Person: Bruña Fernández, Ricardo
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First Name
Ricardo
Last Name
Bruña Fernández
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Radiología, Rehabilitación y Fisioterapia
Area
Radiología y Medicina Física
Identifiers
15 results
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Item 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, FernandoBACKGROUND: 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.Item 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 AmableRecent 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.Item 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, FernandoThe 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.Item Electrophysiological brain signatures for the classification of subjective cognitive decline: towards an individual detection in the preclinical stages of dementia(Alzheimer's Research and Therapy, 2019) López Sanz, David; Bruña Fernández, Ricardo; Delgado Losada, María Luisa; López Sánchez, Ramón; Marcos Dolado, Alberto; Maestu Unturbe, Fernando; Walter, StefanBackground Alzheimer’s disease (AD) prevalence is rapidly growing as worldwide populations grow older. Available treatments have failed to slow down disease progression, thus increasing research focus towards early or preclinical stages of the disease. Subjective cognitive decline (SCD) is known to increase the risk of developing AD and several other negative outcomes. However, it is still very scarcely characterized and there is no neurophysiological study devoted to its individual classification which could improve targeted sample recruitment for clinical trials. Methods Two hundred fifty-two older adults (70 healthy controls, 91 SCD, and 91 MCI) underwent a magnetoencephalography scan. Alpha relative power in the source space was employed to train a LASSO classifier and applied to distinguish between healthy controls and SCD. Moreover, MCI participants were used to further validate the previously trained algorithm. Results The classifier was significantly associated to SCD with an AUC of 0.81 in the whole sample. After randomly splitting the sample in 2/3 for discovery and 1/3 for validation, the newly trained classifier was also able to correctly classify SCD individuals with an AUC of 0.75 in the validation sample. The regions selected by the algorithm included medial frontal, temporal, and occipital areas. The algorithm trained to select SCD individuals was also significantly associated to MCI diagnostic. Conclusions According to our results, magnetoencephalography could be a useful tool for distinguishing individuals with SCD and healthy older adults without cognitive concerns. Furthermore, our classifier showed good external validity, being not only successful for an unseen SCD sample, but also in a different population with MCI cases. This supports its utility in the context of preclinical dementia. These findings highlight the potential applications of electrophysiological techniques to improve sample recruitment at the individual level in the context of clinical trials.Item Cognitive training modulates brain hypersynchrony in a population at risk for Alzheimer’s disease(Journal of Alzheimer's Disease, 2022) Suárez Méndez, Isabel; Bruña Fernández, Ricardo; López Sanz, David; Montejo, Pedro; Montenegro Peña, María Mercedes; Delgado Losada, María Luisa; Marcos Dolado, Alberto; López Sánchez, Ramón; Maestu Unturbe, FernandoBackground: Recent studies demonstrated that brain hypersynchrony is an early sign of dysfunction in Alzheimer's disease (AD) that can represent a proxy for clinical progression. Conversely, non-pharmacological interventions, such as cognitive training (COGTR), are associated with cognitive gains that may be underpinned by a neuroprotective effect on brain synchrony. Objective: To study the potential of COGTR to modulate brain synchrony and to eventually revert the hypersynchrony phenomenon that characterizes preclinical AD. Methods: The effect of COGTR was examined in a sample of healthy controls (HC, n = 41, 22 trained) and individuals with subjective cognitive decline (SCD, n = 49, 24 trained). Magnetoencephalographic activity and neuropsychological scores were acquired before and after a ten-week COGTR intervention aimed at improving cognitive function and daily living performance. Functional connectivity (FC) was analyzed using the phase-locking value. A mixed-effects ANOVA model with factors time (pre-intervention/post-intervention), training (trained/non-trained), and diagnosis (HC/SCD) was used to investigate significant changes in FC. Results: We found an average increase in alpha-band FC over time, but the effect was different in each group (trained and non-trained). In the trained group (HC and SCD), we report a reduction in the increase in FC within temporo-parietal and temporo-occipital connections. In