Memory In aMCI Research Articles

The moderating role of information processing speed in the relationship between brain remodeling and episodic memory in amnestic mild cognitive impairment.

The role of information processing speed (IPS) on relationships between episodic memory (EM) and central remodeling features in amnestic mild cognitive impairment (aMCI) was investigated. Neuropsychological evaluations and multimodal magnetic resonance imaging were performed on 48 patients diagnosed with aMCI and 50 healthy controls (HC). Moderation models explored the moderating effect of IPS on associations between EM and imaging features at single-region, connectivity, and network levels. IPS significantly enhanced the positive correlations between recall and cortical thickness of left inferior temporal gyrus. IPS also notably amplified negative correlations between recognition and functional connectivity (FC) of left inferior parietal lobe and right occipital, as well as between recall/recognition and nodal clustering coefficient of left anterior cingulate cortex. IPS functioned as a moderator of associations between recall and neuroimaging metrics at the "single region-connectivity-network" level, providing new insights for cognitive rehabilitation in aMCI patients. aMCI patients exhibited brain functional and structural remodeling alterations. IPS moderated relations between episodic memory and brain remodeling metrics. Therapy targeted at IPS can be considered for improving episodic memory in aMCI.

Frontal and temporal lobe correlates of verbal learning and memory in aMCI and suspected Alzheimer’s disease dementia

ABSTRACT Alzheimer’s disease is primarily known for deficits in learning and retaining new information. This has long been associated with pathological changes in the mesial temporal lobes. The role of the frontal lobes in memory in Alzheimer’s disease is less well understood. In this study, we examined the role of the frontal lobes in learning, recognition, and retention of new verbal information, as well as the presence of specific errors (i.e., intrusions and false-positive errors). Participants included one hundred sixty-seven patients clinically diagnosed with amnestic mild cognitive impairment or suspected Alzheimer’s disease dementia who were administered the California Verbal Learning Test and completed high-resolution MRI. We confirmed the role of the mesial temporal lobes in learning and retention, including the volumes of the hippocampus, entorhinal cortex, and parahippocampal gyrus. In addition, false-positive errors were associated with all volumes of the mesial temporal lobes and widespread areas within the frontal lobes. Errors of intrusion were related to the supplementary motor cortex and hippocampus. Most importantly, the mesial temporal lobes interacted with the frontal lobes for learning, recognition, and memory errors. Lower volumes in both regions explained more performance variance than any single structure. This study supports the interaction of the frontal lobes with the temporal lobes in many aspects of memory in Alzheimer’s disease.

Hippocampal-Subregion Mechanisms of Repetitive Transcranial Magnetic Stimulation Causally Associated with Amelioration of Episodic Memory in Amnestic Mild Cognitive Impairment.

Altered hippocampal subregions (HIPsub) and their network connectivity relate to episodic memory decline in amnestic mild cognitive impairment (aMCI), which is significantly limited by over-dependence on correlational associations. To identify whether restoration of HIPsub and its network connectivity using repetitive transcranial magnetic stimulation (rTMS) is causally linked to amelioration of episodic memory in aMCI. In the first cohort, analysis of HIPsub grey matter (GM) and its functional connectivity was performed to identify an episodic memory-related circuit in aMCI by using a pattern classification approach. In the second cohort, this circuit was experimentally modulated with rTMS. Structural equation modeling was employed to investigate rTMS regulatory mechanism in amelioration of episodic memory. First, in the first cohort, this study identified HIPsub circuit pathology of episodic memory decline in aMCI patients. Second, in the second cohort, restoration of HIPc GM and its connectivity with left middle temporal gyrus (MTG.L) are causally associated with amelioration of episodic memory in aMCI after 4 weeks of rTMS. Especially important, the effects of HIPc GM changes on the improvement of episodic memory were significantly mediated by HIPc connectivity with MTG.L changes in aMCI. This study provides novel experimental evidence about a biological substrate for the treatment of the disabling episodic memory in aMCI patients. Correction of breakdown in HIPc structure and its connectivity with MTG can causally ameliorate episodic memory in aMCI.

