Robust demographically-adjusted normative data for the Montreal Cognitive Assessment (MoCA): Results from the systolic blood pressure intervention trial.

To generate robust, demographically-adjusted regression-based norms for the Montreal Cognitive Assessment (MoCA) using a large sample of diverse older US adults.Baseline MoCA scores were examined for participants in the Systolic Blood Pressure Intervention Trial (SPRINT). A robust, cognitively-normal sample was drawn from individuals not subsequently adjudicated with cognitive impairment through 4 years of follow-up. Multivariable Beta-Binomial regression was used to model the association of demographic variables with MoCA performance and to create demographically-stratified normative tables.Participants' (N = 5,338) mean age was 66.9 ± 8.8 years, with 35.7% female, 63.1% White, 27.4% Black, 9.5% Hispanic, and 44.5% with a college or graduate education. A large proportion scored below published MoCA cutoffs: 61.4% scored below 26 and 29.2% scored below 23. A disproportionate number falling below these cutoffs were Black, Hispanic, did not graduate from college, or were ≥75 years of age. Multivariable modeling identified education, race/ethnicity, age, and sex as significant predictors of MoCA scores (p<.001), with the best fitting model explaining 24.4% of the variance. Model-based predictions of median MoCA scores were generally 1 to 2 points lower for Black and Hispanic participants across combinations of age, sex, and education. Demographically-stratified norm-tables based on regression modeling are provided to facilitate clinical use, along with our raw data.By using regression-based strategies that more fully account for demographic variables, we provide robust, demographically-adjusted metrics to improve cognitive screening with the MoCA in diverse older adults.

Consensus Parameter: Research Methodologies to Evaluate Neurodevelopmental Effects of Pubertal Suppression in Transgender Youth.

Purpose: Pubertal suppression is standard of care for early pubertal transgender youth to prevent the development of undesired and distressing secondary sex characteristics incongruent with gender identity. Preliminary evidence suggests pubertal suppression improves mental health functioning. Given the widespread changes in brain and cognition that occur during puberty, a critical question is whether this treatment impacts neurodevelopment. Methods: A Delphi consensus procedure engaged 24 international experts in neurodevelopment, gender development, puberty/adolescence, neuroendocrinology, and statistics/psychometrics to identify priority research methodologies to address the empirical question: is pubertal suppression treatment associated with real-world neurocognitive sequelae? Recommended study approaches reaching 80% consensus were included in the consensus parameter. Results: The Delphi procedure identified 160 initial expert recommendations, 44 of which ultimately achieved consensus. Consensus study design elements include the following: a minimum of three measurement time points, pubertal staging at baseline, statistical modeling of sex in analyses, use of analytic approaches that account for heterogeneity, and use of multiple comparison groups to minimize the limitations of any one group. Consensus study comparison groups include untreated transgender youth matched on pubertal stage, cisgender (i.e., gender congruent) youth matched on pubertal stage, and an independent sample from a large-scale youth development database. The consensus domains for assessment includes: mental health, executive function/cognitive control, and social awareness/functioning. Conclusion: An international interdisciplinary team of experts achieved consensus around primary methods and domains for assessing neurodevelopmental effects (i.e., benefits and/or difficulties) of pubertal suppression treatment in transgender youth.

Kidney Disease, Intensive Hypertension Treatment, and Risk for Dementia and Mild Cognitive Impairment: The Systolic Blood Pressure Intervention Trial.

BACKGROUND: Intensively treating hypertension may benefit cardiovascular disease and cognitive function, but at the short-term expense of reduced kidney function. METHODS: We investigated markers of kidney function and the effect of intensive hypertension treatment on incidence of dementia and mild cognitive impairment (MCI) in 9361 participants in the randomized Systolic Blood Pressure Intervention Trial, which compared intensive versus standard systolic BP lowering (targeting <120 mm Hg versus <140 mm Hg, respectively). We categorized participants according to baseline and longitudinal changes in eGFR and urinary albumin-to-creatinine ratio. Primary outcomes were occurrence of adjudicated probable dementia and MCI. RESULTS: Among 8563 participants who completed at least one cognitive assessment during follow-up (median 5.1 years), probable dementia occurred in 325 (3.8%) and MCI in 640 (7.6%) participants. In multivariable adjusted analyses, there was no significant association between baseline eGFR <60 ml/min per 1.73 m2 and risk for dementia or MCI. In time-varying analyses, eGFR decline ≥30% was associated with a higher risk for probable dementia. Incident eGFR <60 ml/min per 1.73 m2 was associated with a higher risk for MCI and a composite of dementia or MCI. Although these kidney events occurred more frequently in the intensive treatment group, there was no evidence that they modified or attenuated the effect of intensive treatment on dementia and MCI incidence. Baseline and incident urinary ACR ≥30 mg/g were not associated with probable dementia or MCI, nor did the urinary ACR modify the effect of intensive treatment on cognitive outcomes. CONCLUSIONS: Among hypertensive adults, declining kidney function measured by eGFR is associated with increased risk for probable dementia and MCI, independent of the intensity of hypertension treatment.

