Person: López Sanz, David
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First Name
David
Last Name
López Sanz
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Educación-Centro Formación Profesor
Department
Psicobiología y Metodología en Ciencias del Comportamiento
Area
Psicobiología
Identifiers
17 results
Search Results
Now showing 1 - 10 of 17
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 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 AmableRecent 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.Item 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, StefanBackground 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.Item 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, BaharThe 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.Item 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, FernandoBackground: 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.Item 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, FernandoBilingualism 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.Item 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, FernandoThe 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.Item Functional Connectivity Disruption in Subjective Cognitive Decline and Mild Cognitive Impairment: A Common Pattern of Alterations(Frontiers in Aging Neuroscience, 2017) Bruña Fernández, Ricardo; López Sanz, David; Garcés, Pilar; Martín-Buro, María Carmen; Walter, Stefan; Delgado Losada, María Luisa; Montenegro Peña, María Mercedes; López Sánchez, Ramón; Marcos Dolado, Alberto; Maestu Unturbe, FernandoItem The Role of Magnetoencephalography in the Early Stages of Alzheimer’s Disease(Frontiers in Neuroscience, 2018) López Sanz, David; Serrano Martínez, Noelia; Maestu Unturbe, FernandoThe ever increasing proportionof aged people in modern societies is leading to a substantial increase in the number of people affected by dementia, and Alzheimer’s Disease (AD) in particular, which is the most common cause for dementia. Throughout the course of the last decades several different compounds have been tested to stop or slow disease progression with limited success, which is giving rise to a strong interest toward the early stages of the disease. Alzheimer’s disease has an extended an insidious preclinical stage in which brain pathology accumulates slowly until clinical symptoms are observable in prodromal stages and in dementia.For this reason, the scientific community is focusing into investigating early signs of AD which could lead to the development of validated biomarkers. While some CSF and PET biomarkers have already been introduced in the clinical practice, the use of non-invasive measures of brain function as early biomarkers is still under investigation. However, the electrophysiological mechanisms and the early functional alterations underlying preclinical Alzheimer’s Disease is still scarcely studied. This work aims to briefly review the most relevant findings in the field of electrophysiological brain changes as measured by magnetoencephalography (MEG). MEG has proven its utility in some clinical areas. However, although its clinical relevance in dementia is still limited, a growing number of studies highlighted its sensitivity in these preclinical stages. Studies focusing on different analytical approaches will be reviewed. Furthermore, their potential applications to establish early diagnosis and determine subsequent progression to dementia are discussed.Item Spatiotemporal oscillatory patterns during working memory maintenance in mild cognitive impairment and subjective cognitive decline(International Journal of Neural Systems, 2019) Serrano Martínez, Noelia; López Sanz, David; Bruña Fernández, Ricardo; Garcés, Pilar; Rodríguez Rojo, Inmaculada Concepción; Marcos Dolado, Alberto; Prada Crespo, David; Maestu Unturbe, FernandoWorking memory (WM) is a crucial cognitive process and its disruption is among the earliest symptoms of Alzheimer’s disease. While alterations of the neuronal processes underlying WM have been evidenced in mild cognitive impairment (MCI), scarce literature is available in subjective cognitive decline (SCD). We used magnetoencephalography during a WM task performed by MCI (n=45), SCD (n=49) and healthy elders (n=49) to examine group differences during the maintenance period (0–4000ms). Data were analyzed using time–frequency analysis and significant oscillatory differences were localized at the source level. Our results indicated significant differences between groups, mainly during the early maintenance (250–1250ms) in the theta, alpha and beta bands and in the late maintenance (2750–3750ms) in the theta band. MCI showed lower local synchronization in fronto-temporal cortical regions in the early theta–alpha window relative to controls (p=2×10−03) and SCD (p=4×10−03), and in the late theta window relative to controls (p=1×1003) and SCD (p=0.01). Early theta–alpha power was significantly correlated with memory scores (rho=0.24,p=0.02) and late theta power was correlated with task performance (rho=0.24,p=0.03) and functional activity scores (rho=−0.23,p=0.02). In the early beta window, MCI showed reduced power in temporo-posterior regions relative to controls (p=3×10−03) and SCD (p=0.02). Our results may suggest that these alterations would reflect that memory-related networks are damaged.