Recognition Discrimination Index Research Articles

87 Examining the use of the Embedded Performance Validity Test in the Brief Visuospatial Memory Test-Revised Among Spanish-Speaking Patients

Objective:The Brief Visuospatial Memory Test-Revised (BVMT-R) Recognition Discrimination (RD) index has emerged as an embedded performance validity test (PVT). However, there do not appear to be any studies that have examined its utility in Spanish-speaking samples. This pilot study examined the classification accuracy of the BVMT-R RD for detecting performance invalidity in a Spanish-speaking forensic sample.Participants and Methods:This cross-sectional study utilized a sample of 89 Spanish speakers that were administered the BVMT-R during an outpatient neuropsychological evaluation. Out of the 89 Spanish speakers, 43 were subjects in litigation, 32 were neurological patients evaluated for clinical purposes, and 14 were healthy controls. The sample was 67% male/33% female, 53% South American, 33% Caribbean (Dominican, Puerto Rican, Cuban), 10% Central American, 3% North American (Mexican), and 1% Spanish, with a mean age of 44.2 years (SD = 14.2; range = 20-78) and mean education of 11 years (SD = 3.7; range = 0-20). Test administration for each patient was completed in Spanish by a fluent, Spanish-speaking examiner. In total, 64/89 (72%) were classified as valid and 25/89 (28%) as invalid based on performance across the Test of Memory Malingering (TOMM), at least one additional PVT (Rey-15 item memory test; Rey Dot Counting Test; Reliable Digit Span; WHO-AVLT recognition trial) and objective diagnostic criteria identifying invalid performance. Analyses included three univariate analyses of variance (ANOVA), with the groups (healthy vs neurological vs litigation) as independent variables and performance on BVMT-RD as the dependent variable.Results:Statistically significant differences among the groups were found F(2,86)=8.32, p < .001). Post-hoc analysis (Scheffe test) showed the mean of the litigation group to be significantly lower than the means of the other two groups (healthy and neurological), which showed no difference between them. An ANOVA with validity groups as the fixed factor and BVMT-R RD index as the dependent variable was significant F(1,85)= 21.02, p <.001). Results of a ROC curve analysis yielded statistically significant AUC (.794). The optimal cut-score was BVMT-R RD < 5 (48% sensitivity/88% specificity).Conclusions:Results of the BVMT-R RD index in this Spanish-speaking population differed by subgroup, with worse performance seen in individuals involved in litigation, compared to those who were not (healthy and neurological). Notably, the BVMT-R RD index significantly differentiated validity groups, maintaining adequate sensitivity and good specificity. Overall, results demonstrate promise for BVMT-RD as a PVT for Spanish-speaking populations.

A - 184 Validity of the Infrequent Patterns of Performance Embedded Performance Validity Indicators in a Mixed Clinical Sample.

Novel performance validity tests (PVTs) for the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R), derived from infrequent patterns of performance (IPOP), were developed to examine invalid memory performance while reducing false positive misclassification. To examine their classification accuracy, these indicators were compared to several existing embedded PVTs in a mixed clinical sample. A chart review was completed for 75 adult outpatients (Mean Age = 52, Range = 19-85) referred to an academic medical center outpatient clinic for neuropsychological evaluation. Twenty-eight percent of the sample failed the Medical Symptom Validity Test (MSVT), which was used as the criterion to indicate invalid performance. Several established embedded validity indicators were calculated from HVLT-R and BVMT-R scores, including the recognition discrimination index (RDI) and percent retention (PR), as well as the Reliable Digit Span (RDS) validity indicator. Classification statistics, including sensitivity, specific, likelihood ratios, predictive values, and overall accuracy, were calculated and compared. The HVLT-R IPOP had a higher overall classification accuracy (72%) compared to the RDI indicator (68%) while maintaining excellent specificity (97%). The BVMT-R IPOP had identical classification accuracy (75%) compared to the RDI and PR indicators with very high specificity (96%). Both indicators were more accurate than RDS (72%). The HVLT-R and BVMT-R IPOP performance validity indicators produced adequate classification statistics when compared to existing embedded PVTs. Both indicators maintained excellent specificity, which is crucial in reducing false positive classification. Future research will focus on further examining the validity of these indicators in other clinical groups and known groups, including medico-legal populations.