The Association between the Montreal Cognitive Assessment and Functional Activity Questionnaire in the Systolic Blood Pressure Intervention Trial (SPRINT).

OBJECTIVE: To examine the association of global cognitive function assessed via the Montreal Cognitive Assessment (MoCA) and deficiencies in instrumental activities of daily living (IADL) on the Functional Activity Questionnaire (FAQ) in hypertensive older adults in the Systolic Blood Pressure Intervention Trial (SPRINT). METHODS: In cross-sectional analysis, 9,296 SPRINT participants completed the MoCA at baseline. The FAQ was obtained from 2,705 informants for SPRINT participants scoring <21 or <22 on the MoCA, depending on education. FAQ severity ranged from no dysfunction (Score = 0) to moderate/severe dysfunction (Score = 5+). RESULTS: Participants who triggered FAQ administration were older, less educated, and more likely to be Black or Hispanic (p < 0.001). Sixty-one percent (n = 1,661) of participants' informants reported no functional difficulties in IADLs. An informant report, however, of any difficulty on the FAQ was associated with lower MoCA scores after controlling for age, sex, race/ethnicity, and education (p < 0.05). Partial proportional odds regression indicates that participants scoring lower on the MoCA (in the 10th to <25th, fifth to <10th, and

Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT).

BACKGROUND: Chronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain. STUDY DESIGN: Cross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS: Participants in SPRINT, a randomized clinical trial of blood pressure targets in older community-dwelling adults with cardiovascular disease, chronic kidney disease, or high cardiovascular disease risk and without diabetes or known stroke, who underwent detailed neurocognitive testing in the cognition substudy, SPRINT-Memory and Cognition in Decreased Hypertension (SPRINT-MIND). PREDICTORS: Urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). OUTCOMES: Cognitive function, a priori defined as 5 cognitive domains based on 11 cognitive tests using z scores, and abnormal white matter volume quantified by brain magnetic resonance imaging. RESULTS: Of 9,361 SPRINT participants, 2,800 participated in SPRINT-MIND and 2,707 had complete data; 637 had brain imaging. Mean age was 68 years, 37% were women, 30% were black, and 20% had known cardiovascular disease. Mean eGFR was 70.8±20.9mL/min/1.73m2 and median urine ACR was 9.7 (IQR, 5.7-22.5) mg/g. In adjusted analyses, higher ACR was associated with worse global cognitive function, executive function, memory, and attention, such that each doubling of urine ACR had the same association with cognitive performance as being 7, 10, 6, and 14 months older, respectively. Lower eGFR was independently associated with worse global cognitive function and memory. In adjusted models, higher ACR, but not eGFR, was associated with larger abnormal white matter volume. LIMITATIONS: Cross-sectional only, no patients with diabetes were included. CONCLUSIONS: In older adults, higher urine ACR and lower eGFR have independent associations with global cognitive performance with different affected domains. Albuminuria concurrently identifies a higher burden of abnormal brain white matter disease, suggesting that vascular disease may mediate these relationships.

Correction: Antidepressant and Neurocognitive Effects of Isoflurane Anesthesia versus Electroconvulsive Therapy in Refractory Depression.

[This corrects the article DOI: 10.1371/journal.pone.0069809.].

Neuropsychological Practice Effects in the Context of Cognitive Decline: Contributions from Learning and Task Novelty.