Normative morphometrics from MRI are associated with episodic memory test performance in amnestic MCI

AbstractBackgroundProprietary software that generate normative scores for brain regions using MRI (e.g. NeuroQuant, Neuroreader) have identified greater atrophy in MCI patients than controls, particularly in the hippocampus, and have associated these measurements with episodic memory performance (Tanpitukpongse et al., 2017; Umfleet et al., 2020). While useful in clinical settings, these may be cost‐prohibitive for research purposes. Our goal was to conduct a validation study using free, non‐proprietary morphometric software (Potvin et al., 2016; 2017) with data from a cross‐sectional study of amnestic MCI (aMCI) and normal controls (NC).Method102 older adults ages 60 to 86 (nNC=75; naMCI=27) underwent 3T brain MRI and neuropsychological testing (Weintraub et al., 2018). T1‐weighted images were segmented using FreeSurfer v5.3, and from these outputs normed z‐scores were generated, adjusting for age, sex, total intracranial volume, and MRI field strength (Potvin et al., 2016a; 2016b; 2017). We hypothesized that volumes of AD‐relevant regions (hippocampus, amygdala, entorhinal cortex, parahippocampus) would be smaller in aMCI than NC with no differences in non‐AD “control regions” (cuneus, lingual gyrus, pericalcarine; Fig. 1.A), and that AD‐relevant volumes would correlate with episodic memory composites (i.e. average of normed scores (percentiles) on immediate, delay, and recognition trials from list‐learning (Rey‐Auditory Verbal Learning Test) and story‐learning (Wechsler‐Logical Memory) tests).ResultBonferroni‐corrected t‐tests showed significantly lower volumes of all AD‐relevant regions in the aMCI versus NC, with large effect sizes (Hedge’s g=0.9 to 1.2), and no group differences in control regions (ps<0.05, Hedge’s g<0.3). Bivariate correlations showed moderate (rs=0.38 to 0.55) associations between memory composites and most AD‐relevant regions in the aMCI but not the NC group (Fig. 1.B.1), and no associations between memory composites and control regions except for a positive association between story‐learning and cuneus volume in aMCI (Fig. 1.B.2).ConclusionSimilar to results using proprietary software, this study validates the potential clinical utility of a non‐proprietary normative morphometric software when distinguishing aMCI from NC, with AD‐relevant volumes associated with episodic memory in aMCI. Future studies are needed to characterize associations between other AD‐relevant brain regions and cognitive domains.

Relationships between oral hypoglycemic drugs and memory decline in people with type 2 diabetes: A stratified longitudinal observational study

AbstractBackgroundThere is increased recognition that diabetes can elevate Alzheimer’s disease (AD) risk and exacerbate memory decline. However, few studies have compared memory decline among patients with diabetes using different oral hypoglycemic drug classes.MethodParticipants using any hypoglycemic medications from 2005 to 2019 were identified from the National Alzheimer's Coordinating Center database. Analyses were conducted separately in elderly with normal cognition (NC), amnestic mild cognitive impairment (aMCI), and dementia due to AD. Drug classes of interest included metformin, sulfonylureas, thiazolidinedione and dipeptidyl peptidase‐4 inhibitors (gliptins). Immediate and delayed recall outcomes were assessed using the Wechsler Memory Scale–Logical Memory test. Linear mixed‐effects models (in NC and aMCI) and mixed‐effects zero‐inflated Poisson or quasi‐Poisson regressions (in AD) were used to examine the associations between drug classes (time‐varying exposures) and memory performance over time. Confounding by indications were corrected by inverse probability treatment weighting. Models were adjusted for covariates including demographics, baseline MMSE, comorbidities and concurrent medications. In post‐hoc analyses, we examined whether ApoE genotype moderated the associations between drug class and memory.ResultIn NC (n=1,201, follow‐up years=3.43±3.27), metformin use was associated with better immediate (β=0.069 [0.011, 0.12]) and delayed (β=0.089 [0.032, 0.15]) memory over time, relative to no metformin use. No oral hypoglycemic drug class exhibited significant associations with memory in aMCI (n=671, follow‐up years=1.50±2.13). In AD (n=807, follow‐up years=1.90±2.21), DPP4 inhibitor use was associated with slower rate of decline in delayed memory (RR=1.22 [1.06, 1.40]), and thiazolidinedione use was associated with a faster rate of decline in immediate memory (RR=0.89 [0.82, 0.97]). In NC, DPP4 inhibitor use was associated with better delayed memory over time specifically among ApoE ε4 carriers (interaction: β=0.038 [0.0039, 0.072]). In AD, ApoE ε4 did not significantly interact with DPP4 inhibitor use, and thiazolidinedione use was associated with a faster rate of decline in immediate memory among non‐ε4 carriers (interaction: RR=1.26 [1.07, 1.47]).ConclusionAssociations between memory and particular oral hypoglycemic medications may depend on the presence of AD symptoms. ApoE ε4 may further modify these relationships. Confirmatory analyses in other cohorts, particularly those with more complete clinical data, are required.

