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 - 10 of 14

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.
Foveal Avascular Zone and Choroidal Thickness Are Decreased in Subjects with Hard Drusen and without High Genetic Risk of Developing Alzheimer’s Disease
(Biomedicines, 2021) López Cuenca, Inés; Hoz Montañana, María Rosa de; Alcántara Rey, Celia; García Martín, Elena Salobrar; Elvira Hurtado, Lorena; Fernández Albarral, José Antonio; Barabash, Ana; Ramírez Toraño, Federico; Frutos Lucas, Jaisalmer de; Salazar Corral, Juan José; Ramírez Sebastián, Ana Isabel; Ramirez Sebastian, Jose Manuel
A family history (FH+) of Alzheimer’s disease (AD) and ε4 allele of the ApoE gene are the main genetic risk factors for developing AD, whereas ε4 allele plays a protective role in age-related macular degeneration. Ocular vascular changes have been reported in both pathologies. We analyzed the choroidal thickness using optical coherence tomography (OCT) and the foveal avascular zone (FAZ) using OCT-angiography and compared the results with ApoE gene expression, AD FH+, and the presence or absence of hard drusen (HD) in 184 cognitively healthy subjects. Choroidal thickness was statistically significantly different in the (FH−, ε4−, HD+) group compared with (i) both the (FH−, ε4−, HD−) and the (FH+, ε4+, HD+) groups in the superior and inferior points at 1500 µm, and (ii) the (FH+, ε4−, HD+) group in the superior point at 1500 µm. There were statistically significant differences in the superficial FAZ between the (FH+, ε4−, HD+) group and (i) the (FH+, ε4−, HD−) group and (ii) the (FH+, ε4+, HD−) group. In conclusion, ocular vascular changes are not yet evident in participants with a genetic risk of developing AD.
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.
Characterization of Retinal Drusen in Subjects at High Genetic Risk of Developing Sporadic Alzheimer’s Disease: An Exploratory Analysis
(Journal of Personalized Medicine, 2022) López Cuenca, Inés; García Martín, Elena Salobrar; Gil Salgado, Inés; Sánchez Puebla, Lídia; Elvira Hurtado, Lorena; Fernández Albarral, José Antonio; Ramírez Toraño, Federico; Barabash, Ana; Frutos Lucas, Jaisalmer de; Salazar Corral, Juan José; Ramirez Sebastian, Jose Manuel; Ramírez Sebastián, Ana Isabel; Hoz Montañana, María Rosa de
Having a family history (FH+) of Alzheimer’s disease (AD) and being a carrier of at least one ɛ4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related macular degeneration (AMD) share one of the main risk factors, such as age, and characteristics including the presence of deposits (Aβ plaques in AD and drusen in AMD); however, the role of apolipoprotein E isoforms in both pathologies is controversial. We analyzed and characterized retinal drusen by optical coherence tomography (OCT) in subjects, classifying them by their AD FH (FH- or FH+) and their allelic characterization of ApoE ɛ4 (ApoE ɛ4- or ApoE ɛ4+) and considering cardiovascular risk factors (hypercholesterolemia, hypertension, and diabetes mellitus). In addition, we analyzed the choroidal thickness by OCT and the area of the foveal avascular zone with OCTA. We did not find a relationship between a family history of AD or any of the ApoE isoforms and the presence or absence of drusen. Subjects with drusen show choroidal thinning compared to patients without drusen, and thinning could trigger changes in choroidal perfusion that may give rise to the deposits that generate drusen
Retinal Vascular Study Using OCTA in Subjects at High Genetic Risk of Developing Alzheimer’s Disease and Cardiovascular Risk Factors
(Journal of Clinical Medicine, 2022) López Cuenca, Inés; García Martín, Elena Salobrar; Sánchez Puebla, Lídia; Espejel Checa, Eva; García del Arco, Lucía; Rojas Lozano, Pilar; Elvira Hurtado, Lorena; Fernández Albarral, José Antonio; Ramírez Toraño, Federico; Barabash, Ana; Salazar Corral, Juan José; Ramirez Sebastian, Jose Manuel; Hoz Montañana, María Rosa de; Ramírez Sebastián, Ana Isabel