Although cognitive decline is typically associated with decreasing practice effects (PEs) (presumably due to declining memory), some studies show increased PEs with declines in cognition. One explanation for these inconsistencies is that PEs reflect not only memory, but also rebounds from adapting to task novelty (i.e., novelty effect), leading to increased PEs. We examined a theoretical model of relationships among novelty effects, memory, cognitive decline, and within-session PEs. Sixty-six older adults ranging from normal to severely impaired completed measures of memory, novelty effects, and two trials each of Wechsler Adult Intelligence Scale, 4 th Edition Symbol Search and Coding. Interrelationships among variables were examined using regression analyses. PEs for Symbol Search and Coding (a) were related to different proposed PE components (i.e., memory and novelty effects), such that novelty effect predicted Symbol Search PE (R2 =.239, p<.001) and memory predicted Coding PE (R2 =.089, p=.015), and (b) showed different patterns across stages of cognitive decline, such that the greatest cognitive decline was associated with smallest Coding PE (R2 =.125, p=.004), whereas intermediate cognitive decline was associated with the greatest Symbol Search PE (R2 =.097, p=.040). The relationship between cognitive decline and PE for Symbol Search was partially mediated by novelty effect among older adults with abnormal cognitive decline (model R2 =.286, p<.001). These findings (a) suggest that PE is not a unitary construct, (b) offer an explanation for contradictory findings in the literature, and (c) highlight the need for a better understanding of component processes of PE across different neuropsychological measures.

Antidepressant and neurocognitive effects of isoflurane anesthesia versus electroconvulsive therapy in refractory depression.

BACKGROUND: Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT). Early research suggested that isoflurane anesthesia may be an effective alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isoflurane's antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition. METHOD: Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20) or isoflurane (n = 8) over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24) and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency) were assessed at Pretreatment, Post all treatments and 4-week Follow-up. RESULTS: Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane) patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement. CONCLUSIONS: Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial.

Using regression equations built from summary data in the psychological assessment of the individual case: extension to multiple regression.

Regression equations have many useful roles in psychological assessment. Moreover, there is a large reservoir of published data that could be used to build regression equations; these equations could then be employed to test a wide variety of hypotheses concerning the functioning of individual cases. This resource is currently underused because (a) not all psychologists are aware that regression equations can be built not only from raw data but also using only basic summary data for a sample, and (b) the computations involved are tedious and prone to error. In an attempt to overcome these barriers, Crawford and Garthwaite (2007) provided methods to build and apply simple linear regression models using summary statistics as data. In the present study, we extend this work to set out the steps required to build multiple regression models from sample summary statistics and the further steps required to compute the associated statistics for drawing inferences concerning an individual case. We also develop, describe, and make available a computer program that implements these methods. Although there are caveats associated with the use of the methods, these need to be balanced against pragmatic considerations and against the alternative of either entirely ignoring a pertinent data set or using it informally to provide a clinical "guesstimate." Upgraded versions of earlier programs for regression in the single case are also provided; these add the point and interval estimates of effect size developed in the present article.

Predicting estimates of premorbid memory functioning: validation in a dementia sample.

Formulae to estimate premorbid memory functioning in a sample of cognitively intact older adults have been developed. These formulae were validated in a small sample of patients with amnestic Mild Cognitive Impairment. However, further validation is clearly needed. The current study applied these formulae to a sample of 1,059 patients referred to a dementia clinic and compared the premorbid estimates of memory functioning with current memory abilities. Large and statistically significant differences were observed in the current sample, with premorbid memory scores exceeding current memory scores. Although some cautions should be observed when using these estimates clinically, growing support for these estimates of premorbid memory abilities may aid clinicians in determining change across time in older patients.

Cognitive decline in the elderly: an analysis of population heterogeneity.

BACKGROUND: studies of cognitive ageing at the group level suggest that age is associated with cognitive decline; however, there may be individual differences such that not all older adults will experience cognitive decline. OBJECTIVE: to evaluate patterns of cognitive decline in a cohort of older adults initially free of dementia. DESIGN, SETTING AND SUBJECTS: elderly Catholic clergy members participating in the Religious Orders Study were followed for up to 15 years. Cognitive performance was assessed annually. METHODS: performance on a composite global measure of cognition was analysed using random effects models for baseline performance and change over time. A profile mixture component was used to identify subgroups with different cognitive trajectories over the study period. RESULTS: from a sample of 1,049 participants (mean age 75 years), three subgroups were identified based on the distribution of baseline performance and change over time. The majority (65%) of participants belonged to a slow decline class that did not experience substantial cognitive decline over the observation period [-0.04 baseline total sample standard deviation (SD) units/year]. About 27% experienced moderate decline (-0.19 SD/year), and 8% belonged to a class experiencing rapid decline (-0.57 SD/year). A subsample analysis revealed that when substantial cognitive decline does occur, the magnitude and rate of decline is correlated with neuropathological processes. CONCLUSIONS: in this sample, the most common pattern of cognitive decline is extremely slow, perceptible on a time scale measured by decades, not years. While in need of cross validation, these findings suggest that cognitive changes associated with ageing may be minimal and emphasise the importance of understanding the full range of age-related pathologies that may diminish brain function.

