Person:
De Frutos Lucas, Jaisalmer

First Name

Jaisalmer

Last Name

De Frutos Lucas

URI

https://hdl.handle.net/20.500.14352/85418

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Psicología

Department

Psicología Experimental, Procesos Cognitivos y Logopedia

Identifiers

Full item page

Search Results

Now showing 1 - 9 of 9

Episodic memory dysfunction and hypersynchrony in brain functional networks in cognitively intact subjects and MCI: a study of 379 individuals
(Geroscience, 2022) Chino, Brenda; Cuesta Prieto, Pablo; Pacios García, Javier; De Frutos Lucas, Jaisalmer; Torres Simón, Lucía; Doval Moreno, Sandra; Marcos Dolado, Alberto; Bruña Fernández, Ricardo; Maestu Unturbe, Fernando
Delayed recall (DR) impairment is one of the most significant predictive factors in defining the progression to Alzheimer’s disease (AD). Changes in brain functional connectivity (FC) could accompany this decline in the DR performance even in a resting state condition from the preclinical stages to the diagnosis of AD itself, so the characterization of the relationship between the two phenomena has attracted increasing interest. Another aspect to contemplate is the potential moderator role of the APOE genotype in this association, considering the evidence about their implication for the disease. 379 subjects (118 mild cognitive impairment (MCI) and 261 cognitively intact (CI) individuals) underwent an extensive evaluation, including MEG recording. Applying cluster-based permutation test, we identified a cluster of differences in FC and studied which connections drove such an effect in DR. The moderation effect of APOE genotype between FC results and delayed recall was evaluated too. Higher FC in beta band in the right occipital region is associated with lower DR scores in both groups. A significant anteroposterior link emerged in the seed-based analysis with higher values in MCI. Moreover, APOE genotype appeared as a moderator between beta FC and DR performance only in the CI group. An increased beta FC in the anteroposterior brain region appears to be associated with lower memory performance in MCI. This finding could help discriminate the pattern of the progression of healthy aging to MCI and the relation between resting state and memory performance.
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; De Frutos Lucas, Jaisalmer; Bruña Fernández, Ricardo; Ramírez Sebastián, Ana Isabel; Ramírez Toraño, Federico; Salazar Corral, Juan José; Barabash Bustelo, Ana; Gil Gregorio, Pedro; Maestu Unturbe, Fernando; Ramírez Sebastián, José Manuel; Hoz Montañana, María 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.
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 Bustelo, Ana; Ramírez Toraño, Federico; De Frutos Lucas, Jaisalmer; Salazar Corral, Juan José; Ramírez Sebastián, Ana Isabel; Ramírez Sebastián, José 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.
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.
Measures of resting state EEG rhythms for clinical trials in Alzheimer's disease: Recommendations of an expert panel
(Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 2021) Babiloni, Claudio; De Frutos Lucas, Jaisalmer; Fernández Lucas, Alberto Amable; López Sanz, David; Maestu Unturbe, Fernando; Guntekin, Bahar
The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate EEG measures for Alzheimer’s disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and “interrelatedness” at posterior alpha (8-12 Hz) and widespread delta (<4 Hz) and theta(4-8 Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (i) Standardization of instructions to patients, rsEEG recording methods, and selection of artifact-free rsEEG periods are needed; (ii) Power density and “interrelatedness” rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (iii) International multisectoral initiatives are mandatory for regulatory purposes.
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 Fernández, Lidia; Elvira Hurtado, Lorena; Fernández Albarral, José Antonio; Ramírez Toraño, Federico; Barabash Bustelo, Ana; De Frutos Lucas, Jaisalmer; Salazar Corral, Juan José; Ramírez Sebastián, José 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
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.
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.
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.