Person:
Cuesta Prieto, Pablo

First Name

Pablo

Last Name

Cuesta Prieto

URI

https://hdl.handle.net/20.500.14352/80709

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Medicina

Department

Radiología, Rehabilitación y Fisioterapia

Area

Radiología y Medicina Física

Identifiers

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Now showing 1 - 10 of 21

Age and APOE genotype affect the relationship between objectively measured physical activity and power in the alpha band, a marker of brain disease
(Alzheimer's Research & Therapy, 2020) De Frutos Lucas, Jaisalmer; Cuesta Prieto, Pablo; Ramírez Toraño, Federico; Nebreda Pérez, Alberto; Cuadrado Soto, Esther; Peral Suárez, África; López Sanz, David; Bruña Fernández, Ricardo; Marcos-de Pedro, Silvia; Delgado Losada, María Luisa; López Sobaler, Ana María; Rodríguez Rojo, Inmaculada Concepción; Barabash Bustelo, Ana; Serrano Rodríguez, Juan Manuel; Laws, Simon M.; Marcos Dolado, Alberto; López Sánchez, Ramón; Brown, Belinda M.; Maestu Unturbe, Fernando
BACKGROUND: Electrophysiological studies show that reductions in power within the alpha band are associated with the Alzheimer’s disease (AD) continuum. Physical activity (PA) is a protective factor that has proved to reduce AD risk and pathological brain burden. Previous research has confirmed that exercise increases power in the alpha range. However, little is known regarding whether other non-modifiable risk factors for AD, such as increased age or APOE ε4 carriage, alter the association between PA and power in the alpha band. METHODS: The relationship between PA and alpha band power was examined in a sample of 113 healthy adults using magnetoencephalography. Additionally, we explored whether ε4 carriage and age modulate this association. The correlations between alpha power and gray matter volumes and cognition were also investigated. RESULTS: We detected a parieto-occipital cluster in which PA positively correlated with alpha power. The association between PA and alpha power remained following stratification of the cohort by genotype. Younger and older adults were investigated separately, and only younger adults exhibited a positive relationship between PA and alpha power. Interestingly, when four groups were created based on age (younger-older adult) and APOE (E3/E3-E3/E4), only younger E3/E3 (least predicted risk) and older E3/E4 (greatest predicted risk) had associations between greater alpha power and higher PA. Among older E3/E4, greater alpha power in these regions was associated with improved memory and preserved brain structure. CONCLUSION: PA could protect against the slowing of brain activity that characterizes the AD continuum, where it is of benefit for all individuals, especially E3/E4 older adults.
Searching for Primary Predictors of Conversion from Mild Cognitive Impairment to Alzheimer’s Disease: A Multivariate Follow-Up Study
(Journal of Alzheimer's Disease, 2016) López García, María Eugenia; Turrero Nogués, Agustín; Cuesta Prieto, Pablo; López Sanz, David; Bruña Fernández, Ricardo; Marcos Dolado, Alberto; Gil Gregorio, Pedro; Yus, Miguel; Barabash Bustelo, Ana; Cabranes Díaz, José Antonio; Maestu Unturbe, Fernando; Fernández Lucas, Alberto Amable
Recent proposals of diagnostic criteria within the healthy aging-Alzheimer’s disease (AD) continuum stressed the role of biomarker information. More importantly, such information might be critical to predict those mild cognitive impairment (MCI) patients at a higher risk of conversion to AD. Usually, follow-up studies utilize a reduced number of potential markers although the conversion phenomenon may be deemed as multifactorial in essence. In addition, not only biological but also cognitive markers may play an important role. Considering this background, we investigated the role of cognitive reserve, cognitive performance in neuropsychological testing, hippocampal volumes, APOE genotype, and magnetoencephalography power sources to predict the conversion to AD in a sample of 33 MCI patients. MCIs were followed up during a 2-year period and divided into two subgroups according to their outcome: The “stable” MCI group (sMCI, 21 subjects) and the “progressive” MCI group (pMCI, 12 subjects). Baseline multifactorial information was submitted to a hierarchical logistic regression analysis to build a predictive model of conversion to AD. Results indicated that the combination of left hippocampal volume, occipital cortex theta power, and clock drawing copy subtest scores predicted conversion to AD with a 100% of sensitivity and 94.7% of specificity. According to these results it might be suggested that anatomical, cognitive, and neurophysiological markers may be considered as “first order” predictors of progression to AD, while APOE or cognitive reserve proxies might play a more secondary role.