Differential patterns of cognitive decline in anterior and posterior white matter hyperintensity progression.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) found on brain MRI in elderly individuals are largely thought to be due to microvascular disease, and its progression has been associated with cognitive decline. The present study sought to determine patterns of cognitive decline associated with anterior and posterior WMH progression. METHODS: Subjects included 110 normal controls, aged >or=60 years, who were participants in the Duke Neurocognitive Outcomes of Depression in the Elderly study. All subjects had comprehensive cognitive evaluations and MRI scans at baseline and after 2 years. Cognitive composites were created in 5 domains: complex processing speed, working memory, general memory, visual-constructional skills, and language. Change in cognition was calculated using standard regression-based models accounting for variables known to impact serial testing. A semiautomated segmentation method was used to measure WMH extent in anterior and posterior brain regions. Hierarchical multiple linear regression models were used to evaluate which of the 5 measured cognitive domains was most strongly associated with regional (anterior and posterior) and total WMH progression after adjusting for demographics (age, sex, and education). RESULTS: Decline in complex processing speed was independently associated with both anterior (r(2)=0.06, P=0.02) and total WMH progression (r(2)=0.05, P=0.04). In contrast, decline in visual-constructional skills was uniquely associated with posterior progression (r(2)=0.05, P<0.05). CONCLUSIONS: Distinct cognitive profiles are associated with anterior and posterior WMH progression among normal elders. These differing profiles need to be considered when evaluating the cognitive correlates of WMHs.

Evidence-based research and practice in clinical neuropsychology.

While a definition for evidence-based clinical neuropsychological practice (EBCNP) has yet to emerge, it is likely to integrate the same core features as evidence-based medicine; namely, best research evidence, clinical expertise, and individual patient needs. Given the nascent stage of EBCNP, suggestions are made to advance evidence-based approaches in both research and practice. The common elements are: recognition that clinical outcomes are recorded at the level of the individual; and to be useful, outcomes research must be presented in a way that can be directly applied on a case-by-case basis. Tracking the outcomes of our clinical services in an evidence-based manner that is publicly verifiable will demonstrate the value of neuropsychological services to our patients, our referral sources, and ultimately to payers.

The prediction of change: normative neuropsychological trajectories.

While the application of normative standards is vital to the practice of clinical neuropsychology, data regarding normative change remains scarce despite the frequency of serial assessments. Based on 285 normal individuals, we provide co-normed baseline data with demographic adjustments and test-retest standardized regression based (SRB) models for three time points for several measures. These models delineate normal, expected change across time, and yield standardized z-scores that are comparable across tests. Using a new approach, performance on any previous trial was accounted for in the subsequent models of change, yielding serial normative formulas that model change trajectories rather than simple change from point to point. These equations provide indices of deviation from expected baseline and change for use in clinical or research settings.

Cognitive-behavioral profiles of neurodegenerative dementias: beyond Alzheimer's disease.

The neurocognitive and behavioral profiles of vascular dementia and vascular cognitive impairment, dementia with Lewy bodies and Parkinson's disease with dementia, and dementia syndromes associated with frontotemporal lobar degenerations are compared and contrasted with Alzheimer's dementia (AD). Vascular dementia/vascular cognitive impairment is characterized by better verbal memory performance, worse quantitative executive functioning, and prominent depressed mood. Dementia with Lewy bodies and Parkinson's disease with dementia are equally contrasted with AD by defective processing of visual information, better performance on executively supported verbal learning tasks, greater attentional variability, poorer qualitative executive functioning, and the presence of mood-congruent visual hallucinations. The frontal variant of frontotemporal lobar degeneration (frontotemporal dementia) differs from AD by better multimodal retention on learning tasks, different patterns of generative word fluency, defective qualitative executive functioning, and by markedly impairment of comportment. For temporal variants of frontotemporal lobar degenerations, progressive aphasia and semantic dementia, worse language performance relative to AD is typically characteristic.

Examining the relationship between WAIS-III premorbid intellectual functioning and WMS-III memory ability to evaluate memory impairment.

