Rey Auditory Verbal Learning Task Research Articles

Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From Chronic Methamphetamine Use.

The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance. Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested. MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus. Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.

Verbal fluency patterns associated with the amnestic conversion from mild cognitive impairment to dementia

Patients with amnestic mild cognitive impairment (aMCI) are at a higher risk of converting to Alzheimer's disease. The aim of this study was to examine the potential use of Verbal Fluency (VF) measures as markers for predicting the conversion to dementia. At baseline, 61 aMCI, aged 65 to 80 years, underwent a comprehensive neuropsychological assessment, including phonemic (PVF) and semantic verbal fluency (SVF) tasks. After 18 months, 14 individuals with aMCI had progressed to a diagnosis of dementia. The findings revealed that aMCI-converter group had lower Mini Mental State Examination and Rey Auditory Verbal Learning Task scores than aMCI-no converter and produced fewer clusters in both VF tasks and a lower number of switches in PVF at baseline (p < 0.05). According to receiver operating characteristic curve analysis, the number of clusters in PVF had the highest predictive value (AUC = 0.80) with a threshold of 5.510 for identifying aMCI-converter at baseline. Additionally, participants with higher levels of education exhibited more clusters and switches in VF tasks (p < 0.05). These results suggest that qualitative measures of VF could serve as neuropsychological markers for predicting cognitive decline in individuals with aMCI. Furthermore, the study highlights the potential influence of the education level on cognitive performance in neuropsychological tasks.

The Effects of Cognitive Ability, Mental Health, and Self-Quarantining on Functional Ability of Older Adults During the COVID-19 Pandemic: Results From the Canadian Longitudinal Study on Aging.

Determine whether levels of anxiety and depression, cognitive ability, and self-quarantining during and prior to the pandemic predict decreases in perceived functional ability. Longitudinal data collected from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Questionnaire Study (2020) and core CLSA study (Follow-Up 1; 2014-2018). 17541 CLSA participants. Self-quarantining behaviours from questionnaires administered at Baseline (April 2020), Monthly, and Exit (December 2020) time points of the CLSA COVID-19 Questionnaire Study, levels of anxiety and depression at Baseline, perceived change in functional ability at Exit, and performance on neuropsychological tests (Rey Auditory Verbal Learning Task, Mental Alternation Task, Animal Fluency Test) and functional ability (Older Americans Resources and Services [OARS] Multidimensional Assessment Questionnaire) from the core CLSA study. Greater cognitive ability pre-pandemic (B = -.003, P < .01), higher levels of anxiety (B = -.024, P < .01) and depressive symptoms (B = -.110, P < .01) at Baseline, and higher frequency of engaging in self-quarantining throughout the COVID-19 survey period (B = -.098, P < .01) were associated with perceived loss in functional ability at Exit. Self-quarantining behaviour was associated with perceived loss in functional ability only at average and high levels of depressive symptoms (B = -.013, P < .01). Older adults with higher cognitive and lower functional ability prior to the pandemic were at greater risk of decreased perceived functional ability during the first year of the pandemic, as were those who experienced greater levels of anxiety and depressive symptoms during the pandemic. Strategies/interventions to preserve functional ability in older adults with cognitive independence prior to future pandemics are warranted.

5 Combining Neurophysiology and Behavioral Measures to Identify Biomarkers of Clinical and Preclinical Hippocampus-Dependent Memory Dysfunction

