Person:
López Sanz, David

First Name

David

Last Name

López Sanz

URI

https://hdl.handle.net/20.500.14352/76845

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Educación-Centro Formación Profesor

Department

Psicobiología y Metodología en Ciencias del Comportamiento

Area

Psicobiología

Identifiers

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Now showing 1 - 10 of 24

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.
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 Amable
Recent 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.
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, Stefan
Background 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.
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.
Brain networks in subjective cognitive decline and mild cognitive impairment: characterizing the predementia stages using magnetoencephalography
(2018) López Sanz, David; Maestú Unturbe, Fernando; Garcés López, Pilar; Vicente Pérez, Francisco de
La demencia es un cuadro que puede ser originado por múltiples causas, produciendo un deterioro cognitivo muy marcado y limitando la independencia del paciente. La causa más común de demencia es la Enfermedad de Alzheimer (EA) que representa aproximadamente el 60% de los casos totales. Aunque existen numerosos factores que parecen modular el riesgo de desarrollar EA tales como factores genéticos (APOE, PS1, etc.) o variables relacionadas con el estilo de vida (estudios, ocupación, dieta, etc.), la edad es sin duda la variable más influyente y el mayor factor de riesgo ante la aparición de la EA. Por este motivo, el número de personas mayores afectadas por esta enfermedad no ha parado de aumentar durante las últimas décadas, y se espera que aumente su incidencia aún más. Debido al fracaso generalizado de los ensayos farmacológicos, numerosos esfuerzos en investigación se centran ahora en la detección temprana de la EA. El curso de la EA es lento e insidioso, y la acumulación de neuropatología puede comenzar hasta 15 años antes de su diagnóstico. A lo largo de esta etapa preclínica los pacientes atraviesan un estadio conocido como deterioro cognitivo leve (DCL). Esta etapa se caracteriza por alteraciones en uno o varios dominios cognitivos que no genera aún graves alteraciones del funcionamiento diario. Este estadio está altamente asociado al desarrollo posterior de EA y por tanto se considera bajo determinadas condiciones una etapa prodrómica de la enfermedad. Las personas mayores con DCL suelen presentar alteraciones a nivel cerebral o metabólico característicos de la EA, tales como atrofia cortical, alteraciones sinápticas o acumulación de proteínas relacionadas con la fisiopatología de la EA. La literatura científica reciente ha descrito una etapa anterior incluso al DCL que podría asociarse al desarrollo de demencia futuro. Las quejas subjetivas de memoria (QSM) se caracterizarían por la presencia de un sentimiento subjetivo de deterioro cognitivo en ausencia de afectación objetiva, es decir, la evaluación neuropsicológica de estas personas mayores se encuentra en el rango normal. Sin embargo, el estado de la actividad cerebral en esta etapa, o su integridad estructural aún no ha sido apenas descrito. Existen resultados contradictorios con respecto a si la presencia de QSM en personas mayores se asocia a un riesgo más elevado de desarrollar demencia. Además, mientras algunos estudios reportan alteraciones a nivel cerebral compatibles con EA en esta etapa, otros no encuentran tales signos. El objetivo fundamental de esta tesis es la caracterización de las alteraciones en las redes cerebrales en personas mayores sanas, personas mayores con QSM y personas mayores con DCL. El estado actual de la literatura nos permite anticipar la presencia de alteraciones cerebrales relacionadas con EA en el grupo con DCL, sin embargo este trabajo pretende estudiar si dichas alteraciones, o formas más sutiles, se encuentran presentes en el grupo con QSM. Esto nos permitirá en primer lugar clarificar si las QSM tienen alguna relevancia clínica y si se encuentran asociadas a cambios objetivos en la actividad cerebral. Además, se podrá describir el curso exacto de las alteraciones que tienen lugar a lo largo de las etapas preclínicas en la EA gracias a la inclusión del grupo con DCL, caracterizando así en cada estudio las dos etapas que anteceden a la EA descritas a día de hoy...
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, Fernando
Background: 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.
Sex Differences in the Complexity of Healthy Older Adults’ Magnetoencephalograms
(Entropy, 2019) Shumbayawonda, Elizabeth; Abásolo, Daniel; López Sanz, David; Bruña Fernández, Ricardo; Maestú Unturbe, Fernando; Fernández Lucas, Alberto Amable
