Person: Ramírez Toraño, Federico
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First Name
Federico
Last Name
Ramírez Toraño
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Psicología
Department
Psicología Experimental, Procesos Cognitivos y Logopedia
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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 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 The relationship between physical activity, apolipoprotein E ε4 carriage, and brain health(Alzheimer's Research & Therapy, 2020) De Frutos Lucas, Jaisalmer; Cuesta Prieto, Pablo; López Sanz, David; Peral Suárez, África; Cuadrado Soto, Esther; Ramírez Toraño, Federico; Brown, Belinda M.; Serrano, Juan M.; Laws, Simon M.; Rodríguez Rojo, Inmaculada Concepción; Verdejo Román, Juan; Bruña Fernández, Ricardo; Delgado Losada, María Luisa; Barabash Bustelo, Ana; López Sobaler, Ana María; López Sánchez, Ramón; Marcos Dolado, Alberto; Maestu Unturbe, FernandoBackground: Neuronal hyperexcitability and hypersynchrony have been described as key features of neurophysiological dysfunctions in the Alzheimer’s disease (AD) continuum. Conversely, physical activity (PA) has been associated with improved brain health and reduced AD risk. However, there is controversy regarding whether AD genetic risk (in terms of APOE ε4 carriage) modulates these relationships. The utilization of multiple outcome measures within one sample may strengthen our understanding of this complex phenomenon. Method: The relationship between PA and functional connectivity (FC) was examined in a sample of 107 healthy older adults using magnetoencephalography. Additionally, we explored whether ε4 carriage modulates this association. The correlation between FC and brain structural integrity, cognition, and mood was also investigated. Results: A relationship between higher PA and decreased FC (hyposynchrony) in the left temporal lobe was observed among all individuals (across the whole sample, in ε4 carriers, and in ε4 non-carriers), but its effects manifest differently according to genetic risk. In ε4 carriers, we report an association between this region-specific FC profile and preserved brain structure (greater gray matter volumes and higher integrity of white matter tracts). In this group, decreased FC also correlated with reduced anxiety levels. In ε4 non-carriers, this profile is associated with improved cognition (working and episodic memory). Conclusions: PA could mitigate the increase in FC (hypersynchronization) that characterizes preclinical AD, being beneficial for all individuals, especially ε4 carriers.Item Brain signal complexity in adults with Down syndrome: Potential application in the detection of mild cognitive impairment(Frontiers in Aging Neuroscience, 2022) Fernández Lucas, Alberto Amable; Ramírez Toraño, Federico; Bruña Fernández, Ricardo; Zuluaga Arias, María Del Pilar; Esteba Castillo, Susanna; Abásolo, Daniel; Moldenhauer, Fernando; Shumbayawonda, Elizabeth; Maestu Unturbe, Fernando; García Alba, JavierBackground: Down syndrome (DS) is considered the most frequent cause of early-onset Alzheimer’s disease (AD), and the typical pathophysiological signs are present in almost all individuals with DS by the age of 40. Despite of this evidence, the investigation on the pre-dementia stages in DS is scarce. In the present study we analyzed the complexity of brain oscillatory patterns and neuropsychological performance for the characterization of mild cognitive impairment (MCI) in DS. Materials and methods: Lempel-Ziv complexity (LZC) values from restingstatemagnetoencephalography recordings and the neuropsychological performance in 28 patients with DS [control DS group (CN-DS) (n = 14), MCI group (MCI-DS) (n = 14)] and 14 individuals with typical neurodevelopment (CN-no-DS) were analyzed. Results: Lempel-Ziv complexity was lowest in the frontal region within the MCI-DS group, while the CN-DS group showed reduced values in parietal areas when compared with the CN-no-DS group. Also, the CN-no-DS group exhibited the expected pattern of significant increase of LZC as a function of age, while MCI-DS cases showed a decrease. The combination of reduced LZC values and a divergent trajectory of complexity evolution with age, allowed the discrimination of CN-DS vs. MCI-DS patients with a 92.9% of sensitivity and 85.7% of specificity. Finally, a pattern of mnestic and praxic impairment was significantly associated in MCI-DS cases with the significant reduction of LZC values in frontal and parietal regions (p = 0.01). Conclusion: Brain signal complexity measured with LZC is reduced in DS and its development with age is also disrupted. The combination of both features