Objective:Memory is a critical piece of the human experience and impairments in neural memory networks can have devastating consequences for the affected person. A subtype of memory, episodic memory generates context for the present based on past experience and allows us to make predictions about the future. Episodic memories become stable fixtures through long-term memory consolidation. It is believed that consolidation of episodic memory requires a dynamic interplay between connected hippocampal-cortical networks, mainly during sleep. Sleep oscillations, slow oscillations and thalamocortical spindles, coupled with hippocampal sharp wave ripples (SWR) is proposed to be mechanistically involved in establishing the crucial cortical-subcortical dialog. The current study aimed to determine alterations in typical sleep oscillations and oscillation coupling in patients with and without structural hippocampal damage and correlate them with neuropsychological measures believed to be sensitive to hippocampal dysfunction, i.e., Rey Auditory Verbal Learning Task (RAVLT) and Verbal Paired Associates (VPA-II).Participants and Methods:We used intracranial electroencephalography (iEEG) in 14 patients with epilepsy to directly record hippocampal and neocortical oscillations and neuropsychological measures obtained prior to implantation. Half of the participants were diagnosed with mesial temporal sclerosis (MTS) in the left hippocampus and healthy tissue in the right hippocampus. The other half did not have MTS and had either mesial temporal epilepsy without MTS or extra-temporal seizures. We analyzed hippocampal SWR output from both hippocampi and characterized neocortical slow oscillations and spindles and their coupling for each participant. We correlated electrophysiological data with behavioral results of neuropsychological testing in order to characterize the clinical relevance.Results:SWR analysis revealed significant differences in the frequency, t(7639) = 15.52, p&gt;.001, p &gt; .001), amplitude, t(7664) = -23.93, p &gt; .001, and waveforms (p &gt; .001) of SWR in the sclerotic versus healthy hippocampi. Patients with a sclerotic hippocampus but relatively preserved verbal memory scores (RAVLT, VPA-II) showed increased SWR amplitudes in the contralateral hippocampus compared to patients with low verbal memory scores. Additionally, we found differences between hemispheres in phase amplitude coupling of SWRs to spindles and SOs (p &gt; 0.001). Results of our correlational analysis were variable and dependent upon additional factors, such as age of onset and diagnosis duration.Conclusions:Results from this work will aid in establishing a criterion for characterizing a relationship between subcortical and cortical oscillations as they relate to memory performance. Besides aiding our understanding of the neural mechanisms underpinning memory consolidation this will ideally help with developing neurophysiological biomarkers that may predict possible memory decline in resective or ablative neurosurgery absent of structural lesion. In addition, this work may potentially provide first evidence of a neurophysiological biomarker directly recorded from the human hippocampus to support possible reorganization of memory functioning in the non-sclerotic hippocampus.

4 Misinterpreting cognitive change over multiple timepoints: When practice effects meet age-related decline

Objective:Practice effects (PE) on cognitive testing impede our ability to accurately assess change. In particular, they hamper the detection of mild cognitive impairment (MCI) and progression to dementia by delaying the point at which test scores fall below diagnostic impairment cutoffs. When decline over time is expected, as with older adults or progressive diseases, failure to adequately address PEs may lead to inaccurate conclusions because PEs artificially boost scores while pathology-related or age-related decline reduces scores. The participant-replacement method accounts for PEs by comparing performance of demographically-matched replacement participants to returnees who have been tested previously. Unlike most methods, the participant-replacement method can separate pathology- or age-related decline from PEs; however, this method has only been used across two timepoints. Neuropsychologists tend to think that PEs level out after the first follow-up, but this issue has not been evaluated in models that allow PEs in the presence of overall decline. Including more than two timepoints makes it possible to determine if PEs level out after the first follow-up, but it is analytically challenging because individuals may not be assessed at every timepoint.Participants and Methods:We examined 1190 older adults in the Alzheimer’s Disease Neuroimaging Initiative who were cognitively unimpaired (n=809) or had MCI (n=381) at baseline. Participants completed six neuropsychological measures (Trails A, Trials B, Boston Naming Test, Category Fluency, Logical Memory, Rey Auditory Verbal Learning Task) at three timepoints (baseline, 12-month, 24-month). We implemented the participant-replacement method using generalized estimating equations in comparisons of matched returnees and replacements to calculate PEs. Propensity scores matched individuals on age, education, sex, and an estimate of premorbid functioning. Generalized estimating equations modeled PEs and age-related decline separately for each cognitive measure.Results:We observed significant PEs for 5 of the 6 measures in the cognitively unimpaired group and 4 measures in the baseline MCI group. PEs did not uniformly decrease across time; some—specifically on episodic memory measures—continued to increase beyond the first follow-up for both groups of participants. Without accounting for PEs, cognitive function appeared to improve or stay the same. In contrast, when PEs were included in the models, cognitive function appeared to decline or stay the same across time.Conclusions:The replacement method of PE adjustment revealed significant PEs across two follow-ups. PEs for episodic memory, in particular, did not level out, but actually increased after the first follow-up, two years after baseline. As expected in these older adults, accounting for PEs revealed cognitive decline, in some cases, even when PE-unadjusted scores improved. This method of assessing PEs, in turn, means earlier detection of cognitive deficits, including progression to MCI, and more accurate characterization of longitudinal change.