Sex differences in cortisol and memory following acute social stress in amnestic mild cognitive impairment

ABSTRACT Objective Older adults with amnestic mild cognitive impairment (aMCI) develop Alzheimer’s type dementia approximately 10 times faster annually than the normal population. Adrenal hormones are associated with aging and cognition. We investigated the relationship between acute stress, cortisol, and memory function in aMCI with an exploratory analysis of sex. Method Salivary cortisol was sampled diurnally and during two test sessions, one session with the Trier Social Stress Test (TSST), to explore differences in the relationship between cortisol and memory function in age-normal cognition (NA) and aMCI. Participants with aMCI (n = 6 women, 9 men; mean age = 75) or similarly aged NA (n = 9 women, 7 men, mean age = 75) were given tests of episodic, associative, and spatial working memory with a psychosocial stressor (TSST) in the second session. Results The aMCI group performed worse on the memory tests than NA as expected, and males with aMCI had elevated cortisol levels on test days. Immediate episodic memory was enhanced by social stress in NA but not in the aMCI group, indicating that stress-induced alterations in memory are different in individuals with aMCI. High cortisol was associated with impaired performance on episodic memory in aMCI males only. Cortisol in Session 1 moderated the relationship with spatial working memory, whereby higher cortisol was associated with worse performance in NA, but better spatial working memory in aMCI. In addition, effects of aMCI on perceived anxiety in response to stress exposure were moderated by stress-induced cortisol in a sex-specific manner. Conclusions We show effects of aMCI on Test Session cortisol levels and effects on perceived anxiety, and stress-induced impairments in memory in males with aMCI in our exploratory sample. Future studies should explore sex as a biological variable as our findings suggest that effects at the confluence of aMCI and stress can be obfuscated without sex as a consideration.

Insight into memory and functional abilities in individuals with amnestic mild cognitive impairment

ABSTRACT Objective Accurate insight into one’s abilities facilitates engagement in rehabilitation and implementation of compensatory strategies. In this study, self-awareness, self-monitoring, and a new self-updating construct of insight were examined in amnestic mild cognitive impairment (aMCI). Method Individuals with aMCI and healthy older adults (HOAs) completed a list-learning task in a laboratory setting, and a naturalistic task of everyday functioning in a campus apartment along with other standardized neuropsychological tests. Participants made predictions about performance on the memory and functional tasks prior to task experience (self-awareness), immediately after task experience (self-monitoring), and after a delay (self-updating). Results Individuals with aMCI performed more poorly than HOAs on the memory task and other neuropsychological tests but not the functional task. For both the memory and functional task, performance predictions and prediction accuracy measures revealed that the aMCI group exhibited intact self-awareness, self-monitoring, and self-updating. Prediction accuracy measures showed some association with an executive composite but not a memory composite. Discussion Participants with aMCI demonstrated intact self-awareness, self-monitoring, and self-updating for a memory and functional task despite exhibiting poorer performance on neurocognitive tests compared to HOAs. These findings suggest that, even as memory in aMCI degrades, executive abilities may help sustain insight into difficulties, enabling adoption of cognitive strategies to support difficulties.

Focal white matter disruptions along the cingulum tract explain cognitive decline in amnestic mild cognitive impairment (aMCI)

White matter abnormalities of the human brain are implicated in typical aging and neurodegenerative diseases. However, our understanding of how fine-grained changes in microstructural properties along white matter tracts are associated with memory and cognitive decline in normal aging and mild cognitive impairment remains elusive. We quantified tract profiles with a newer method that can reliably measure fine-grained changes in white matter properties along the tracts using advanced multi-shell diffusion magnetic resonance imaging in 25 patients with amnestic mild cognitive impairment (aMCI) and 23 matched healthy controls (HC). While the changes in tract profiles were parallel across aMCI and HC, we found a significant focal shift in the profile at specific locations along major tracts sub-serving memory in aMCI. Particularly, our findings depict white matter alterations at specific locations on the right cingulum cingulate, the right cingulum hippocampus and anterior corpus callosum (CC) in aMCI compared to HC. Notably, focal changes in white matter tract properties along the cingulum tract predicted memory and cognitive functioning in aMCI. The results suggest that white matter disruptions at specific locations of the cingulum bundle may be a hallmark for the early prediction of Alzheimer’s disease and a predictor of cognitive decline in aMCI.

