Development and assessment of algorithms for predicting brain amyloid positivity in a population without dementia
Alz Res Therapy. 2024-10-11; 16(1):
DOI: 10.1186/s13195-024-01595-5
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1. Alzheimers Res Ther. 2024 Oct 11;16(1):219. doi: 10.1186/s13195-024-01595-5.
Development and assessment of algorithms for predicting brain amyloid positivity
in a population without dementia.
Le Scouarnec L(1)(2), Bouteloup V(3)(4), van der Veere PJ(5)(6)(7), van der
Flier WM(5)(6)(7), Teunissen CE(8), Verberk IMW(8), Planche V(9)(10), Chêne
G(3)(4), Dufouil C(3)(4).
Author information:
(1)Univ. Bordeaux, Bordeaux Population Health, UMR1219, Inserm, Bordeaux,
France. .
(2)CIC 1401 de Bordeaux – Module Epidémiologique Clinique / Bâtiment ISPED,
Université de Bordeaux, 146, rue Léo Saignat, Bordeaux cedex, CS61292 33076,
France. .
(3)Univ. Bordeaux, Bordeaux Population Health, UMR1219, Inserm, Bordeaux,
France.
(4)CIC 1401 de Bordeaux – Module Epidémiologique Clinique / Bâtiment ISPED,
Université de Bordeaux, 146, rue Léo Saignat, Bordeaux cedex, CS61292 33076,
France.
(5)Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam,
Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
(6)Department of Epidemiology and Biostatistics, Amsterdam Neuroscience, VU
University Medical Center, De Boelelaan 1117, Amsterdam, 1081 HV, the
Netherlands.
(7)Amsterdam Neuroscience, De Boelelaan 1117, Neurodegeneration, Amsterdam, 1081
HV, The Netherlands.
(8)Neurochemistry Laboratory, Laboratory Medicine, Vrije Universiteit Amsterdam,
Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
(9)Institut des Maladies Neurodégénératives, Univ. Bordeaux, CNRS, UMR 5293,
Bordeaux, France.
(10)Pôle de Neurosciences Cliniques, Centre Mémoire de Ressources et de
Recherche, CHU de, Bordeaux, France.
BACKGROUND: The accumulation of amyloid-β (Aβ) peptide in the brain is a
hallmark of Alzheimer’s disease (AD), occurring years before symptom onset.
Current methods for quantifying in vivo amyloid load involve invasive or costly
procedures, limiting accessibility. Early detection of amyloid positivity in
non-demented individuals is crucial for aiding early AD diagnosis and for
initiating anti-amyloid immunotherapies at early stages. This study aimed to
develop and validate predictive models to identify brain amyloid positivity in
non-demented patients, using routinely collected clinical data.
METHODS: Predictive models for amyloid positivity were developed using data from
853 non-demented participants in the MEMENTO cohort. Amyloid levels were
measured potentially repeatedly during study course through Positron Emision
Tomography or CerebroSpinal Fluid analysis. The probability of amyloid
positivity was modelled using mixed-effects logistic regression. Predictors
included demographic information, cognitive assessments, visual brain MRI
evaluations of hippocampal atrophy and lobar microbleeds, AD-related blood
biomarkers (Aβ42/40 and P-tau181), and ApoE4 status. Models were subjected to
internal cross-validation and external validation using data from the Amsterdam
Dementia Cohort. Performance also was evaluated in a subsample that met the main
criteria of the Appropriate Use Recommendations (AUR) for lecanemab.
RESULTS: The most effective model incorporated demographic data, cognitive
assessments, ApoE status, and AD-related blood biomarkers, achieving AUCs of
0.82 [95%CI 0.81-0.82] in MEMENTO sample and 0.90 [95%CI 0.86-0.94] in the
external validation sample. This model significantly outperformed a reference
model based solely on demographic and cognitive data, with an AUC difference in
MEMENTO of 0.10 [95%CI 0.10-0.11]. A similar model without ApoE genotype
achieved comparable discriminatory performance. MRI markers did not improve
model performance. Performances in AUR of lecanemab subsample were comparable.
CONCLUSION: A predictive model integrating demographic, cognitive, and blood
biomarker data offers a promising method to help identify amyloid status in
non-demented patients. ApoE genotype and brain MRI data were not necessary for
strong discriminatory ability, suggesting that ApoE genotyping may be deferred
when assessing the risk-benefit ratio of immunotherapies in amyloid-positive
patients who desire treatment. The integration of this model into clinical
practice could reduce the need for lumbar puncture or PET examinations to
confirm amyloid status.
© 2024. The Author(s).
DOI: 10.1186/s13195-024-01595-5
PMCID: PMC11468062
PMID: 39394180 [Indexed for MEDLINE]
Conflict of interest statement: During the past three years, VP was a local
unpaid investigator or sub-investigator for clinical trials granted by
NovoNordisk, Biogen, TauRx Pharmaceuticals, Janssen and Alector. He received
consultant fees for animal studies from Motac Neuroscience Ltd.All other authors
declare no competing interests. All other authors declare no competing
interests.