Sex-specific impulsivity, but not other facets of executive function, predicts fat and sugar intake two-years later amongst adolescents with a healthy weight: Findings from the ABCD study

During adolescence, processes that control food intake (executive functions [EF]) undergo extensive refinement; underlying differences in EF may explain the inability to resist overeating unhealthy foods. Yet, overeating fat and sugar also causes changes to EF and cognition but disentangling these relationships has been difficult, as previous studies included youth with obesity. Here, amongst youth initially of a healthy weight, we evaluate whether 1) sex-specific underlying variation in EF/cognition at 9/10-years-old predict fat/sugar two-years later (Y2) and 2) if these relationships are moderated by body mass index (BMI), using linear mixed effects models (controlled for puberty, caregiver education; random effect: study site). Data were leveraged from Adolescent Brain Cognitive Development Study (n = 2987; 50.4% male; 15.4% Latino/a/x; 100% healthy weight at baseline; 12.4% overweight/obese by Y2, data release 4.0). EF and cognition (e.g., inhibition, cognition, motor, memory, impulsivity) were assessed with the NIH toolbox, Rey Auditory Verbal Learning Task, Little Man Task, the BIS/BAS, and UPPS-P. A saturated fat/added sugar (kcals) composite score was extracted from the validated Kids Food Block Screener. For males, greater baseline impulsivity (e.g., Positive Urgency, Lack of Planning and Perseverance) and reward (e.g., Fun seeking, Drive) was related to greater Y2 intake. For both sexes, greater baseline Negative Urgency and higher BMI was related to greater Y2 intake. No other relationships were observed. Our findings highlight a phenotype that may be more at risk for weight gain due to overconsumption of fat/sugar. Thus, prevention efforts may wish to focus on impulsive tendencies for these foods.

Vitamin D is associated with visual memory in young northern adolescents

ABSTRACT Background Vitamin D status has been linked to visual memory in adults. We hypothesized a similar association in young adolescents. Methods Participants were 9–13 years. The Rey-Osterrieth Complex Figure Task (ROCF), Rey Auditory Verbal Learning Task (RAVLT), Digit Span (Forward, Backward), and verbal fluency task assessed visual and verbal learning/memory, attention/working memory, and executive functioning/language, respectively. An at-home, mail-in blood spot test assessed 25(OH)D levels. Results Participants (N = 56) were 10.7 ± 1.3 years, 61% females, 25(OH)D levels 84.2 ± 25 nmol/L(39.9 - 167.2 nmol/L) and 41% had insufficient vitamin D status (<75 nmol/L). Only measures of visual memory (ROCF-Recall, -%Recall of Copy) were significantly correlated with 25(OH)D, r = .34, p < .01 and r = .33, p < .01, respectively, and 25(OH)D remained a significant independent predictor on multiple regression analyses, which included age and sex.(ROCF-Recall overall model: Adj R2 = .24, p < .001; for 25(OH)D: p = .009; ROCF-%Recall of Copy overall model: Adj R2 = .20 p < .002; for 25(OH)D: p = .01). Individuals with sufficient vitamin D performed significantly better only on these measures (t-tests; ROCF-Recall, p = .016, d = 0.68; ROCF-%Recall of Copy, p = .022, d = 0.64). Despite moderate effect sizes (d = 0.4–0.5) in the Younger Age Group (9–10 years), only in the Older Age Group (11–13 years) was 25(OH)D significantly correlated with ROCF-Recall, r = .64, p = .0001 and ROCF-%Recall of Copy, r = .64, p = .0001, as well as working memory (Digit Span-Backward), Spearman’s r = .46, p = .013. Similarly, those in the Older Age Group with sufficient vitamin D performed significantly better on ROCF-Recall, p = .01, d = 1.07; and ROCF-%Recall of Copy, p = .009, d = 1.08. Conclusions Vitamin D insufficiency was common in young adolescents. Similar to adults, visual memory was better among participants with higher 25(OH)D and those with sufficient levels. This effect was especially pronounced among older participants, suggesting possible time- and/or age-related implications of vitamin D status on cognition.

