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Is verbal episodic memory in elderly with amyloid deposits preserved through altered neuronal function?

ABSTRACT: A potential mechanism that enables intellectual preservation in cognitively normal elderly that harbor beta-amyloid (A?) pathology is heightened cerebral glucose metabolism. To investigate cross-sectional inter-relationships between A?, glucose metabolism, and cognition, 81 subjects (mean age: 75 ± 7 years) underwent [(11)C]Pittsburgh Compound-B and [(18)F]fluorodeoxyglucose positron emission tomography scans and neuropsychological testing. They were divided into low-A? (n = 53), intermediate-A? (n = 13) and high-A? (n = 15) groups as defined by their global cortical [(11)C]PIB retention. Glucose metabolism was assessed using a MetaROI mask that covers metabolically critical regions in Alzheimer's disease (AD) (i.e., posterior cingulate and bilateral angular and inferior temporal gyri). Previously validated factor scores for verbal and visual episodic memory, semantic memory, working memory, and executive functioning were used to evaluate cognitive performances. Greater A? deposition in the precuneus was associated with higher metabolic activity (at trend level) and lower visual episodic memory scores. Glucose metabolism did not correlate with cognition across all subjects. However, heightened metabolic activity was associated with better verbal episodic memory performance in subjects with elevated amyloid levels. This preliminary study suggests that neural compensation, as a manifestation of brain reserve, enables elderly supposedly on the path to AD, at least temporarily, to preserve cognitive function.

SUBMITTER: Ossenkoppele R

PROVIDER: S-EPMC4089385 | biostudies-other | 2014 Aug

REPOSITORIES: biostudies-other

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Is verbal episodic memory in elderly with amyloid deposits preserved through altered neuronal function?

Ossenkoppele Rik R Madison Cindee C Oh Hwamee H Wirth Miranka M van Berckel Bart N M BN Jagust William J WJ

Cerebral cortex (New York, N.Y. : 1991) 20130328 8

A potential mechanism that enables intellectual preservation in cognitively normal elderly that harbor beta-amyloid (Aβ) pathology is heightened cerebral glucose metabolism. To investigate cross-sectional inter-relationships between Aβ, glucose metabolism, and cognition, 81 subjects (mean age: 75 ± 7 years) underwent [(11)C]Pittsburgh Compound-B and [(18)F]fluorodeoxyglucose positron emission tomography scans and neuropsychological testing. They were divided into low-Aβ (n = 53), intermediate-Aβ ...[more]

PMID: 23537530

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Project description:The aim of this study was to determine the neural correlates of different stages of episodic memory function and their modulation by Alzheimer's disease (AD). Several decades of work has supported the role of the medial temporal lobes (MTL) in episodic memory function. However, a more recent work, derived in part from functional neuroimaging studies, has suggested that other brain structures make up a large-scale network that appears to support successful encoding and retrieval of episodic memories. Furthermore, controversy exists as to whether dissociable MTL regions support qualitatively different aspects of memory (hippocampus: contextual memory or 'recollection'; perirhinal/lateral entorhinal cortex: item memory or 'familiarity'). There is limited neuropsychological support for these models and most work in AD only has examined free recall memory measures. We studied the relationship between performance on different stages of the Rey Auditory Verbal Learning Test (AVLT), a 15-item word list learning task, and structural MRI measures in mild AD patients. Structural measures included hippocampal volume and cortical thickness of several ROIs known to undergo atrophy in AD. Correlation and multiple regression analyses, controlling for age, education, and gender, were performed in 146 mild AD patients (MMSE 23.3±2.0). To evaluate the robustness of these relationships, similar analyses were performed with additional standardized verbal memory measures. Early immediate recall trials (e.g. Trial 1 of the AVLT) were not associated with the size of MTL regions, but correlated most strongly with inferior parietal, middle frontal gyrus, and temporal pole ROIs. After repeated exposure (e.g. Trial 5 of the AVLT), immediate recall was correlated with both MTL and a similar distribution of isocortical structures, but most strongly the temporal pole. For delayed recall, only the hippocampus correlated with performance. In contrast, for delayed recognition discrimination, the perirhinal/entorhinal cortex correlated more strongly than the hippocampus; no other isocortical regions were strongly associated with performance. Convergent results were found for immediate and delayed trials of other memory tests. The current results suggest that a richer understanding of the memory deficits in AD can be gained by examining multiple measures, which tap different aspects of memory function. Furthermore, the present findings are consistent with models hypothesizing different stages of verbal list learning map onto dissociable brain regions. These data have implications for understanding the anatomic basis of processes underlying episodic memory, particularly related to a division of labor within the medial temporal lobes and within the large-scale MTL-cortical memory network.

Project description:Healthy ageing is accompanied by cognitive decline that affects episodic memory processes in particular. Studies showed that anodal transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) may counteract this cognitive deterioration by increasing excitability and inducing neuroplasticity in the targeted cortical region. While stimulation gains are more consistent in initial low performers, relying solely on behavioural measures to predict treatment benefits does not suffice for a reliable implementation of this method as a therapeutic option. Hence, an exploration of the underlying neurophysiological mechanisms regarding the differential stimulation effect is warranted. Glutamatergic metabolites (Glx) and ?-aminobutyric acid (GABA) are involved in learning and memory processes and can be influenced with tDCS; wherefore, they present themselves as potential biomarkers for tDCS-induced behavioural gains, which are affiliated with neuroplasticity processes. In the present randomized, double-blind, sham-controlled, crossover study, 33 healthy young and 22 elderly participants received anodal tDCS to their left DLPFC during the encoding phase of a verbal episodic memory task. Using MEGA-PRESS edited magnetic resonance spectroscopy (MRS), Glx and GABA levels were measured in the left DLPFC before and after the stimulation period. Further, we tested whether baseline performance and neurotransmitter levels predicted subsequent gains. No beneficial group effects of tDCS emerged in either verbal retrieval performances or neurotransmitter concentrations. Moreover, baseline performance levels did not predict stimulation-induced cognitive gains, nor did Glx or GABA levels. Nevertheless, exploratory analyses suggested a predictive value of the Glx?:?GABA ratio, with lower ratios at baseline indicating greater tDCS-related gains in delayed recall performance. This highlights the importance of further studies investigating neurophysiological mechanisms underlying previously observed stimulation-induced cognitive benefits and their respective interindividual heterogeneity.

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Is verbal episodic memory in elderly with amyloid deposits preserved through altered neuronal function?

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Is verbal episodic memory in elderly with amyloid deposits preserved through altered neuronal function?

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