Differential effects of the APOE genotype on brain function across the lifespan

Filippini, Nicola; Ebmeier, Klaus P.; MacIntosh, Bradley J.; Trachtenberg, Aaron J.; Frisoni, Giovanni B.; Wilcock, Gordon; Beckmann, Christian F.; Smith, Stephen M.; Matthews, Paul M.; Mackay, Clare E.

doi:10.1016/j.neuroimage.2010.08.009

Cited by 176 publications

(165 citation statements)

References 83 publications

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“…Findings of connectivity changes inside and to the DMN in relation to APOE‐ε4 carriership have not been consistent, mostly due to the different age groups being studied (Filippini et al., 2011; Heise, Filippini, Ebmeier, & Mackay, 2011; Mevel, Chételat, Eustache, & Desgranges, 2011). Overall, the most frequently reported changes are weakened DMN connectivity in middle‐aged and older subjects (Goveas et al., 2013; Machulda et al., 2011; Reiman et al., 1996; Sheline et al., 2010; Wang et al., 2012) and, less frequently, increased DMN connectivity in young adults (Filippini et al., 2009; Fleisher et al., 2009).…”

Section: Discussionmentioning

confidence: 99%

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

et al. 2018

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IntroductionAmyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)‐ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE‐ε4 carriership is associated with EC disruptions in cognitively normal individuals.MethodsA total of 261 healthy middle‐aged to older adults (mean age 56.6 years) were divided into high‐risk (APOE‐ε4 carriers) and low‐risk (noncarriers) groups. EC was computed from resting‐state functional MRI data. Clusters of between‐group differences were assessed with a permutation‐based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed.ResultsDecreased EC in the visual cortex was associated with APOE‐ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail‐making and 15‐object recognition tests.ConclusionOur findings suggest that the APOE‐ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease‐related pathology. These differences were too subtle in healthy elderly to use EC for single‐subject prediction of APOE genotype.

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Section: Discussionmentioning

confidence: 99%

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

et al. 2018

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“…Assessment of asymptomatic familial Alzheimer gene carriers has highlighted the added sensitivity of functional neuroimaging [Chhatwal et al, 2013] in keeping with the age‐dependent impact of APOE ε4 status on both fMRI [Filippini et al, 2011] and MEG [Cuesta et al, 2015] in the task‐free state. It remains an open question to what extent symptoms of ALS are preceded by temporally remote cellular abnormalities [Eisen et al, 2014].…”

Section: Discussionmentioning

confidence: 99%

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

Proudfoot

Rohenkohl

Quinn

et al. 2016

Human Brain Mapping

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Continuous rhythmic neuronal oscillations underpin local and regional cortical communication. The impact of the motor system neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) on the neuronal oscillations subserving movement might therefore serve as a sensitive marker of disease activity. Movement preparation and execution are consistently associated with modulations to neuronal oscillation beta (15–30 Hz) power. Cortical beta‐band oscillations were measured using magnetoencephalography (MEG) during preparation for, execution, and completion of a visually cued, lateralized motor task that included movement inhibition trials. Eleven “classical” ALS patients, 9 with the primary lateral sclerosis (PLS) phenotype, and 12 asymptomatic carriers of ALS‐associated gene mutations were compared with age‐similar healthy control groups. Augmented beta desynchronization was observed in both contra‐ and ipsilateral motor cortices of ALS patients during motor preparation. Movement execution coincided with excess beta desynchronization in asymptomatic mutation carriers. Movement completion was followed by a slowed rebound of beta power in all symptomatic patients, further reflected in delayed hemispheric lateralization for beta rebound in the PLS group. This may correspond to the particular involvement of interhemispheric fibers of the corpus callosum previously demonstrated in diffusion tensor imaging studies. We conclude that the ALS spectrum is characterized by intensified cortical beta desynchronization followed by delayed rebound, concordant with a broader concept of cortical hyperexcitability, possibly through loss of inhibitory interneuronal influences. MEG may potentially detect cortical dysfunction prior to the development of overt symptoms, and thus be able to contribute to the assessment of future neuroprotective strategies. Hum Brain Mapp 38:237–254, 2017. © 2016 Wiley Periodicals, Inc.

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“…Some studies have reported greater activation in memory-related areas, notably the hippocampus, in healthy old adults who were ε4 carriers compared with non-carriers of the ε4 allele [162][163][164] , and even in young ε4 carriers relative to non-carriers 165 , suggesting an increase in demand on these regions prior to the appearance of any symptoms of memory loss. However, a couple of studies 166,167 have found evidence of lower brain activity in the hippocampus of aged ε4 allele carriers during memory tasks. These inconsistent findings regarding brain activity in high-risk individuals compared to their low-risk counterparts could be due to differences in specific task demands, the influence of any number of lifestyle or health factors, or where in the trajectory of longitudinal change one happens to measure brain activity and cognition.…”

Section: Risk Factors For Alzheimer's Disease: Apoementioning

confidence: 99%

The cognitive neuroscience of ageing

2012

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PrefaceThe availability of neuroimaging technology has spurred a marked increase in the human cognitive neuroscience literature, including the study of cognitive aging. Although there is a growing consensus that the aging brain retains considerable plasticity of function, currently measured primarily by means of functional magnetic resonance imaging, it is less clear how age differences in brain activity relate to cognitive performance. The field also is hampered by the complexity of the aging process itself and the large number of factors that are influenced by age. In this review, current trends and unresolved issues in the cognitive neuroscience of aging are discussed.

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Differential effects of the APOE genotype on brain function across the lifespan

Cited by 176 publications

References 83 publications

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

The cognitive neuroscience of ageing

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