The influence of Apolipoprotein E ε4 carrier status on posterior cingulate cortex thickness and learning

AbstractBackgroundThinning of the posterior cingulate cortex (PCC) is implicated in Alzheimer’s disease (AD). Though some evidence suggests ApolipoproteinE (APOE) ε4 carriers (ε4+) have thinner PCCs than non‐carriers (ε4‐), the evidence is conflicting and lacks association with learning outcomes relevant to AD.MethodA subset from an ongoing clinical trial (NIH/NIA: R01AG058919) was used for analyses and included 26 ε4+ (73% female, Agemean=55.81±5.53) and 42 ε4‐ (88% female, Agemean= 57.54±5.10), who were all cognitively normal, sedentary, and had a family history of AD. Genetic sampling was completed via passive drool. Structural MRI was completed to assess PCC cortical thickness, and the Rey Auditory Verbal Learning Task (AVLT) was used to assess learning. Brain segmentation was completed with Freesurfer’s automated pipeline, and left and right PCC cortical thickness was extracted for analysis. A learning over trials (LOT) composite score from the AVLT was calculated to represent learning. An analysis of covariance was completed to assess the effect of carrier status on left/right PCC thickness, controlling for age and sex. Linear regressions were completed to assess main effects and interaction of carrier status and left/right PCC thickness in predicting LOT when controlling for age and sex.Resultε4+ had less cortical thickness in the left PCC (F(1,64)=5.07, p=.03), but not the right PCC (p=.33), relative to ε4‐. Carrier status predicted LOT (Left: F(1,62)=10.37, p&lt;.01; Right: F(1,62)=10.66, p&lt;.01), however this was superseded by significant interactions between carrier status and PCC thickness predicting LOT (Left: F(1,62)=10.72, p&lt;.01; Right: F(1, 62)=11.10, p&lt;.01), with post‐hoc analyses demonstrating PCC thickness predicts LOT for ε4+ (Left:β=‐21.07, p=.04; Right:β=‐24.33, p&lt;.01), but not ε4‐ (p’s&gt;.09).ConclusionIn cognitively normal sedentary adults with a family history of AD, carrying the APOE ε4 allele was associated with a thinner left PCC. Further, thinner bilateral PCCs in ε4+ were associated with greater learning during the AVLT task. This suggests that ε4+ may have compensatory neural pathways to account for losses in the PCC, which temporarily bolster learning to delay the onset of AD. However, additional research is needed to continue understanding the neural mechanisms affected by carrying the APOE ε4 allele.

The effects of physical activity timing and complexity on episodic memory: A randomized controlled trial

The role of two types of acute physical activity (PA) bouts were assessed on young adults’ free-recall and recognition memory in two experiments, which differed in the temporal relation of PA and word encoding. Before or following training on the Rey Auditory Verbal Learning Task, participants performed a simple two-step dance, a complex four-step dance, or remained seated. Hypotheses proposed that PA prior to encoding and complex PA would enhance PA’s mnemonic benefits. Memory assessed post-PA, 24 h, and 7 days after training indicated that timing and complexity of PA did not impact free-recall or recognition memory. Findings differ from a previous study showing complex PA benefited motor learning more than simple PA (Tomporowski & Pendleton, 2018). The inconsistency may be due to different working memory processes underlying consolidation and retrieval of procedural or episodic information. Theory-based explanations regarding memory storage and retrieval are proposed to elucidate this selective process.

Verbal Learning and Longitudinal Hippocampal Network Connectivity in Temporal Lobe Epilepsy Surgery.

