Montreal Cognitive Assessment and Mini-Mental State Examination reliable change indices in healthy older adults.

OBJECTIVE: Cognitive tests are used repeatedly to assess the treatment response or progression of cognitive disorders. The Montreal Cognitive Assessment (MoCA) is a valid screening test for mild cognitive impairment. The aim of our study was to establish 90% reliable change indices (RCI) for the MoCA together with the Mini-Mental State Examination (MMSE) in cognitively healthy older adults. METHOD: We analyzed 197 cognitively healthy and functional independent volunteers aged 60-94 years, who met strict inclusion criteria for four consecutive years. The RCI methods by Chelune and Hsu were used. RESULTS: For 1, 2, and 3 years, the 90% RCI for MoCA using Chelune's formula were -4 ≤, ≥4; -4 ≤, ≥4 and -5 ≤, ≥4 points, respectively, and -3 ≤, ≥3 for the MMSE each year. Ninety percent RCI for MoCA using Hsu's formula ranged from -6 to 0, respectively, and +3 to +8 dependent on the baseline MoCA. CONCLUSION: Our study demonstrated RCI for the MoCA and MMSE in a 3-year time period that can be used for the estimation of cognitive decline or improvement in clinical settings. Copyright © 2016 John Wiley & Sons, Ltd.

Toward the processing speed theory of activities of daily living in healthy aging: normative data of the Functional Activities Questionnaire.

BACKGROUND: The aim of this study was to describe an instrumental activities of daily living (IADL) measure: Functional Activities Questionnaire (FAQ), which is often used in clinical settings as a self- or informant-based measure of IADL. However, the FAQ's relationship with age or education in healthy aging has not been investigated. METHODS: FAQ and a neuropsychological battery were administered to old and very old Czech adults (n = 540). Participants met strict inclusion criteria for the absence of any active or past neurodegenerative disorders. RESULTS: FAQ is significantly dependent on age and education, but not gender. Younger subjects and those with higher education have the lowest scores in the FAQ and show a higher degree of functional independence. FAQ moderately correlates with speed of processing, visual-perceptual and executive functions measures (Trail Making Tests, Stroop Test) and depressive symptoms, but not with episodic memory (WMS-III logical memory). We present normative percentile values for different age groups from 60 to 96 years of age. CONCLUSIONS: The present study shows conclusively that IADL measures, such as FAQ, should not be used without appropriate normative data, especially in very old adults. Thus, it has the ability to differentiate functional dependence due to age-related decline from neurodegenerative disease.

Age-related differences in NMDA receptor subunits of prenatally methamphetamine-exposed male rats.

There is accumulating evidence that methamphetamine (MA) is a widely abused drug popular among pregnant women. MA exposure is associated with changes in the function of neurotransmitter systems, namely the dopaminergic, serotonergic and glutamatergic systems. Since N-methyl-D-aspartate receptors (NMDA) are affected by MA-induced glutamate release, we assessed the expression of NMDAR subunits (NR1, NR2A, and NR2B) and postsynaptic density protein 95 (PSD-95), which is connected with NMDAR. We measured the expression of these proteins in adolescent (30 days old) and adult (60 days old) rat males exposed to MA during the entire prenatal period and compared them with the same parameters in age matched saline-exposed rats. There was a significant increase in the NR1 and NR2B subunits in the hippocampus of adult males, but not in adolescent males. We identified a significant change in adult MA-induced rats when compared to adult controls for NR2A and NR2B, while in adolescent MA rats this change was close to the boundary of significance. In summary, our study suggests that prenatal MA exposure is connected with changes in NMDAR subunit expression in adult rats but not in adolescent rats.

Unveiling the nanotoxicological aspects of Se nanomaterials differing in size and morphology.

