BACKGROUND: Assessment of human brain atrophy in temporal regions using magnetic resonance imaging (MRI), resting state functional MRI connectivity in the left parietal cortex, and limbic electroencephalographic (rsEEG) rhythms as well as plasma amyloid peptide 42 (Aβ42) has shown that each is a promising biomarker of disease progression in amnestic mild cognitive impairment (aMCI) patients with prodromal Alzheimer's disease (AD). However, the value of their combined use is unknown. OBJECTIVE: To evaluate the association with cognitive decline and the effect on sample size calculation when using a biomarker composite matrix in prodromal AD clinical trials. METHODS: Multicenter longitudinal study with follow-up of 2 years or until development of incident dementia. APOE ɛ4-specific cerebrospinal fluid (CSF) Aβ42/P-tau cut-offs were used to identify aMCI with prodromal AD. Linear mixed models were performed 1) with repeated matrix values and time as factors to explain the longitudinal changes in ADAS-cog13, 2) with CSF Aβ42/P-tau status, time, and CSF Aβ42/P-tau status×time interaction as factors to explain the longitudinal changes in matrix measures, and 3) to compute sample size estimation for a trial implemented with the selected matrices. RESULTS: The best composite matrix included the MRI volumes of hippocampal dentate gyrus and lateral ventricle. This matrix showed the best sensitivity to track disease progression and required a sample size 31% lower than that of the best individual biomarker (i.e., volume of hippocampal dentate gyrus). CONCLUSION: Optimal matrices improved the statistical power to track disease development and to measure clinical progression in the short-term period. This might contribute to optimize the design of future clinical trials in MCI.

Biomarker matrix to track short term disease progression in amnestic mild cognitive impairment patients with prodromal Alzheimer's disease / Marizzoni, Moira; Ferrari, Clarissa; Macis, Ambra; Jovicich, Jorge; Albani, Diego; Babiloni, Claudio; Cavaliere, Libera; Didic, Mira; Forloni, Gianluigi; Galluzzi, Samantha; Hoffmann, Karl-Titus; Molinuevo, José Luis; Nobili, Flavio; Parnetti, Lucilla; Payoux, Pierre; Pizzini, Francesca; Rossini, Paolo Maria; Salvatore, Marco; Schönknecht, Peter; Soricelli, Andrea; Del Percio, Claudio; Hensch, Tilman; Hegerl, Ulrich; Tsolaki, Magda; Visser, Pieter Jelle; Wiltfang, Jens; Richardson, Jill C; Bordet, Régis; Blin, Olivier; Frisoni, Giovanni B. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 69:1(2019), pp. 49-58. [10.3233/JAD-181016]

Biomarker matrix to track short term disease progression in amnestic mild cognitive impairment patients with prodromal Alzheimer's disease

Macis, Ambra;Babiloni, Claudio;Del Percio, Claudio;
2019

Abstract

BACKGROUND: Assessment of human brain atrophy in temporal regions using magnetic resonance imaging (MRI), resting state functional MRI connectivity in the left parietal cortex, and limbic electroencephalographic (rsEEG) rhythms as well as plasma amyloid peptide 42 (Aβ42) has shown that each is a promising biomarker of disease progression in amnestic mild cognitive impairment (aMCI) patients with prodromal Alzheimer's disease (AD). However, the value of their combined use is unknown. OBJECTIVE: To evaluate the association with cognitive decline and the effect on sample size calculation when using a biomarker composite matrix in prodromal AD clinical trials. METHODS: Multicenter longitudinal study with follow-up of 2 years or until development of incident dementia. APOE ɛ4-specific cerebrospinal fluid (CSF) Aβ42/P-tau cut-offs were used to identify aMCI with prodromal AD. Linear mixed models were performed 1) with repeated matrix values and time as factors to explain the longitudinal changes in ADAS-cog13, 2) with CSF Aβ42/P-tau status, time, and CSF Aβ42/P-tau status×time interaction as factors to explain the longitudinal changes in matrix measures, and 3) to compute sample size estimation for a trial implemented with the selected matrices. RESULTS: The best composite matrix included the MRI volumes of hippocampal dentate gyrus and lateral ventricle. This matrix showed the best sensitivity to track disease progression and required a sample size 31% lower than that of the best individual biomarker (i.e., volume of hippocampal dentate gyrus). CONCLUSION: Optimal matrices improved the statistical power to track disease development and to measure clinical progression in the short-term period. This might contribute to optimize the design of future clinical trials in MCI.
2019
Alzheimer’s disease; biomarker matrices; clinical trial; magnetic resonance imaging; mild cognitive impairment
01 Pubblicazione su rivista::01a Articolo in rivista
Biomarker matrix to track short term disease progression in amnestic mild cognitive impairment patients with prodromal Alzheimer's disease / Marizzoni, Moira; Ferrari, Clarissa; Macis, Ambra; Jovicich, Jorge; Albani, Diego; Babiloni, Claudio; Cavaliere, Libera; Didic, Mira; Forloni, Gianluigi; Galluzzi, Samantha; Hoffmann, Karl-Titus; Molinuevo, José Luis; Nobili, Flavio; Parnetti, Lucilla; Payoux, Pierre; Pizzini, Francesca; Rossini, Paolo Maria; Salvatore, Marco; Schönknecht, Peter; Soricelli, Andrea; Del Percio, Claudio; Hensch, Tilman; Hegerl, Ulrich; Tsolaki, Magda; Visser, Pieter Jelle; Wiltfang, Jens; Richardson, Jill C; Bordet, Régis; Blin, Olivier; Frisoni, Giovanni B. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 69:1(2019), pp. 49-58. [10.3233/JAD-181016]
File allegati a questo prodotto
File Dimensione Formato  
Marizzoni_Biomarker_2019.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 154.61 kB
Formato Adobe PDF
154.61 kB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1263271
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 9
social impact