In 103 subjects with a high genetic risk of developing Alzheimer’s disease (AD), family history (FH) of AD and ApoE ɛ4 characterization (ApoE ɛ4) were analyzed for changes in the retinal vascular network by OCTA (optical coherence tomography angiography), and AngioTool and Erlangen-Angio-Tool (EA-Tool) as imaging analysis software. Retinal vascularization was analyzed by measuring hypercholesterolemia (HCL) and high blood pressure (HBP). Angio-Tool showed a statistically significant higher percentage of area occupied by vessels in the FH+ ApoE ɛ4- group vs. in the FH+ ApoE ɛ4+ group, and EA-Tool showed statistically significant higher vascular densities in the C3 ring in the FH+ ApoE ɛ4+ group when compared with: i)FH- ApoE ɛ4- in sectors H3, H4, H10 and H11; and ii) FH+ ApoE ɛ4- in sectors H4 and H12. In participants with HCL and HBP, statistically significant changes were found, in particular using EA-Tool, both in the macular area, mainly in the deep plexus, and in the peripapillary area. In conclusion, OCTA in subjects with genetic risk factors for the development of AD showed an apparent increase in vascular density in some sectors of the retina, which was one of the first vascular changes detectable. These changes constitute a promising biomarker for monitoring the progression of pathological neuronal degeneration.
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.
The relationship between retinal layers and brain areas in asymptomatic first-degree relatives of sporadic forms of Alzheimer’s disease: an exploratory analysis
(Alzheimer's Research & Therapy, 2022) López Cuenca, Inés; Marcos Dolado, Alberto; Yus Fuertes, Miguel; García Martín, Elena Salobrar; Elvira Hurtado, Lorena; Fernández Albarral, José Antonio; Salazar Corral, Juan José; Ramírez Sebastián, Ana Isabel; Sánchez Puebla, Lídia; Fuentes Ferrer, Manuel Enrique; Barabash, Ana; Ramírez Toraño, Federico; Gil Martínez, Lidia; Arrazola García, Juan Lorenzo; Gil Gregorio, Pedro; Hoz Montañana, María Rosa de; Ramirez Sebastian, Jose Manuel
Background: Two main genetic risks for sporadic Alzheimer’s disease (AD) are a family history and ɛ4 allele of apolipoprotein E. The brain and retina are part of the central nervous system and share pathophysiological mechanisms in AD. Methods: We performed a cross-sectional study with 30 participants without a family history of sporadic AD (FH−) and noncarriers of ApoE ɛ4 (ApoE ɛ4−) as a control group and 34 participants with a family history of sporadic AD (FH+) and carriers of at least one ɛ4 allele (ApoE ɛ4+). We analyzed the correlations between macular volumes of retinal layers and thickness of the peripapillary retinal nerve fiber layer (pRNFL) measured by optical coherence tomography (OCT) with the brain area parameters measured by magnetic resonance imaging (MRI) in participants at high genetic risk of developing AD (FH+ ApoE ɛ4+). Results: We observed a significant volume reduction in the FH+ ApoE ɛ4+ group compared with the control group in some macular areas of (i) macular RNFL (mRNFL), (ii) inner plexiform layer (IPL), (iii) inner nuclear layer (INL), and (iv) outer plexiform layer (OPL). Furthermore, in the FH+ ApoE ɛ4+ group, the retinal sectors that showed statistically significant volume decrease correlated with brain areas that are affected in the early stages of AD. In the same group, the peripapillary retinal nerve fiber layer (pRNFL) did not show statistically significant changes in thickness compared with the control group. However, correlations of these sectors with the brain areas involved in this disease were also found. Conclusions: In cognitively healthy participants at high genetic risk of developing sporadic forms of AD, there are significant correlations between retinal changes and brain areas closely related to AD such as the entorhinal cortex, the lingual gyrus, and the hippocampus.
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.