Although the general concept of nanotechnology relies on exploitation of size-dependent properties of nanoscaled materials, the relation between the size/morphology of nanoparticles with their biological activity remains not well understood. Therefore, we aimed at investigating the biological activity of Se nanoparticles, one of the most promising candidates of nanomaterials for biomedicine, possessing the same crystal structure, but differing in morphology (nanorods vs. spherical particles) and aspect ratios (AR, 11.5 vs. 22.3 vs. 1.0) in human cells and BALB/c mice. Herein, we report that in case of nanorod-shaped Se nanomaterials, AR is a critical factor describing their cytotoxicity and biocompatibility. However, spherical nanoparticles (AR 1.0) do not fit this statement and exhibit markedly higher cytotoxicity than lower-AR Se nanorods. Beside of cytotoxicity, we also show that morphology and size substantially affect the uptake and intracellular fate of Se nanomaterials. In line with in vitro data, in vivo i.v. administration of Se nanomaterials revealed the highest toxicity for higher-AR nanorods followed by spherical nanoparticles and lower-AR nanorods. Moreover, we revealed that Se nanomaterials are able to alter intracellular redox homeostasis, and affect the acidic intracellular vesicles and cytoskeletal architecture in a size- and morphology-dependent manner. Although the tested nanoparticles were produced from the similar sources, their behavior differs markedly, since each type is promising for several various application scenarios, and the presented testing protocol could serve as a concept standardizing the biological relevance of the size and morphology of the various types of nanomaterials and nanoparticles.

The Anti-Proliferative Activity of Coordination Compound-Based ZnO Nanoparticles as a Promising Agent Against Triple Negative Breast Cancer Cells.

PURPOSE: The present study deals with the in vitro evaluation of the potential use of coordination compound-based zinc oxide (ZnO) nanoparticles (NPs) for the treatment of triple negative breast cancer cells (TNBrCa). As BrCa is one of the most prevalent cancer types and TNBrCa treatment is difficult due to poor prognosis and a high metastasis rate, finding a more reliable treatment option should be of the utmost interest. METHODS: Prepared by reacting zinc carboxylates (formate, acetate, propionate, butyrate, isobutyrate, valerate) and hexamethylenetetramine, 4 distinct coordination compounds were further subjected to two modes of conversion into ZnO NPs - ultrasonication with oleic acid or heating of pure precursors in an air atmosphere. After detailed characterization, the resulting ZnO NPs were subjected to in vitro testing of cytotoxicity toward TNBrCa and normal breast epithelial cells. Further, their biocompatibility was evaluated. RESULTS: The resulting ZnO NPs provide distinct morphological features, size, biocompatibility, and selective cytotoxicity toward TNBrCa cells. They internalize into two types of TNBrCa cells and imbalance their redox homeostasis, influencing their metabolism, morphology, and ultimately leading to their death via apoptosis or necrosis. CONCLUSION: The crucial properties of ZnO NPs seem to be their morphology, size, and zinc content. The ZnO NPs with the most preferential values of all three properties show great promise for a future potential use in the therapy of TNBrCa.

Cognitive deficits in the euthymic phase of unipolar depression.

Although neuropsychological deficits have been reported in patients with major depressive disorder (MDD) during an acute episode, relatively little is known about the persistence of these deficits in remission. This study investigated the performance of attention, executive function and verbal memory during remission from unipolar depressive episodes. We tested the hypothesis that outpatients do not differ in cognitive variables from controls. We did this using a well-defined outpatient sample, consisting of medicated and unmedicated patients, with a history of MDD. Ninety-seven subjects with MDD in remission ranging from young to old were compared with 97 healthy control subjects. Both samples were balanced for age, gender, and education levels. The Auditory Verbal Learning Test (AVLT) and the Trail Making Test (TMT) were used. Patients with remitted MDD, in comparison with controls, were impaired on tasks of attention, executive function and verbal memory. The individual level of depressive symptoms was not related to the cognitive performance. Small- to medium-sized significant correlations exist between cognitive test variables (as represented by Trail Making B and AVLT delayed recall) and level of depressive symptomatology (as measured by MADRS or BDI-II) in the total sample, indicating that higher levels of depressive symptomatology are associated with lower cognitive function. These findings suggest deficits in attention and delayed verbal recall can serve as an indicator for MDD in outpatients.

