Prodromal frontotemporal dementia: clinical features and predictors of progression

Abstract

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.

Classification accuracy of blood-based and neurophysiological markers in the differential diagnosis of Alzheimer’s disease and frontotemporal lobar degeneration

“…Disease severity was assessed with the clinical dementia rating plus National Alzheimer’s Coordinating Center (NACC) behaviour and language domains (CDR plus NACC FTLD) global and sum of boxes, whilst the level of functional independence was assessed with the basic activities of daily living (BADL) and the instrumental activities of daily living (IADL) questionnaire. Furthermore, neuropsychiatric and behavioural disturbances were evaluated with the neuropsychiatric inventory (NPI) [ 24 ].…”

Differences and similarities between familial and sporadic frontotemporal dementia: An Italian single‐center cohort study

“…Serum NfL levels have already been shown to be a consistent and reliable marker of disease severity in both genetic and sporadic FTD, 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 with levels increasing already in the prodromal phases of disease, 47 and correlating with disease survival. 43 Also in this study, serum NfL levels were the most significant predictors of survival.…”

“…Moreover, f-FTD showed a shorter survival rate than s-FTD, and this finding is supported by several studies showing that disease survival is generally shorter in the genetic forms of FTD. 16,[36][37][38] Serum NfL levels have already been shown to be a consistent and reliable marker of disease severity in both genetic and sporadic FTD, [39][40][41][42][43][44][45][46] with levels increasing already in the prodromal phases of disease, 47 and correlating with disease survival. 43 Also in this study, serum NfL levels were the most significant predictors of survival.…”

Behavioral Reserve in Behavioral Variant Frontotemporal Dementia

“…This can be attributed to the narrow distribution of the FBI scores for positive symptoms. Although the positive symptoms were more diagnostic for bvFTD, the negative symptoms were the most prominent symptoms at all stages ( Benussi et al, 2021 ). According to the FBI manual, scores 25–30, 30–40, and >40 indicate mild, moderate, and severe disease states, respectively.…”