Sleep-disordered breathing and neurocognitive function in multiple sclerosis: Differential associations across cognitive domains

Background: Sleep disorders are common in people with multiple sclerosis (PwMS) and could contribute to cognitive dysfunction. However, effects of pathological sleep on cognitive domains are insufficiently characterized. Objective: To evaluate associations between cognitive performance and polysomnographic (PSG)-based sleep disturbances in PwMS. Methods: PwMS with known/suspected untreated obstructive sleep apnea (OSA, N = 131) underwent PSG and cognitive tests: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test-II (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R Total and Delayed), Judgment of Line Orientation (JLO), Controlled Oral Word Association Test (COWAT), Trail Making Test, Go/No-Go, and Nine-Hole Peg Test (NHPT). Results: Apnea severity measures were associated with worse processing speed, attention, and working memory (SDMT); immediate and delayed visual memory (BVMT-R Total and Delayed); attention, psychomotor speed, and cognitive flexibility (Trails); and manual dexterity and visuomotor coordination (NHPT) (ps ⩽ 0.011). Sleep macrostructure measures showed stronger associations with verbal memory and response inhibition (CVLT-II Total Recognition Discriminability Index), and immediate visual memory (BVMT-R Total) (ps ⩽ 0.011). Conclusions: Pathological sleep, including hypoxia, sleep fragmentation, and disturbances in sleep/wake states, are differentially associated with worse cognitive performance in PwMS. These findings could inform future personalized approaches to cognitive impairment in PwMS with sleep disorders. Trial registration: ClinicalTrials.gov identifier: NCT02544373 (https://clinicaltrials.gov/ct2/show/NCT02544373).

Examining brain structural and functional changes in mTBI with biomarkers of neurodegeneration

AbstractBackgroundMild traumatic brain injury (mTBI) in former contact sports athletes is a risk factor for dementia. However, it is unknown why only some individuals with mTBI develop dementia, suggesting that head injury exposure alone is not sufficient to produce the condition. We hypothesize that mTBI could be associated with neurodegenerative processes that target specific brain structures and connectivity networks and increase vulnerability to dementia.Method46 male former professional athletes with a history of multiple concussions were recruited. To compare participants with evidence of underlying pathology versus participants without any evidence, the sample was divided into neurodegenerative biomarker positive (N+, n = 25) and negative (N‐, n = 21) groups. The division was based on the positivity in at least one of these biomarkers: cerebrospinal fluid total tau (> 300 pg/ml), cortical positron emission tomography tau standardized uptake value ratio (>1.30) and serum neurofilament light‐chain (> 12.5 pg/ml). Groups were matched for age and number of concussions. Cognitive profiles were assessed by comparing the following scores between groups: Trail Making Test ratio, Digit Span Backwards, Paced Auditory Serial Addition Test, verbal fluency, and Rey Auditory Verbal Learning Test (RAVLT). Grey matter volume was calculated by voxel‐based morphometry and compared between groups. Functional connectivity differences were evaluated for the default mode (DMN), the salience (SN) and the dorsal attention (DAN) networks.Results(N+) presented more number of intrusions at immediate (p = 0.04, FDR corrected) and short delay recall (p = 0.02, FDR corrected) and worse recognition discrimination index (p = 0.02, FDR corrected) in the RAVLT in comparison to (N‐). In addition, (N+) displayed more atrophy in the left frontal superior and middle gyrus (p < 0.001, extended threshold = 50 voxels) and disconnection of the DAN (p < 0.001, FWE cluster correction) versus (N‐). No significant differences were obtained for the DMN and SN.ConclusionFrontal atrophy and DAN abnormal connectivity may underlie cognitive deficits in the (N+) group. Biomarkers of neurodegeneration provide a sensitive tool to detect participants with structural and functional changes and may associate with higher risk to develop dementia after mTBI.

