Prodromal frontotemporal dementia: clinical features and predictors of progression

被引:18
作者
Benussi, Alberto [1 ]
Ashton, Nicholas J. [2 ,3 ,4 ,5 ,6 ,7 ]
Karikari, Thomas K. [2 ,3 ]
Alberici, Antonella [1 ]
Saraceno, Claudia [8 ]
Ghidoni, Roberta [8 ]
Benussi, Luisa [8 ]
Zetterberg, Henrik [2 ,3 ,9 ,10 ,11 ]
Blennow, Kaj [2 ,3 ,9 ]
Borroni, Barbara [1 ]
机构
[1] Univ Brescia, Dept Clin & Expt Sci, Neurol Unit, Ple Spedali Civili 1, I-25123 Brescia, Italy
[2] Sahlgrens Acad, Inst Neurosci & Physiol, Molndal, Sweden
[3] Univ Gothenburg, Molndal, Sweden
[4] Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Molndal, Sweden
[5] Kings Coll London, Inst Psychiat Psychol & Neurosci, Maurice Wohl Clin Neurosci Inst, London, England
[6] South London & Maudsley NHS Fdn, NIHR Biomed Res Ctr Mental Hlth, London, England
[7] South London & Maudsley NHS Fdn, Biomed Res Unit Dementia, London, England
[8] IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, Mol Markers Lab, Brescia, Italy
[9] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
[10] UCL, UK Dementia Res Inst, London, England
[11] UCL Inst Neurol, Dept Neurodegenerat Dis, London, England
基金
欧洲研究理事会; 瑞典研究理事会;
关键词
Frontotemporal dementia; Serum neurofilament light; Prodromal; Mild; Progression; Conversion; NEUROFILAMENT LIGHT-CHAIN; DIAGNOSTIC-CRITERIA; BEHAVIORAL VARIANT; DISEASE; BIOMARKER; PROTEIN; SURVIVAL;
D O I
10.1186/s13195-021-00932-2
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background The prodromal phase of frontotemporal dementia (FTD) is still not well characterized, and conversion rates to dementia and predictors of progression at 1-year follow-up are currently unknown. Methods In this retrospective study, disease severity was assessed using the global CDR plus NACC FTLD. Prodromal FTD was defined to reflect mild cognitive or behavioural impairment with relatively preserved functional independence (global CDR plus NACC = 0.5) as well as mild, moderate and severe dementia (classified as global CDR plus NACC = 1, 2, 3, respectively). Disease progression at 1-year follow-up and serum NfL measurements were acquired in a subgroup of patients. Results Of 563 participants, 138 were classified as prodromal FTD, 130 as mild, 175 as moderate and 120 as severe FTD. In the prodromal and mild phases, we observed an early increase in serum NfL levels followed by behavioural disturbances and deficits in executive functions. Negative symptoms, such as apathy, inflexibility and loss of insight, predominated in the prodromal phase. Serum NfL levels were significantly increased in the prodromal phase compared with healthy controls (average difference 14.5, 95% CI 2.9 to 26.1 pg/mL), but lower than in patients with mild FTD (average difference -15.5, 95% CI -28.4 to -2.7 pg/mL). At 1-year follow-up, 51.2% of patients in the prodromal phase had converted to dementia. Serum NfL measurements at baseline were the strongest predictors of disease progression at 1-year follow-up (OR 1.07, 95% CI 1.03 to 1.11, p < 0.001). Conclusions Prodromal FTD is a mutable stage with high rate of progression to fully symptomatic disease at 1-year follow-up. High serum NfL levels may support prodromal FTD diagnosis and represent a helpful marker to assess disease progression.
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