Executive functions and working memory in motor control: Does the type of MCI matter?

The purpose of this study was to evaluate the association between functional mobility performance and executive functions in older adults with the amnestic (aMCI) and nonamnestic (naMCI) type of mild cognitive impairment (MCI), as well as in a control group. A cross-sectional study was conducted among 800 older adults (147 with MCI) who participated in a longitudinal study consisting in an interdisciplinary geriatric assessment and rehabilitation program in Kraków. Motor performance was measured with the Timed Up and Go test (TUG), while standard neuropsychological tests were used to assess different cognitive domains. Analysis of the entire sample showed that almost all cognitive domains and the presence of MCI are associated with functional mobility. Executive functions, letter fluency, and working memory were associated with TUG in the MCI group. The MCI type was not a significant moderator of the relationship between cognitive and motor performance. In group analyses, various cognitive predictors for TUG in the aMCI group, naMCI, and control group were demonstrated. Our results suggest that executive functions and working memory in aMCI and letter fluency in naMCI are independently associated with functional mobility performance. Executive functions are important for gait control in MCI.

Self-Reference Effect and Self-Reference Recollection Effect for Trait Adjectives in Amnestic Mild Cognitive Impairment - Erratum.

Objectives: The self-reference effect (SRE), enhanced memory for self-related information, has been studied in healthy young and older adults but has had little investigation in people with age-related memory disorders, such as amnestic mild cognitive impairment (aMCI). Self-referential encoding may help to improve episodic memory in aMCI. Additionally, self-referential processing has been shown to benefit recollection, the vivid re-experiencing of past events, a phenomenon that has been termed the self-reference recollection effect (SRRE; Conway & Dewhurst, 1995). Furthermore, it remains unclear whether the valence of stimuli influences the appearance of the SRE and SRRE. Methods: The current study investigated the SRE and SRRE for trait adjective words in 20 individuals with aMCI and 30 healthy older adult controls. Ninety trait adjective words were allocated to self-reference, semantic, or structural encoding conditions; memory was later tested using a recognition test. Results: While healthy older adults showed a SRE, individuals with aMCI did not benefit from self-referential encoding over and above that of semantic encoding (an effect of “deep encoding”). A similar pattern was apparent for the SRRE; healthy controls showed enhanced recollection for words encoded in the self-reference condition, while the aMCI group did not show specific benefit to recollection for self-referenced over semantically encoded items. No effects of valence were found. Conclusions: These results indicate that while memory for trait adjective words can be improved in aMCI with deep encoding strategies (whether self-reference or semantic), self-referencing does not provide an additional benefit. (JINS, 2018, 24, 821–832)

Effects of Gender and Apolipoprotein E on Novelty MMN and P3a in Healthy Elderly and Amnestic Mild Cognitive Impairment

Background: The apolipoprotein E epsilon4 (ApoE ε4) allele and female gender may be important risk factors for the development of Alzheimer’s disease and amnestic mild cognitive impairment (aMCI). Novelty mismatch negativity (MMN) represents the pre-attentive index of deviance detection and P3a represents the attention orienting response. Furthermore, MMN and P3a components have been reported to be potential markers in aMCI. Therefore, this study will investigate the effects of gender and ApoE on auditory novelty MMN and P3a and their relationship to neuropsychological performance in aMCI.Methods: Thirty nine aMCI subjects and 44 controls underwent neuropsychological assessment and ApoE genotyping. Novelty MMN and P3a components were investigated during an auditory novelty oddball task.Results: Firstly, novelty MMN latency was significantly shorter in aMCI than in healthy control (HC) group. Secondly, novelty MMN latency was negatively correlated with episodic memory in aMCI, but not in HC. Novelty P3a latency was negatively correlated with information processing speed in all subjects. For gender effect, novelty MMN latency was shorter in aMCI females than in HC females. Moreover, novelty P3a amplitudes were lower in males than in females in both aMCI and HC. For the effect of ApoE status, novelty MMN latency was shorter in aMCI ApoE ε4- than HC ApoE ε4-.Conclusion: aMCI presents altered pre-attentive processing indexed by novelty MMN components. Furthermore, there may be a compensatory mechanism on the impaired processing in aMCI. It further suggests that aMCI female and ApoE ε4- recruited the compensatory mechanism.