Source recognition discriminability impairment in Huntington’s versus Alzheimer’s disease: Evidence from the CVLT-3

Research suggests that individuals with Huntington’s disease (HD) perform better than individuals with Alzheimer’s disease (AD) on the California Verbal Learning Test (CVLT) Yes/No Recognition trial. However, those with HD have been shown to have deficits comparable to those with AD on the Source Recognition Discriminability (RD) index (which assesses the ability to distinguish between List A targets and List B distractors), suggesting that HD may involve selective impairment in aspects of yes/no recognition that rely on source memory. However, whether individuals with HD and AD show comparable deficits on Source RD across stages of dementia severity has not been adequately investigated. We examined performance on the CVLT-3 List A vs. List B RD index in individuals with HD or AD and mild or moderate dementia. Among individuals with mild dementia, scores were higher in the HD versus AD group, whereas among individuals with moderate dementia, scores were comparable between the HD and AD groups; this corresponded to differential performance across dementia stages among individuals with HD, but not AD. The present findings suggest that, relative to AD, HD may be associated with disproportionate decline in aspects of yes/no recognition that rely on source memory.

Examining independent and combined accuracy of embedded performance validity tests in the California Verbal Learning Test-II and Brief Visuospatial Memory Test-Revised for detecting invalid performance

The California Verbal Learning Test-Second Edition (CVLT-II) Forced Choice Recognition (FC) and Brief Visuospatial Memory Test-Revised (BVMT-R) Recognition Discrimination Index (RD) are embedded performance validity tests (PVTs) assessing material-specific neuropsychological processes (i.e., verbal and visual memory, respectively). Prior research demonstrated the utility of these PVTs independently; however, no study has compared their diagnostic accuracy for identifying invalid performance relative to each other and in combination within a single sample. This cross-sectional study included an adult neuropsychiatric sample who underwent neuropsychological evaluation. Validity groups were determined via independent criterion PVT performance, and consisted of 103 participants with valid and 25 with invalid neurocognitive performance. FC and RD were not significantly correlated (r = .154), yet both differed between validity groups (ηp 2 = .14–.19). Previously established FC (≤14) and RD (≤4) cutoffs evidenced 32–40% sensitivity/90–98% specificity, though receiver operating characteristic (ROC) analyses indicated a more liberal FC cutoff (≤15) was optimal. Logistic regression models utilizing both embedded PVTs indicated that FC did not significantly improve classification accuracy above and beyond RD. Results support the clinical utility of existing cutoffs for FC and RD for independently identifying invalid performance, though the latter showed relatively better ability to detect invalid performance when both are used together.

Normative performance of older individuals on the Hopkins Verbal Learning Test-Revised (HVLT-R) according to ethno-racial group, gender, age and education level

Objective The Hopkins Verbal Learning Test-Revised (HVLT-R) provides a measure of verbal learning and memory. The aim of this study was to provide normative performance data on the HVLT-R for community-dwelling older individuals according to ethno-racial group, age, gender, and years of completed education, in Australia and the U.S. Method The ASPirin in Reducing Events in the Elderly (ASPREE) study recruited 19,114 generally healthy community dwelling individuals aged 70 years and over (65 years and over for U.S minorities), who were without a diagnosis of dementia and scored above 77 on the modified Mini-Mental State (3MS) examination. Included in the analysis presented here were 16,251 white Australians, and in the U.S. 1,082 white, 894 African American and 314 Hispanic/Latino individuals at baseline. Results Performance on each of the components of the HVLT-R (trials 1–3, total, learning, delayed recall, delayed recognition, percentage retention and recognition discrimination index [RDI]) differed by demographic variables. In country and ethno-racial stratified analyses, female gender, younger age and higher education were significantly associated with better total recall, delayed recall and RDI. Among white Australians these characteristics were also associated with better retention. Age, education and gender-specific reference values across ethno-racial categories were determined. Conclusions Ethno-racial, age, gender and education-stratified normative data from this large cohort of community-dwelling older individuals will serve as important reference standards in Australia and the U.S. to assess cognition in older individuals.

