Memory Test Performance Research Articles

Association between sub‐classified white matter hyperintensities (WMH) volume and and cognitive function in patients with Alzheimer`s disease

AbstractBackgroundWMH in MRI are common among the elderly. WMH are associated with increased cognitive impairment and risk of Alzheimer`s disease (AD). Although WMH contribute to AD pathology, their clinical implications are not fully understood. This study aimed to assess whether WMH predict AD and investigate the association between WMH (including subclassified WMH volume) and cognitive function in AD.MethodThis study enrolled 171 patients with AD. All participants underwent clinical evaluations including brain MRI study and neuropsychological tests using the CERAD‐K neuropsychological assessment battery. In addition, Charlson comorbidity index, the Korean version of the Geriatric Depression Scale short from were administered. WMH volume was calculated using automated quantification method with SPM and MATLAB image processing software. WMH were classified according to the distance from the ventricular surface. WMH located in juxtaventricular areas, within 3 mm from the ventricular surface, were classified as juxtaventricular with matter hyperintensities (JVWMH). WMH located within 3–13 mm or farther than 13 mm from the ventricular surface were classified as periventricular white matter hyperintensities (PVWMH) or deep white matter hyperintensities (DWMH), respectively. WMH volume data were right‐skewed. Consequently, WMH volume data were logarithmic transformed.ResultThe AD group had a higher mean WMH volume(20.7 ± 18.2 ml). Multivariate linear regression analysis showed that total WMH volume in AD was associated with poor performance in categorical verbal fluency test (p = 0.008) and word list memory test (p = 0.023). JVWMH volume in AD was associated with poor performance on categorical verbal fluency test (p = 0.013) and digit span test forward (p = 0.037). PVWMH volume in AD was associated with poor performance on categorical verbal fluency test (p = 0.011) and word list memory test (p = 0.021), whereas DWMH volume showed no association with cognitive dysfunction in AD.ConclusionTotal WMH, JVWMH and PVWMH were associated specifically with executive function, immediate memory, and working memory, independently of hippocampal atrophy in AD. WMH were associated with AD risk and cognitive dysfunction differentially according to the distance from the ventricular surface.

Empirically derived “discourse phenotypes” are associated with neuropsychological performance, cognitive status, and global atrophy: A latent profile analysis of connected speech measures

AbstractBackgroundEvidence suggests that “connected speech” (i.e., spoken language, as in discourse) is related to early cognitive decline and early Alzheimer’s disease and related dementias (ADRD), yet performance on speech tasks and cognitive performance in ADRD are notably heterogeneous. Here we examined whether unique spoken language phenotypes could be ascertained using latent profile analysis (LPA), and we examined the association of identified clusters to demographic, clinical and cognitive characteristics. In the subsets with amyloid PET and structural MR, we analyzed cluster associations with estimated amyloid DVR and/or global atrophy at or near the speech sample.Method1,039 participants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) completed comprehensive neuropsychological testing and provided a spoken language digital recording describing the Cookie Theft picture from the Boston Diagnostic Aphasia Examination. Cognitive status was determined by consensus conference. Five speech‐language metrics based on previous literature (Table 1) were automatically extracted from transcriptions of recordings utilizing Computerized Language Analysis (CLAN), including: semantic content, sentence length, speaking rate, and fluency. Baseline speech metric Z‐scores were included in the LPA; model fits were evaluated using BIC criteria. T‐tests, chi‐square tests, and ANCOVAs were used to the compare demographic, clinical, cognitive and imaging characteristics of the resulting discourse phenotypes (alpha = .05).ResultFit indices suggested a 3‐profile model: normal content‐normal fluency (n = 558), low content‐normal fluency (n = 224), and low content‐low fluency (n = 257) (Figure 1). The three phenotypes differed on gender and cognitive status, with more men and a higher proportion of MCI in the low content‐low fluency phenotype than the other groups; the phenotypes also differed on concurrent neuropsychological tests of language, memory and executive function. In the subset with imaging, the low content‐low fluency phenotype showed the most global atrophy. There were no differences in concurrent estimated amyloid accumulation (Table 2, Figure 2).ConclusionThree phenotypes of narrative discourse were identified and were associated with multiple neuropsychological tests, overall cognitive status and global brain atrophy. While connected speech metrics are generally viewed as a promising ADRD digital biomarker, the underlying taxonomy identified here suggests a more precision‐based approach is possible.