Self-Reference Effect and Self-Reference Recollection Effect for Trait Adjectives in Amnestic Mild Cognitive Impairment

The self-reference effect (SRE), enhanced memory for self-related information, has been studied in healthy young and older adults but has had little investigation in people with age-related memory disorders, such as amnestic mild cognitive impairment (aMCI). Self-referential encoding may help to improve episodic memory in aMCI. Additionally, self-referential processing has been shown to benefit recollection, the vivid re-experiencing of past events, a phenomenon that has been termed the self-reference recollection effect (SRRE; Conway & Dewhurst, 1995). Furthermore, it remains unclear whether the valence of stimuli influences the appearance of the SRE and SRRE. The current study investigated the SRE and SRRE for trait adjective words in 20 individuals with aMCI and 30 healthy older adult controls. Ninety trait adjective words were allocated to self-reference, semantic, or structural encoding conditions; memory was later tested using a recognition test. While healthy older adults showed a SRE, individuals with aMCI did not benefit from self-referential encoding over and above that of semantic encoding (an effect of "deep encoding"). A similar pattern was apparent for the SRRE; healthy controls showed enhanced recollection for words encoded in the self-reference condition, while the aMCI group did not show specific benefit to recollection for self-referenced over semantically encoded items. No effects of valence were found. These results indicate that while memory for trait adjective words can be improved in aMCI with deep encoding strategies (whether self-reference or semantic), self-referencing does not provide an additional benefit. (JINS, 2018, 24, 821-832).

Face-specific memory deficits and changes in eye scanning patterns among patients with amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer’s disease (AD). Previous studies have shown functional and structural degradation of the fusiform face area, which is a core region for face processing, in addition to medial temporal lobe degradation. We predicted that patients with aMCI exhibit a loss of face processing and/or face memory, accompanied by abnormal eye scanning patterns, since patients who have deficits in face perception (i.e. prosopagnosia) exhibit such tendencies. Eighteen patients with aMCI and age-matched healthy controls were tested for perception and short-term memory of visually presented faces and houses while their gaze was recorded. Patients with aMCI showed a decline in memory, compared with control observers, for faces, but not for houses. Patients looked more at the mouth of faces, compared with control observers. We demonstrate here the loss of short-term face memory in aMCI with abnormal scanning patterns that might reflect the cerebral abnormality found in patients with aMCI.

DISTINCT EFFECTS OF COGNITIVE RESERVE ON ERPS ASSOCIATED WITH WORKING MEMORY IN HEALTHY ELDERLY AND AMCI

DISTINCT EFFECTS OF COGNITIVE RESERVE ON ERPS ASSOCIATED WITH WORKING MEMORY IN HEALTHY ELDERLY AND AMCI

Cognitive reserve moderates the association between functional network anti-correlations and memory in MCI

Cognitive reserve (CR) shows protective effects on cognitive function in older adults. Here, we focused on the effects of CR at the functional network level. We assessed in patients with amnestic mild cognitive impairment (aMCI) whether higher CR moderates the association between low internetwork cross-talk on memory performance. In 2 independent aMCI samples (n = 76 and 93) and healthy controls (HC, n = 36), CR was assessed via years of education and intelligence (IQ). We focused on the anti-correlation between the dorsal attention network (DAN) and an anterior and posterior default mode network (DMN), assessed via sliding time window analysis of resting-state functional magnetic resonance imaging (fMRI). The DMN-DAN anti-correlation was numerically but not significantly lower in aMCI compared to HC. However, in aMCI, lower anterior DMN-DAN anti-correlation was associated with lower memory performance. This association was moderated by CR proxies, where the association between the internetwork anti-correlation and memory performance was alleviated at higher levels of education or IQ. In conclusion, lower DAN-DMN cross-talk is associated with lower memory in aMCI, where such effects are buffered by higher CR.