The Uniform Data Set, Czech Version: Normative Data in Older Adults from an International Perspective.

BACKGROUND: Outside of the United States, international perspectives on normative data for neuropsychological test performance, within diverse populations, have been scarce. The neuropsychological test battery from the Uniform Data Set (UDS) of the Alzheimer's Disease Centers (ADC) program of the United States National Institute on Aging (NIA) is one of the most sensitive batteries for the evaluation of both normal cognitive aging and pathological cognitive decline. OBJECTIVE: This study aimed to determine the feasibility of the Czech Neuropsychological Test Battery from the Uniform Data Set (UDS-Cz 2.0), while also evaluating the results obtained from an international perspective. METHODS: This paper describes data from 520 cognitively normal participants. Regression analyses were used to describe the influence of demographic variables on UDS-Cz test performance. RESULTS: Cognitive performance on all measures declined with age, with patient education level serving as a protective factor. Therefore, the present study provides normative data for the UDS-Cz, adjusted for the demographic variables of age and education. CONCLUSION: The present study determines the psychometric properties of the UDS-Cz and establishes normative values in the aging Czech population, which can be used in clinical settings.

Semantic verbal fluency impairment is detectable in patients with subjective cognitive decline.

Patients with subjective cognitive decline (SCD) are at higher risk for conversion to dementia due to Alzheimer's disease (AD). Semantic verbal fluency (SVF) seems to be impaired in the early stages of AD. The goal of the present study was to identify the discriminative potential of verbal fluency (VF) in patients with SCD to show if very early signs of cognitive decline may be detected in SCD. We examined 93 normal controls (NC) and 61 participants with SCD. Each participant was administered a comprehensive neuropsychological battery. All participants underwent tests of VF: phonemic verbal fluency (PVF), letters K and P and SVF (animals and vegetables categories). In addition to the total score, two 30-second intervals, and clustering and switching indices in SVF were evaluated. SCD generated fewer words in the total score and 30- to 60-second interval in vegetables category and they performed more switches in animals category. There was no significant difference between the SCD and the NC groups in all other VF measures. Quantitative measures of SVF (a decreased number of vegetables) as well as qualitative measures were detected in SCD group and could be considered as an early neuropsychological marker of subtle cognitive impairment.

The temperament and character inventory-revised (TCI-R): a psychometric characteristics of the Czech version.

We explore psychometric characteristics of a modified version of the Cloninger's personality questionnaire, the Temperament and Character Inventory-Revised (TCI-R) in a 200-subject sample. This sample was stratified in accordance with the Czech population. We performed principal component analyses and explored the factorial structure of the questionnaire, to establish internal consistency of each dimension. The factorial structure of the TCI-R was well defined for temperament, but not for character. A robust factor was obtained for Persistence. All dimensions obtained higher alpha Cronbach coefficients with the TCI-R than with the TCI. There were high reliability coefficients in test-retest for TCI-R and lower for TCI/TCI-R were found. Significant correlations were obtained between age and NS, RD and SD. The TCI-R seems to have similar psychometric characteristics to TCI, with significant improvements in temperament factor structure and internal consistency of most dimensions.

The Reliability of Clock Drawing Test Scoring Systems Modeled on the Normative Data in Healthy Aging and Nonamnestic Mild Cognitive Impairment.

The Clock Drawing Test (CDT) is a commonly used tool in clinical practice and research for cognitive screening among older adults. The main goal of the present study was to analyze the interrater reliability of three different CDT scoring systems (by Shulman et al., Babins et al., and Cohen et al.). We used a clock with a predrawn circle. The CDT was evaluated by three independent raters based on the normative data set of healthy older and very old adults and patients with nonamnestic mild cognitive impairment (naMCI; N = 438; aged 61-94). We confirmed a high interrater reliability measured by the intraclass correlation coefficients (ICCs): Shulman ICC = .809, Babins ICC = .894, and Cohen ICC = .862, all p < .001. We found that age and education levels have a significant effect on CDT performance, yet there was no influence of gender. Finally, the scoring systems differentiated between naMCI and age- and education-matched controls: Shulman's area under the receiver operating characteristic curve (AUC) = .84, Cohen AUC = .71, all p < .001; and a slightly lower discriminative ability was shown by Babins: AUC = .65, p = .012.