Project number: 378
Creación de Prácticas Virtuales de Protección Radiológica
(2021) García Pinto, Diego; Cuesta Prieto, Pablo; Delgado Martinez, Victor; Guibelalde Del Castillo, Eduardo; Rodríguez Rodríguez, César; Sánchez Casanueva, Roberto Mariano; Vaño Carruana, Eliseo; Menéndez Muñoz, Susana Rosario; Muñoz Pérez, Javier
La situación creada por la pandemia debida a la COVID-19 plantea un modelo de enseñanza distinto al que se ha venido desarrollando hasta ahora, ya que implica una docencia semipresencial o incluso completamente virtual. Esta situación es aún más drástica para aquellas titulaciones que requieren de prácticas clínicas que se realizan en hospitales. En este contexto las tecnologías de la información y la creación de material multimedia juegan un papel cada vez más importante para proveer herramientas de enseñanza virtual que permitan conseguir los objetivos docentes, y que además cuenten con el apoyo del docente. En este ámbito planteamos en este proyecto la creación de un conjunto de prácticas virtuales que permitirán cumplir con las exigencias docentes del módulo de protección radiológica dentro de la asignatura Odontología Legal, Profesión y Ética y que a su vez cumplan con los posibles escenarios de semipresencialidad o virtual. Para ello se crearán un conjunto de videos cortos demostrativos elaborados por el personal docente del grupo en los que se mostrará cómo sería la realización de la práctica. Junto con la visualización de dichos videos se proponen una serie de actividades interactivas que el alumno deberá realizar bajo la supervisión del personal docente. La realización de estas prácticas es también esencial para obtener el título correspondiente al curso de Protección Radiológica para Dirigir Instalaciones de Rayos X con fines de Diagnóstico Médico emitido por Consejo de Seguridad Nuclear, de modo que es necesario proveer de una alternativa a la realización de las prácticas y que por tanto se puede seguir obteniendo el título correspondiente que es tan importante para los alumnos del Grado de Odontología. Así mismo la metodología desarrollada permitirá la creación de material nuevo que podrá ser utilizado en otras asignaturas.
BDNF Val66Met polymorphism and gamma band disruption in resting state brain functional connectivity: A magnetoencephalography study in cognitively intact older females
(Frontiers in Neuroscience, 2018) Rodríguez Rojo, Inmaculada Concepción; Cuesta Prieto, Pablo; López García, María Eugenia; De Frutos Lucas, Jaisalmer; Bruña Fernández, Ricardo; Pereda de Pablo, Ernesto; Barabash Bustelo, Ana; Montejo, Pedro; Montenegro Peña, María Mercedes; Marcos Dolado, Alberto; López-Higes, Ramón; Fernández Lucas, Alberto Amable; Maestu Unturbe, Fernando
The pathophysiological processes undermining brain functioning decades before the onset of the clinical symptoms associated with dementia are still not well understood. Several heritability studies have reported that the Brain Derived Neurotrophic Factor (BDNF) Val66Met genetic polymorphism could contribute to the acceleration of cognitive decline in aging. This mutation may affect brain functional connectivity (FC), especially in those who are carriers of the BDNF Met allele. The aim of this work was to explore the influence of the BDNF Val66Met polymorphism in whole brain eyes-closed, resting-state magnetoencephalography (MEG) FC in a sample of 36 cognitively intact (CI) older females. All of them were ε3ε3 homozygotes for the apolipoprotein E (APOE) gene and were divided into two subgroups according to the presence of the Met allele: Val/Met group (n = 16) and Val/Val group (n = 20). They did not differ in age, years of education, Mini-Mental State Examination scores, or normalized hippocampal volumes. Our results showed reduced antero-posterior gamma band FC within the Val/Met genetic risk group, which may be caused by a GABAergic network impairment. Despite the lack of cognitive decline, these results might suggest a selective brain network vulnerability due to the carriage of the BDNF Met allele, which is linked to a potential progression to dementia. This neurophysiological signature, as tracked with MEG FC, indicates that age-related brain functioning changes could be mediated by the influence of particular genetic risk factors.
