MEG spectral analysis in subtypes of mild cognitive impairment

Mild cognitive impairment (MCI) has been described as an intermediate stage between normal aging and dementia. Previous studies characterized the alterations of brain oscillatory activity at this stage, but little is known about the differences between single and multidomain amnestic MCI patients. In order to study the patterns of oscillatory magnetic activity in amnestic MCI subtypes, a total of 105 subjects underwent an eyes-closed resting-state magnetoencephalographic recording: 36 healthy controls, 33 amnestic single domain MCIs (a-sd-MCI), and 36 amnestic multidomain MCIs (a-md-MCI). Relative power values were calculated and compared among groups. Subsequently, relative power values were correlated with neuropsychological tests scores and hippocampal volumes. Both MCI groups showed an increase in relative power in lower frequency bands (delta and theta frequency ranges) and a decrease in power values in higher frequency bands (alpha and beta frequency ranges), as compared with the control group. More importantly, clear differences emerged from the comparison between the two amnestic MCI subtypes. The a-md-MCI group showed a significant power increase within delta and theta ranges and reduced relative power within alpha and beta ranges. Such pattern correlated with the neuropsychological performance, indicating that the a-md-MCI subtype is associated not only with a "slowing" of the spectrum but also with a poorer cognitive status. These results suggest that a-md-MCI patients are characterized by a brain activity profile that is closer to that observed in Alzheimer disease. Therefore, it might be hypothesized that the likelihood of conversion to dementia would be higher within this subtype

Impact of the BDNF Val66Met polymorphism within and beyond the retrosplenial cortex in females with Mild Cognitive Impairment: A magnetoencephalography study

Mild Cognitive Impairment (MCI) can be influenced by genetic risk factors. The Brain Derived Neurotrophic Factor Val66Met polymorphism is one of them. This mutation may affect the brain functional connectivity (FC), especially for those carriers of the Met allele (A). The retrosplenial cortex (RSC), essential component of the Default Mode Network (DMN), could be altered by this polymorphism. Our aim was to examine the influence of the Val66Met polymorphism within the RSC?s functional network, and its interconnections between the frontal medial cortex (FMC) and the anterior cingulate (ACC)

Age and APOE genotype affect the relationship between objectively measured physical activity and power in the alpha band, a marker of brain disease

BACKGROUND: Electrophysiological studies show that reductions in power within the alpha band are associated with the Alzheimer\u27s 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

Vasorreactividad y resistencia vascular periférica en el diagnóstico diferencial de la demencia vascular y la demencia tipo Alzheimer

JUSTIFICACION: La diferenciación clínica y radióloga de la Demencia vascular frente a las demencias degenerativas es a menudo difícil y costoso, debido a la heterogeneidad de la primera. OBJETIVO: Encontrar parámetros hemodinámicos y en resistencia vascular periférica por Sonografía Doppler Trascraneal válidos para diferenciar ambos tipos de demencias. MATERIAL Y METODOS: Se realizaron a un total de 130 individuos divididos en 5 grupos con diagnósticos de Demencia Vascular, Demencia Tipo Alzheimer, Demencia Mixta, Controles sanos y sujetos con patología vascular cerebral sin deterioro cognitivo, estudio Doppler Trascraneal de velocidad basal en arteria cerebral media, y cambios ante estímulos fisiológicos, y estudio de resistencias vasculares periféricas. RESULTADOS: La vasorreactividad cerebral medida por el Rango de Vasodilatación Máxima ante apnea o respiración en circuito cerrado ofrece una sensibilidad entre 87-89% y una especificidad entre 86-92% en el diagnóstico diferencial de la demencia Vascular y la tipo Alzheimer, frente al estándar de oro actual, los criterios clínicos. Además, existe correlación entre el rango de vasodilatación máxima y el grado de deterioro en la demencia vascular y mixta, y entre la resistencia vascular cerebral y la edad. CONCLUSION: La vasorreactividad cerebral y las resistencias vasculares periféricas, medidas por Doppler Trascraneal, son parámetros válidos en el diagnóstico diferencial de las demencias vasculares y degenerativa tipo Alzheimer

Brain Structural and Functional Changes in Cognitive Impairment Due to Alzheimer's Disease.

Cognitive neuropsychology seeks a potential alignment between structural and functional brain features to explain physiological or pathological processes, such as Alzheimer's disease (AD). Several structural and functional brain changes occurring during the disease, including cognitive impairment, are found at the end of the patient's life, but we need to know more about what happens before its onset. In order to do that, we need earlier biomarkers at preclinical stages, defined by those biomarkers, to prevent the cognitive impairment. In this minireview, we have tried to describe the structural and functional changes found at different stages during AD, focusing on those features taking place before clinical diagnosis

Electrophysiological brain signatures for the classification of subjective cognitive decline: towards an individual detection in the preclinical stages of dementia

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.Depto. de Psicología Experimental, Procesos Cognitivos y LogopediaFac. de PsicologíaTRUEpu

A multivariate model of time to conversion from mild cognitive impairment to Alzheimer’s disease

The present study was aimed at determining which combination of demographic, genetic, cognitive, neurophysiological, and neuroanatomical factors may predict differences in time to progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). To this end, a sample of 121 MCIs was followed up during a 5-year period. According to their clinical outcome, MCIs were divided into two subgroups: (i) the “progressive” MCI group (n = 46; mean time to progression 17 ± 9.73 months) and (ii) the “stable” MCIgroup (n = 75; mean time of follow-up 31.37 ± 14.58 months). Kaplan–Meier survival analyses were applied to explore each variable’s relationship with the progression to AD. Once potential predictors were detected, Cox regression analyses were utilized to calculate a parsimonious model to estimate differences in time to progression. The final model included three variables (in order of relevance): left parahippocampal volume (corrected by intracranial volume, LP_ ICV), delayed recall (DR), and left inferior occipital lobe individual alpha peak frequency (LIOL_IAPF). Those MCIs with LP_ICV volume, DR score, and LIOL_IAPF value lower than the defined cutoff had 6 times, 5.5 times, and 3 times higher risk of progression to AD, respectively. Besides, when the categories of the three variables were “unfavorable” (i.e., values below the cutoff), 100% of cases progressed to AD at the end of follow-up. Our results highlighted the relevance of neurophysiological markers as predictors of conversion (LIOL_IAPF) and the importance of multivariate models that combine markers of different nature to predict time to progression from MCI to dementia.Depto. de Medicina Legal, Psiquiatría y PatologíaFac. de MedicinaTRUEpu

Spatiotemporal oscillatory patterns during working memory maintenance in mild cognitive impairment and subjective cognitive decline

Working 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.Ministerio de Economía y CompetitividadDepto. de Psicología Experimental, Procesos Cognitivos y LogopediaDepto. de Radiología, Rehabilitación y FisioterapiaFac. de PsicologíaFac. de MedicinaTRUEpu

A Structural Connectivity Disruption One Decade before the Typical Age for Dementia: A Study in Healthy Subjects with Family History of Alzheimer’s Disease

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.Ministerio de Economía y CompetitividadDepto. de Psicología Experimental, Procesos Cognitivos y LogopediaFac. de PsicologíaTRUEpu

Episodic memory dysfunction and hypersynchrony in brain functional networks in cognitively intact subjects and MCI: a study of 379 individuals

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.Universidad Autónoma de BarcelonaDepto. de Radiología, Rehabilitación y FisioterapiaFac. de MedicinaTRUEpu