Searching for Primary Predictors of Conversion from Mild Cognitive Impairment to Alzheimer’s Disease: A Multivariate Follow-Up Study
Authors: López, María Eugenia | Turrero, Agustín | Cuesta, Pablo | López-Sanz, David | Bruña, Ricardo | Marcos, Alberto | Gil, Pedro | Yus, Miguel | Barabash, Ana | Cabranes, José Antonio | Maestú, Fernando | Fernández, Alberto
Article Type: Research Article
Abstract: 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. Show more
Keywords: Alzheimer’s disease, APOE, cognitive reserve, hippocampal volume, magnetoencephalography; mild cognitive impairment, neuropsychological tests, predictive model
DOI: 10.3233/JAD-151034
Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 133-143, 2016
Source Analysis of Spontaneous Magnetoencephalograpic Activity in Healthy Aging and Mild Cognitive Impairment: Influence of Apolipoprotein E Polymorphism
Authors: Cuesta, Pablo | Barabash, Ana | Aurtenetxe, Sara | Garcés, Pilar | López, María Eugenia | Bajo, Ricardo | Llanero-Luque, Marcos | Ancín, Inés | Cabranes, José Antonio | Marcos, Alberto | Sancho, Miguel | Nakamura, Akinori | Maestú, Fernando | Fernandez, Alberto
Article Type: Research Article
Abstract: The apolipoprotein E (APOE) ε4 allele is a genetic risk factor for the development of late-onset Alzheimer's disease (AD), which affects cholinergic system functioning. The association between reduced cholinergic levels and increase of magnetoencephalographic (MEG) low-frequency has been used to explain spectral changes found in AD patients. However, the investigation in predementia stages is scarce. We obtained MEG recordings from 25 aged controls and 36 mild cognitive impairment (MCI) patients during a resting-state condition. According to their APOE genotype, MCIs and controls were subdivided in carriers and non-carriers of the ε4 allele. Sources of spectral variations in these groups were …calculated through beamforming. MCI patients exhibited a significant increase of relative power within the low-frequency domain, accompanied by a power decrease within the high-frequency range. APOEε4 carriers showed an increased relative power in the 4.5–6.5 Hz frequency range over frontal lobes. The power increase observed in controls carrying ε4 was significantly higher as compared with MCI non-carriers, while MCI carriers exhibited the highest relative power within the 4.5–6.5 Hz range. Higher power values within the low-frequency ranges correlated with a poorer cognitive performance in MCIs and controls. Our investigation demonstrates that APOEε4 affects resting-state activity to an extent that makes it more proximate to the pattern observed in early stages of AD. Therefore, a combination of genetic and neurophysiological information might help to detect MCI patients at higher risk of conversion to AD, and asymptomatic subjects at higher risk of developing a manifest cognitive deterioration. Show more
Keywords: Aging, APOEε4, magnetoencephalography, mild cognitive impairment, relative power, source analysis
DOI: 10.3233/JAD-140633
Citation: Journal of Alzheimer's Disease, vol. 43, no. 1, pp. 259-273, 2015
Influence of the APOE ε4 Allele and Mild Cognitive Impairment Diagnosis in the Disruption of the MEG Resting State Functional Connectivity in Sources Space
Authors: Cuesta, Pablo | Garcés, Pilar | Castellanos, Nazareth P. | López, Maria Eugenia | Aurtenetxe, Sara | Bajo, Ricardo | Pineda-Pardo, José Angel | Bruña, Ricardo | Marín, Antonio García | Delgado, Marisa | Barabash, Ana | Ancín, Inés | Cabranes, Jose Antonio | Fernandez, Alberto | del Pozo, Francisco | Sancho, Miguel | Marcos, Alberto | Nakamura, Akinori | Maestú, Fernando
Article Type: Research Article
Abstract: The apolipoprotein E (APOE) ε4 allele constitutes the major genetic risk for the development of late onset Alzheimer's disease (AD). However, its influence on the neurodegeneration that occurs in early AD remains unresolved. In this study, the resting state magnetoencephalography(MEG) recordings were obtained from 27 aged healthy controls and 36 mild cognitive impairment (MCI) patients. All participants were divided into carriers and non-carriers of the ε4 allele. We have calculated the functional connectivity (FC) in the source space along brain regions estimated using the Harvard-Oxford atlas and in the classical bands. Then, a two way ANOVA analysis (diagnosis and APOE) …was performed in each frequency band. The diagnosis effect consisted of a diminished FC within the high frequency bands in the MCI patients, affecting medial temporal and parietal regions. The APOE effect produced a decreased long range FC in delta band in ε4 carriers. Finally, the interaction effect showed that the FC pattern of the right frontal-temporal region could be reflecting a compensatory/disruption process within the ε4 allele carriers. Several of these results correlated with cognitive decline and neuropsychological performance. The present study characterizes how the APOE ε4 allele and MCI status affect the brain's functional organization by analyzing the FC patterns in MEG resting state in the sources space. Therefore a combination of genetic, neuropsychological, and neurophysiological information might help to detect MCI patients at higher risk of conversion to AD and asymptomatic subjects at higher risk of developing a manifest cognitive deterioration. Show more
Keywords: Aging, APOE ε4, functional connectivity, magnetoencephalography, mild cognitive impairment, source analysis
DOI: 10.3233/JAD-141872
Citation: Journal of Alzheimer's Disease, vol. 44, no. 2, pp. 493-505, 2015