Childhood perceived financial status, current financial concerns, and late‐life cognition: Study of Healthy Aging in African Americans (STAR)

AbstractBackgroundLow socioeconomic status in childhood has been associated with worse late‐life cognition. However, few studies have examined the association between perceived childhood financial status on late‐life cognition in this population.Method764 participants of the Study of Healthy Aging in African Americans (STAR), a cohort of Black Americans aged 50+ (mean age 62) reported their childhood financial status (response options: pretty well off (henceforth above average), about average (henceforth average) varied, or poor) and frequency of current financial concerns (coded as always/often, sometimes, never). Baseline executive function, semantic memory, and verbal episodic memory were assessed through the Spanish and English Neuropsychological Assessment Scales. Linear regression models estimated the associations of childhood financial status and current financial concerns with domain‐specific scores adjusting for age, sex, and education. Sensitivity analyses concurrently included childhood financial status and current financial concerns.ResultAmong participants, 68% were female, 28% reported poor childhood financial status, and 12% reported “always” or “often” having current financial concerns (Table 1). Compared to individuals reporting above average childhood finances, sematic memory scores were lower among those reporting average (β = ‐0.16; 95% CI: ‐0.32, 0.001; Figure 2), varied (β = ‐0.34; 95% CI: ‐0.61, ‐0.07), or poor childhood financial status (β = ‐0.20; 95% CI: ‐0.37, ‐0.03). There were no differences in executive function scores or verbal episodic memory scores by childhood financial status (Figures 1 and 3). Frequency of current financial concern was not associated with executive function, semantic memory, nor verbal episodic memory scores (Figures 1‐3). The association between childhood financial status and semantic memory scores persisted when additionally adjusted for frequency of current financial concerns. There were no associations between childhood financial status and current financial concerns with executive function or verbal episodic memory scores.ConclusionChildhood financial status was associated with lower semantic memory test performance, even after accounting for current financial concerns. Future studies including direct measurement of brain health (e.g. brain imaging) are needed to better illuminate associations between childhood socioeconomic status with late‐life brain health.

Potential Reversal of Alzheimer’s Disease pathology by Antibody TB006 Targeting Galectin‐3, the Root Cause of Oligomerization of Amyloid Proteins

AbstractBackgroundAlzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder caused by multiple pathogenic factors including Amyloid‐β (Aβ), phospho‐Tau (pTau), alpha‐synuclein, and ApoE4, etc. It is widely accepted that intermediate oligomeric forms, rather than monomers or mature fibrils, are more neurotoxic. Galectin‐3 (Gal‐3) was reported to be involved in Aβ oligomerization. Here, we show that Gal‐3 promotes oligomerization of Aβ and other pathogenic factors, and TB006, a monoclonal antibody targeting Gal‐3, acts as a possible treatment for AD by degrading neurotoxic oligomers.MethodWe used two anti‐Gal‐3 antibodies, our clinical lead TB006 and a mouse cross‐reactive surrogate, mTB001, to establish the benefits of Gal‐3 neutralization in AD in vitro and in vivo. The effects of mTB001 were tested in three AD mouse models (two transgenic mouse models (APPSwe, 5xFAD) and an Aβ42‐injected mouse model). After two‐week treatment, a spatial memory function test was conducted, followed by biochemical and immunohistochemical characterizations.ResultAmyloid aggregation is a hallmark of several neurodegenerative diseases (AD, PD and ALS) affecting the brain or peripheral tissues, whose intermediates (oligomers, protofibrils) and final mature fibrils display different toxicity. In vitro, Gal‐3 intrinsically and selectively promotes, while mTB001 and TB006 degrade, oligomerization of only pathogenic proteins like Aβ42/40, α‐synuclein, pTau and ApoE4, but not of normal proteins like normal Tau and ApoE2/3. Gal‐3 enhanced, while mTB001 blocked, Aβ42‐induced microglia activation. Additionally, Aβ42 and Gal‐3 synergistically induced, while mTB001 reversed, neuronal death. In vivo, in three mouse models of AD, cognitive deficits were strongly attenuated after just two weeks of mTB001 treatment. Mechanistically, Gal‐3 antibody blocked the initiating events in AD (Aβ aggregates), reduced inflammation and rescued neuronal damage. Furthermore, microhemorrhages, a potential safety liability seen in clinical stage drugs, were reduced.ConclusionPre‐clinical studies show that TB006 is an efficacious therapeutic entity through degradation of toxic oligomers and blocking or even reversing AD progression. Clinically, TB006 has shown a superior safety profile without any drug‐related adverse events in a nearly finished healthy volunteer trial. Promising efficacious data are expected in Q2/2022 from the ongoing phase I/II AD trial.