Protective effect of APOE epsilon 2 on intrinsic functional connectivity of the entorhinal cortex is associated with better episodic memory in elderly individuals with risk factors for Alzheimer's disease.

The apolipoprotein E (APOE) ε4 allele associates with accelerating the conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD), whereas the protectiveAPOEε2 allele appears to be against the disease. Moreover, entorhinal cortex (ERC) is one of the earliest brain regions of AD pathology that disrupts the formation of episodic memory. To investigate the effects of APOE ε2 and ε4alleles on functional connectivity (FC) of ERC and cognition in aMCI. Methods The FC analyses of ERC were performed in 83 aMCI (9 ε2-carrier, 44 ε3ε3, and 30 ε4-carrier) and 88 healthy controls (HC, 15 ε2-carrier, 40 ε3ε3, and 33 ε4-carrier). Multiple linear regression model was performed between the altered ERC connectivities and cognition. In the ERC network, aMCI with ε4-carriers showed decreased FC in the bilateral middle temporal gyrus (MTG), right precuneus, and right precentral gyrus (PreCG), while ε2-carriers showed increased FC in these regions (except the right PreCG) compared to HC. The altered FC between ERC and right MTG correlated with episodic memory performance in aMCI carried ε2 and ε4 alleles. These results suggest that the effects ofAPOEon the ERC network are closely linked to the role of this gene on AD risk, which aMCI with ε4-carriers can accelerate the pathological progression of network-based mechanisms while ε2-carriers may play a protective role in contributing to a compensatory mechanism. It further suggests that APOE can appear to directly affect the ERC-MTG neural pathway associated with the impairment of episodic memory in aMCI.

Enhanced resting-state functional connectivity between core memory-task activation peaks is associated with memory impairment in MCI

Resting-state functional connectivity (FC) is altered in Alzheimer's disease (AD) but its predictive value for episodic memory impairment is debated. Here, we aimed to assess whether resting-state FC in core brain regions activated during memory-task functional magnetic resonance imaging is altered and predictive of memory performance in AD and amnestic mild cognitive impairment (aMCI). Twenty-three elderly cognitively healthy controls (HC), 76 aMCI subjects, and 19 AD dementia patients were included. We computed resting-state FC between 18 meta-analytically determined peak coordinates of brain activation during successful memory retrieval. Higher FC between the parahippocampus, parietal cortex, and the middle frontal gyrus was observed in both AD and mild cognitive impairment compared to HC (false-discovery rate—corrected p < 0.05). The increase in FC between the parahippocampus and middle frontal gyrus was associated with reduced episodic memory in aMCI, independent of amyloid-beta positron emission tomography binding and apolipoprotein E ε4-carrier status. In conclusion, increased parahippocampal-prefrontal FC is predictive of impaired episodic memory in aMCI and may reflect a dysfunctional change within the episodic memory–related neural network.

Differential contributions of subregions of medial temporal lobe to memory system in amnestic mild cognitive impairment: insights from fMRI study.

Altered function of the medial temporal lobe (MTL) is a valuable indicator of conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease. This study is to delineate the functional circuitry of multiple subdivisions of parahippocampal gyrus and hippocampus (HIP) and to examine how this knowledge contributes to a more principled understanding of the contributions of its subregions to memory in aMCI. The functional connectivity (FC) analysis was performed in 85 aMCI and 129 healthy controls. The aMCI demonstrated the distinct disruptive patterns of the MTL subregional connectivity with the whole-brain. The right entorhinal cortex (ERC) and perirhinal cortex (PRC) showed increased connectivity with the left inferior and middle occipital gyrus, respectively, which potentially indicated a compensatory mechanism. Furthermore, the right altered MTL subregional FC was associated with episodic memory performance in aMCI. These results provide novel insights into the heterogeneous nature of its large-scale connectivity in MTL subregions in memory system underlying the memory deficits in aMCI. It further suggests that altered FC of MTL subregions is associated with the impairment of the differential encoding stages of memories and the functional changes in the specific right HIP-ERC-PRC-temporal circuitry may contribute to the impairment of episodic memory in aMCI.

