KIBRA gene polymorphism has no association with verbal or visual episodic memory performance.
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ABSTRACT:
SUBMITTER: Franks KH
PROVIDER: S-EPMC4189412 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
KIBRA gene polymorphism has no association with verbal or visual episodic memory performance.
Franks Katherine H KH Summers Mathew J MJ Vickers James C JC
Frontiers in aging neuroscience 20141008
Inter-individual variability in memory performance has been suggested to result, in part, from genetic differences in the coding of proteins involved in long-term potentiation (LTP). The present study examined the effect of a single-nucleotide polymorphism (SNP) in the KIBRA gene (rs17070145) on episodic memory performance, using multiple measures of verbal and visual episodic memory. A total of 256 female and 130 male healthy, older adults (mean age = 60.86 years) were recruited from the Tasman ...[more]
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Project description:KIBRA single nucleotide polymorphism (SNP) rs17070145 was identified in a genome-wide association study (GWAS) of memory performance, with some but not all follow-up studies confirming association of its T allele with enhanced memory. This allele was associated with reduced Alzheimer's disease (AD) risk in 1 study, which also found overexpression of KIBRA in memory-related brain regions of AD. We genotyped rs17070145 and 14 additional SNPs in 2571 late onset Alzheimer's disease (LOAD) patients vs. 2842 controls, including African-Americans. We found significantly reduced risk for rs17070145 T allele in the older African-American subjects (p = 0.007) and a suggestive effect in the older Caucasian series. Meta-analysis of this allele in > 8000 subjects from our and published series showed a suggestive protective effect (p = 0.07). Analysis of episodic memory in control subjects did not identify associations with rs17070145, though other SNPs showed significant associations in 1 series. KIBRA showed evidence of overexpression in the AD temporal cortex (p = 0.06) but not cerebellum. These results suggest a modest role for KIBRA as a cognition and AD risk gene, and also highlight the multifactorial complexity of its genetic associations.
| S-EPMC3065956 | biostudies-literature
Project description:BACKGROUND:In order to retrieve episodic past events, the missing information needs to be reconstructed using information stored in semantic memory. Failures in these reconstructive processes are expressed as false memories. KIBRA single nucleotide polymorphism (rs17070145) has been linked to episodic memory performance as well as an increased risk of Alzheimer's disease and post-traumatic stress disorder (PTSD). METHODS:Here, the role of KIBRA rs17070145 polymorphism (male and female CC vs. CT/TT carriers) in reconstructive episodic memory in the Deese-Roediger-McDermott (DRM) paradigm was investigated in N =?219 healthy individuals. RESULTS:Female participants outperformed males in the free recall condition. Furthermore, a trend towards a gender x genotype interaction was found for false recognition rates. Female CT/TT carriers exhibited a lower proportion of false recognition rates for associated critical lures as compared to male CT/TT. Additionally, an association between KIBRA rs17070145 genotype, familiarity and recollection based recognition performance was found. In trials with correct recognition of listed items CT/TT carriers showed more "remember", but fewer "know" responses as compared to CC carriers. DISCUSSION AND CONCLUSION:Our findings suggest that the T-allele of KIBRA rs17070145 supports recollection based episodic memory retrieval and contributes to memory accuracy in a gender dependent manner. Findings are discussed in the context of the specific contribution of KIBRA related SNPs to reconstructive episodic memory and its implications for cognitive and emotional symptoms in dementia and PTSD.
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Project description:Episodic memory, the ability to consciously recollect information and its context, varies substantially among individuals. While prior fMRI studies have identified certain brain regions linked to successful memory encoding at a group level, their role in explaining individual memory differences remains largely unexplored. Here, we analyze fMRI data of 1,498 adults participating in a picture encoding task in a single MRI scanner. We find that individual differences in responsivity of the hippocampus, orbitofrontal cortex, and posterior cingulate cortex account for individual variability in episodic memory performance. While these regions also emerge in our group-level analysis, other regions, predominantly within the lateral occipital cortex, are related to successful memory encoding but not to individual memory variation. Furthermore, our network-based approach reveals a link between the responsivity of nine functional connectivity networks and individual memory variability. Our work provides insights into the neurofunctional correlates of individual differences in visual episodic memory performance.
