Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer’s dementia in mild cognitive impairment patients
Pichet Binette, Alexa LU ; Palmqvist, Sebastian LU
; Bali, Divya
LU
; Farrar, Gill
; Buckley, Christopher J.
; Wolk, David A.
; Zetterberg, Henrik
LU
; Blennow, Kaj
LU
; Janelidze, Shorena
LU
and Hansson, Oskar
LU
(2022)
In Alzheimer's Research and Therapy
14(1).
- Abstract
Background: Up to now, there are no clinically available minimally invasive biomarkers to accurately identify mild cognitive impairment (MCI) patients who are at greater risk to progress to Alzheimer’s disease (AD) dementia. The recent advent of blood-based markers opens the door for more accessible biomarkers. We aimed to identify which combinations of AD related plasma biomarkers and other easily accessible assessments best predict progression to AD dementia in patients with mild cognitive impairment (MCI). Methods: We included patients with amnestic MCI (n = 110) followed prospectively over 3 years to assess clinical status. Baseline plasma biomarkers (amyloid-β 42/40, phosphorylated tau217 [p-tau217], neurofilament light and glial... (More)
Background: Up to now, there are no clinically available minimally invasive biomarkers to accurately identify mild cognitive impairment (MCI) patients who are at greater risk to progress to Alzheimer’s disease (AD) dementia. The recent advent of blood-based markers opens the door for more accessible biomarkers. We aimed to identify which combinations of AD related plasma biomarkers and other easily accessible assessments best predict progression to AD dementia in patients with mild cognitive impairment (MCI). Methods: We included patients with amnestic MCI (n = 110) followed prospectively over 3 years to assess clinical status. Baseline plasma biomarkers (amyloid-β 42/40, phosphorylated tau217 [p-tau217], neurofilament light and glial fibrillary acidic protein), hippocampal volume, APOE genotype, and cognitive tests were available. Logistic regressions with conversion to amyloid-positive AD dementia within 3 years as outcome was used to evaluate the performance of different biomarkers measured at baseline, used alone or in combination. The first analyses included only the plasma biomarkers to determine the ones most related to AD dementia conversion. Second, hippocampal volume, APOE genotype and a brief cognitive composite score (mPACC) were combined with the best plasma biomarker. Results: Of all plasma biomarker combinations, p-tau217 alone had the best performance for discriminating progression to AD dementia vs all other combinations (AUC 0.84, 95% CI 0.75–0.93). Next, combining p-tau217 with hippocampal volume, cognition, and APOE genotype provided the best discrimination between MCI progressors vs. non-progressors (AUC 0.89, 0.82–0.95). Across the few best models combining different markers, p-tau217 and cognition were consistently the main contributors. The most parsimonious model including p-tau217 and cognition had a similar model fit, but a slightly lower AUC (0.87, 0.79–0.95, p = 0.07). Conclusion: We identified that combining plasma p-tau217 and a brief cognitive composite score was strongly related to greater risk of progression to AD dementia in MCI patients, suggesting that these measures could be key components of future prognostic algorithms for early AD. Trial registration: NCT01028053, registered December 9, 2009.
(Less)
- author
- Pichet Binette, Alexa
LU
; Palmqvist, Sebastian
LU
; Bali, Divya
LU
; Farrar, Gill
; Buckley, Christopher J.
; Wolk, David A.
; Zetterberg, Henrik
LU
; Blennow, Kaj
LU
; Janelidze, Shorena
LU
and Hansson, Oskar
LU
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer’s disease, Dementia, Mild cognitive impairment, p-tau, Plasma biomarkers
- in
- Alzheimer's Research and Therapy
- volume
- 14
- issue
- 1
- article number
- 46
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85127268851
- pmid:35351181
- ISSN
- 1758-9193
- DOI
- 10.1186/s13195-022-00990-0
- language
- English
- LU publication?
- yes
- id
- dcf61035-4d34-4e4a-aebf-52e27711b37b
- date added to LUP
- 2022-06-03 14:29:04
- date last changed
- 2024-04-18 14:46:27
@article{dcf61035-4d34-4e4a-aebf-52e27711b37b,
abstract = {{<p>Background: Up to now, there are no clinically available minimally invasive biomarkers to accurately identify mild cognitive impairment (MCI) patients who are at greater risk to progress to Alzheimer’s disease (AD) dementia. The recent advent of blood-based markers opens the door for more accessible biomarkers. We aimed to identify which combinations of AD related plasma biomarkers and other easily accessible assessments best predict progression to AD dementia in patients with mild cognitive impairment (MCI). Methods: We included patients with amnestic MCI (n = 110) followed prospectively over 3 years to assess clinical status. Baseline plasma biomarkers (amyloid-β 42/40, phosphorylated tau217 [p-tau217], neurofilament light and glial fibrillary acidic protein), hippocampal volume, APOE genotype, and cognitive tests were available. Logistic regressions with conversion to amyloid-positive AD dementia within 3 years as outcome was used to evaluate the performance of different biomarkers measured at baseline, used alone or in combination. The first analyses included only the plasma biomarkers to determine the ones most related to AD dementia conversion. Second, hippocampal volume, APOE genotype and a brief cognitive composite score (mPACC) were combined with the best plasma biomarker. Results: Of all plasma biomarker combinations, p-tau217 alone had the best performance for discriminating progression to AD dementia vs all other combinations (AUC 0.84, 95% CI 0.75–0.93). Next, combining p-tau217 with hippocampal volume, cognition, and APOE genotype provided the best discrimination between MCI progressors vs. non-progressors (AUC 0.89, 0.82–0.95). Across the few best models combining different markers, p-tau217 and cognition were consistently the main contributors. The most parsimonious model including p-tau217 and cognition had a similar model fit, but a slightly lower AUC (0.87, 0.79–0.95, p = 0.07). Conclusion: We identified that combining plasma p-tau217 and a brief cognitive composite score was strongly related to greater risk of progression to AD dementia in MCI patients, suggesting that these measures could be key components of future prognostic algorithms for early AD. Trial registration: NCT01028053, registered December 9, 2009.</p>}},
author = {{Pichet Binette, Alexa and Palmqvist, Sebastian and Bali, Divya and Farrar, Gill and Buckley, Christopher J. and Wolk, David A. and Zetterberg, Henrik and Blennow, Kaj and Janelidze, Shorena and Hansson, Oskar}},
issn = {{1758-9193}},
keywords = {{Alzheimer’s disease; Dementia; Mild cognitive impairment; p-tau; Plasma biomarkers}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Alzheimer's Research and Therapy}},
title = {{Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer’s dementia in mild cognitive impairment patients}},
url = {{http://dx.doi.org/10.1186/s13195-022-00990-0}},
doi = {{10.1186/s13195-022-00990-0}},
volume = {{14}},
year = {{2022}},
}