The emergence of age-related changes in recognition memory in healthy middle-aged adults using the CVLT-II

ABSTRACT Although age-related memory differences between young and older adults have been well documented, fewer studies have investigated memory changes in middle age. We examined the performance of healthy middle-aged adults (40–55 years of age; n = 32) in relation to healthy young (18–25 years of age; n = 57) and older adults (65+ years of age; n = 55) on variations of recognition discriminability (RD) indices derived from the California Verbal Learning Test-Second Edition (CVLT-II). Middle-aged adults performed significantly worse (ps < .05) than young adults on multiple RD indices that incorporate semantically related distractor items, suggesting memory changes in middle age may be associated with increased susceptibility to semantic interference. Moreover, middle-aged adults performed comparably to older adults across all RD indices, indicating the recognition profile of middle-aged adults on RD indices more closely resembles that of older adults than young adults.

Revisiting total recognition discriminability in Huntington’s and Alzheimer’s disease: New insights from the CVLT-3

The original and second editions of the California Verbal Learning Test (CVLT) used nonparametric and parametric methods, respectively, to assess Total Recognition Discriminability (RD). In a previous study, we found evidence that the nonparametric formula may be more sensitive than the parametric formula to high false positive (FP) rates and provide more accurate assessments of yes/no recognition in neurodegenerative populations prone to high FP rates, including Alzheimer’s disease (AD). In the present study, we extended our investigation to examine the utility of CVLT-3 nonparametric and parametric Total RD indices in the assessment and comparison of yes/no recognition in individuals with Huntington’s disease (HD) and AD in mild and moderate stages of dementia. Findings suggested that the CVLT-3 nonparametric Total RD index was more sensitive than the parametric index to HD and AD differences in yes/no recognition across mild and moderate stages of dementia. Additionally, group differences on total FP errors were more closely mirrored by group differences on the nonparametric Total RD index. The present results bolster our previous findings and highlight the utility of examining nonparametric (in addition to parametric) Total RD on the CVLT-3 in assessments of yes/no recognition involving clinical populations prone to high FP rates.

New Yes/No Recognition Memory Analysis on the California Verbal Learning Test-3: Clinical Utility in Alzheimer's and Huntington's Disease.

The third edition of the California Verbal Learning Test (CVLT-3) includes a new index termed List A versus Novel/Unrelated recognition discriminability (RD) on the Yes/No Recognition trial. Whereas the Total RD index incorporates false positive (FP) errors associated with all distractors (including List B and semantically related items), the new List A versus Novel/Unrelated RD index incorporates only FP errors associated with novel, semantically unrelated distractors. Thus, in minimizing levels of source and semantic interference, the List A versus Novel/Unrelated RD index may yield purer assessments of yes/no recognition memory independent of vulnerability to source memory difficulties or semantic confusion, both of which are often seen in individuals with primarily frontal-system dysfunction (e.g., early Huntington's disease [HD]). We compared the performance of individuals with Alzheimer's disease (AD) and HD in mild and moderate stages of dementia on CVLT-3 indices of Total RD and List A versus Novel/Unrelated RD. Although AD and HD subgroups exhibited deficits on both RD indices relative to healthy comparison groups, those with HD generally outperformed those with AD, and group differences were more robust on List A versus Novel/Unrelated RD than on Total RD. Our findings highlight the clinical utility of the new CVLT-3 List A versus Novel/Unrelated RD index, which (a) maximally assesses yes/no recognition memory independent of source and semantic interference; and (b) provides a greater differentiation between individuals whose memory disorder is primarily at the encoding/storage level (e.g., as in AD) versus at the retrieval level (e.g., as in early HD). (JINS, 2018, 24, 833-841).

Correlations between CSF proteins and spontaneous neuronal activity in Parkinson’s disease

The relationship between cerebrospinal fluid (CSF) proteins and brain function in Parkinson’s disease (PD) is not explained clearly. We investigated the correlations between CSF proteins and spontaneous neuronal activity in PD patients via fractional amplitude of low-frequency fluctuation (fALFF) using the Parkinson’s Progression Markers Initiative database. Twenty-eight PD patients underwent resting-state functional magnetic resonance imaging in “off” status and lumbar puncture within a month. Correlation analyses between CSF proteins and fALFF value in whole brain as well as clinical assessment scores were performed. We found CSF total tau (t-tau) level was negatively correlated with fALFF in posterior cingulate gyrus. And fALFF in posterior cingulate gyrus was positively correlated with Hopkins Verbal Learning Test-Revised recognition discrimination index. Besides, alpha-synuclein (α-syn) level was correlated with fALFF in bilateral inferior frontal gyrus. This study provides evidence that CSF proteins may have a relationship with brain function related to cognitive status in PD patients.

