Impairment of delayed recall as a predictor of amnestic mild cognitive impairment development in normal older adults: a 7-year of longitudinal cohort study in Shanghai.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is considered a prodromal phase of Alzheimer's disease (AD). However, little is known about the neuropsychological characteristic at pre-MCI stage. This study aimed to investigate which neuropsychological tests could significantly predict aMCI from a seven-year longitudinal cohort study. METHODS: The present study included 123 individuals with baseline cognitive normal (NC) diagnosis and a 7-year follow-up visit. All the subjects were from the China Longitudinal Aging Study (CLAS) study. Participants were divided into two groups, non-converter and converter based on whether progression to aMCI at follow-up. All participants underwent standardized comprehensive neuropsychological tests, including the mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), auditory verbal learning test (AVLT), the digital span test, the verbal fluency test, the visual recognition test, the WAIS picture completion task, and WAIS block design. Logistic regression analysis was used to evaluate the predictive power of baseline cognitive performance for the transformation of amnestic mild cognitive impairment. Receiver operating characteristic (ROC) curve was used to test the most sensitive test for distinguishing different groups. RESULTS: Between the non-converter group and converter group, there were significant differences in the baseline scores of AVLT-delayed recall (AVLT-DR) (8.70 ± 3.61 vs. 6.81 ± 2.96, p = 0.001) and WAIS block design (29.86 ± 7.07 vs. 26.53 ± 8.29, p = 0.041). After controlling for gender, age, and education level, converter group showed lower baseline AVLT-DR than non-converter group, while no significant difference was found in WAIS block design. Furthermore, converter group had lower AVLT-DR score after controlling for somatic disease. The area under the curve of regression equation model was 0.738 (95%CI:0.635-0.840), with a sensitivity 83.9%, specificity of 63.6%. CONCLUSIONS: Our results proved the value of delayed recall of AVLT in predicting conversion to aMCI. Early and careful checking of the cognitive function among older people should be emphasized.

Chinese version of the auditory verbal learning test: normative study and clinical applications in Chinese-speaking population in Shijiazhuang city.

OBJECTIVE: The purposes were to establish standardized values for the Auditory Verbal Learning Test (AVLT) in the communities of Shijiazhuang city (China), with particular focus on the influences of age, education and sex, and to detect the discriminant validity data of the AVLT in patients with acute ischemic stroke (AIS). METHODS: 406 Chinese-speaking subjects (age: 50-84 years old) from Shijiazhuang city, were brought into this study. Using linear regression analyses, standardized values were developed for three variables of interest, including scores on short-term memory (sum of AVLT trials 1-3), delayed recall (AVLT trial 4), and an index representing recognition memory corrected for false-positive identifications (AVLT trial 5). 177 patients with AIS were included to probe the discriminant validity of the AVLT. RESULTS: The linear regression analysis showed statistically significant effect of age and sex on all trials of the AVLT. Years of education contributed significantly to trial 1-3 and trial 4 but not trial 5. Based on the results obtained, trail 1-3 and trail 4 of AVLT norms were stratified by age (3 strata), education (2 strata), and sex (2 strata). Trail 5 norms were stratified by age (3 strata) and sex (2 strata). Moreover, AIS groups performed significantly worse on most AVLT trials than matched cognitively healthy controls. CONCLUSIONS: Normative data stratified by age, education and sex for the Chinese-speaking community-residents in Shijiazhuang was presented for use in research and clinical settings. The AVLT measures adequately differentiated between the cognitive performance (especially memory decline) of healthy adults and patients with AIS.

The effects of obstructive sleep apnea-hypopnea syndrome (OSAHS) on learn and memory function of 6-12 years old children.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep disorder causing cognitive impairments. AIMS: We use the auditory verbal learning test (AVLT), clock drawing test (CDT), Wechsler intelligence scale for children (WISC) and Montreal cognitive assessment (MoCA) to evaluate the memory and spatial impairments of OSHAS in 6-12 years old children patients with different severity. MATERIAL AND METHODS: A total of 137 children of snoring were enrolled following the inclusion criteria of this study. According to the apnea-hypopnea indices (AHI), they were divided into three groups. The AVLT, CDT, WISC and MoCA tests were executed by physicians. The self-rating depression scale (SDS) test was performed for depression screening. RESULTS: Compared with the children in the primary snoring group, the other two groups had higher body mass index (BMI), longer periods of snoring and older age. The AHI, oxygen desaturation index (ODI) and 90% oxygen saturation (TS90%) showed increasing trends whereas the lowest blood oxygen saturation (LSaO2) showed a decreasing trend. Besides, compared with the primary snoring group, the two groups had lower immediate recall scores in AVLT. CONCLUSION: AVLT had clinical values for evaluation of impaired memory function in OSAHS children, suggesting a correlation between cognitive impairments and nocturnal hypoxia.

