Cerebrospinal fluid biomarkers predict frontotemporal dementia trajectory

Abstract

ObjectiveThe prognostic value of cerebrospinal fluid neurofilament light chain, total tau, phosphorylated tau181, and amyloid beta1‐42 was examined in frontotemporal dementia subtypes.MethodsWe compared baseline biomarkers between 49 controls, 40 patients with behavioral variant frontotemporal dementia, 24 with semantic variant primary progressive aphasia, and 26 with nonfluent variant primary progressive aphasia. Linear mixed effect models were used to assess the value of baseline biomarkers in predicting clinical and radiographic change in patient cohorts over multiple yearly follow up visits.ResultsNeurofilament light chain concentrations were lowest in controls. Elevated baseline neurofilament light chain predicted faster worsening in clinical severity, frontotemporal volume and frontotemporal fractional anisotropy in patients with behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. High total tau similarly predicted faster progression in nonfluent variant primary progressive aphasia. In behavioral variant frontotemporal dementia, higher phosphorylated tau181 predicted faster clinical progression whereas lower amyloid beta1‐42 predicted faster volumetric and fractional anisotropy reduction. Neurofilament light chain and phosphorylated tau181 were of greater predictive value in patients with tau pathology as compared to TDP‐43 pathology. Baseline neurofilament light chain correlated with baseline clinical severity and frontotemporal volume in behavioral variant frontotemporal dementia. Baseline total tau correlated with baseline clinical severity in semantic variant primary progressive aphasia.InterpretationHigh cerebrospinal fluid neurofilament light chain predicts more aggressive disease in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Total tau, phosphorylated tau181, and amyloid beta1‐42 also predict some measures of disease aggressiveness in frontotemporal dementia.

The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta‐analysis

“…Twenty-six studies compared CSF NfL concentration in 1827 FTD cases and 1113 cognitively unimpaired controls, with a ROM of 3.41 (95% CI 2.96-3.93, P , 0.0001; Fig. 3A) [16][17][18][20][21][22][26][27][28]31,32,35,36,38,[44][45][46][54][55][56][57][58][59][60][61][62]. Four studies investigated 113 FTD cases and 110 MCI controls [9,22,43,44], with no observable difference in CSF NfL concentration (ROM 5 1.87, 95% CI 0.88-3.98, P 5 0.077; Fig.…”

Lower CSF Amyloid-Beta1–42 Predicts a Higher Mortality Rate in Frontotemporal Dementia

“…There is a lack of good FTD diagnostic and prognostic biomarkers. Neurofilament light chain, total Tau [11], and phosphorylated-Tau/total-Tau ratio have been reported to have some clinical value [5,[12][13][14][15]. Neurofilament light chain has also been shown to be correlated with disease severity, brain atrophy, annualized brain atrophy, and survival [16].…”

“…Additionally, some studies have shown that amyloid-positive patients perform significantly worse in cognitive tests [4]. Also, low baseline amyloid-beta has been associated with faster radiographic change in bvFTD [5].…”

“…Interestingly, in FTD patients with pathogenic mutations, amyloid has also been shown to be associated with a worse performance in several cognitive tests [4]. Additionally, CSF amyloid has been shown to be associated with higher volumetric loss in sporadic FTD patients [5].…”

Impact of long- and short-range fiber depletion on the cognitive deficits of fronto-temporal dementia

“…FTLDNI is a multicentric longitudinal database, collecting MRIs, PET and CSF biomarkers in FTD patients and age-matched controls. All patients were clinically diagnosed by a multidisciplinary consensus panel (Ljubenkov et al, 2018;Staffaroni et al, 2019). For the present analysis, we included a total of 155 participants with cross- degrees) was also used to measure GM volume.…”