Montreal cognitive assessment (MoCA): Normative data for old and very old Czech adults.

The principal aim of our study was to present norms for old and very old Czech adults on the Czech version of the Montreal Cognitive Assessment (MoCA) and investigate the influence of social and demographic factors on MoCA performance. We analyzed 540 adults aged ≥ 60 years (5-year age categories; nationally representative sample in terms of sex and educational level), who met strict inclusion criteria for the absence of neurodegenerative disorders and performed within normal range in neuropsychological assessment. Using multiple regression model, we found that MoCA performance was affected by age and education (both p < .001) but not sex. The study provides normed percentile estimates for MoCA performance stratified by age (60-74 years; ≥ 75 years) and education lower versus higher. We also present percentile equivalents for the MoCA and Mini-Mental State Examination (MMSE) for use in clinical practice. We found age- and education-related effects on MoCA performance which support the use of culturally adapted normative data.

A parsimonious scoring and normative calculator for the Parkinson's disease mild cognitive impairment battery.

OBJECTIVE: The aim of the present study was to provide a regression-based calculator that takes premorbid functioning into account to detect subtle cognitive decline, as is often present in pre-dementia states, especially mild cognitive impairment in Parkinson's disease (PD-MCI). METHOD: We used demographic adjustments based on sex, age, and education of 699 normative participants that fulfilled exclusion criteria for ascertaining the diagnostic accuracy of the Movement Disorders Society PD-MCI battery at Level II. We examined the clinical validity of the battery on 36 PD patients. RESULTS: An estimated z-score was calculated for any raw score based on different models that adjust for the demographic predictors of gender, age, and education, either concurrently, individually or without covariates. We provide a useful online z-score, SD, and percentile calculator that yields estimates of cognitive impairment based on normative sample for each of the ten neuropsychological tests and enables actuarial decision-making regarding its level and profile (number of domains impaired). We document the clinical utility and applicability of the calculator on a patient with PD-MCI and show the discriminative validity of all measures in the battery by comparing PD-MCI and PD without cognitive impairment with the highest area under the curve (.94) for Tower of London at -2 SD threshold. CONCLUSIONS: Our normative calculator introduces a practical web-based psychometric tool for the evaluation of PD-MCI status in clinical settings. We show the detection potential of each of ten measures included in the battery and delineate the diagnostic precision of the PD-MCI battery.

Clinimetric validity of the Trail Making Test Czech version in Parkinson's disease and normative data for older adults.

OBJECTIVE: The influence of demographic variables on the Trail Making Test (TMT) performance in older individuals and empirical findings on clinical validity in predementia states, such as Parkinson's disease mild cognitive impairment (PD-MCI), are limited. The principal aim of this study was to add normative data for the Czech population of older adults and explore the clinimetric properties between PD-MCI and PD patients with normal cognition (PD-NC). METHOD: The study included 125 PD patients classified as 77 PD-MCI and 48 PD-NC and 528 older individuals (60-74 years, further subdivided for normative tables into 60-64, 65-69 and 70-74 age groups) and very old individuals (aged 75-96, further subdivided into 75-79, 80-84, 85-96) cognitively intact Czech adults. RESULTS: Mostly age, to a lesser extent education but not gender, was associated with most TMT basic and derived indices (TMT-B - A). However, the ratio of TMT-B/TMT-A was independent of both age and education. We provide corresponding T-scores that minimize the effect of demographic variables. The results showed a high discriminative validity of TMT basic and derived indices for the differentiation of PD-MCI from PD-NC (all p < .05). The classification accuracy for the differentiation of PD-MCI from controls was optimal for the TMT-B only (80% area under the curve) based on norm adjusted scores. The classification accuracy of the TMT for PD-MCI vs. PD-NC was suboptimal. CONCLUSIONS: The cut-offs and normative standards are useful in clinical practice for those working with PD patients and very old adults.

