References of "Neurobiology of Aging"
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See detailGenome-Wide Association Interaction Analysis for Alzheimer’s Disease
Gusareva, Elena ULg; Carrasquillo, Minerva M.; Bellenguez, Céline et al

in Neurobiology of Aging (2014)

We propose a minimal protocol for exhaustive genome-wide association interaction analysis that involves screening for epistasis over large-scale genomic data combining strengths of different methods and ... [more ▼]

We propose a minimal protocol for exhaustive genome-wide association interaction analysis that involves screening for epistasis over large-scale genomic data combining strengths of different methods and statistical tools. The different steps of this protocol are illustrated on a real-life data application for Alzheimer's disease (AD) (2259 patients and 6017 controls from France). Particularly, in the exhaustive genome-wide epistasis screening we identified AD-associated interacting SNPs-pair from chromosome 6q11.1 (rs6455128, the KHDRBS2 gene) and 13q12.11 (rs7989332, the CRYL1 gene) (p = 0.006, corrected for multiple testing). A replication analysis in the independent AD cohort from Germany (555 patients and 824 controls) confirmed the discovered epistasis signal (p = 0.036). This signal was also supported by a meta-analysis approach in 5 independent AD cohorts that was applied in the context of epistasis for the first time. Transcriptome analysis revealed negative correlation between expression levels of KHDRBS2 and CRYL1 in both the temporal cortex (β = -0.19, p = 0.0006) and cerebellum (β = -0.23, p < 0.0001) brain regions. This is the first time a replicable epistasis associated with AD was identified using a hypothesis free screening approach. [less ▲]

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See detailVerbal learning in Alzheimer’s disease and mild cognitive impairment:fine-grained acquisition and short-delay consolidation performance and neural correlates
Genon, Sarah ULg; Collette, Fabienne ULg; Moulin, Chris et al

in Neurobiology of Aging (2013), 34

The aim of this study was to examine correlations between acquisition and short-delay consolidation and brain metabolism at rest measured by fluorodeoxyglucose positron emission tomography (FDG-PET) in 44 ... [more ▼]

The aim of this study was to examine correlations between acquisition and short-delay consolidation and brain metabolism at rest measured by fluorodeoxyglucose positron emission tomography (FDG-PET) in 44 Alzheimer’s disease (AD) patients, 16 patients with mild cognitive impairment (MCI) who progressed to dementia (MCI-AD), 15 MCI patients who remained stable (MCI-S, 4–8 years of follow-up), and 20 healthy older participants. Acquisition and short-delay consolidation were calculated respectively as mean gained (MG) and lost (ML) access to items of the California Verbal Learning Task. MG performance suggests that acquisition is impaired in AD patients even at predementia stage (MCI-AD). ML performance suggests that short-delay consolidation is deficient only in confirmed AD patients. Variations in acquisition performance in control participants are related to metabolic activity in the anterior parietal cortex, an area supporting task-positive attentional processes. In contrast, the acquisition deficit is related to decreased activity in the lateral temporal cortex, an area supporting semantic processes, in patients at an early stage of AD and is related to metabolic activity in the hippocampus, an area supporting associative processes, in confirmed AD patients. [less ▲]

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See detailInterindividual differences in circadian rhythmicity and sleep homeostasis in older people: effect of a PER3 polymorphism.
Viola, Antoine U.; Chellappa, Sarah Laxhmi ULg; Archer, Simon N. et al

in Neurobiology of Aging (2012), 33(5), 101017-27

Aging is associated with marked changes in the timing, consolidation and structure of sleep. Older people wake up frequently, get up earlier and have less slow wave sleep than young people, although the ... [more ▼]