Refining CVLT-II recognition discriminability indices to enhance the characterization of recognition memory changes in healthy aging

ABSTRACTThe present study examined age-related differences on the four false-positive (FP) error subtypes found on the California Verbal Learning Test-Second Edition yes/no recognition memory trial and the influence of these subtypes on source and novel recognition discriminability (SoRD and NRD, respectively) index calculations. Healthy older (n = 55) adults generally made more FP errors than healthy young adults (n = 57). Accordingly, older adults performed worse than young adults on all SoRD and NRD indices. However, the manner in which FP error subtypes were incorporated into SoRD and NRD index calculations impacted the magnitudes of observed differences between and within the two age groups on SoRD and NRD indices. The present findings underline the importance of examining FP errors in assessments of recognition memory abilities, and using more refined indices of recognition discriminability to further elucidate the nature of age-related recognition memory impairment.

Neurocognitive function testing and health related quality of life in stage IV lung cancer patients with and without brain metastases.

2073 Background: Survival in stage IV lung cancer (S4LC) patients (pts) continues to improve, highlighting the importance of assessing health related quality of life (HRQoL). Lung cancer, involvement with brain metastases (BM), and systemic or brain-specific treatment can all impact neurocognitive function (NCF) and HRQoL. We evaluated the relationship between NCF and HRQoL in S4LC pts by BM status. Methods: S4LC pts with BM (BM+) were frequency distributionally-matched to pts without BM (NBM). NCF was measured using the Hopkins Verbal Learning Test – Revised (HVLT-R), the Controlled Oral Word Association Test (COWAT) and Trail Making Tests (TMT-A/B); scores were correlated with health utility score (HUS) data from EQ5D-3L surveys (Pearson Coefficient, R). Results: BM+ (n = 54) and matched NBM (n = 40) pts had similar demographics. The overall median age was 61years; 59% were female; of 89% that were adenocarcinomas, half had EGFR/ALK alterations; mean time since diagnosis was 2.6 years; mean time since BM were diagnosed in BM+ pts was 0.5 years. Mean HUS (mHUS) were similar between groups: 0.77 for BM+ vs. 0.78 for NBM; p = 0.86. However, pts with stable BM had higher HUS than those with progressive BM (mHUS: 0.80 vs 0.69; p = 0.045). Of BM+ pts, 44% had received whole brain radiation (WBRT). Correlations of NCF and HUS specific for BM+ pts were observed for several HLVT scores, including Total Recall (TR), which was correlated with HUS in BM+ (R = 0.35, p = 0.01) but not in NBM (R = 0.04, p = 0.84) and Recognition Discrimination Index (BM+: R = 0.32, p = 0.03 vs NBM: R = 0.13, p = 0.51). In contrast, TMT-A/B NCF test results had slightly stronger associations with HUS in NBM pts. COWAT was least associated with HUS in BM+ or NBM pts. In BM+ pts treated vs untreated with WBRT, HLVT scores were better in untreated patients (TR, p &lt; 0.0001; delayed recall, p = 0.006; retention, p = 0.089), associations not seen with either TMT-A/B or COWAT. Mutation status had no bearing on these associations. Conclusions: NCF impacts HUS in S4LC pts and should be considered in treatment planning. HVLT scores are useful to assess specifically the impact of BM and WBRT in S4LC pts, and is reflected in associations with HRQoL.

Determining the Association between Language and Cognitive Tests in Poststroke Aphasia.