A multivariate model of time to conversion from mild cognitive impairment to Alzheimer’s disease
(GeroScience, 2020) López García, María Eugenia; Turrero Nogués, Agustín; Cuesta Prieto, Pablo; Rodríguez Rojo, Inmaculada Concepción; Barabash Bustelo, Ana; Marcos Dolado, Alberto; Maestu Unturbe, Fernando; Fernández Lucas, Alberto Amable
The present study was aimed at determining which combination of demographic, genetic, cognitive, neurophysiological, and neuroanatomical factors may predict differences in time to progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). To this end, a sample of 121 MCIs was followed up during a 5-year period. According to their clinical outcome, MCIs were divided into two subgroups: (i) the “progressive” MCI group (n = 46; mean time to progression 17 ± 9.73 months) and (ii) the “stable” MCIgroup (n = 75; mean time of follow-up 31.37 ± 14.58 months). Kaplan–Meier survival analyses were applied to explore each variable’s relationship with the progression to AD. Once potential predictors were detected, Cox regression analyses were utilized to calculate a parsimonious model to estimate differences in time to progression. The final model included three variables (in order of relevance): left parahippocampal volume (corrected by intracranial volume, LP_ ICV), delayed recall (DR), and left inferior occipital lobe individual alpha peak frequency (LIOL_IAPF). Those MCIs with LP_ICV volume, DR score, and LIOL_IAPF value lower than the defined cutoff had 6 times, 5.5 times, and 3 times higher risk of progression to AD, respectively. Besides, when the categories of the three variables were “unfavorable” (i.e., values below the cutoff), 100% of cases progressed to AD at the end of follow-up. Our results highlighted the relevance of neurophysiological markers as predictors of conversion (LIOL_IAPF) and the importance of multivariate models that combine markers of different nature to predict time to progression from MCI to dementia.
Enhancement of posterior brain functional networks in bilingual older adults
(Bilingualism: Language and Cognition, 2019) De Frutos Lucas, Jaisalmer; López Sanz, David; Cuesta Prieto, Pablo; Bruña Fernández, Ricardo; Fuente, Sofía de la; Serrano Martínez, Noelia; López García, María Eugenia; Delgado Losada, María Luisa; López Sánchez, Ramón; Marcos Dolado, Alberto; Maestu Unturbe, Fernando
Bilingualism has been said to improve cognition and even delay the onset of Alzheimer's disease (AD). This research aimed to investigate whether bilingualism leaves a neurophysiological trace even when people are highly educated. We expected bilinguals to present better preserved brain functional networks, which could be a trace of higher cognitive reserve. With this purpose, we conducted a magnetoencephalographic study with a group of healthy older adults. We estimated functional connectivity using phase-locking value and found five clusters in parieto-occipital regions in which bilinguals exhibited greater functional connectivity than monolinguals. These clusters included brain regions typically implicated in language processing. Furthermore, these functional changes correlated with caudate volumes (a key region in language shifting and control) in the bilingual sample. Interestingly, decreased Functional Connectivity between posterior brain regions had already been identified as an indicator of aging/preclinical AD but, according to our study, bilingualism seems to exert the opposite effect.
How to Build a Functional Connectomic Biomarker for Mild Cognitive Impairment From Source Reconstructed MEG Resting-State Activity: The Combination of ROI Representation and Connectivity Estimator Matters
(Frontiers in Neuroscience, 2018) López García, María Eugenia; Bruña Fernández, Ricardo; Cuesta Prieto, Pablo; Marcos Dolado, Alberto; Maestu Unturbe, Fernando