Subjective Cognitive Complaints in Cognitively Healthy Older Adults and Their Relationship to Cognitive Performance and Depressive Symptoms.

BACKGROUND: Subjective cognitive complaints (SCCs) may be an early marker of prodromal Alzheimer's disease. OBJECTIVES: Using a 10-item yes/no SCCs questionnaire (Le Questionnaire de Plainte Cognitive [QPC]), we evaluated the prevalence and distribution of SCCs in cognitively healthy Czech older adults and examined total score and specific QPC items in relation to depressive symptomology and cognitive performance. METHODS: A sample of 340 cognitively healthy older community-dwelling volunteers aged 60 or older from the third wave of the longitudinal project National Normative Study of Cognitive Determinants of Healthy Aging, who underwent a comprehensive neuropsychological assessment and completed the QPC and the 15-item Geriatric Depression Scale (GDS-15). Regression analysis was controlled for age when GDS-15 was the outcome and for age and GDS-15 with cognitive domains as the outcome. RESULTS: 71% reported 1 + SCCs, with prevalence of individual complaints ranging from 4% to 40%. The number of SCCs was associated with GDS-15 (p < 0.001). Personality change (p < 0.001) and Limitation in daily activities (p = 0.002) were significantly associated with higher GDS-15 score and Spatial orientation difficulties (p = 0.019) and Impression of worse memory in comparison to peers (p = 0.012) were significantly associated with lower memory performance. CONCLUSIONS: We identified some cognitive complaints that were very common in our sample. Overall, a higher number of SCCs in well cognitively functioning individuals was most closely related to depressive symptomatology, while some specific complaints reflected lower memory performance and should be considered when screening for people at risk of cognitive decline.

Propositional Density in Spoken and Written Language of Czech-Speaking Patients With Mild Cognitive Impairment.

Purpose: Propositional density (PD) is a measure of content richness in language production that declines in normal aging and more profoundly in dementia. The present study aimed to develop a PD scoring system for Czech and use it to compare PD in language productions of older people with amnestic mild cognitive impairment (aMCI) and control participants matched on age, gender, and education. Method: Groups of patients with aMCI and cognitively healthy control participants (N = 20 each) provided short spoken and written language samples. Two samples were elicited for each modality, 1 describing recent events and 1 describing childhood memories. Series of neuropsychological tests were administered. The groups were compared using t-tests and the relations between measures using correlation coefficients. Results: PD was lower in spoken productions of patients with aMCI, compared with control participants, but only in language samples using remote memories. PD in these samples was related to verbal fluency and education but not to working memory. PD in written samples did not differ between participants with aMCI and control participants. Conclusions: PD in spoken language reflects the cognitive decline in people with aMCI, but the effect is relatively mild. The results support the existing findings that PD is related to verbal fluency.

The Prague Stroop Test: Normative standards in older Czech adults and discriminative validity for mild cognitive impairment in Parkinson's disease.

OBJECTIVE: The aim of this study was to provide normative data for older and very old Czech adults on the Prague Stroop Test (PST) and to test its discriminative validity in individuals with Parkinson's disease mild cognitive impairment (PD-MCI). METHOD: The construction of the PST was modeled after the Victoria Stroop Test. We examined 539 participants aged 60-96 that met strict inclusion criteria. After, we compared the PST scores for a group of 45 PD-MCI patients with a healthy adult sample (HAS) of 45 age- and education-matched individuals. RESULTS: I. In the non-clinical sample, robust age- and education-related influences were observed on all PST scores. No gender effect was noted. II. For clinical cases, interference condition (PST-C) was able to discriminate between PD-MCI and HAS (all scores ps < .01). Area under the curve (AUC) was 77% when a screening cut-off of ≤ 27 s was used, showing sensitivity of 82% and specificity of 53%. A more conservative diagnostic cut-off of ≤ 33 s showed sensitivity of 60% and specificity of 80%. DISCUSSION: The present study provides PST normative data for basic, interference, and error scores stratified by age (60-96 years). PST appears to be a helpful tool for the diagnostics of PD-MCI especially in research settings at Level II (Litvan et al., 2012) and for PD-MCI attention/working memory and executive function subtyping.

