Person:
Ramírez Toraño, Federico

First Name

Federico

Last Name

Ramírez Toraño

URI

https://hdl.handle.net/20.500.14352/84540

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Psicología

Department

Psicología Experimental, Procesos Cognitivos y Logopedia

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Now showing 1 - 8 of 8

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.
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, Federico
The 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.
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, Fernando
Background: 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.
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, Javier
Background: 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.
Early visual alterations in individuals at-risk of Alzheimer’s disease: a multidisciplinary approach
(Alzheimer's Research & Therapy, 2023) López Cuenca, Inés; Nebreda Pérez, Alberto; García Colomo, Alejandra; García Martín, Elena Salobrar; Frutos Lucas, Jaisalmer de; Bruña Fernández, Ricardo; Ramírez Sebastián, Ana Isabel; Ramírez Toraño, Federico; Salazar Corral, Juan José; Barabash, Ana; Gil, Pedro; Maestú Unturbe, Fernando; Ramirez Sebastian, Jose Manuel; Hoz Montañana, Rosa de
Background: The earliest pathological features of Alzheimer’s disease (AD) appear decades before the clinical symptoms. The pathology affects the brain and the eye, leading to retinal structural changes and functional visual alterations. Healthy individuals at high risk of developing AD present alterations in these ophthalmological measures, as well as in resting-state electrophysiological activity. However, it is unknown whether the ophthalmological alterations are related to the visual-related electrophysiological activity. Elucidating this relationship is paramount to understand the mechanisms underlying the early deterioration of the system and an important step in assessing the suitability of these measures as early biomarkers of disease. Methods: In total, 144 healthy subjects: 105 with family history of AD and 39 without, underwent ophthalmologic analysis, magnetoencephalography recording, and genotyping. A subdivision was made to compare groups with less demographic and more risk differences: 28 high-risk subjects (relatives/APOEɛ4 +) and 16 low-risk (non-relatives/APOEɛ4 −). Differences in visual acuity, contrast sensitivity, and macular thickness were evaluated. Correlations between each variable and visual-related electrophysiological measures (M100 latency and time–frequency power) were calculated for each group. Results: High-risk groups showed increased visual acuity. Visual acuity was also related to a lower M100 latency and a greater power time–frequency cluster in the high-risk group. Low-risk groups did not show this relationship. High-risk groups presented trends towards a greater contrast sensitivity that did not remain significant after correction for multiple comparisons. The highest-risk group showed trends towards the thinning of the inner plexiform and inner nuclear layers that did not remain significant after correction. The correlation between contrast sensitivity and macular thickness, and the electrophysiological measures were not significant after correction. The difference between the high- and low- risk groups correlations was no significant. Conclusions: To our knowledge, this paper is the first of its kind, assessing the relationship between ophthalmological and electrophysiological measures in healthy subjects at distinct levels of risk of AD. The results are novel and unexpected, showing an increase in visual acuity among high-risk subjects, who also exhibit a relationship between this measure and visual-related electrophysiological activity. These results have not been previously explored and could constitute a useful object of research as biomarkers for early detection and the evaluation of potential interventions’ effectiveness.
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 Amable
Down 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.
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, Fernando
Alzheimer’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.
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, Fernando
Alzheimer’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.