Individuals with aphasia are often excluded from studies exploring poststroke cognition because so many of the standard cognitive assessments rely on language ability. Our primary objective was to examine the association between performance on cognitive tests and performance on comprehension and naming tests in poststroke aphasia. Second, we aimed to determine the association between language performance and a real-life measure of cognition (Kettle Test). Third, we explored the feasibility of administering cognitive tests in aphasia. Thirty-six participants with poststroke aphasia and 32 controls were assessed on a battery of pen-and-paper cognitive tests recommended in stroke. Auditory comprehension was measured using the Comprehensive Aphasia Test and naming was measured using the Boston Naming Test. Twenty-two community dwelling participants with aphasia and controls were also asked to complete the Kettle Test. Multiple linear regressions were used to explore the relationship between language performance and performance on the cognitive tests. Feasibility was determined by quantifying missing data. The cognitive tests with the highest variance accounted for by auditory comprehension and naming were animal fluency (R2 = 0.67, R2 = 0.78) and the Hopkins Verbal Learning Test (recognition discrimination index) (R2 = 0.65, R2 = 0.78). All cognitive tests were significantly associated with auditory comprehension and naming, except for the Star Cancellation Test and the Kettle Test. Thirty-three percent of participants with aphasia were unable to complete all the cognitive tests. Language and non-linguistic cognitive processes are often interrelated. Most pen-and-paper cognitive tests were significantly associated with both auditory comprehension and naming, even in tests that do not require a verbal response. Language performance was not significantly associated with a real-life cognitive performance measure. Task instructions, stimuli, and responses for completion need to be tailored for individuals with aphasia to minimize the influence of language deficits when testing non-linguistic cognitive performance.

Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative.

Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up.Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD.Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ2 = 38.23, df = 14, p < 0.001).Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI.

Embedded performance validity tests within the Hopkins Verbal Learning Test – Revised and the Brief Visuospatial Memory Test – Revised

Objective: Various research studies and neuropsychology practice organizations have reiterated the importance of developing embedded performance validity tests (PVTs) to detect potentially invalid neurocognitive test data. This study investigated whether measures within the Hopkins Verbal Learning Test – Revised (HVLT-R) and the Brief Visuospatial Memory Test – Revised (BVMT-R) could accurately classify individuals who fail two or more PVTs during routine clinical assessment.Method: The present sample of 109 United States military veterans (Mean age = 52.4, SD = 13.3), all consisted of clinically referred patients and received a battery of neuropsychological tests. Based on performance validity findings, veterans were assigned to valid (n = 86) or invalid (n = 23) groups. Of the 109 patients in the overall sample, 77 were administered the HLVT-R and 75 were administered the BVMT-R, which were examined for classification accuracy.Results: The HVLT-R Recognition Discrimination Index and the BVMT-R Retention Percentage showed good to adequate discrimination with an area under the curve of .78 and .70, respectively. The HVLT-R Recognition Discrimination Index showed sensitivity of .53 with specificity of .93. The BVMT-R Retention Percentage demonstrated sensitivity of .31 with specificity of .92.Conclusions: When used in conjunction with other PVTs, these new embedded PVTs may be effective in the detection of invalid test data, although they are not intended for use in patients with dementia.

APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease.

Cognitive impairment is a common and disabling problem in Parkinson disease (PD) that is not well understood and is difficult to treat. Identification of genetic variants that influence the rate of cognitive decline or pattern of early cognitive deficits in PD might provide a clearer understanding of the etiopathogenesis of this important nonmotor feature. To determine whether common variation in the APOE, MAPT, and SNCA genes is associated with cognitive performance in patients with PD. We studied 1079 PD patients from 6 academic centers in the United States who underwent assessments of memory (Hopkins Verbal Learning Test-Revised [HVLT-R]), attention and executive function (Letter-Number Sequencing Test and Trail Making Test), language processing (semantic and phonemic verbal fluency tests), visuospatial skills (Benton Judgment of Line Orientation test), and global cognitive function (Montreal Cognitive Assessment). Participants underwent genotyping for the APOE ε2/ε3/ε4 alleles, MAPT H1/H2 haplotypes, and SNCA rs356219. We used linear regression to test for association between genotype and baseline cognitive performance with adjustment for age, sex, years of education, disease duration, and site. We used a Bonferroni correction to adjust for the 9 comparisons that were performed for each gene. Nine variables derived from 7 psychometric tests. The APOE ε4 allele was associated with lower performance on the HVLT-R Total Recall (P = 6.7 × 10(-6); corrected P [Pc] = 6.0 × 10(-5)), Delayed Recall (P = .001; Pc = .009), and Recognition Discrimination Index (P = .004; Pc = .04); a semantic verbal fluency test (P = .002; Pc = .02); the Letter-Number Sequencing Test (P = 1 × 10(-5); Pc = 9 × 10(-5)); and Trail Making Test B minus Trail Making Test A (P = .002; Pc = .02). In a subset of 645 patients without dementia, the APOE ε4 allele was associated with lower scores on the HVLT-R Total Recall (P = .005; Pc = .045) and the semantic verbal fluency (P = .005; Pc = .045) measures. Variants of MAPT and SNCA were not associated with scores on any tests. Our data indicate that the APOE ε4 allele is an important predictor of cognitive function in PD across multiple domains. Among PD patients without dementia, the APOE ε4 allele was only associated with lower performance on word list learning and semantic verbal fluency, a pattern more typical of the cognitive deficits seen in early Alzheimer disease than PD.