the trained SCD group, this reduction was stronger and showed a tentative correlation with improved performance in different cognitive tests. Conclusion: COGTR interventions could mitigate aberrant increases in FC in preclinical AD, promoting brain synchrony normalization in groups at a higher risk of developing dementia.Item 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, FernandoBilingualism 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.Item A Structural Connectivity Disruption One Decade before the Typical Age for Dementia: A Study in Healthy Subjects with Family History of Alzheimer’s Disease(Cerebral Cortex Communications, 2021) Abbas, Kausar; Marcos de Pedro, Silvia; Gómez-Ruiz, Natividad; Pereda, Ernesto; Goñi, Joaquín; López Sánchez, Ramón; Maestu Unturbe, Fernando; Marcos Dolado, Alberto; Barabash Bustelo, Ana; Bruña Fernández, Ricardo; Ramírez Toraño, FedericoThe concept of the brain has shifted to a complex system where different subnetworks support the human cognitive functions. Neurodegenerative diseases would affect the interactions among these subnetworks and, the evolution of impairment and the subnetworks involved would be unique for each neurodegenerative disease. In this study, we seek for structural connectivity traits associated with the family history of Alzheimer’s disease, that is, early signs of subnetworks impairment due to Alzheimer’s disease.The sample in this study consisted of 123 first-degree Alzheimer’s disease relatives and 61 nonrelatives. For each subject, structural connectomes were obtained using classical diffusion tensor imaging measures and different resolutions of cortical parcellation. For the whole sample, independent structural-connectome-traits were obtained under the framework of connICA. Finally, we tested the association of the structural-connectome-traits with different factors of relevance for Alzheimer’s disease by means of a multiple linear regression. The analysis revealed a structural-connectome-trait obtained from fractional anisotropy associated with the family history of Alzheimer’s disease. The structural-connectome-trait presents a reduced fractional anisotropy pattern in first-degree relatives in the tracts connecting posterior areas and temporal areas. The family history of Alzheimer’s disease structural-connectome-trait presents a posterior–posterior and posterior–temporal pattern, supplying new evidences to the cascading network failure model.Item 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, FernandoOur 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.Item Functional Connectivity Disruption in Subjective Cognitive Decline and Mild Cognitive Impairment: A Common Pattern of Alterations(Frontiers in Aging Neuroscience, 2017) Bruña Fernández, Ricardo; López Sanz, David; Garcés, Pilar; Martín-Buro, María Carmen; Walter, Stefan; Delgado Losada, María Luisa; Montenegro Peña, María Mercedes; López Sánchez, Ramón; Marcos Dolado, Alberto; Maestu Unturbe, FernandoItem Spatiotemporal oscillatory patterns during working memory maintenance in mild cognitive impairment and subjective cognitive decline(International Journal of Neural Systems, 2019) Serrano Martínez, Noelia; López Sanz, David; Bruña Fernández, Ricardo; Garcés, Pilar; Rodríguez Rojo, Inmaculada Concepción; Marcos Dolado, Alberto; Prada Crespo, David; Maestu Unturbe, FernandoWorking memory (WM) is a crucial cognitive process and its disruption is among the earliest symptoms of Alzheimer’s disease. While alterations of the neuronal processes underlying WM have been evidenced in mild cognitive impairment (MCI), scarce literature is available in subjective cognitive decline (SCD). We used magnetoencephalography during a WM task performed by MCI (n=45), SCD (n=49) and healthy elders (n=49) to examine group differences during the maintenance period (0–4000ms). Data were analyzed using time–frequency analysis and significant oscillatory differences were localized at the source level. Our results indicated significant differences between groups, mainly during the early maintenance (250–1250ms) in the theta, alpha and beta bands and in the late maintenance (2750–3750ms) in the theta band. MCI showed lower local synchronization in fronto-temporal cortical regions in the early theta–alpha window relative to controls (p=2×10−03) and SCD (p=4×10−03), and in the late theta window relative to controls (p=1×1003) and SCD (p=0.01). Early theta–alpha power was significantly correlated with memory scores (rho=0.24,p=0.02) and late theta power was correlated with task performance (rho=0.24,p=0.03) and functional activity scores (rho=−0.23,p=0.02). In the early beta window, MCI showed reduced power in temporo-posterior regions relative to controls (p=3×10−03) and SCD (p=0.02). Our results may suggest that these alterations would reflect that memory-related networks are damaged.