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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.
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Project description:Polymorphisms in the gene encoding catenin-β-like 1 (CTNNBL1) were recently reported to be associated with verbal episodic memory performance--in particular, delayed verbal free recall assessed between 5 and 30 min after encoding--in a genome-wide association study on healthy young adults. To further examine the genetic effects of CTNNBL1, we tested for association between 455 single-nucleotide polymorphisms (SNPs) in or near CTNNBL1 and 14 measures of episodic memory performance from three different tasks in 1743 individuals. Probands were part of a population-based study of mentally healthy adult men and women, who were between 20 and 70 years old and were recruited as participants for the Berlin Aging Study II. Associations were assessed using linear regression analysis. Despite having sufficient power to detect the previously reported effect sizes, we found no evidence for statistically significant associations between the tested CTNNBL1 SNPs and any of the 14 measures of episodic memory. The previously reported effects of genetic polymorphisms in CTNNBL1 on episodic memory performance do not generalize to the broad range of tasks assessed in our cohort. If not altogether spurious, the effects may be limited to a very narrow phenotypic domain (that is, verbal delayed free recall between 5 and 30 min). More studies are needed to further clarify the role of CTNNBL1 in human memory.
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Project description:Recent theoretical accounts propose that atypical predictive processing can explain the diverse cognitive and behavioral features associated with autism, and that difficulties in making predictions may be related to reduced contextual processing. In this pre-registered study, 30 autistic children aged 6-14 years and 30 typically developing children matched in age and non-verbal IQ completed visual extrapolation and false memory tasks to assess predictive abilities and contextual processing, respectively. In the visual extrapolation tasks, children were asked to predict when an occluded car would reach the end of a road and when an occluded set of lights would fill up a grid. Autistic children made predictions that were just as precise as those made by typically developing children, across a range of occlusion durations. In the false memory task, autistic and typically developing children did not differ significantly in their discrimination between items presented in a list and semantically related, non-presented items, although the data were insensitive, suggesting the need for larger samples. Our findings help to refine theoretical accounts by challenging the notion that autism is caused by pervasively disordered prediction abilities. Further studies will be required to assess the relationship between predictive processing and context use in autism, and to establish the conditions under which predictive processing may be impaired. Autism Res 2018, 11: 509-518. © 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY:It has been suggested that autistic individuals have difficulties making predictions and perceiving the overall gist of things. Yet, here we found that autistic children made similar predictions about hidden objects as non-autistic children. In a memory task, autistic children were slightly less confused about whether they had heard a word before, when words were closely related in meaning. We conclude that autistic children do not show difficulties with this type of prediction.
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Project description:A common T-->C polymorphism of the KIBRA gene has been recently associated with worse performance on tests of episodic memory. This should aimed to determine whether older adults with the KIBRA CC genotype (1) have worse episodic memory than T-allele carriers and, (2) are more likely to express the phenotype of amnestic mild cognitive impairment (MCI). Our Cross-sectional investigation of 312 adults aged 50-89 years free of dementia included genotyping of the KIBRA rs17070145 gene and the assessment of episodic memory to Establish a Registry for Alzheimer's Disease (CERAD). Participants were considered to have MCI if their memory scores were 1.5 standard deviations below the mean norm for the population. 138/312 participants carried the KIBRA CC genotype. Their immediate and delayed recall scores were significantly lower than the scores of carriers of the T allele (P < 0.05; adjusted for age, gender and pre-morbid IQ), although the effect size of the CC genotype was weak (0.2). Amongst our volunteers, 133 had MCI, of whom 63 (47.4%) had the CC genotype. There was no association between KIBRA genotype and MCI phenotype (TT/CT versus CC; adjusted odds ratio = 1.70, 95%CI = 0.74, 3.90). We concluded that the KIBRA T-->C polymorphism contributes to modulate episodic memory amongst community-dwelling older adults free of dementia, but plays no obvious role in the phenotypic expression of MCI. Future studies should aim to clarify the long term implications of this polymorphism on cognitive function and to identify other genes involved in the modulation of memory that might confer greater risk of MCI in later life.