Association of Subjective Cognitive Decline With Progression to Dementia in a Cognitively Unimpaired Multiracial Community Sample.

This prospective study seeks to examine the utility of subjective cognitive decline (SCD) as a marker of future progression to dementia in a community-based cohort of non-Latinx White, non-Latinx Black, and Latinx individuals. Debate surrounds the utility of SCD, the subjective perception of decline in one's cognition before such impairment is evident in traditional neuropsychological assessments, as an early indicator of impending Alzheimer disease. Unfortunately, most studies examining SCD have been conducted in non-Latinx White samples and commonly exclude groups of individuals shown to be most vulnerable to dementia. Participants were enrolled into this cohort study from the Washington Heights-Inwood Columbia Aging Project if they were cognitively unimpaired, had baseline measurement of SCD, and self-identified as non-Latinx White, non-Latinx Black, or Latinx. SCD was measured as a continuous sum of 10 items assessing cognitive complaints. Competing risk models tested the main effects of baseline SCD on progression to dementia. Models were adjusted for age, sex/gender, years of education, medical comorbidity burden, enrollment cohort, and baseline memory test performance with death jointly modelled as a function of race/ethnicity. A total of 4,043 (1,063 non-Latinx White, 1,267 non-Latinx Black, and 1,713 Latinx) participants were selected for this study with a mean age of 75 years, 67% women, and with a mean follow-up of 5 years. Higher baseline SCD was associated with increased rates of incident dementia over time in the full sample (hazard ratio [HR] 1.085, CI 1.047-1.125, p < 0.001) and within Latinx (HR 1.084, CI 1.039-1.130, p < 0.001) and non-Latinx Black individuals (HR 1.099, CI 1.012-1.194, p = 0.024). Overall results of this study support SCD as a prodromal marker of dementia in a multiracial community sample, and in Latinx and non-Latinx Black individuals in particular. Because models examining the risk of dementia were adjusted for baseline memory test performance, the results support the idea that SCD, a subjective reflection of one's own current cognitive functioning, contributes information above and beyond standard memory testing. Current findings highlight the importance of carefully evaluating any memory concerns raised by older adults during routine visits and underscore the potential utility of screening older adults for SCD.

Monitoring cognitive and psychological alterations in COVID-19 patients: A longitudinal neuropsychological study

BackgroundSARS-COV-2 infection has been associated to long-lasting neuropsychiatric sequelae, including cognitive deficits, that persist after one year. However, longitudinal monitoring has been scarcely performed. Here, in a sample of COVID-19 patients, we monitor cognitive, psychological and quality of life-related profiles up to 22 months from resolution of respiratory disease. MethodsOut of 657 COVID-19 patients screened at Manzoni Hospital (Lecco, Italy), 22 underwent neuropsychological testing because of subjective cognitive disturbances at 6 months, 16 months, and 22 months. Tests of memory, attention, and executive functions were administered, along with questionnaires for depressive and Post-traumatic stress disorder (PTSD) symptoms, psychological well-being and quality of life. Cross-sectional descriptives, correlational, as well as longitudinal analyses considering COVID19-severity were carried out. A preliminary comparison with a sample of obstructive sleep apneas patients was also performed. ResultsAround 50% of COVID-19 patients presented with cognitive deficits at t0. The most affected domain was verbal memory. Pathological scores diminished over time, but a high rate of borderline scores was still observable. Longitudinal analyses highlighted improvements in verbal and non-verbal long term memory, as well as attention, and executive functioning. Depression and PTSD-related symptoms were present in 30% of patients. The latter decreased over time and were associated to attentional-executive performance. ConclusionsCognitive dysfunctions in COVID-19 patients may extend over 1 year, yet showing a significant recovery in several cases. Cognitive alterations are accompanied by a significant psychological distress. Many patients displaying borderline scores, especially those at higher risk of dementia, deserve clinical monitoring.