Our work aimed to demonstrate the combination of machine learning and graph theory for the designing of a connectomic biomarker for mild cognitive impairment (MCI) subjects using eyes-closed neuromagnetic recordings. The whole analysis based on source-reconstructed neuromagnetic activity. As ROI representation, we employed the principal component analysis (PCA) and centroid approaches. As representative bi-variate connectivity estimators for the estimation of intra and cross-frequency interactions, we adopted the phase locking value (PLV), the imaginary part (iPLV) and the correlation of the envelope (CorrEnv). Both intra and cross-frequency interactions (CFC) have been estimated with the three connectivity estimators within the seven frequency bands (intra-frequency) and in pairs (CFC), correspondingly. We demonstrated how different versions of functional connectivity graphs single-layer (SL-FCG) and multi-layer (ML-FCG) can give us a different view of the functional interactions across the brain areas. Finally, we applied machine learning techniques with main scope to build a reliable connectomic biomarker by analyzing both SL-FCG and ML-FCG in two different options: as a whole unit using a tensorial extraction algorithm and as single pair-wise coupling estimations. We concluded that edge-weighed feature selection strategy outperformed the tensorial treatment of SL-FCG and ML-FCG. The highest classification performance was obtained with the centroid ROI representation and edge-weighted analysis of the SL-FCG reaching the 98% for the CorrEnv in α1:α2 and 94% for the iPLV in α2. Classification performance based on the multi-layer participation coefficient, a multiplexity index reached 52% for iPLV and 52% for CorrEnv. Selected functional connections that build the multivariate connectomic biomarker in the edge-weighted scenario are located in default-mode, fronto-parietal, and cingulo-opercular network. Our analysis supports the notion of analyzing FCG simultaneously in intra and cross-frequency whole brain interactions with various connectivity estimators in beamformed recordings.
Perfiles biomagnéticos de la actividad en reposo cerebral en las fases preclínica y prodrómica de la Enfermedad de Alzheimer: influencia del alelo APOE-ε4 y de la acumulación de β-amiloide
(2015) Cuesta Prieto, Pablo; Sancho Ruiz, Miguel; Nakamura, Akinori; Maestú Unturbe, Fernando
Introducción La acumulación de beta-amiloide (Ab) es una característica principal de la Enfermedad de Alzheimer (EA) y está muy relacionada con el alelo 4 de la Apoliproteina E (APOE). Existen dos enfoques principales para el estudio de la actividad cerebral. El primero (potencia espectral), da una visión estática y caracteriza la activación cerebral en cada región. El segundo, da una perspectiva dinámica y analiza la dependencia estadística entre las señales registradas en distintas partes de cerebro mediante la conectividad funcional (FC). El uso de ambas aproximaciones se basa en que la Ab se acumula principalmente en aquellas áreas del cerebro que muestran una mayor actividad como la Red por Defecto (DMN, Default Mode Network). El objetivo principal ha sido contribuir a la comprensión del efecto que produce el alelo APOE-¿4 y la acumulación de Ab en la actividad cerebral, medida con Magnetoencefalografía (MEG) en los estados preclínicos y prodrómicos de la EA de cara a conseguir nuevos biomarcadores de la progresión de la EA. Resultados Todos los estudios fueron realizados en el espacio de fuentes generadoras. Estudio 1: APOE-Potencia. Se analizaron los registros MEG de 25 CN y 36 pacientes con DCL. Ambos grupos fueron divididos en portadores o no del alelo APOE-¿4. Los pacientes con DCL mostraron un incremento en la potencia de baja frecuencia además de un decremento en el rango de alta frecuencia. Los sujetos con APOE-¿4 tenían mayor potencia entre 4.5-6.5 Hz en los lóbulos frontales. Estudio 2: APOE-FC. Se estudió la actividad de 27 CN y 36 pacientes con DCL divididos en portadores o no del alelo APOE-¿4. Los sujetos DCL mostraron una disminución de la FC en alfa y beta en las regiones temporales mediales y parietales. Los portadores mostraron un decremento de FC en la banda delta en regiones fronto-occipitales. Por último, se halló un patrón de hipo/hipersincronización en las regiones fronto-temporales derechas. Estudio 3: Ab-Potencia. Participaron 37 CN y 27 pacientes con DCL. En base a la acumulación de Ab, se obtuvieron cuatro grupos: 25 CN-, 12 CN +, 11 DCL- y 15 DCL+. El efecto asociado al diagnóstico mostró un típico patrón de enlentecimiento de la actividad cerebral. El efecto de la acumulación de Ab consistió en un incremento en la potencia alfa en regiones fronto-mediales. Estudio 4: Ab-FC. Participaron 32CN- y 13 CN+. Los resultados fueron: 1) en delta, el precuneus (Pc) mostró una disminución de la FC a nivel intra-ROI en el grupo CN+; 2) la comunicación entre el Pc y ambos lóbulos parietales inferiores (IPL) se vio incrementada en los sujetos CN+. Discusión Análisis de Potencia Esta tesis ha añadido información sobre la influencia del genotipo APOE y