Aging is associated with marked changes in the timing, consolidation and structure of sleep. Older people wake up frequently, get up earlier and have less slow wave sleep than young people, although the extent of these age-related changes differs considerably between individuals. Interindividual differences in homeostatic sleep regulation in young volunteers are associated with the variable-number, tandem-repeat (VNTR) polymorphism (rs57875989) in the coding region of the circadian clock gene PERIOD3 (PER3). However, predictors of these interindividual differences have yet to be identified in older people. Sleep electroencephalographic (EEG) characteristics and circadian rhythms were assessed in 26 healthy older volunteers (55-75 years) selected on the basis of homozygosity for either the long or short allele of the PER3 polymorphism. Homozygosity for the longer allele (PER3(5/5)) associated with a phase-advance in the circadian melatonin profile and an earlier occurrence of the melatonin peak within the sleep episode. Furthermore, older PER3(5/5) participants accumulated more nocturnal wakefulness, had increased EEG frontal delta activity (0.75-1.50 Hz), and decreased EEG frontal sigma activity (11-13 Hz) during non-rapid eye movement (REM) sleep compared with PER3(4/4) participants. Our results indicate that the polymorphism in the clock gene PER3 may contribute to interindividual differences in sleep and circadian physiology in older people. [less ▲]

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See detailSpecificity of Inhibitory Deficits in Normal Aging and Alzheimer's Disease
Collette, Fabienne ULg; Schmidt, Christina ULg; Scherrer, Christine et al

in Neurobiology of Aging (2009), 30

Deficits of suppression abilities are frequently observed in normal aging and Alzheimer's disease. However, few studies have explored these deficits in the two populations simultaneously using a large ... [more ▼]

Deficits of suppression abilities are frequently observed in normal aging and Alzheimer's disease. However, few studies have explored these deficits in the two populations simultaneously using a large battery of tasks. The aim of the present study was to explore if the pattern of performance presented by elderly subjects and AD patients is in agreement with theoretical frameworks [Wilson, S.P., Harnishfeger, K.K., 1998. The development of efficient inhibition: Evidence from directed forgetting tasks. Dev. Rev. 18, 86-123; see also Nigg J.T., 2000. On inhibition/disinhibition in developmental psychopathology: views from cognitive and personality psychology and a working inhibition taxonomy. Psychol. Bull. 126, 220-246], distinguishing between the concepts of inhibition (a voluntary suppression of irrelevant information) and interference (an automatic suppression process occurring prior to conscious awareness). The results obtained demonstrated that (1) there is an alteration of the inhibitory process in normal elderly subjects; (2) inhibitory and interference resolution processes are quantitately less efficient in AD, since these patients present a correct performance only for information which leaves weak traces in memory. [less ▲]

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See detailOn the multivariate nature of brain metabolic impairment in Alzheimer’s disease
Salmon, Eric ULg; Kerrouche, Nacer; Perani, Daniela et al

in Neurobiology of Aging (2009), 30

We used principal component analysis to decompose functional images of patients with AD in orthogonal ensembles of brain regions with maximal metabolic covariance. Three principal components explained 38 ... [more ▼]

We used principal component analysis to decompose functional images of patients with AD in orthogonal ensembles of brain regions with maximal metabolic covariance. Three principal components explained 38% of the total variance in a large sample of FDG-PET images obtained in 225 AD patients. One functional ensemble (PC2) included limbic structures from Papez's circuit (medial temporal regions, posterior and anterior cingulate cortex, thalamus); its disruption in AD patients was related to episodic memory impairment. Another principal component (PC1) illustrated major metabolic variance in posterior cerebral cortices, and patients' scores were correlated to instrumental functions (language and visuospatial abilities). PC3 comprised frontal, parietal, temporal and posteromedial (posterior cingulate and precuneus) cortices, and patients' scores were related to executive dysfunction and global cognitive impairment. The three main metabolic covariance networks converged in the posterior cingulate area that showed complex relationships with medial temporal structures within each PC. Individual AD scores were distributed as a continuum along PC axes: an individual combination of scores would determine specific clinical symptoms in each patient. [less ▲]

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See detailPerspective taking to assess self-personality: What's modified in Alzheimer's disease?
Ruby, Perrine; Collette, Fabienne ULg; D'Argembeau, Arnaud ULg et al

in Neurobiology of Aging (2009), 30(10), 1637-1651

Personality changes are frequently described by caregivers of patients with Alzheimer's disease, while they are less often reported by the patients. This relative anosognosia of Alzheimer disease (AD ... [more ▼]