Cognitive Performance following Single- or Multi-Session Exercise Intervention in Middle Age: A Systematic Review

ABSTRACT Background Research in modifiable behaviors, like exercise, on risk for dementia is increasing. Although many studies focus on older adults, brain pathology for Alzheimer’s Disease can begin in middle age, suggesting an ideal target for intervention. Methods We conducted a systematic review from exercise intervention studies on cognitive function among healthy, middle-aged participants (45-65). We searched multiple databases (PubMed, PsycINFO, MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar) for studies using standard, validated, neuropsychological measures following either single- or multi-session interventions in cognitively-unimpaired, middle-aged adults. Results We identified 13 eligible studies. There was notable heterogeneity across studies, with varying design, measures, interventions, and results. Results from single-session studies showed improvement in response inhibition, while results for cognitive flexibility were mixed. No significant changes were found on measures of attention, working memory, or processing speed. Results from multi-session studies were more varied. Verbal memory was found to improve while performance on tests of attention and working memory, processing speed, and executive function were mixed. Conclusion Importantly, for both single-session and multi-session studies, there was no standard set of neuropsychological tests administered, making it more difficult to synthesize the findings into a single narrative. We end with a discussion on future directions and implementation.

Cognition, Symptomatology, and Community Living Skills in Schizophrenia

Background: Independence in community living is an important aspect of rehabilitation in schizophrenia. Previous studies investigating relationships of coginitive, symptomatic, and demographic factors in community living ability of schizophrenia showed inconsistent findings. These findings may be due to variations in functional measures used or a heterogenous sample of participants recruited. Aim: To investigate the relationships of cognitive, symptomatic and demographic factors with community living skills for people with schizophrenia living in supported living facilities. Method: This is a cross-sectional study. Thirty-seven adults with schizophrenia and 32 matched healthy controls were recruited. Both groups completed the Verbal Fluency Test, subtests of Cognistat, and the Color Trail Test. Additional assessments (i.e., Chinese version of St. Louis Inventory of Community Living Skills – SLICLS-C and Positive and Negative Syndrome Scale – PANSS) were used to evaluate participants with schizophrenia. Cognitive profile was compared between the two groups. Correlation analysis was used to explore the relationships of cognitive abilities, symptomatology, and demographic factors with community living skills in schizophrenia. Results: Results showed that participants with schizophrenia performed worse than the control group in verbal fluency, visual memory, immediate memory, delayed memory, and executive function tests. Significant moderate correlations between SLICLS-C score and participants’ years of education, positive symptoms, general psychopathology, and PANSS total score were identified. Discussions and conclusion: Results indicated cognitive impairments are persistent in schizophrenia who are in remission and have been partially integrated back into the community. Cognitive deficits that people with schizophrenia experience might be stable over most of the course of the illness. Participants’ years of education, positive symptoms, general psychopathology, and PANSS total score might be important moderating variables to include in future investigations related to predicting community living performance in schizophrenia.

Association between Sedentary Behavior and Cognitive Performance in Middle-Aged and Elderly Adults: Cross-Sectional Results from ELSA-Brasil.

This study aimed to verify the association between Sedentary Behavior (SB) and performance on cognitive function tests in middle-aged and elderly adults. This cross-sectional study included 6505 participants (55.2% women) of ELSA-Brasil, with a median age of 61 years. The different types of SB considered were sitting time and screen time. The scores obtained in the memory, language, and executive function tests were used to assess cognitive performance (CP). The association between SB and CP was assessed using linear regression. For men, sitting time was associated with better performance in memory, language, and executive function tests. Screen time on the weekend, showed a favorable association with performance in the executive function test. Occupational screen time on weekdays was positively associated with language test performance. For women, sitting time and occupational screen time were positively associated with performance on memory tests. SB was favorably associated with performance in language tests and executive function tests. SB seems to favor CP in this population without evident dementia and with a high level of education. The type of SB (mentally active or passive) and the schooling seem to be of particular interest for cognitive performance.

Novel Anti-Neuroinflammatory Properties of a Thiosemicarbazone-Pyridylhydrazone Copper(II) Complex.