Differential effects of APOE genotypes on intrinsic functional connectivity of the entorhinal cortex associated with episodic memory in amnestic mild cognitive impairment

Background The apolipoprotein E ( APOE ) gene is a well-established genetic susceptibility factor for the conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD). Moreover, entorhinal cortex (ERC) is one of the earliest brain regions of AD pathology that disrupts the formation of episodic memory. The present study was the first to investigate whether there are differential effects of APOE polymorphism on functional connectivity (FC) of ERC and cognition in aMCI. Methods The FC analyses of ERC in whole-brain were performed in 83 aMCI and 88 healthy controls (HC). Results In the ERC network, aMCI with APOE epsilon 4 (ɛ4)-carriers showed decreased FC with the bilateral middle temporal gyrus (MTG) and the right precuneus (PCUN), and the right precentral gyrus (PreCG), while APOE ɛ2-carriers showed increased FC (except decreased FC with the right PreCG) compared to HC. The altered FC between ERC and right MTG correlated with the impairment of episodic memory in aMCI carried APOE ɛ4 and ɛ2 allele. Conclusions These results provide novel evidence that APOE ɛ4 and ɛ2 alleles affect multiple physiopathologic pathways in the ERC network, which aMCI with ɛ4-carriers can accelerate the pathological progression of network-based mechanisms while ɛ2-carriers may play a protective role in contributing to a compensatory mechanism. It further suggests that APOE can appear to indirectly mediate the ERC-MTG neural pathway associated with the impairment of episodic memory in aMCI.

Frontal-parietal alpha networks reflect a compensatory mechanism to overcome the associative deficit in mild cognitive impairment

Event Abstract Back to Event Frontal-parietal alpha networks reflect a compensatory mechanism to overcome the associative deficit in mild cognitive impairment Laura Prieto Del Val1*, José Luis Cantero Lorente1 and Mercedes Atienza Ruiz1 1 University Pablo de Olavide, Department of Physiology, Anatomy, and Cellular Biology, Spain People with amnestic mild cognitive impairment (aMCI), like healthy older adults (HO), present a disproportionate deficit in associative memory; but unlike HO, they do not benefit from semantic congruence. The presence of the e4 allele of the apolipoprotein E gene (APOE) makes this memory loss worse. Here, we show that encoding of face-location associations are accompanied by different patterns of large-scale EEG oscillatory dynamics under semantically congruent and incongruent conditions. These differences were reflected by theta power increases and alpha/beta power decreases in both HO and aMCI. However, after localizing the brain sources of these oscillations, enhanced theta and decreased beta revealed higher activation of temporal regions in HO, and of frontal regions in aMCI. Source analysis of EEG oscillations yielded two further important results. On the one hand, dynamics of beta oscillations indicated that aMCI, mainly APOE-e4 carriers, have problems to activate an extensive neural network related to associative memory in the right hemisphere. And on the other, the better memory performance shown by aMCI e4 non-carriers relative to e4 carriers not only was similar to that of HO, but was also related to alpha power decreases in left frontal and parietal regions. All together, these findings suggest that associative memory deficits in aMCI are linked to abnormal beta oscillatory dynamics in the right hemisphere, whereas impaired semantic memory might be related to activation deficits of left temporal regions. Most important, these results suggest that associative memory in aMCI can be improved through activation of an alpha oscillatory network comprising frontal and parietal regions, and that recruitment of such a compensatory mechanism depends on the APOE genotype. Keywords: Associative Memory, brain oscillations, compensatory mechanisms, amnestic mild cognitive impairment, APOE e4 Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Memory and Learning Citation: Prieto Del Val L, Cantero Lorente J and Atienza Ruiz M (2015). Frontal-parietal alpha networks reflect a compensatory mechanism to overcome the associative deficit in mild cognitive impairment. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00360 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Mrs. Laura Prieto Del Val, University Pablo de Olavide, Department of Physiology, Anatomy, and Cellular Biology, Seville, Spain, lpridel@upo.es Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Laura Prieto Del Val José Luis Cantero Lorente Mercedes Atienza Ruiz Google Laura Prieto Del Val José Luis Cantero Lorente Mercedes Atienza Ruiz Google Scholar Laura Prieto Del Val José Luis Cantero Lorente Mercedes Atienza Ruiz PubMed Laura Prieto Del Val José Luis Cantero Lorente Mercedes Atienza Ruiz Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.