The malleability of working memory and visuospatial skills: a randomized controlled study in older adults.

There is accumulating evidence that training on working memory (WM) generalizes to other nontrained domains, and there are reports of transfer effects extending as far as to measures of fluid intelligence. Although there have been several demonstrations of such transfer effects in young adults and children, they have been difficult to demonstrate in older adults. In this study, we investigated the generalizing effects of an adaptive WM intervention on nontrained measures of WM and visuospatial skills. We randomly assigned healthy older adults to train on a verbal n-back task over the course of a month for either 10 or 20 sessions. Their performance change was compared with that of a control group. Our results revealed reliable group effects in nontrained standard clinical measures of WM and visuospatial skills in that both training groups outperformed the control group. We also observed a dose-response effect, that is, a positive relationship between training frequency and the gain in visuospatial skills; this finding was further confirmed by a positive correlation between training improvement and transfer. The improvements in visuospatial skills emerged even though the intervention was restricted to the verbal domain. Our work has important implications in that our data provide further evidence for plasticity of cognitive functions in old age.

Development, validity, and normative data study for the 12-word Philadelphia Verbal Learning Test [czP(r)VLT-12] among older and very old Czech adults.

The aim of the present study was to assess the validity of a 12-word Czech version of the Philadelphia (repeatable) Verbal Learning Test [czP(r)VLT-12]. The construction of the czP(r)VLT-12 was modeled after the California Verbal Learning Test (CVLT) and the nine-word Philadelphia (repeatable) Verbal Learning Test [P(r)VLT]. The czP(r)VLT-12 was constructed from a large corpus of old (60-74) and very old (75-96) Czech adults (n = 540). Participants met strict inclusion criteria for the absence of any active or past neurodegenerative disorders and performed within normal limits on other neuropsychological measures. Principal component analysis (PCA) and correlations between czP(r)VLT-12 factor structure and other memory tests were conducted. The czP(r)VLT-12 produced a four-factor solution, accounting for 70.90% of variance, with factors related to: (1) recall, (2) extra-list intrusion errors/recognition foils, (3) interference, and (4) acquisition rate; a solution similar to the CVLT and P(r)VLT. Increasing age resulted in a decline in most czP(r)VLT-12 indices, women outperformed men, and higher education led to higher scores. Memory performance in normal aging did not correlate with instrumental activities of daily living. Low, but significant, correlations were seen with other tests of cognitive performance (divergent validity). Appendices are available that provide normed percentile estimates of individual czP(r)VLT-12 performance stratified by age, education, and gender. In accordance with previous studies, these results demonstrate the usefulness of czP(r)VLT-12 in assessing declarative memory in older adults.

Czech version of Rey Auditory Verbal Learning test: normative data.

The present study provides normative data stratified by age for the Rey Auditory Verbal Learning test Czech version (RAVLT) derived from a sample of 306 cognitively normal subjects (20-85 years). Participants met strict inclusion criteria (absence of any active or past neurological or psychiatric disorder) and performed within normal limits on other neuropsychological measures. Our analyses revealed significant relationships between most RAVLT indices and age and education. Normative data are provided not only for basic RAVLT scores, but for the first time also for a variety of derived (gained/lost access, primacy/recency effect) and error scores. The study confirmed a logarithmic character of the learning slope and is consistent with other studies. It enables the clinician to evaluate more precisely subject's RAVLT memory performance on a vast number of indices and can be viewed as a concrete example of Quantified Process Approach to neuropsychological assessment.