): 147-57.
[http://dx.doi.org/10.1007/s00401-008-0395-x] [PMID: 18536926]
[19]
Josephs KA, Lin WL, Ahmed Z, Stroh DA, Graff-Radford NR, Dickson DW. Frontotemporal lobar degeneration with ubiquitin-positive, but TDP-43-negative inclusions. Acta Neuropathol 2008; 116(2): 159-67.
[http://dx.doi.org/10.1007/s00401-008-0397-8] [PMID: 18553091]
[20]
Mackenzie IRA, Foti D, Woulfe J, Hurwitz TA. Atypical frontotemporal lobar degeneration with ubiquitin-positive, TDP-43-negative neuronal inclusions. Brain 2008; 131(5): 1282-93.
[http://dx.doi.org/10.1093/brain/awn061] [PMID: 18362096]
[21]
Samanci B, Bilgiç B, Gelişin Ö, et al. TREM2 variants as a possible cause of frontotemporal dementia with distinct neuroimaging features. Eur J Neurol 2021; 28(8): 2603-13.
[http://dx.doi.org/10.1111/ene.14908] [PMID: 33969597]
[22]
Redaelli V, Salsano E, Colleoni L, et al. Frontotemporal dementia and chorea associated with a compound heterozygous TREM2 mutation. J Alzheimers Dis 2018; 63(1): 195-201.
[http://dx.doi.org/10.3233/JAD-180018] [PMID: 29578490]
[23]
Picková T, Matěj R, Bezdicek O, et al. Genetic alzheimer disease and sporadic dementia with lewy bodies: a comorbidity presenting as primary progressive aphasia. Cogn Behav Neurol 2017; 30(1): 23-9.
[http://dx.doi.org/10.1097/WNN.0000000000000116] [PMID: 28323683]
[24]
Bernardi L, Anfossi M, Gallo M, et al. PSEN1 and PRNP gene mutations: co-occurrence makes onset very early in a family with FTD phenotype. J Alzheimers Dis 2011; 24(3): 415-9.
[http://dx.doi.org/10.3233/JAD-2011-101890] [PMID: 21297264]
[25]
Wong JC, Chow TW, Hazrati LN. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia can present as frontotemporal dementia syndrome. Dement Geriatr Cogn Disord 2011; 32(2): 150-8.
[http://dx.doi.org/10.1159/000331422] [PMID: 21986056]
[26]
Baizabal-Carvallo JF, Jankovic J. Parkinsonism, movement disorders and genetics in frontotemporal dementia. Nat Rev Neurol 2016; 12(3): 175-85.
[http://dx.doi.org/10.1038/nrneurol.2016.14] [PMID: 26891767]

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