IntroductionLearning new verbal information can be impaired in 20–40% of patients after mesial temporal lobe resection. In recent years, understanding epilepsy as a brain network disease, and investigating the relationship between large-scale resting networks and cognition has led to several advances. Aligned studies suggest that it is the integrity of the hippocampal connectivity with these large-scale networks what is relevant for cognition, with evidence showing a functional and structural heterogeneity along the long axis hippocampus bilaterally.ObjectiveOur aim is to examine whether pre-operative resting-state connectivity along the long hippocampal axis is associated with verbal learning decline after anterior temporal lobe resection.MethodsThirty-one patients with epilepsy who underwent an anterior temporal lobe resection were pre-surgically scanned at 3-tesla, and pre/post-surgery evaluated for learning deficits using the Rey Auditory Verbal Learning Task (RAVLT). Eighteen controls matched by age, gender and handedness were also scanned and evaluated with the RAVLT. We studied the functional connectivity along the (anterior/posterior) long axis hippocampal subregions and resting-state functionally-defined brain networks involved in learning [executive (EXE), dorsal attention (DAN) and default-mode (DMN) networks]. Functional connectivity differences between the two groups of patients (learning intact or with learning decline) and controls were investigated with MANOVA and discriminant analysis.ResultsThere were significant differences in the pattern of hippocampal connectivity among the groups. Regarding the anterior connectivity hippocampal pattern, our data showed an increase of connectivity in the pathological side with the DAN (p = 0.011) and the EXE (p = 0.008) when comparing learning-decline vs. learning-intact patients. Moreover, the non-pathological side showed an increase in the anterior connectivity pattern with the DAN (p = 0.027) between learning-decline vs. learning-intact patients. In contrast, the posterior hippocampus showed a reduction of connectivity in the learning-decline patients with the DMN, both in the pathological (p = 0.004) and the non-pathological sides (p = 0.036). Finally, the discriminant analysis based on the pre-operative connectivity pattern significantly differentiated the learning-decline patients from the other groups (p = 0.019).ConclusionOur findings reveal bilateral connectivity disruptions along the longitudinal axis of the hippocampi with resting-state networks, which could be key to identify those patients at risk of verbal learning decline after epilepsy surgery.

Sex differences in the acute effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC).

Cannabis is the most common illicit drug used in the USA and its use has been rising over the past decade, while the historical gap in rates of use between men and women has been decreasing. Sex differences in the effects of cannabinoids have been reported in animal models, but human studies are sparse and inconsistent. We investigated the sex differences in the acute subjective, psychotomimetic, cognitive, and physiological effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis. Healthy male and female individuals, with limited exposure to cannabis, participated in a double blind, placebo-controlled study of intravenous (IV) placebo or THC at two doses (0.015mg/kg and 0.03mg/kg). Visual analog scale (VAS) was used to measure subjective effects, Psychotomimetic States Inventory (PSI) and the Clinician-Administered Dissociative Symptoms Scale (CADSS) were used to assess the psychotomimetic effects and perceptual alterations, respectively, and Rey Auditory Verbal Learning Task (RAVLT) was used to evaluate cognitive effects. Outcome variables were represented as the peak change from baseline for each variable, except RAVLT which was used only once per the test day after the subjective effects. A total of 42 individuals participated in this study. There were no significant differences between male and female participants in background characteristics. There was a significant main effect of sex on the VAS scores for THC-induced "High" (F1,38 = 4.27, p < 0.05) and a significant dose × sex interaction (F2,77 = 3.38, p < 0.05) with female participants having greater "High" scores than male participants at the lower THC dose (0.015mg/kg). No other sex differences were observed in acute subjective, psychotomimetic, cognitive, or physiological effects of THC. There were significant sex differences in subjective effects of feeling "High" at a lower dose of THC. However, there were no other sex-related differences in the subjective, physiological, or cognitive effects of THC.