Lateralized differences for verbal learning across trials in temporal lobe epilepsy are not affected by surgical intervention.

This research aimed to broaden understanding of learning verbal material in participants with left- and right-sided mesial temporal lobe epilepsy (MTLE). We modeled word list-learning to determine how anterior temporal lobe resection affects verbal learning. Verbal learning (across trials) was assessed using the first five trials of the Rey Auditory Verbal Learning Test (RAVLT) in 128 participants with MTLE. Mixedeffects modeling was used to determine whether learning curves differed between participants with left- and right-sided MTLE pre- and post- anterior temporal lobe resection. Laterality of MTLE had a significant effect on both the model intercept and the linear slope, whereby participants with left-sided MTLE retained fewer words on both the first trial and on each subsequent trial than participants with right-sided MTLE; and this held regardless of anterior temporal lobe resection status (t(117) = -3.516, p < .001; t(120.50) = -2.049, p = .042, for intercept and linear slope, respectively). There were no significant differences in the learning curves after anterior temporal lobe resection surgery in either left- or right-sided MTLE. Our findings suggest that acquisition of verbal information may be especially impaired in patients with left-sided MTLE. Further, we show that verbal learning across trials was not affected by surgical intervention. This finding contributes to the broader understanding of the impacts of anterior temporal lobe resection on verbal memory function, and has important implications for the clinical management and surgical planning for patients with temporal lobe epilepsy.

Tualang honey supplementation as cognitive enhancer in patients with schizophrenia.

INTRODUCTION: Schizophrenia is a chronic mental illness with clusters of symptoms, including cognitive impairment. This study aimed to explore the effect of Tualang Honey (TH) on cognitive domains, especially as it pertained to the verbal memory of schizophrenia patients. METHOD: This was a cross-sectional study involved 80 individuals, diagnosed with schizophrenia. The Malay Version Auditory Verbal Learning Test (MVAVLT) was used. Data were analysed using SPSS 20.0 software. Intention to treat analysis was applied. RESULT: A comparison of the total learning score at eight weeks between the two groups based on time effect and time-treatment interaction favoured TH group. CONCLUSION: This study concludes that by supplementing schizophrenia patients with 8-week of TH did improve total learning performance across domains in the immediate memory among patients with schizophrenia.

WHO-AVLT recognition trial: Initial validation for a new malingering index for Spanish-speaking patients.

Several methods for identifying suboptimal effort on Spanish neuropsychological assessment have been established. The purpose of this retrospective study was to determine whether recognition data from the WHO-AVLT could be employed for determination of malingering in a Spanish-speaking sample. Sixteen subjects in litigation, 25 neurological patients, and 14 healthy controls completed neuropsychological testing. All subjects completed the Test of Memory Malingering (TOMM). Inclusion criteria for neurological patients and controls included performance above the standard TOMM cutoff. Subjects in litigation were classified as probable malingering, through lower than cutoff performance on the TOMM and at least one other performance validity measure. Cut-off scores for classification of malingering were determined based on the number of recognition hits on the WHO-AVLT. The probable malingering group performed significantly worse than both groups on recognition hits. A score <10 was determined to be the optimal group cutoff, with 56.25% sensitivity and specificity greater than 92%. A combination score of 14 increased sensitivity to 68.75%. These findings provide initial validation of a new malingering index, based on the number of hits on the WHO-AVLT recognition trial. This index will provide valuable information to neuropsychologists conducting forensic or clinical evaluations on Spanish-speaking individuals.

Deep brain stimulation for dementias.