Neuroinflammation has a major role in several brain disorders including Alzheimer’s disease (AD), yet at present there are no effective anti-neuroinflammatory therapeutics available. Copper(II) complexes of bis(thiosemicarbazones) (CuII(gtsm) and CuII(atsm)) have broad therapeutic actions in preclinical models of neurodegeneration, with CuII(atsm) demonstrating beneficial outcomes on neuroinflammatory markers in vitro and in vivo. These findings suggest that copper(II) complexes could be harnessed as a new approach to modulate immune function in neurodegenerative diseases. In this study, we examined the anti-neuroinflammatory action of several low-molecular-weight, charge-neutral and lipophilic copper(II) complexes. Our analysis revealed that one compound, a thiosemicarbazone–pyridylhydrazone copper(II) complex (CuL5), delivered copper into cells in vitro and increased the concentration of copper in the brain in vivo. In a primary murine microglia culture, CuL5 was shown to decrease secretion of pro-inflammatory cytokine macrophage chemoattractant protein 1 (MCP-1) and expression of tumor necrosis factor alpha (Tnf), increase expression of metallothionein (Mt1), and modulate expression of Alzheimer’s disease-associated risk genes, Trem2 and Cd33. CuL5 also improved the phagocytic function of microglia in vitro. In 5xFAD model AD mice, treatment with CuL5 led to an improved performance in a spatial working memory test, while, interestingly, increased accumulation of amyloid plaques in treated mice. These findings demonstrate that CuL5 can induce anti-neuroinflammatory effects in vitro and provide selective benefit in vivo. The outcomes provide further support for the development of copper-based compounds to modulate neuroinflammation in brain diseases.

Why do mothers never stop grieving for their deceased children? Enduring alterations of brain connectivity and function.

A child’s death is a profound loss for mothers and affects hundreds of thousands of women. Mothers report inconsolable and progressive grief that is distinct from depression and impacts daily emotions and functions. The brain mechanisms responsible for this relatively common and profound mental health problem are unclear, hampering its clinical recognition and care. In an initial exploration of this condition, we used resting state functional MRI (fMRI) scans to examine functional connectivity in key circuits, and task-based fMRI to examine brain network activity in grieving mothers in response to pictures of their deceased child and as well as recognizable deceased celebrities and unfamiliar individuals. We compared nine mothers who had lost an adult child and aged-matched control mothers with a living child of a similar age. Additionally, we collected diffusion imaging scans to probe structural connectivity and complemented the imaging studies with neuropsychological assessments. Increased functional activation in Ventral Attention/Salience Networks accompanied by a reduced activation in the medial prefrontal cortex in response to the deceased child’s picture robustly distinguished the grieving mothers from controls. Heightened resting-state functional connectivity between the paraventricular thalamic nucleus (PVT) and the amygdala distinguished the grieving mothers from the controls and correlated with subjective grief severity. Structurally, maternal grief and its severity were associated with alterations in corticolimbic white matter tracts. Finally, grieving mothers performed worse than controls on neuropsychological tests of learning, memory, and executive function, linked with grief severity. Reduced activation in cortical regions inhibiting emotions and changes in the PVT circuitry—a region involved in long-term emotional memories and decision making under conflict—distinguish grieving mothers from controls. Notably, the magnitude of neurobiological changes correlates with the subjective severity of grief. Together, these new discoveries delineate a prevalent and under-recognized mental health syndrome and chart a path for its appreciation and care.

Plasma Serotonin 2A Receptor Autoantibodies Predict Rapid, Substantial Decline in Neurocognitive Performance in Older Adult Veterans with TBI.

Traumatic brain injury (TBI) was associated with increased plasma serotonin 2A receptor (5-HT2AR) autoantibodies in adults who experienced neurodegenerative complications. We tested whether the baseline presence of plasma serotonin 2A receptor (5-HT2AR) autoantibodies was a significant predictor of the two-year rate of cognitive decline in middle-aged and older adult TBI. Plasma from thirty-five middle-aged and older adult veterans (mean 65 years old) who had suffered traumatic brain injury was subjected to protein-A affinity chromatography. One-fortieth dilution of the resulting immunoglobulin (Ig) G fraction was tested for binding (in ELISA) to a linear synthetic peptide corresponding to the second extracellular loop region of the human 5-HT2A receptor. All available patients completed baseline and two-year follow-up neurocognitive tests of memory (St Louis University Mental Status), processing speed (Digit Symbol Substitution Test) and executive function (Trails-making Test, Part B). Change in cognitive performance was computed as (two-year - baseline) raw test score. Eighteen patients completed both baseline and two-year follow up neurocognitive tests. TBI patients harboring plasma 5-HT2AR autoantibodies at the baseline examination (n=13) did not differ significantly in their baseline clinical characteristics (age, education level) compared to TBI patients lacking baseline plasma autoantibodies (n=5). Plasma serotonin 2AR antibody-positive patients experienced a significantly greater post-baseline decline in performance on the St Louis University Mental Status test (P=0.0118) and in the Digit Symbol Substitution Test (P=0.011), but not in Trails-making Part B (P=0.129) compared to serotonin 2AR antibody-negative patients. In multivariable linear regression analyses that adjusted for age, baseline presence of plasma 5-HT2AR autoantibody was a significant predictor of the two-year rate of decline in memory, and processing speed. Binding of plasma autoantibody to the serotonin 2A receptor peptide in the enzyme linked immunosorbent assay was also significantly higher (at 1/160th titer of the protein-A eluate= 1 μg/mL IgG) in TBI patients harboring vs. those not harboring baseline plasma 5-HT2AR autoantibodies. These data suggest that plasma 5-hydroxytryptamine 2A receptor autoantibodies which were increased in approximately two-thirds of middle-aged and older adults following traumatic brain injury predicts rapid and substantial declines in cognitive function (memory and processing speed), independent of age.