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Project description:Women are thought to fare better in verbal abilities, especially in verbal-fluency and verbal-memory tasks. However, the last meta-analysis on sex/gender differences in verbal fluency dates from 1988. Although verbal memory has only recently been investigated meta-analytically, a comprehensive meta-analysis is lacking that focuses on verbal memory as it is typically assessed, for example, in neuropsychological settings. On the basis of 496 effect sizes and 355,173 participants, in the current meta-analysis, we found that women/girls outperformed men/boys in phonemic fluency (ds = 0.12-0.13) but not in semantic fluency (ds = 0.01-0.02), for which the sex/gender difference appeared to be category-dependent. Women/girls also outperformed men/boys in recall (d = 0.28) and recognition (ds = 0.12-0.17). Although effect sizes are small, the female advantage was relatively stable over the past 50 years and across lifetime. Published articles reported stronger female advantages than unpublished studies, and first authors reported better performance for members of their own sex/gender. We conclude that a small female advantage in phonemic fluency, recall, and recognition exists and is partly subject to publication bias. Considerable variance suggests further contributing factors, such as participants' language and country/region.
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Project description:The resource modulation hypothesis suggests that the influence of genes on cognitive functioning increases with age. The KIBRA single nucleotide polymorphism rs17070145, associated with episodic memory and working memory, has been suggested to follow such a pattern, but few studies have tested this assertion directly. The present study investigated the relationship between KIBRA alleles (T carriers vs. CC homozygotes), cognitive performance, and brain volumes in three groups of cognitively healthy adults-middle aged (ages 52-64, n = 38), young old (ages 65-72, n = 45), and older old (ages 73-92, n = 62)-who were carefully matched on potentially confounding variables including apolipoprotein ?4 status and hypertension. Consistent with our prediction, T carriers maintained verbal memory performance with increasing age while CC homozygotes declined. Voxel-based morphometric analysis of magnetic resonance images showed an advantage for T carriers in frontal white matter volume that increased with age. Focusing on the older old group, this advantage for T carriers was also evident in left lingual gyrus gray matter and several additional frontal white matter regions. Contrary to expectations, neither KIBRA nor the interaction between KIBRA and age predicted hippocampal volumes. None of the brain regions investigated showed a CC homozygote advantage. Taken together, these data suggest that KIBRA results in decreased verbal memory performance and lower brain volumes in CC homozygotes compared to T carriers, particularly among the oldest old, consistent with the resource modulation hypothesis.
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Project description:Negative subsequent memory effects in functional MRI studies of memory formation have been linked to individual differences in memory performance, yet the effect of age on this association is currently unclear. To provide insight into the brain systems related to memory across the lifespan, we examined functional neuroimaging data acquired during episodic memory formation and behavioral performance from a memory recognition task in a sample of 109 participants, including three developmental age groups (8-12, 13-17, 18-25 year-olds) and one additional group of older adults (55-85 year-olds). Young adults showed the highest memory performance and strongest negative subsequent memory effects, while older adults showed reduced negative subsequent memory effects relative to young adults. Across the sample, negative subsequent memory effects were associated with better memory performance, and there was a significant interaction between negative subsequent memory effects and memory performance by age group. Posthoc analyses revealed that this moderation effect was driven by a stronger association between negative subsequent memory effects and memory performance in young adults than children, and that neither children nor older adults showed a significant association. These findings suggest that negative subsequent memory effects may differentially support memory performance across a lifespan trajectory characterized by developmental maturation and support further investigation of this effect in aging.
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