OBJECTIVE The aim of this article is to review the authors' and published experience with deep brain stimulation (DBS) therapy for the treatment of patients with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). METHODS Two targets are current topics of investigation in the treatment of AD and PDD, the fornix and the nucleus basalis of Meynert. The authors reviewed the current published clinical experience with attention to patient selection, biological rationale of therapy, anatomical targeting, and clinical results and adverse events. RESULTS A total of 7 clinical studies treating 57 AD patients and 7 PDD patients have been reported. Serious adverse events were reported in 6 (9%) patients; none resulted in death or disability. Most studies were case reports or Phase 1/2 investigations and were not designed to assess treatment efficacy. Isolated patient experiences demonstrating improved clinical response after DBS have been reported, but no significant or consistent cognitive benefits associated with DBS treatment could be identified across larger patient populations. CONCLUSIONS PDD and AD are complex clinical entities, with investigation of DBS intervention still in an early phase. Recently published studies demonstrate acceptable surgical safety. For future studies to have adequate power to detect meaningful clinical changes, further refinement is needed in patient selection, metrics of clinical response, and optimal stimulation parameters.

Laser ablation for mesial temporal epilepsy: a multi-site, single institutional series.

OBJECTIVEAlthough it is still early in its application, laser interstitial thermal therapy (LiTT) has increasingly been employed as a surgical option for patients with mesial temporal lobe epilepsy. This study aimed to describe mesial temporal lobe ablation volumes and seizure outcomes following LiTT across the Mayo Clinic's 3 epilepsy surgery centers.METHODSThis was a multi-site, single-institution, retrospective review of seizure outcomes and ablation volumes following LiTT for medically intractable mesial temporal lobe epilepsy between October 2011 and October 2015. Pre-ablation and post-ablation follow-up volumes of the hippocampus were measured using FreeSurfer, and the volume of ablated tissue was also measured on intraoperative MRI using a supervised spline-based edge detection algorithm. To determine seizure outcomes, results were compared between those patients who were seizure free and those who continued to experience seizures.RESULTSThere were 23 patients who underwent mesial temporal LiTT within the study period. Fifteen patients (65%) had left-sided procedures. The median follow-up was 34 months (range 12-70 months). The mean ablation volume was 6888 mm3. Median hippocampal ablation was 65%, with a median amygdala ablation of 43%. At last follow-up, 11 (48%) of these patients were seizure free. There was no correlation between ablation volume and seizure freedom (p = 0.69). There was also no correlation between percent ablation of the amygdala (p = 0.28) or hippocampus (p = 0.82) and seizure outcomes. Twelve patients underwent formal testing with computational visual fields. Visual field changes were seen in 67% of patients who underwent testing. Comparing the 5 patients with clinically noticeable visual field deficits to the rest of the cohort showed no significant difference in ablation volume between those patients with visual field deficits and those without (p = 0.94). There were 11 patients with follow-up neuropsychological testing. Within this group, verbal learning retention was 76% in the patients with left-sided procedures and 89% in those with right-sided procedures.CONCLUSIONSIn this study, there was no significant correlation between the ablation volume after LiTT and seizure outcomes. Visual field deficits were common in formally tested patients, much as in patients treated with open temporal lobectomy. Further studies are required to determine the role of amygdalohippocampal ablation.

Cognitive Plasticity in Young-Old Adults and Old-Old Adults and Its Relationship with Successful Aging.

The general objective of this study was to analyze cognitive plasticity as a variable related to successful aging in a group of young-old adults and old-old adults using the Auditory Verbal Learning Test-Learning Potential (AVLT-LP). METHOD: A total of 569 persons, with mean age 76.67 years (379 between the ages of 65 and 80 years, and 190 older than age 80). They were assessed with a socio-health questionnaire, with the AVLT-LP, and with the Spanish version of the Mini Mental State Examination. RESULTS: The results showed significant differences on the test, in favor of the younger group, while the over 80 group gave poorer performance and showed less cognitive plasticity. With relation to gender, slight differences appeared in favor of the women, on the first four test trials, but not on the last two, nor in delayed recall or cognitive plasticity. As for cognitive status, the results showed significantly better task performance levels in healthy elders, as well as greater plasticity. Nonetheless, certain persons with high plasticity were also found among those with cognitive impairment. CONCLUSIONS: The data obtained here offers evidence for the importance of cognitive plasticity in elders and its relation to longevity and successful aging. It also provides information about the influence of variables like age, gender and cognitive status on a verbal memory and plasticity assessment task that is in wide use today.

