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Prognostic value of Alzheimer’s biomarkers in mild cognitive impairment : the effect of age at onset

Altomare, Daniele ; Ferrari, Clarissa ; Caroli, Anna ; Galluzzi, Samantha ; Prestia, Annapaola ; van der Flier, Wiesje M. ; Ossenkoppele, Rik LU ; Van Berckel, Bart ; Barkhof, Frederik and Teunissen, Charlotte E. , et al. (2019) In Journal of Neurology 266(10). p.2535-2545
Abstract

Objective: The aim of this study is to assess the impact of age at onset on the prognostic value of Alzheimer’s biomarkers in a large sample of patients with mild cognitive impairment (MCI). Methods: We measured Aβ42, t-tau, hippocampal volume on magnetic resonance imaging (MRI) and cortical metabolism on fluorodeoxyglucose–positron emission tomography (FDG-PET) in 188 MCI patients followed for at least 1 year. We categorised patients into earlier and later onset (EO/LO). Receiver operating characteristic curves and corresponding areas under the curve (AUCs) were performed to assess and compar the biomarker prognostic performances in EO and LO groups. Linear Model was adopted for estimating the time-to-progression in relation with... (More)

Objective: The aim of this study is to assess the impact of age at onset on the prognostic value of Alzheimer’s biomarkers in a large sample of patients with mild cognitive impairment (MCI). Methods: We measured Aβ42, t-tau, hippocampal volume on magnetic resonance imaging (MRI) and cortical metabolism on fluorodeoxyglucose–positron emission tomography (FDG-PET) in 188 MCI patients followed for at least 1 year. We categorised patients into earlier and later onset (EO/LO). Receiver operating characteristic curves and corresponding areas under the curve (AUCs) were performed to assess and compar the biomarker prognostic performances in EO and LO groups. Linear Model was adopted for estimating the time-to-progression in relation with earlier/later onset MCI groups and biomarkers. Results: In earlier onset patients, all the assessed biomarkers were able to predict cognitive decline (p < 0.05), with FDG-PET showing the best performance. In later onset patients, all biomarkers but t-tau predicted cognitive decline (p < 0.05). Moreover, FDG-PET alone in earlier onset patients showed a higher prognostic value than the one resulting from the combination of all the biomarkers in later onset patients (earlier onset AUC 0.935 vs later onset AUC 0.753, p < 0.001). Finally, FDG-PET showed a different prognostic value between earlier and later onset patients (p = 0.040) in time-to-progression allowing an estimate of the time free from disease. Discussion: FDG-PET may represent the most universal tool for the establishment of a prognosis in MCI patients and may be used for obtaining an onset-related estimate of the time free from disease.

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@article{8af8d8ac-4af4-4858-971a-b703405185fc,
  abstract     = {{<p>Objective: The aim of this study is to assess the impact of age at onset on the prognostic value of Alzheimer’s biomarkers in a large sample of patients with mild cognitive impairment (MCI). Methods: We measured Aβ42, t-tau, hippocampal volume on magnetic resonance imaging (MRI) and cortical metabolism on fluorodeoxyglucose–positron emission tomography (FDG-PET) in 188 MCI patients followed for at least 1 year. We categorised patients into earlier and later onset (EO/LO). Receiver operating characteristic curves and corresponding areas under the curve (AUCs) were performed to assess and compar the biomarker prognostic performances in EO and LO groups. Linear Model was adopted for estimating the time-to-progression in relation with earlier/later onset MCI groups and biomarkers. Results: In earlier onset patients, all the assessed biomarkers were able to predict cognitive decline (p &lt; 0.05), with FDG-PET showing the best performance. In later onset patients, all biomarkers but t-tau predicted cognitive decline (p &lt; 0.05). Moreover, FDG-PET alone in earlier onset patients showed a higher prognostic value than the one resulting from the combination of all the biomarkers in later onset patients (earlier onset AUC 0.935 vs later onset AUC 0.753, p &lt; 0.001). Finally, FDG-PET showed a different prognostic value between earlier and later onset patients (p = 0.040) in time-to-progression allowing an estimate of the time free from disease. Discussion: FDG-PET may represent the most universal tool for the establishment of a prognosis in MCI patients and may be used for obtaining an onset-related estimate of the time free from disease.</p>}},
  author       = {{Altomare, Daniele and Ferrari, Clarissa and Caroli, Anna and Galluzzi, Samantha and Prestia, Annapaola and van der Flier, Wiesje M. and Ossenkoppele, Rik and Van Berckel, Bart and Barkhof, Frederik and Teunissen, Charlotte E. and Wall, Anders and Carter, Stephen F. and Schöll, Michael and Choo, Il Han and Grimmer, Timo and Redolfi, Alberto and Nordberg, Agneta and Scheltens, Philip and Drzezga, Alexander and Frisoni, Giovanni B}},
  issn         = {{0340-5354}},
  keywords     = {{Alzheimer; Biomarkers; Cognition; FDG-PET; Imaging}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{2535--2545}},
  publisher    = {{Springer}},
  series       = {{Journal of Neurology}},
  title        = {{Prognostic value of Alzheimer’s biomarkers in mild cognitive impairment : the effect of age at onset}},
  url          = {{http://dx.doi.org/10.1007/s00415-019-09441-7}},
  doi          = {{10.1007/s00415-019-09441-7}},
  volume       = {{266}},
  year         = {{2019}},
}