might assist in the detection of MCI within this population.Item Neuropsychological and neurophysiological characterization of mild cognitive impairment and Alzheimer's disease in Down syndrome(Neurobiology of Aging, 2019) García Alba, Javier; Ramírez Toraño, Federico; Esteba Castillo, Susanna; Bruña Fernández, Ricardo; Moldenhauer, Fernando; Novell, Ramón; Romero Medina, Verónica; Maestu Unturbe, Fernando; Fernández Lucas, Alberto AmableDown syndrome (DS) has been considered a unique model for the investigation of Alzheimer’s disease AD) but intermediate stages in the continuum are poorly defined. Considering this, we investigated the neurophysiological (i.e., magnetoencephalography [MEG]) and neuropsychological patterns of mild cognitive impairment (MCI) and AD in middle-aged adults with DS. The sample was composed of four groups: Control-DS (n ¼ 14, mean age 44.64 3.30 years), MCI-DS (n ¼ 14, 51.64 3.95 years), AD-DS (n ¼ 13, 53.54 6.58 years), and Control-no-DS (healthy controls, n ¼ 14, 45.21 4.39 years). DS individuals were studied with neuropsychological tests and MEG, whereas the Control-no-DS group completed only the MEG session. Our results showed that the AD-DS group exhibited a significantly poorer performance as compared with the Control-DS group in all tests. Furthermore, this effect was crucially evident in AD-DS individuals when compared with the MCI-DS group in verbal and working memory abilities. In the neurophysiological domain, the Control-DS group showed a widespread increase of theta activity when compared with the Control-no-DS group. With disease progression, this increased theta was substituted by an augmented delta, accompanied with a reduction of alpha activity. Such spectral patterndspecifically observed in occipital, posterior temporal, cuneus, and precuneus regionsdcorrelated with the performance in cognitive tests. This is the first MEG study in the field incorporating both neuropsychological and neurophysiological information, and demonstrating that this combination of markers is sensitive enough to characterize different stages along the AD continuum in DS.Item Functional Connectivity Hypersynchronization in Relatives of Alzheimer’s Disease Patients: An Early E/I Balance Dysfunction?(Cerebral Cortex, 2020) Ramírez Toraño, Federico; Bruña Fernández, Ricardo; De Frutos Lucas, Jaisalmer; Rodríguez Rojo, Inmaculada Concepción; Marcos de Pedro, Silvia; Delgado Losada, María Luisa; Gómez Ruiz, N; Barabash Bustelo, Ana; Marcos Dolado, Alberto; López Higes, Ramón; Maestu Unturbe, FernandoAlzheimer’s disease (AD) studies on animal models, and humans showed a tendency of the brain tissue to become hyperexcitable and hypersynchronized, causing neurodegeneration. However, we know little about either the onset of this phenomenon or its early effects on functional brain networks. We studied functional connectivity (FC) on 127 participants (92 middle-age relatives of AD patients and 35 age-matched nonrelatives) using magnetoencephalography. FC was estimated in the alpha band in areas known both for early amyloid accumulation and disrupted FC in MCI converters to AD. We found a frontoparietal network (anterior cingulate cortex, dorsal frontal, and precuneus) where relatives of AD patients showed hypersynchronization in high alpha (not modulated by APOE-ε4 genotype) in comparison to age-matched nonrelatives. These results represent the first evidence of neurophysiological events causing early network disruption in humans, opening a new perspective for intervention on the excitation/inhibition unbalance.Item Alzheimer’s disease: a continuum with visual involvements(Frontiers in psychology, 2023) Elvira Hurtado, Lorena; López Cuenca, Inés; Hoz Montañana, María Rosa De; Salas, Mario; Sánchez-Puebla Fernández, Lidia; Ramírez Toraño, Federico; Matamoros, José Antonio; Fernández Albarral, José; Rojas Lozano, María Del Pilar; Alfonsín, Soraya; Delgado Losada, María Luisa; Ramírez, Ana I.; Salazar Corral, Juan José; Maestu Unturbe, Fernando; Gil Gregorio, Pedro; Ramírez Sebastián, José Manuel; García Martín, Elena SalobrarIntroduction: Alzheimer’s disease (AD) is the most common form of dementia affecting the central nervous system, and alteration of several visual structures has been reported. Structural retinal changes are usually accompanied by changes in visual function in this disease. The aim of this study was to analyse the differences in visual function at different stages of the pathology (family history group (FH+), mild cognitive impairment (MCI), mild AD and moderate AD) in comparison with a control group of subjects with no cognitive decline and no family history of AD. Methods: We included 53 controls, 13 subjects with FH+, 