Life span strategy implementation in verbal learning: size and type of cluster adoption

ABSTRACT Temporal and semantic associative processes during the acquisition of new verbal information undergo various changes across the life span. Temporal order clusters and subjective clusters were monitored during verbal learning trials using the Rey (Auditory Verbal Learning Task) for 1471 participants aged 8–91. Pairs, three-word, and four-word clusters were measured. Subjective clusters were generated at similar frequency across the whole life span. By contrast, a clear inverted-U curve across life span was indicated for temporal clusters. More words were subjectively clustered than clustered by temporal presentation order. The number of words clustered increased across trials, and cluster types showed a different increase profile across trials. The subjective cluster increment was faster and steeper than the temporal cluster increment in most of the age segments. Life span trajectory tendencies in the formation of temporal and semantic associations in recall were interpreted in relation to different frameworks of cognitive life span changes.

Initiation of Moderately Frequent Cannabis use in Adolescence and Young Adulthood is Associated with Declines in Verbal Learning and Memory: A Longitudinal Comparison of Pre- versus Post-Initiation Cognitive Performance.

Cannabis use is associated with relative cognitive weaknesses as observed by cross-sectional as well as longitudinal research. Longitudinal studies, controlling for relevant confounds, are necessary to differentiate premorbid from post-initiation contributions to these effects. We followed a sample of adolescents and young adults across ten years. Participants provided neurocognitive data and substance use information at two-year intervals. Participants who initiated cannabis and/or alcohol use were identified (n = 86) and split into alcohol-only initiators (n = 39) and infrequent (n = 29) and moderately frequent (n = 18) cannabis initiators. Participants completed the Rey Auditory Verbal Learning Task (RAVLT) and the Iowa Gambling Task (IGT). Group differences before and after substance use initiation and the extent to which alcohol, nicotine, and cannabis use frequencies contributed to cognitive functions over time were examined. After controlling for parental education, RAVLT new learning was worse in moderately frequent cannabis users prior to use initiation. RAVLT total learning and delayed recall showed significant declines from pre- to post-initiation in moderately frequent cannabis users. Regression analyses confirmed that frequencies of cannabis, but not alcohol, use contributed to post-initiation variations. Nicotine use showed an independent negative association with delayed memory. Findings for the IGT were not significant. Verbal learning and memory may be disrupted following the initiation of moderately frequent cannabis use while decreased new learning may represent a premorbid liability. Our use of a control group of alcohol-only users adds interpretive clarity to the findings and suggests that future studies should carefully control for comorbid substance use.

From Learning to Memory: A Comparison Between Verbal and Non-verbal Skills in 22q11.2 Deletion Syndrome.

Background: Previous studies on possible memory deficits in 22q11DS often focused on quantifying the information memorized, whereas learning processes have been mostly overlooked. Furthermore, methodological differences in task design have made verbal and non-verbal comparison challenging and mixed results have been observed depending on chosen stimuli.Method: 135 participants (78 with 22q11DS) completed a multi-trial memory task modeled after the Rey Auditory Verbal Learning Task, comparing verbal and non-verbal learning as well as retention over time. Performance in the 22q11DS group were compared to controls and learning curves were analyzed.Results: In 22q11DS, slower acquisition of non-verbal material and higher rates of errors in both verbal and non-verbal tasks was observed. After 30 min, free recall performance, when corrected for initial learning rate, was similar between 22q11DS and controls. Conversely, recognition performance was overall weaker for 22q11DS in both modalities (verbal and non-verbal).Conclusion: This study examined how information is acquired, retained in memory over time and how different recall modalities (free recall vs. recognition) could yield different performances. Clinical implications of the findings are discussed.

One Hour-Post-load Plasma Glucose ≥155 mg/dl in Healthy Glucose Normotolerant Subjects Is Associated With Subcortical Brain MRI Alterations and Impaired Cognition: A Pilot Study.

