FMRI of working memory in patients with mild cognitive impairment and probable Alzheimer’s disease

Yetkin, Funda; Rosenberg, Roger N.; Weiner, Myron; Purdy, Phillip D.; Cullum, C. Munro

doi:10.1007/s00330-005-2794-x

Cited by 173 publications

(127 citation statements)

References 55 publications

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“…The hemodynamic changes seem to become established very early in the pathological process, as they are manifest in populations at risk of developing AD, i.e., individuals with mild cognitive impairment or those expressing the e4 allele of apolipoprotein E, the most consistent genetic factor linked to increased AD risk and lower age of onset (Poirier et al, 1993;Strittmatter et al, 1993). In these groups, neurovascular coupling is either impaired (Lind et al, 2006) or increased in a compensatory manner as in AD patients, being characterized by a larger response magnitude, and neuronal recruitment to achieve performance at the level of healthy elderly controls (Bookheimer et al, 2000;Yetkin et al, 2006;reviewed in Wermke et al (2008)). As shown by Bookheimer et al (2000), the local perfusion increase during verbal recall was greater in cognitively normal apolipoprotein E e4 relative to apolipoprotein E e3 carriers, involved a larger number of brain regions, and correlated with cognitive decline in the apolipoprotein E e4 subjects two years later.…”

Section: Neurovascular Dysfunction In Alzheimer's Diseasementioning

confidence: 99%

Neurovascular function in Alzheimer's disease patients and experimental models

Nicolakakis

Hamel

2011

J Cereb Blood Flow Metab

131

118

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The ability of the brain to locally augment glucose delivery and blood flow during neuronal activation, termed neurometabolic and neurovascular coupling, respectively, is compromised in Alzheimer's disease (AD). Since perfusion deficits may hasten clinical deterioration and have been correlated with negative treatment outcome, strategies to improve the cerebral circulation should form an integral element of AD therapeutic efforts. These efforts have yielded several experimental models, some of which constitute AD models proper, others which specifically recapture the AD cerebrovascular pathology, characterized by anatomical alterations in brain vessel structure, as well as molecular changes within vascular smooth muscle cells and endothelial cells forming the bloodbrain barrier. The following paper will present the elements of AD neurovascular dysfunction and review the in vitro and in vivo model systems that have served to deepen our understanding of it. It will also critically evaluate selected groups of compounds, the FDA-approved cholinesterase inhibitors and thiazolidinediones, for their ability to correct neurovascular dysfunction in AD patients and models. These and several others are emerging as compounds with pleiotropic actions that may positively impact dysfunctional cerebrovascular, glial, and neuronal networks in AD.

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Section: Neurovascular Dysfunction In Alzheimer's Diseasementioning

confidence: 99%

Neurovascular function in Alzheimer's disease patients and experimental models

Nicolakakis

Hamel

2011

J Cereb Blood Flow Metab

131

118

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“…Functional neuroimaging results revealed a robust negative correlation between the L1CAM interactions genetic score and the differences in activity in left superior and inferior frontal gyri, which have been implicated in the recognition of words and pictures and in working memory in healthy individuals (31, 52-54) and Alzheimer's patients (55,56). The superior frontal gyrus has been implicated in cognitive control (57), and the inferior frontal gyrus has been implicated in retrieval attempt and effort (58,59) and depth of memory (60).…”

Section: Discussionmentioning

confidence: 99%

Computational dissection of human episodic memory reveals mental process-specific genetic profiles

Luksys

Fastenrath

Coynel

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.learning and memory | computational model | gene set enrichment analysis | functional neuroimaging | frontal lobe H uman memory is a highly heritable and complex trait that is the outcome of numerous neurocognitive processes (1, 2). Although many genetic variations associated with human memory performance have been identified (3-9), most were based on general memory scores, such as the number of recalled items. Such scores may serve as good correlates of overall memory ability, but they offer little insight into the genetic underpinnings of specific memory-related mental processes, such as encoding, memory maintenance, modulation by emotional arousal, or guessing strategies. Importantly, neurobiological and molecular profiles of such processes are known to be partly distinct (10-12). Because some of the mental processes involved in memory are not readily amenable to direct observation, computational modeling can be used to make inferences about them (13,14). Modelbased analyses provided insights into neurocomputational mechanisms of reward-based learning and decision making (15-17), related model parameters such as the learning rate to genetic polymorphisms (18,19), and provided a computational explanation for the inverted-U-shaped relation between stress intensity and behavioral performance (20). As a relatively recent development, the model-based analysis approach has largely been missing from studies of human episodic memory and genome-wide association studies (GWAS).GWAS already had identified a number of associations betwee...

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“…Dans un autre ordre d'idées, Yetkin, Rosenberg, Weiner, Purdy & Cullum (2006) ont observé, auprès d'un groupe de personnes avec ACL, un accroissement de l'activité physiologique des régions cérébrales désignées comme étant impliquées dans le fonctionnement de la mémoire de travail (MdT). Cette augmentation de l'activité physiologique, toujours selon Yetkin et al (2006), serait le reflet d'un processus de réorganisation, attribuable au déclin général du fonctionnement, mais possiblement aussi attribuable à un déclin de l'efficience de la MdT.…”

Section: Illunclassified

“…Cette augmentation de l'activité physiologique, toujours selon Yetkin et al (2006), serait le reflet d'un processus de réorganisation, attribuable au déclin général du fonctionnement, mais possiblement aussi attribuable à un déclin de l'efficience de la MdT. Or, celle-ci réfère à la capacité d'emmagasinage temporaire et à la manipulation de l'information durant une très courte période (Belleville, Peretz, & Malenfant, 1996;Baddeley, 2003).…”

Section: Illunclassified

Évaluation de l'implication de la mémoire de travail sur des tâches de «théorie de l'esprit» chez la personne âgée avec altération cognitive légère /

Lavoie¹

2013

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FMRI of working memory in patients with mild cognitive impairment and probable Alzheimer’s disease

Cited by 173 publications

References 55 publications

Neurovascular function in Alzheimer's disease patients and experimental models

Neurovascular function in Alzheimer's disease patients and experimental models

Computational dissection of human episodic memory reveals mental process-specific genetic profiles

Évaluation de l'implication de la mémoire de travail sur des tâches de «théorie de l'esprit» chez la personne âgée avec altération cognitive légère /

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