Cognitive function in non-hospitalized patients 8-13 months after acute COVID-19 infection: A cohort study in Norway.

Studies have reported reduced cognitive function following COVID-19 illness, mostly from hospital settings with short follow-up times. This study recruited non-hospitalized COVID-19 patients from a general population to study prevalence of late cognitive impairment and associations with initial symptoms. We invited patients with PCR-confirmed COVID-19. A postal questionnaire addressed basic demographics, initial COVID-19 symptoms and co-morbidity about 4 months after diagnosis. About 7 months later, we conducted cognitive tests using the Cambridge Neuropsychological Test Automated Battery, comprising four tests for short-term memory, attention and executive function. We present descriptive statistics using z-scores relative to UK population norms and defined impairment as z-score <-1.5. We used multivariable logistic regression with impairment as outcome. Continuous domain scores were analysed by multiple linear regression. Of the initial 458 participants; 305 were invited, and 234 (77%) completed cognitive testing. At median 11 (range 8-13) months after PCR positivity, cognitive scores for short term memory, visuospatial processing, learning and attention were lower than norms (p≤0.001). In each domain, 4-14% were cognitively impaired; 68/232 (29%) were impaired in ≥ 1 of 4 tests. There was no association between initial symptom severity and impairment. Multivariable linear regression showed association between spatial working memory and initial symptom load (6-9 symptoms vs. 0-5, coef. 4.26, 95% CI: 0.65; 7.86). No other dimension scores were associated with symptom load. At median 11 months after out-of-hospital SARS-Cov-2 infection, minor cognitive impairment was seen with little association between COVID-19 symptom severity and outcome.

A-202 Cognitive Predictors of Verbal Memory Test Performance in an Outpatient Clinical Sample

Abstract Objective: Investigate the influence of non-memory cognitive abilities on auditory-verbal memory test performance in a clinical sample. Method: Archival data were analyzed for 129 patients [53.5% female; mean (SD): age = 46.48 (13.95), education = 13.82 (2.75)] who completed neuropsychological evaluation at a neurology/neuropsychology clinic. Five separate hierarchical regression analyses were conducted with these dependent variables: the California Verbal Learning Test-II (CVLT-II) Total Recall, Short-Delay Free Recall, and Long-Delay Free Recall, Logical Memory (LM) I and II subtests of the Wechsler Memory Scale, 4th edition (WMS-IV); independent variables were the same for each analysis and included neuropsychological tests of attention/working memory, visual-spatial/construction, language, and executive functions. Results: Delis-Kaplan Executive Function System Trails Switching accounted for 31-39% of the variance in the Total and Free Recall trials of the CVLT-II (p &amp;lt; .001). Wechsler Adult Intelligence Scale, Fourth Edition Vocabulary subtest accounted for 28 and 29% of the variance in LM I and LM II (p &amp;lt; .001). Conclusions: While language ability accounts for most of the variance in narrative verbal memory test performance, executive functions related to set shifting and processing speed account for most of the variance in word list learning. When interpreting below average scores on these verbal memory tests, it is important to consider the differential impact of non-memory cognitive abilities related to the memory test format.

A-201 Attention Span, Verbal Memory, and Spatial Memory as Variables in Neuropsychological Test Performance