Iron overload accelerates neuronal amyloid-β production and cognitive impairment in transgenic mice model of Alzheimer's disease

Iron dyshomeostasis is proving increasingly likely to be involved in the pathology of Alzheimer's disease (AD); yet, its mechanism is not well understood. Here, we investigated the AD-related mechanism(s) of iron-sulfate exposure in vitro and in vivo, using cultured primary cortical neurons and APP/PS1 AD-model mice, respectively. In both systems, we observed iron-induced disruptions of amyloid precursor protein (APP) processing, neuronal signaling, and cognitive behavior. Iron overload increased production of amyloidogenic KPI-APP and amyloid beta. Further, this APP misprocessing was blocked by MK-801 in vitro, suggesting the effect was N-methyl-d-aspartate receptor (NMDAR) dependent. Calcium imaging confirmed that 24 hours iron exposure led to disrupted synaptic signaling by augmenting GluN2B-containing NMDAR expression–GluN2B messenger RNA and protein levels were increased and promoting excessing extrasynaptic NMDAR signaling. The disrupted GluN2B expression was concurrent with diminished expression of the splicing factors, sc35 and hnRNPA1. In APP/PS1 mice, chronic iron treatment led to hastened progression of cognitive impairment with the novel object recognition discrimination index, revealing a deficit at the age of 4 months, concomitant with augmented GluN2B expression. Together, these data suggest iron-induced APP misprocessing and hastened cognitive decline occur through inordinate extrasynaptic NMDAR activation.

Identifying the “source” of recognition memory deficits in patients with Huntington's disease or Alzheimer's disease: Evidence from the CVLT-II

The present study compared the performance of individuals with Huntington's disease (HD) and Alzheimer's disease (AD) on three types of California Verbal Learning Test–Second Edition (CVLT-II) recognition discriminability indices (RDI): Source, Novel, and Total. The HD and AD groups did not differ significantly on Source RDI (all 16 targets versus the 16 previously presented, List B, distractors). However, HD patients performed significantly better than AD patients on Total RDI (all 16 targets versus all 32 distractors) and Novel RDI (all 16 targets versus 16 new distractors). Implications of these findings on the differentiation of the memory disorders associated with HD and AD are discussed.

Criterion validity of the California Verbal Learning Test-Second Edition (CVLT-II) after traumatic brain injury

The California Verbal Learning Test-Second Edition (CVLT-II) was performed by 200 participants, divided into moderate–severe traumatic brain injury ( n = 43), mild traumatic brain injury ( n = 57) and demographically matched control ( n = 100) groups. Participants with complicating premorbid histories or who scored below 15/16 on the CVLT-II forced choice recognition trial were excluded. There were statistically significant ( p < .0001) effects of group status on the CVLT-II total recall discriminability and recognition discriminability indices. Logistic regression revealed that, in the classification of control versus moderate–severe traumatic brain injury, CVLT-II variables were accurate 66–71% overall, but false positive rates ranged from 49 to 54%. In conclusion, average scores on the CVLT-II differ meaningfully between patients with various degrees of severity of traumatic brain injury and controls, but this test should not be used in isolation to determine the presence or absence of acquired memory impairment.