23 patients with MCI, 25 patients with mild AD and, 21 patients with moderate AD. All were ophthalmologically healthy. Visual acuity (VA), contrast sensitivity (CS), colour perception, visual integration, and fundus examination were performed. Results: The analysis showed a statistically significant decrease in VA, CS and visual integration score between the MCI, mild AD and moderate AD groups compared to the control group. In the CS higher frequencies and in the colour perception test (total errors number), statistically significant differences were also observed in the MCI, mild AD and moderate AD groups with respect to the FH+ group and also between the control and AD groups. The FH+ group showed no statistically significant difference in visual functions compared to the control group. All the test correlated with the Mini Mental State Examination score and showed good predictive value when memory decline was present, with better values when AD was at a more advanced stage. Conclusion: Alterations in visual function appear in subjects with MCI and evolve when AD is established, being stable in the initial stages of the disease (mild AD and moderate AD). Therefore, visual psychophysical tests are a useful, simple and complementary tool to neuropsychological tests to facilitate diagnosis in the preclinical and early stages of AD.Item Exploratory Longitudinal Study of Ocular Structural and Visual Functional Changes in Subjects at High Genetic Risk of Developing Alzheimer’s Disease(Biomedicines, 2023) López Cuenca, Inés; García Martín, Elena Salobrar; Barabash Bustelo, Ana; Nebreda Pérez, Alberto; Ramírez Toraño, Federico; Sánchez Puebla, Lidia; García Colomo, Alejandra; Fernández Albarral, José; Ramírez Sebastián, Ana Isabel; Ramírez Sebastián, José Manuel; Maestu Unturbe, Fernando; Salazar Corral, Juan José; Gil Gregorio, Pedro; Álvarez Gutierrez, María; Elvira Hurtado, Lorena; Matamoros, José A.; Hoz Montañana, María Rosa DeThis study aimed to analyze the evolution of visual changes in cognitively healthy individuals at risk for Alzheimer’s disease (AD). Participants with a first-degree family history of AD (FH+) and carrying the Ε4+ allele for the ApoE gene (ApoE ε4+) underwent retinal thickness analysis using optical coherence tomography (OCT) and visual function assessments, including visual acuity (VA), contrast sensitivity (CS), color perception, perception digital tests, and visual field analysis. Structural analysis divided participants into FH+ ApoE ε4+ and FH− ApoE ε4− groups, while functional analysis further categorized them by age (40–60 years and over 60 years). Over the 27-month follow-up, the FH+ ApoE ε4+ group exhibited thickness changes in all inner retinal layers. Comparing this group to the FH− ApoE ε4− group at 27 months revealed progressing changes in the inner nuclear layer. In the FH+ ApoE ε4+ 40–60 years group, no progression of visual function changes was observed, but an increase in VA and CS was maintained at 3 and 12 cycles per degree, respectively, compared to the group without AD risk at 27 months. In conclusion, cognitively healthy individuals at risk for AD demonstrated progressive retinal structural changes over the 27-month follow-up, while functional changes remained stable.Item Functional Connectivity Hypersynchronization in Relatives of Alzheimer’s Disease Patients: An Early E/I Balance Dysfunction?(Cerebral Cortex, 2020) Ramírez Toraño, Federico; Bruña Fernández, Ricardo; De Frutos Lucas, Jaisalmer; Rodríguez Rojo, Inmaculada Concepción; Marcos de Pedro, Silvia; Delgado Losada, María Luisa; Gómez-Ruiz, N.; Barabash Bustelo, Ana; Marcos Dolado, Alberto; López Sánchez, Ramón; Maestu Unturbe, FernandoAlzheimer’s disease (AD) studies on animal models, and humans showed a tendency of the brain tissue to become hyperexcitable and hypersynchronized, causing neurodegeneration. However, we know little about either the onset of this phenomenon or its early effects on functional brain networks. We studied functional connectivity (FC) on 127 participants (92 middle-age relatives of AD patients and 35 age-matched nonrelatives) using magnetoencephalography. FC was estimated in the alpha band in areas known both for early amyloid accumulation and disrupted FC in MCI converters to AD. We found a frontoparietal network (anterior cingulate cortex, dorsal frontal, and precuneus) where relatives of AD patients showed hypersynchronization in high alpha (not modulated by APOE-ε4 genotype) in comparison to age-matched nonrelatives. These results represent the first evidence of neurophysiological events causing early network disruption in humans, opening a new perspective for intervention on the excitation/inhibition unbalance.