la acumulación de Ab en la actividad cerebral. En particular, la presencia del alelo APOE-¿4 pareció estar relacionada con un mayor enlentecimiento de la actividad mientras que la Ab se encontró especialmente relacionada con una anteriorización de la actividad alfa. Estos efectos son clave para discernir qué cambios en la actividad espontánea se deben al envejecimiento y cuales a la EA. Análisis de FC El hallazgo de patrones de hiposincronización/hipersincronización en los sujetos con APOE-¿4 o acumulación de Ab puede explicarse de la siguiente forma: 1) en la etapa no sintomática, los sujetos APOE-¿4 o Ab+ tratarían de compensar incrementando la FC; 2) además en la etapa con DCL, la red perdería su capacidad para compensar, lo que conduciría a la interrupción de la FC normal entre regiones fronto-temporales derechas y el resto del cerebro. Estos resultados casan bien con los hechos de que la Ab se acumula fundamentalmente en la DMN y que afecta la actividad sináptica a nivel local. Este daño podría estar ocasionando la desestabilización de la actividad de la red cortical generando la ocurrencia de una diasquisis caracterizada por una aparición de circuitos de compensación.
The effects of white matter hyperintensities on MEG power spectra in population with mild cognitive impairment
(Frontiers in Human Neuroscience, 2023) Torres Simón, Lucía; Cuesta Prieto, Pablo; del Cerro León, Alberto; Chino, Brenda; Orozco, Lucia H.; Marsh, Elisabeth B.; Gil Gregorio, Pedro; Maestu Unturbe, Fernando
Cerebrovascular disease is responsible for up to 20% of cases of dementia worldwide, but also it is a major comorbid contributor to the progression of other neurodegenerative diseases, like Alzheimer’s disease. White matter hyperintensities (WMH) are the most prevalent imaging marker in cerebrovascular disease. The presence and progression of WMH in the brain have been associated with general cognitive impairment and the risk to develop all types of dementia. The aim of this piece of work is the assessment of brain functional differences in an MCI population based on the WMH volume. One-hundred and twenty-nine individuals with mild cognitive impairment (MCI) underwent a neuropsychological evaluation, MRI assessment (T1 and Flair), and MEG recordings (5 min of eyes closed resting state). Those participants were further classified into vascular MCI (vMCI; n = 61, mean age 75 ± 4 years, 35 females) or non-vascular MCI (nvMCI; n = 56, mean age 72 ± 5 years, 36 females) according to their WMH total volume, assessed with an automatic detection toolbox, LST (SPM12). We used a completely data-driven approach to evaluate the differences in the power spectra between the groups. Interestingly, three clusters emerged: One cluster with widespread larger theta power and two clusters located in both temporal regions with smaller beta power for vMCI compared to nvMCI. Those power signatures were also associated with cognitive performance and hippocampal volume. Early identification and classification of dementia pathogenesis is a crucially important goal for the search for more effective management approaches. These findings could help to understand and try to palliate the contribution of WMH to particular symptoms in mixed dementia progress.
Differential patterns of functional connectivity in Progressive and Stable Mild Cognitive Impairment subjects
(Brain Connectivity, 2012) Bajo Bretón, Ricardo; Castellanos, Nazareth P.; Cuesta Prieto, Pablo; Aurtenetxe, Sara; Gil Gregorio, Pedro; Pozo, Francisco del; Maestu Unturbe, Fernando
It is now widely accepted that Alzheimer's disease is characterized by a functional disconnection between brain regions. The disease appears to begin up to decades prior to clinical diagnosis. Therefore, in the present study, we combined magnetoencephalography, a memory task, and functional connectivity analysis in mild cognitive impairment subjects in order to identify functional connectivity patterns that could characterize subjects who would eventually go on to develop the disease. We monitored 19 subjects and finally 5 of them developed Alzheimer's disease. These progressive patients showed a differential profile of functional connectivity values compared with those patients who remained stable over time. Specifically there were higher synchronization values over the parieto-occipital region in α and β frequency bands. The involvement of this brain region in amyloid-β accumulation and its possible association with hyper-synchronization are also discussed.