Abstract Objective: We investigated (a) the role of attention span, verbal, and spatial memory in performance on widely used neuropsychological tests, and; (b) the impact of anxiety and depression on tests of attention span and verbal and spatial memory. Participants and Method: 579 referrals to memory disorders clinic, 60% women, 84% white non-Hispanic, average age 59.8±15.7 and education 14.9±2.9 years. Referred to help diagnose symptoms of forgetfulness, distractibility, and/or word finding difficulties. Used comprehensive battery (HRNES-R) and protocols were screened for performance invalidity. Results: Ten measures of attention and memory were factor analyzed (PCA/Varimax) yielding three factors: Spatial Recall (SR), Verbal Recall (VR), and Attention Span (AS). Age, not education, was related to AS (-.34) and SR (-.32), ps&amp;lt;.001, but not to VR. AS and SR were respectively predictive of performance on Category Test (rs=.37,.41), Trails B (.32,.48), TPT-Total Time (.35,.53), Coding (.31,.29), Block Design (.31,.37) and the Average Impairment Scale (AIS) (.45,.68), all ps&amp;lt;.001. In contrast, VR was less predictive across all measures. Levels of anxiety (MMPI-2 ANX) and depression (DEP) were not predictive of AS (-.01,.00), SR (.02,.02), or VR (.03,.02), n.s. Conclusions: After controlling for “incomplete effort”, attention span and spatial memory play a significant role in performance on widely used neuropsychological tests that tap multiple cognitive domains. The role of verbal memory in performance on these tests, while statistically significant, was less predictive. In general, findings suggest that when protocols are screened for performance invalidity, MMPI-2 levels of anxiety and depression have no relation to attention span or verbal/spatial memory test performance.

Associations between red blood cell indices and iron status and neurocognitive function in young adults: Evidence from memory and executive function tests and event-related potentials.

Cognitive impairment has been associated with anemia and iron deficiency; however, brain electrophysiological studies correlating red blood cell (RBC) indices and iron status to cognition in adulthood are scarce. We aimed to assess neurocognitive function in young adults of the general population and its correlation with RBC indices and iron status. Neurocognitive function was investigated using scalp-recorded event-related potentials (ERPs) within the context of a task-switching paradigm. ERPs and test performance were also compared across groups of "high"/"low" RBC and iron indices. Working memory was examined using the digit span test, in which mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), and ferritin were found to be significant predictors of test performance, with higher MCH/MCV/ferritin being associated with better test scores. In the switching task, MCH, MCV, and ferritin were found to be significant predictors of task performance, with higher MCH/MCV/ferritin levels associated with a lower percentage of errors. Electrophysiological results showed that MCH and MCV were significant predictors of ERPs amplitude, with lower MCH/MCV levels associated with greater amplitude, which may reflect compensatory processes. P1, N1, P2, and P3 were greater for the low MCH/MCV groups. This is the first evidence of association between levels of MCH/MCV and brain function while engaged in an executive function task; possibly reflecting brain iron availability.

The Cognitive Profile of Atypical Parkinsonism: A Meta-Analysis.

Atypical Parkinsonism (AP) syndromes are characterized by a wide spectrum of non-motor symptoms including prominent attentional and executive deficits. However, the cognitive profile of AP and its differences and similarities with that of Parkinson's Disease (PD) are still a matter of debate. The present meta-analysis aimed at identifying patterns of cognitive impairment in AP by comparing global cognitive functioning, memory, executive functions, visuospatial abilities, language, non-verbal reasoning, and processing speed test performances of patients with AP relative to healthy controls and patients with PD. All investigated cognitive domains showed a substantial impairment in patients with AP compared to healthy controls. When AP syndromes were considered separately, their cognitive functioning was distributed along a continuum from Multiple Systemic Atrophy at one extreme, with the least impaired cognitive profile (similar to that observed in PD) to Progressive Supranuclear Palsy, with the greatest decline in global cognitive and executive functioning (similar to Corticobasal Syndrome). These findings indicate that widespread cognitive impairment could represent an important clinical indicator to distinguish AP from other movement disorders.

Hippocampal intracerebral evoked potentials as a marker of its functionality in drug-resistant epilepsy

ObjectivesTo assess hippocampal function during stereoelectroencephalography (SEEG) investigations through the study of the medial temporal lobe event-related potential (ERP) MTL-P300. MethodsWe recorded the MTL-P300 during a visual oddball task, using hippocampal electrodes implanted for SEEG in 71 patients, in a preoperative epilepsy investigation. The presence of an MTL-P300 and its amplitude were correlated with hippocampal involvement during seizures and memory function. ResultsAnalysis using ROC curves revealed that an MTL-P300 amplitude below -46 µV, has a specificity of 93.3% in detecting the epileptogenic zone, and absence of the MTL-P300 in the left hippocampus of patients with typical language organization was associated with marked alteration of verbal memory scores. There was a significant correlation between performance in non-verbal memory tests and the amplitude of the MTL-P300 in the right hippocampus of patients with left hemispheric seizures (immediate visual recall: r = 0.67, p = 0.005; delayed visual recall: r = 0.56, p = 0.025). Using a linear regression, we confirmed that the absence of the MTL-P300 in the left hippocampus, the involvement of the left hippocampus during seizures, and the duration of epilepsy were predictors of verbal memory deficits. ConclusionAnalysis of the MTL-P300 during SEEG recording provides relevant information for the analysis of hippocampal functionality and can help to localize the epileptogenic zone.

