@article {aCumplido-Mayoral,
	title = {The mediating role of neuroimaging-derived biological brain age between risk factors for dementia and cognitive decline in middle/late-aged asymptomatic individuals: a cohort study},
	journal = {The Lancet Healthy Longevity},
	year = {2024},
	month = {04/2024},
	abstract = {<p>Summary Background Neuroimaging-based brain-age delta has been shown to be a mediator linking cardiovascular risk factors to cognitive function. We aimed to assess the mediating role of brain-age delta in the association between modifiable risk factors of dementia and longitudinal cognitive decline in middle-aged and older individuals who are asymptomatic, stratified by Alzheimer{\textquoteright}s disease pathology. We also explored whether the mediation effect is specific to cognitive domain. Methods In this cohort study, we included participants from the ALFA+ cohort aged between 45 years and 65 years who were cognitively unimpaired and who had available structural MRI, cerebrospinal fluid β-amyloid (Aβ)42 and Aβ40 measurements obtained within 1 year of each other, modifiable risk factors assessment, and cognitive evaluation over 3 years. Participants were recruited from the Barcelonaβeta Brain Research Center (Barcelona, Spain). Included individuals underwent a first assessment between Oct 25, 2016, and Jan 28, 2020, and a follow-up cognitive assessment 3{\textperiodcentered}28 (SD 0{\textperiodcentered}27) years later. We computed brain-age delta and composites of different cognitive function domains (preclinical Alzheimer{\textquoteright}s cognitive composite [PACC], attention, executive function, episodic memory, visual processing, and language). We used partial least squares path modelling to explore mediation effects in the associations between modifiable risk factors (including cardiovascular, mental health, mood, metabolic or endocrine history, and alcohol use) and changes in cognitive composites. To assess the role of Alzheimer{\textquoteright}s disease pathology, we computed separate models for Aβ-negative and Aβ-positive individuals. Findings Of the 419 participants enrolled in ALFA+, 302 met our inclusion criteria, of which 108 participants were classified as Aβ-positive and 194 as Aβ-negative. In Aβ-positive individuals, brain-age delta partially mediated (percent mediation proportion 15{\textperiodcentered}73\% [95\% CI 14{\textperiodcentered}22{\textendash}16{\textperiodcentered}66]) the association between modifiable risk factors and decline in overall cognition (across cognitive domains). Brain-age delta fully mediated (mediation proportion 28{\textperiodcentered}03\% [26{\textperiodcentered}25{\textendash}29{\textperiodcentered}21]) the effect of modifiable risk factors on the PACC, wherein increased values for risk factors correlated with an older brain-age delta, and, consequently, an older brain-age delta was linked to greater PACC decline. This effect appears to be primarily driven by memory decline. Mediation was not significant in Aβ-negative individuals (3{\textperiodcentered}52\% [0{\textperiodcentered}072{\textendash}4{\textperiodcentered}17]) on PACC, although path coefficients were not significantly different from those in the Aβ-positive group. Interpretation Our findings suggest that brain-age delta captures the association between modifiable risk factors and longitudinal cognitive decline in middle-aged and older people. In asymptomatic middle-aged and older individuals who are Aβ-positive, the pathology might be the strongest driver of cognitive decline, whereas the effect of risk factors is smaller. Our results highlight the potential of brain-age delta as an objective outcome measure for preventive lifestyle interventions targeting cognitive decline.</p>},
	doi = {10.1016/S2666-7568(24)00025-4},
	author = {Irene Cumplido-Mayoral and Anna Brugulat-Serra and Gonzalo S{\'a}nchez-Benavides and Jose Luis Molinuevo and Marc Suarez-Calvet and Ver{\'o}nica Vilaplana and Juan Domingo Gispert}
}
@conference {cMayoral21,
	title = {Machine learning on combined neuroimaging and plasma biomarkers for triaging participants of secondary prevention trials in Alzheimer{\textquoteright}s Disease},
	booktitle = {Alzheimer{\textquoteright}s Association International Conference},
	year = {2021},
	month = {07/2021},
	author = {Irene Cumplido-Mayoral and Gemma Salvad{\'o} and Mahnaz Shekari and Carles Falcon and Marta Mil{\`a} Alom{\`a} and Aida Ni{\~n}erola Baiz{\'a}n and Jose Luis Molinuevo and Henrik Zetterberg and Kaj Blennow and Marc Suarez Calvet and Ver{\'o}nica Vilaplana and Juan D. Gispert}
}
@article {aCasamitjana,
	title = {MRI-Based Screening of Preclinical Alzheimer{\textquoteright}s Disease for Prevention Clinical Trials},
	journal = {Journal of Alzheimer{\textquoteright}s Disease},
	volume = {64},
	year = {2018},
	month = {07/2018},
	chapter = {1099},
	abstract = {<p class="p1">The identification of healthy individuals harboring amyloid pathology constitutes one important challenge for secondary prevention clinical trials in Alzheimer{\textquoteright}s disease (AD). Consequently, noninvasive and cost-efficient techniques to detect preclinical AD constitute an unmet need of critical importance. In this manuscript, we apply machine learning to structural MRI (T1 and DTI) of 96 cognitively normal subjects to identify amyloid-positive ones. Models were trained on public ADNI data and validated on an independent local cohort. Used for subject classification in a simulated clinical trial setting, the proposed method is able to save 60\% unnecessary CSF/PET tests and to reduce 47\% of the cost of recruitment when used in a simulated clinical trial setting. This recruitment strategy capitalizes on already acquired MRIs to reduce the overall amount of invasive PET/CSF tests in prevention trials, demonstrating a potential value as a tool for AD screening. This protocol could foster the development of secondary prevention strategies for AD.</p>},
	author = {Adri{\`a} Casamitjana and Paula Petrone and Alan Tucholka and Carles Falcon and Stavros Skouras and Jose Luis Molinuevo and Ver{\'o}nica Vilaplana and Juan D. Gispert}
}