Background: Glucose alterations are associated with impaired cognition. The 1-h-post-load plasma glucose ≥155 mg/dl in non-diabetic subjects confers an increased risk of cardiovascular events and diabetes. This pilot study aimed to investigate whether the 1-h-post-load plasma glucose ≥155 mg/dl negatively affects the subcortical regions of the brain and the cognitive functions.Methods: We enrolled 32 non-diabetic subjects. Patients were divided into two groups based on 1-h- post-load plasma glucose value > or < 155 mg/dl: normal glucose tolerance (NGT) 1-h-high and NGT 1-h-low subjects. All subjects underwent 3 Tesla MRI and standard neuropsychological tests.Results: NGT 1-h-high subjects showed significantly lower values of both right (4.9 ± 0.9 vs. 5.1 ± 0.9 ml) and left (4.8 ± 1.1 vs. 5.1 ± 1.1 ml) hippocampal hemisphere volume, while right hemisphere hippocampal diffusivity was lower in the NGT 1-h-high group (10.0 ± 0.6 vs. 10.6 ± 0.5 10−4 mm2s−1). NGT 1-h-high subjects also showed a poorer memory performance. In particular, for both Rey Auditory Verbal Learning Task (RAVLT)—immediate-recall and Free and Cued Selective Reminding Test (FCSRT)—delayed total recall, we found lower cognitive test scores in the NGT-1 h-high group (26.5 ± 6.3 and 10.4 ± 0.3, respectively).Conclusions: One-hour-post-load hyperglycemia is associated with morpho-functional subcortical brain alterations and poor memory performance tests.

Elevated systolic blood pressure is associated with episodic memory decline in healthy aging

AbstractBackgroundElevated blood pressure (BP) is associated with poorer cognitive performance in ageing but not in the very old (Obisesan et al., 2008). Likewise, hypertension causes vascular dysregulation and eventually decreased blood flow in several regions including the hippocampus (Glodzik et al., 2019) and is associated with faster cognitive decline in Mild Cognitive Impairment (MCI) patients (Goldstein et al., 2013). However, the association between BP and memory performance remains controversial with studies finding different results (reviewed in Forte et al., 2020). Longitudinal examinations are also non‐conclusive. One study showed association between poorer memory performance and higher systolic BP (SBP) at baseline, but not at follow‐up examination (Waldstein et al., 2005); and a previous one found that elevated SBP predicted greater number of errors in a memory task over time (Glynn eta l., 1999). We aim to explore the association between baseline SBP and memory change in healthy aging.Method77 healthy elders (age range 65‐78) were selected from the Institute of Aging (Barcelona). Rey Auditory verbal learning Task (RAVLT) was administered at baseline and follow‐up examination (mean interval period was 4.15 years, SD=0.44). Partial correlations were conducted between SBP and percent of change in RAVLT total learning and delayed scores. Control variables included age at baseline, interval period between assessments, medication for hypertension (medicated versus unmedicated) and years of education. All individuals presented normal global cognitive function (Mini Mental state Examination ≥ 25) and RAVLT delayed scores ≥ 5, to exclude possible MCI cases.ResultA significant negative correlation was found between SBP at baseline and percent of change in delayed episodic memory (r=‐0.338, p=0.003, Bonferroni corrected p=0.021). Interestingly, no significant associations were found between SBP and cross‐sectional measures of delayed RAVLT.ConclusionElevated SBP was associated with increased decline in delayed verbal memory in healthy aging. Delayed episodic memory is a key factor for characterizing subjects at risk of dementia and therefore, targeting measures to maintain optimal levels of BP should be a priority for primary care medicine.

Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis

Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case–control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58–3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current work supports further evaluation of NMDAR autoantibodies as a possible prognostic biomarker and aetiological factor in a subset of people already meeting CHR criteria.

Self-awareness and underestimation of cognitive abilities in patients with adult temporal lobe epilepsy after surgical treatment