The Metabolic Syndrome Is Associated With Lower Cognitive Performance and Reduced White Matter Integrity in Midlife: The CARDIA Study.

BackgroundCardiovascular disease risk factors play a critical role in brain aging. The metabolic syndrome (MetS), a constellation of cardiovascular risk factors, has been associated with poorer cognition in old age; however, it is unclear if it is connected to brain health earlier in life.MethodsWe investigated the association of MetS (n = 534, 18.5%) vs. no MetS (n = 2,346, 81.5%) with cognition in midlife within the prospective study, Coronary Artery Risk Development in Young Adults (CARDIA). At midlife (mean age 50), MetS was defined using National Cholesterol Education Program guidelines. At the 5-year follow-up, a cognitive battery was administered including tests of processing speed (Digit Symbol Substitution Test, DSST), executive function (the Stroop Test), verbal memory (Rey Auditory Verbal Learning Test, RAVLT), verbal fluency (category and letter fluency), and global cognitive function (Montreal Cognitive Assessment, MoCA). A sub-sample (n = 453) underwent brain MRI.ResultsParticipants with MetS had worse performance on tests of verbal fluency, processing speed, executive function, and verbal memory (p < 0.05), but not on global cognition. MetS was also associated with lower frontal, parietal, temporal, and total white matter integrity (p < 0.05), as assessed with fractional anisotropy.ConclusionsMetS is associated with lower cognition and microstructural brain alterations already at midlife, suggesting that MetS should be targeted earlier in life in order to prevent adverse brain and cognitive outcomes.

Mesial-Temporal Epileptic Ripples Correlate With Verbal Memory Impairment

RationaleHigh frequency oscillations (HFO; ripples = 80–200, fast ripples 200–500 Hz) are promising epileptic biomarkers in patients with epilepsy. However, especially in temporal epilepsies differentiation of epileptic and physiological HFO activity still remains a challenge. Physiological sleep-spindle-ripple formations are known to play a role in slow-wave-sleep memory consolidation. This study aimed to find out if higher rates of mesial-temporal spindle-ripples correlate with good memory performance in epilepsy patients and if surgical removal of spindle-ripple-generating brain tissue correlates with a decline in memory performance. In contrast, we hypothesized that higher rates of overall ripples or ripples associated with interictal epileptic spikes correlate with poor memory performance.MethodsPatients with epilepsy implanted with electrodes in mesial-temporal structures, neuropsychological memory testing and subsequent epilepsy surgery were included. Ripples and epileptic spikes were automatically detected in intracranial EEG and sleep-spindles in scalp EEG. The coupling of ripples to spindles was automatically analyzed. Mesial-temporal spindle-ripple rates in the speech-dominant-hemisphere (left in all patients) were correlated with verbal memory test results, whereas ripple rates in the non-speech-dominant hemisphere were correlated with non-verbal memory test performance, using Spearman correlation).ResultsIntracranial EEG and memory test results from 25 patients could be included. All ripple rates were significantly higher in seizure onset zone channels (p < 0.001). Patients with pre-surgical verbal memory impairment had significantly higher overall ripple rates in left mesial-temporal channels than patients with intact verbal memory (Mann–Whitney-U-Test: p = 0.039). Spearman correlations showed highly significant negative correlations of the pre-surgical verbal memory performance with left mesial-temporal spike associated ripples (rs = −0.458; p = 0.007) and overall ripples (rs = −0.475; p = 0.006). All three ripple types in right-sided mesial-temporal channels did not correlate with pre-surgical nonverbal memory. No correlation for the difference between post- and pre-surgical memory and pre-surgical spindle-ripple rates was seen in patients with left-sided temporal or mesial-temporal surgery.DiscussionThis study fails to establish a clear link between memory performance and spindle ripples. This highly suggests that spindle-ripples are only a small portion of physiological ripples contributing to memory performance. More importantly, this study indicates that spindle-ripples do not necessarily compromise the predictive value of ripples in patients with temporal epilepsy. The majority of ripples were clearly linked to areas with poor memory function.