Personality changes are frequently described by caregivers of patients with Alzheimer's disease, while they are less often reported by the patients. This relative anosognosia of Alzheimer disease (AD) patients for personality changes might be related to impaired self-judgment and to decreased ability to understand their caregiver's perspective. To investigate this issue, we explored the cerebral correlates of self-assessment and perspective taking in patients with mild AD, elderly and young volunteers. All subjects assessed relevance of personality traits adjectives for self and a relative, taking either their own or their relative's perspective, during a functional imaging experiment. The comparison of subject's and relative's answers provided congruency scores used to assess self-judgment and perspective taking performance. The self-judgment "accuracy" score was diminished in AD, and when patients assessed adjectives for self-relevance, they predominantly activated bilateral intraparietal sulci (IPS). Previous studies associated IPS activation with familiarity judgment, which AD patients would use more than recollection when retrieving information to assess self-personality. When taking a third-person perspective, patients activated prefrontal regions (similarly to young volunteers), while elderly controls recruited visual associative areas (also activated by young volunteers). This suggests that mild AD patients relied more on reasoning processes than on visual imagery of autobiographical memories to take their relative's perspective. This strategy may help AD patients to cope with episodic memory impairment even if it does not prevent them from making some mind-reading errors. [less ▲]

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See detailLevodopa increases memory encoding and dopamine release in the striatum in the elderly.
Floel, Agnes; Garraux, Gaëtan ULg; Xu, Ben et al

in Neurobiology of Aging (2008), 29(2), 267-79

Normal aging is associated with a decrease in dopaminergic function and a reduced ability to form new motor memories with training. This study examined the link between both phenomena. We hypothesized ... [more ▼]

Normal aging is associated with a decrease in dopaminergic function and a reduced ability to form new motor memories with training. This study examined the link between both phenomena. We hypothesized that levodopa would (a) ameliorate aging-dependent deficits in motor memory formation, and (b) increase dopamine availability at the dopamine type 2-like (D2) receptor during training in task-relevant brain structures. The effects of training plus levodopa (100mg, plus 25mg carbidopa) on motor memory formation and striatal dopamine availability were measured with [(11)C]raclopride (RAC) positron emission tomography (PET). We found that levodopa did not alter RAC-binding potential at rest but it enhanced training effects on motor memory formation as well as dopamine release in the dorsal caudate nucleus. Motor memory formation during training correlated with the increase of dopamine release in the caudate nucleus. These results demonstrate that levodopa may ameliorate dopamine deficiencies in the elderly by replenishing dopaminergic presynaptic stores, actively engaged in phasic dopamine release during motor training. [less ▲]

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See detailMetabolic correlates of clinical heterogeneity in questionable Alzheimer’s disease
Salmon, Eric ULg; Lekeu, Françoise ULg; Garraux, Gaëtan ULg et al

in Neurobiology of Aging (2008), 29

Thirty-four subjects with questionable Alzheimer's disease (QAD) were included in a 3-year prospective study and underwent neuropsychological testing and measurement of brain metabolism using FDG-PET at ... [more ▼]

Thirty-four subjects with questionable Alzheimer's disease (QAD) were included in a 3-year prospective study and underwent neuropsychological testing and measurement of brain metabolism using FDG-PET at entry. Seventeen patients (50%) did not convert to AD during the follow-up period. Compared to elderly controls of similar age, the cerebral activity of non-converters was reduced in the dorsolateral prefrontal cortex. Moreover, the variability of metabolism in the posterior cingulate cortex was related to their visuospatial memory performance, while disparity in parietal activity was related to their verbal memory performance. These results demonstrate the cerebral metabolic heterogeneity of patients with QAD. Initial functional images of converters showed that activity was already impaired in the posterior cingulate, lateral temporal cortex, anterior cingulate and orbitofrontal cortex. This metabolic pattern is consistent with a pre-dementia stage of AD, and highlights the fact that significant frontal metabolic involvement may be associated with impaired activity in posterior associative cortices in very early AD. [less ▲]

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