IntroductionSelf-awareness of cognitive, emotional, functional, and social performance is critical for compliance with treatment. However, few studies have investigated self-awareness and the associated effects on other cognitive variables in patients with temporal lobe epilepsy (TLE) after surgical treatment. AimThis study was designed to investigate the prevalence of impaired self-awareness (ISA) in patients with TLE who have undergone surgical treatment. Associated correlations with clinical variables (frequency of seizures before surgery, time elapsed since the epilepsy diagnosis, depression, and anxiety) and verbal and visual episodic memory function and differences between patients with right and left TLE were also investigated. MethodTwenty-three adults with TLE after surgical treatment were assessed with the Patient Competency Rating Scale (PCRS-R-BR), the Rey Auditory Verbal Learning Task (RAVLT), and the Modified Ruche Visuospatial Learning Test (RUCHE-M). Patients were considered to have memory dysfunction if delayed recall as assessed with the RUCHE-M or RAVLT was at or below the 25th percentile. Patients were considered to have ISA if PCRS-R-BR discrepancy scores were at or above the 75th percentile. Underestimated cognitive ability (UCA) was defined as a PCRS-R-BR discrepancy percentile score ≤25. Results were analyzed using frequency, Spearman correlation, regression analyses, and the Mann–Whitney test. ResultsFrequency analysis of the total sample indicated ISA in 39.13% of patients (n = 9), UCA in 39.13% of patients (n = 9), and impaired verbal and/or visual memory performance in 69.56% of patients (n = 16). Moderate positive correlations were found between the frequency of seizures before surgical treatment and relatives' reports, as well as between the duration of time that had elapsed since the epilepsy diagnosis and patient reports. Negative and moderate correlations were found between the frequency of seizures and the discrepancy score, as well as between depression and patient reports. No differences in PCRS-R-BR were found between patients with right vs. left TLE. No clinical variables significantly predicted self-report or self-awareness. ConclusionPatients with TLE exhibit various patterns of ISA and negative effects on cognitive function after surgical treatment. Emotional factors and relatives' reports must be considered when assessing these patients.

Degree of cognitive impairment does not signify early versus late mild cognitive impairment: confirmation based on Alzheimer’s disease polygenic risk

Degree of memory impairment is often used to infer early versus late amnestic mild cognitive impairment (aMCI). Previously, 318 Alzheimer's Disease Neuroimaging Initiative participants with aMCI—determined by a single memory test—were divided based on Rey Auditory Verbal Learning Task (AVLT) delayed recall: AVLT-impaired (n = 225) and AVLT-normal (n = 93). Equally consistent with differential progression or differential diagnosis, the AVLT-impaired group had more abnormal Alzheimer’s disease (AD) biomarkers, more neurodegeneration over time, and was more likely to develop AD. In the present study, higher AD polygenic risk scores were associated with increased odds of being AVLT-impaired (odds ratio 1.8, p < 0.001). Thus, impairment severity does not necessarily reflect early versus late aMCI because disease progression cannot alter polygenic risk. Presumed early MCI is likely a heterogeneous category that includes excess false-positives. The additional cognitive test improved diagnostic precision by reducing false positives. Impairment severity may reflect differences in underlying disease risk but cannot be used to infer early versus late MCI based on cross-sectional data alone.

Memory response and neuroimaging correlates of a novel cognitive rehabilitation program for memory problems in epilepsy: A pilot study.

Memory deficits are very common in epilepsy, but no standard of care exists to effectively manage them. We assessed effectiveness of cognitive rehabilitation (CR) on memory and neural plasticity in people with epilepsy (PWE) reporting memory impairments. Nine PWE completed 6 weekly sessions adapted from 2 generic CR programs enriched with information regarding epilepsy. Participants completed neuropsychological, mood, and quality of life (QOLIE-31) measures prior and after completion of CR; 5/9 participants also completed pre- and post-CR fMRI while performing a verbal paired associates learning task. FMRI data were analyzed using group spatial independent components analysis methods; paired t-tests compared spatial activations for pre-/post-CR. Improvements were seen in immediate recall in Rey Auditory Verbal Learning Task, QOLIE-31, and read word recognition in paired associates task (all p's≤0.05). FMRI changes comparing pre-to-post CR were noted through increased activation in the left inferior frontal gyrus (IFG) and anterior cingulate and decreased activation in the left superior temporal gyrus; also noted were decreased activations in the default mode network (DMN), right cingulate, right middle temporal gyrus, right supramarginal gyrus, and increased DMN activation in the left cuneus. This study demonstrates feasibility of conducting CR program in PWE with fMRI as a mechanistic biomarker. Improvements in cognition and cortical plasticity await confirmation in larger samples.