The analysis of resting-state brain activity recording in magnetoencephalograms (MEGs) with new algorithms of symbolic dynamics analysis could help obtain a deeper insight into the functioning of the brain and identify potential differences between males and females. Permutation Lempel-Ziv complexity (PLZC), a recently introduced non-linear signal processing algorithm based on symbolic dynamics, was used to evaluate the complexity of MEG signals in source space. PLZC was estimated in a broad band of frequencies (2–45 Hz), as well as in narrow bands (i.e., theta (4–8 Hz), alpha (8–12 Hz), low beta (12–20 Hz), high beta (20–30 Hz), and gamma (30–45 Hz)) in a sample of 98 healthy elderly subjects (49 males, 49 female) aged 65–80 (average age of 72.71 ± 4.22 for males and 72.67 ± 4.21 for females). PLZC was significantly higher for females than males in the high beta band at posterior brain regions including the precuneus, and the parietal and occipital cortices. Further statistical analyses showed that higher complexity values over highly overlapping regions than the ones mentioned above were associated with larger hippocampal volumes only in females. These results suggest that sex differences in healthy aging can be identified from the analysis of magnetoencephalograms with novel signal processing methods.
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, Fernando
Bilingualism 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.
Alpha band disruption in the AD-continuum starts in the Subjective Cognitive Decline stage: a MEG study
(Scientific Reports, 2016) López Sanz, David; Bruña Fernández, Ricardo; Garcés, P.; Camara, C.; Serrano Martínez, Noelia; Rodríguez Rojo, Inmaculada Concepción; Delgado Losada, María Luisa; Montenegro Peña, María Mercedes; López Sánchez, Ramón; Yus, M.; Maestu Unturbe, Fernando
The consideration of Subjective Cognitive Decline (SCD) as a preclinical stage of AD remains still a matter of debate. Alpha band alterations represent one of the most significant changes in the electrophysiological profile of AD. In particular, AD patients exhibit reduced alpha relative power and frequency. We used alpha band activity measured with MEG to study whether SCD and MCI elders present these electrophysiological changes characteristic of AD, and to determine the evolution of the observed alterations across AD spectrum. The total sample consisted of 131 participants: 39 elders without SCD, 41 elders with SCD and 51 MCI patients. All of them underwent MEG and MRI scans and neuropsychological assessment. SCD and MCI patients exhibited a similar reduction in alpha band activity compared with the no SCD group. However, only MCI patients showed a slowing in their alpha peak frequency compared with both SCD and no SCD. These changes in alpha band were related to worse cognition. Our results suggest that AD-related alterations may start in the SCD stage, with a reduction in alpha relative power. It is later, in the MCI stage, where the slowing of the spectral profile takes place, giving rise to objective deficits in cognitive functioning.
Influence of cognitive reserve on neuropsychological performance in subjective cognitive decline and mild cognitive impairment older adults
(Current Psychology, 2023) López-Higes, Ramón; Rubio Valdehita, Susana; Delgado Losada, María Luisa; López Sanz, David
The analysis of the relationships between cognitive reserve and different cognitive domains has become a matter of interest since it can help us detect deviations from the typical ageing process. The main objective of our study was to analyse a structural equation model representing cognitive reserve’s relationships with three cognitive domains (episodic memory, working memory, and sentence comprehension) in older adults with subjective cognitive decline and mild cognitive impairment patients, in a cross-sectional study. A total of 266 Spanish-speaking older adults, from 65 to 80 years old, voluntarily participated in the study. The assessment protocol includes questionnaires as well as screening and domain-specific tests, providing relevant information for the classification of participants in the two groups previously mentioned (n1 = 150 and n2 = 116). The proposed model presented metric and configural invariance as well as stability across groups, since the indices reflecting goodness-of-fit reach acceptable values. Our hypotheses are partially confirmed since cognitive reserve strongly influences working memory and it does moderately in sentence comprehension in both groups, but it hardly influences episodic memory in the subjective cognitive decline group, while both are inversely associated in the patients’ group. Working memory could be considered as a mechanism through which cognitive reserve exerts its protector role on other cognitive domains: on sentence comprehension in both groups, and on episodic memory in the subjective cognitive decline group. However, in mild cognitive impairments patients, cognitive reserve does no longer influence episodic memory via working memory in a significant manner.