False-Positive Error Rates for Reliable Digit Span and Auditory Verbal Learning Test Performance Validity Measures in Amnestic Mild Cognitive Impairment and Early Alzheimer Disease.

OBJECTIVE: The objective is to examine failure on three embedded performance validity tests [Reliable Digit Span (RDS), Auditory Verbal Learning Test (AVLT) logistic regression, and AVLT recognition memory] in early Alzheimer disease (AD; n = 178), amnestic mild cognitive impairment (MCI; n = 365), and cognitively intact age-matched controls (n = 206). METHOD: Neuropsychological tests scores were obtained from subjects participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). RESULTS: RDS failure using a ≤7 RDS threshold was 60/178 (34%) for early AD, 52/365 (14%) for MCI, and 17/206 (8%) for controls. A ≤6 RDS criterion reduced this rate to 24/178 (13%) for early AD, 15/365 (4%) for MCI, and 7/206 (3%) for controls. AVLT logistic regression probability of ≥.76 yielded unacceptably high false-positive rates in both clinical groups [early AD = 149/178 (79%); MCI = 159/365 (44%)] but not cognitively intact controls (13/206, 6%). AVLT recognition criterion of ≤9/15 classified 125/178 (70%) of early AD, 155/365 (42%) of MCI, and 18/206 (9%) of control scores as invalid, which decreased to 66/178 (37%) for early AD, 46/365 (13%) for MCI, and 10/206 (5%) for controls when applying a ≤5/15 criterion. Despite high false-positive rates across individual measures and thresholds, combining RDS ≤ 6 and AVLT recognition ≤9/15 classified only 9/178 (5%) of early AD and 4/365 (1%) of MCI patients as invalid performers. CONCLUSIONS: Embedded validity cutoffs derived from mixed clinical groups produce unacceptably high false-positive rates in MCI and early AD. Combining embedded PVT indicators lowers the false-positive rate.

Verbal learning across the lifespan: an analysis of the components of the learning curve.

Previous studies on the acquisition process of verbal material, conducted separately on child and adult populations, reveal that the lifespan is characterized by an inverted-U performance curve with similar achievements at its two poles. To clarify the acquisition mechanism across the entire lifespan, the learning curve for the Rey Auditory Verbal Learning Test was reproduced for participants aged 8-91. The study utilized typical trial summary scores and a more refined analysis of trial-by-trial single-word recalls, including omissions (missed words that were previously recalled), additions (recalled words previously missed), and touched words (a count for the first recall time only, for each word during the five learning trial). A clear age effect was shown for the number of words recalled - symmetrically increases during childhood and decreases in adulthood. Similarly, increased turnover of words omitted and added characterized both incremental and decremental age differences. Measurement patterns differed for the age segments on the two sides of the lifespan, despite the similar total number of words recalled by the two sides. Acquisition pattern in children was characterized by a higher number of touched words and higher turnover than for adult groups. In contrast, older adults achieved fewer touched words and lower turnover than the child groups. This study shows that it is possible to reach the same quantitative results via different cognitive processes. The results are interpreted in terms of specific mechanisms of maturational characteristics.

Memory factors in Rey AVLT: Implications for early staging of cognitive decline.

Supraspan verbal list learning is widely used to assess dementia and related cognitive disorders where declarative memory deficits are a major clinical sign. While the overall learning rate is important for diagnosis, serial position patterns may give insight into more specific memory processes in patients with cognitive impairment. This study explored these patterns in a memory clinic clientele. One hundred eighty three participants took the Rey Auditory-Verbal Learning Test (RAVLT). The major groups were patients with Alzheimer's disease (AD), Vascular Dementia (VD), Mild Cognitive Impairment (MCI), and Subjective Cognitive Impairment (SCI) as well as healthy controls (HC). Raw scores for the five trials and five serial partitions were factor analysed. Three memory factors were found and interpreted as Primacy, Recency, and Resistance to Interference. AD and MCI patients had impaired scores in all factors. SCI patients were significantly impaired in the Resistance to Interference factor, and in the Recency factor at the first trial. The main conclusion is that serial position data from word list testing reflect specific memory capacities which vary with levels of cognitive impairment.

Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa monnieri has a long history in Ayurvedic medicine for neurological and behavioral defects. To assess its efficacy in improving cognitive function. MATERIALS AND METHODS: MEDLINE, EMBASE, CINAHL, AMED, Cochrane Central of clinical trial, WHO registry, Thai Medical Index, Index Medicus Siriraj library and www.clinicaltrial.gov were searched from the inception date of each database to June 2013 using scientific and common synonyms of Bacopa monnieri, cognitive performance or memory. The reference lists of retrieved articles were also reviewed. Randomized, placebo controlled human intervention trials on chronic ≥ 12 weeks dosing of standardized extracts of Bacopa monnieri without any co-medication were included in this study. The methodological quality of studies was assessed using Cochrane's risk of bias assessment and Jadad's quality scales. The weighted mean difference and 95% confidence interval (95% CI) were performed using the random-effects model of the Dersimonian-Laird method. RESULTS: Nine studies met the inclusion criteria using 518 subjects. Overall quality of all included trials was low risk of bias and quality of reported information was high. Meta-analysis of 437 eligible subjects showed improved cognition by shortened Trail B test (-17.9 ms; 95% CI -24.6 to -11.2; p<0.001) and decreased choice reaction time (10.6 ms; 95% CI -12.1 to -9.2; p<0.001). CONCLUSION: This meta-analysis suggests that Bacopa monnieri has the potential to improve cognition, particularly speed of attention but only a large well designed 'head-to-head' trial against an existing medication will provide definitive data on its efficacy on healthy or dementia patients using a standardized preparation.

Relationship between excitability, plasticity and thickness of the motor cortex in older adults.

The relationship between brain structure, cortical physiology, and learning ability in older adults is of particular interest in understanding mechanisms of age-related cognitive decline. Only a few studies addressed this issue so far, yielding mixed results. Here, we used comprehensive multiple regression analyses to investigate associations between brain structure on the one hand, i.e., cortical thickness (CT), fractional anisotropy (FA) of the pyramidal tract and individual coil-to-cortex distance, and cortical physiology on the other hand, i.e. motor cortex excitability and long-term potentiation (LTP)-like cortical plasticity, in healthy older adults (mean age 64 years, 14 women). Additional exploratory analyses assessed correlations between cortical physiology and learning ability in the verbal domain. In the regression models, we found that cortical excitability could be best predicted by CT of the hand knob of the primary motor cortex (CT-M1HAND) and individual coil-to-cortex distance, while LTP-like cortical plasticity was predicted by CT-M1HAND and FA of the pyramidal tract. Exploratory analyses revealed a significant inverse correlation between cortical excitability and learning ability. In conclusion, higher cortical excitability was associated with lower CT and lower learning ability in a cohort of healthy older adults, in line with previous reports of increased cortical excitability in patients with cortical atrophy and cognitive deficits due to Alzheimer's Disease. Cortical excitability may thus be a parameter to identify individuals at risk for cognitive decline and gray matter atrophy, a hypothesis to be explored in future longitudinal studies.

No effect of acute tryptophan depletion on verbal declarative memory in young persons with ADHD.

OBJECTIVE: Animal experiments and studies in adults have shown that the neurotransmitter serotonin (5-HT) plays an important role in learning and memory processes. However, data on this relationship in young persons are scarce, and neurodietary research in this age group is limited compared with the extensive literature on adults. Here, we aimed to explore the effects of a diminished central nervous 5-HT synthesis, which is achieved by acute tryptophan depletion (ATD) Moja-De , on memory function in young males with attention deficit hyperactivity disorder (ADHD). METHOD: Twenty-two male patients with ADHD (ages 9-15 years, mean 10.95 ± 1.17 years) received ATD, thus diminishing central nervous 5-HT synthesis, and a tryptophan-balanced amino acid load (BAL) in a randomized, double-blind, within-subject, crossover design study. Approximately 1.7 h after administration of ATD/BAL, verbal declarative memory was assessed using the 'Auditory Verbal-Learning-Test' (AVLT). RESULTS: There were no significant effects of ATD administration on verbal declarative memory function. CONCLUSION: In this study, changes in 5-HT neurotransmission were not associated with specific aspects of verbal declarative memory in young persons with ADHD. Future studies with healthy control groups that address effects of covarying attentional processes are warranted.