The purpose of this study was to extend previous research by Lange and Chelune (2006) by evaluating the clinical utility of GAI-memory discrepancy scores to detect memory impairment using estimated premorbid GAI scores (i.e., GAI-E) rather than obtained GAI scores. Participants were 34 patients with Alzheimer's-type dementia and a sub-sample of 34 demographically matched participants from the WAIS-III/WMS-III standardization sample. GAI-memory discrepancy scores were more effective at differentiating Alzheimer's patients versus healthy controls when using estimated premorbid GAI scores than obtained GAI scores. However, GAI(E)-memory discrepancy scores failed to provide unique interpretive information beyond that which is gained from interpretation of the memory index scores alone. This was most likely due to the prevalence of obvious memory impairment in this patient population. Future research directions are discussed.

Clinical validation of the General Ability Index--Estimate (GAI-E): estimating premorbid GAI.

The clinical utility of the General Ability Index--Estimate (GAI-E; Lange, Schoenberg, Chelune, Scott, & Adams, 2005) for estimating premorbid GAI scores was investigated using the WAIS-III standardization clinical trials sample (The Psychological Corporation, 1997). The GAI-E algorithms combine Vocabulary, Information, Matrix Reasoning, and Picture Completion subtest raw scores with demographic variables to predict GAI. Ten GAI-E algorithms were developed combining demographic variables with single subtest scaled scores and with two subtests. Estimated GAI are presented for participants diagnosed with dementia (n = 50), traumatic brain injury (n = 20), Huntington's disease (n = 15), Korsakoff's disease (n = 12), chronic alcohol abuse (n = 32), temporal lobectomy (n = 17), and schizophrenia (n = 44). In addition, a small sample of participants without dementia and diagnosed with depression (n = 32) was used as a clinical comparison group. The GAI-E algorithms provided estimates of GAI that closely approximated scores expected for a healthy adult population. The greatest differences between estimated GAI and obtained GAI were observed for the single subtest GAI-E algorithms using the Vocabulary, Information, and Matrix Reasoning subtests. Based on these data, recommendations for the use of the GAI-E algorithms are presented.

Development of WAIS-III General Ability Index Minus WMS-III memory discrepancy scores.

Analysis of the discrepancy between intellectual functioning and memory ability has received some support as a useful means for evaluating memory impairment. In recent additions to Wechlser scale interpretation, the WAIS-III General Ability Index (GAI) and the WMS-III Delayed Memory Index (DMI) were developed. The purpose of this investigation is to develop base rate data for GAI-IMI, GAI-GMI, and GAI-DMI discrepancy scores using data from the WAIS-III/WMS-III standardization sample (weighted N = 1250). Base rate tables were developed using the predicted-difference method and two simple-difference methods (i.e., stratified and non-stratified). These tables provide valuable data for clinical reference purposes to determine the frequency of GAI-IMI, GAI-GMI, and GAI-DMI discrepancy scores in the WAIS-III/WMS-III standardization sample.

Is depth of anesthesia, as assessed by the Bispectral Index, related to postoperative cognitive dysfunction and recovery?

We randomized 74 patients to either a lower Bispectral Index (BIS) regimen (median BIS, 38.9) or a higher BIS regimen (mean BIS, 50.7) during the surgical procedure. Preoperatively and 4-6 wk after surgery, the patients' cognitive status was assessed with a cognitive test battery consisting of processing speed index, working memory index, and verbal memory index. Processing speed index was 113.7 +/- 1.5 (mean +/- se) in the lower BIS group versus 107.9 +/- 1.4 in the higher BIS group (P = 0.006). No difference was observed in the other two test battery components. Somewhat deeper levels of anesthesia were therefore associated with better cognitive function 4-6 wk postoperatively, particularly with respect to the ability to process information.

Development of demographic norms for four new WAIS-III/WMS-III indexes.

Following the publication of the third edition Wechsler scales (i.e., WAIS-III and WMS-III), demographically corrected norms were made available in the form of a computerized scoring program (i.e., WAIS-III/WMS-III/WIAT-II Scoring Assistant). These norms correct for age, gender, ethnicity, and education. Since then, four new indexes have been developed: the WAIS-III General Ability Index, the WMS-III Delayed Memory Index, and the two alternate Immediate and Delayed Memory Indexes. The purpose of this study was to develop demographically corrected norms for the four new indexes using the standardization sample and education oversample from the WAIS-III and WMS-III. These norms were developed using the same methodology as the demographically corrected norms made available in the WAIS-III/WMS-III/WIAT-II Scoring Assistant.