Predicting progression of cognitive decline to dementia using dyadic patterns of subjective reporting: evidence from the CompAS longitudinal study.

Objective: To analyze the validity of self and informant reports, depressive symptomatology, and some sociodemographic variables to predict the risk of cognitive decline at different follow-up times. Methods: A total of 337 participants over 50 years of age included in the CompAS and classified as Cognitively Unimpaired (CU), Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) groups were assessed at baseline and three follow-ups. A short version of the QAM was administered to assess the severity of subjective cognitive complaints (SCCs), and the GDS-15 was used to evaluate the depressive symptoms. At each follow-up assessment, participants were reclassified according to the stability, regression or progression of their conditions. Logistic regression analysis was used to predict which CU, SCD and MCI participants would remain stable, regress or progress at a 3rd follow-up by using self- and informant-reported complaints, depressive symptomatology, age and education at baseline and 2nd follow-ups as the predictive variables. Results: Overall, self-reported complaints predicted progression between the asymptomatic and presymptomatic stages. As the objective deterioration increased, i.e., when SCD progressed to MCI or dementia, the SCCs reported by informants proved the best predictors of progression. Depressive symptomatology was also a predictor of progression from CU to SCD and from SCD to MCI. Conclusion: A late increase in self-reported complaints make valid estimates to predict subjective decline at asymptomatic stages. However, an early increase in complaints reported by informants was more accurate in predicting objective decline from asymptomatic stages. Both, early and late decrease in self-reported complaints successfully predict dementia from prodromic stage. Only late decrease in self-reported complaints predict reversion from prodromic and pre-symptomatic stages.

Do informant-reported subjective cognitive complaints predict progression to mild cognitive impairment and dementia better than self-reported complaints in old adults? A meta-analytical study.

BACKGROUND: Subjective cognitive complaints (SCCs) are considered a risk factor for objective cognitive decline and conversion to dementia. The aim of this study was to determine whether self-reported or informant-reported SCCs best predict progression to mild cognitive impairment (MCI) and/or dementia. METHODS: We reviewed prospective longitudinal studies of Cognitively Unimpaired (CU) older adults with self-reported and informant-reported SCCs at baseline, assessed by questions or questionnaires that considered the transition to MCI and/or dementia. A random-effects meta-analysis was performed to obtain pooled estimates and 95% CIs. RESULTS: Both self-reported and informant-reported SCCs are associated with an elevated risk of transition from CU to MCI and/or dementia. The association appears stronger and more robust for informant-reported data [1.38, with a 95% CI of 1.16 -1.64, p < 0.001] than for self-reported data [1.27 (95% CI 1.06 - 1.534, p = 0.011]. CONCLUSIONS: Our results suggest that corroborated information from one informant could provide important details for distinguishing between normal aging and clinical states.

Cognitive reserve and mental health in cognitive frailty phenotypes: Insights from a study with a Portuguese sample.

Background: Research on prevalence of cognitive frailty phenotypes in community-dwelling older adults in different countries is important to estimate their prevalence and to determine the influence of cognitive reserve and mental health in order to prevent frailty. The aims of this study were to estimate the prevalence of reversible and potentially reversible cognitive frailty (R-CF, PR-CF) in a Portuguese sample of old adults and explore the associations between these phenotypes and demographic, comorbidity, social support, cognitive reserve and mental health factors. Methods: We assessed frailty (Fried criteria) in 250 community-dwelling older adults (179 women) aged 60 years or over (mean 71.04 years) without dementia, neurological or psychiatric disorders. Subjective cognitive decline and Mild cognitive impairment were diagnosed according to standard criteria. The questionnaires Charlson Index, Medical Outcomes Study Social Support, Cognitive Reserve Index and General Health were used for assessing comorbidity, social support, cognitive reserve and mental health, respectively. Results: Prevalence of R-CF was 14%, and that of PR-CF, 15.2%. Cognitive frailty profiles differed significantly in relation to education, comorbidity, mental health, and cognitive reserve, but not in age or sex. Multivariate logistic regression showed that age, sex, comorbidity, social support, mental health, and cognitive reserve together predicted R-CF and PR-CF (90% specificity 75% sensitivity) with significant OR for mental health and cognitive reserve. Discussion: Cognitive reserve and mental health are important factors predicting R-CF and PR-CF. We recommend assessing these factors for early detection of cognitive frailty and promoting psychological well-being and lifestyles that increase cognitive reserve in adults.

[Adaptation and validation of aged adults' adaptation scale to their residence (EAPAR) in Chile]. / Adaptación y validación chilena de la escala de adaptación de la persona mayor a su residencia.

BACKGROUND: The adaptation of older people to nursing homes may be problematic. Scales to assess the degree of adaptation are required. AIM: To adapt and evaluate the psychometric characteristics of the Scale of Adaptation of the Older Adults to their Residence (EAPAR) in the Chilean population. MATERIAL AND METHODS: EAPAR and self-esteem scales were applied to 106 people aged 79 ± 7 years (57% women) living in nursing homes. Reliability was measured using Cronbach's alpha. RESULTS: The instrument was adequately understood by the Chilean participants. In the content validity, the structure of the scale appears homogeneous and with an acceptable statistical significance. CONCLUSIONS: EAPAR is a reliable and valid instrument to be used by health professionals.

Adaptación y validación chilena de la escala de adaptación de la persona mayor a su residencia / Adaptation and validation of aged adults' adaptation scale to their residence (EAPAR) in Chile

BACKGROUND: The adaptation of older people to nursing homes may be problematic. Scales to assess the degree of adaptation are required. AIM: To adapt and evaluate the psychometric characteristics of the Scale of Adaptation of the Older Adults to their Residence (EAPAR) in the Chilean population. MATERIAL AND METHODS: EAPAR and self-esteem scales were applied to 106 people aged 79 ± 7 years (57% women) living in nursing homes. Reliability was measured using Cronbach's alpha. RESULTS: The instrument was adequately understood by the Chilean participants. In the content validity, the structure of the scale appears homogeneous and with an acceptable statistical significance. CONCLUSIONS: EAPAR is a reliable and valid instrument to be used by health professionals.

Dual-task performance in old adults: cognitive, functional, psychosocial and socio-demographic variables.

BACKGROUND: Dual tasking, or the ability to executing two tasks simultaneously, has been used in recent research to predict cognitive impairments, physical frailty, and has been linked with cognitive frailty in old adults. AIM: This study aimed to determine age-related variables can predict dual-task (DT) performance in the older population. METHODS: A total of 258 healthy community-dwelling participants + 60 years were assessed in relation to their functional capacity, health, well-being, social support and years of education. Performance of a cognitive (Fluency) task and a cognitive-motor (Tracking) task was recorded under single and DT conditions. Multiple linear regression analysis was carried out for each dependent variable, in separate models including cognitive, functional and psychosocial variables. RESULTS: Performance in Fluency in DT conditions was predicted by cognitive variables, whereas performance in Tracking DT conditions was predicted by positive interaction, health status, age and motor variables. DISCUSSION: The findings suggest that a wide range of cognitive, psychological, social, physical and functional variables influence cognitive and motor performance in aging. CONCLUSION: DT methodology is sensitive to different age-related changes and could be related to frailty conditions in aging.

Normative scores for the Timed Up & Go in a Spanish sample of community-dweller adults with preserved functionality / Puntuaciones normativas para el test Timed Up & Go en una muestra comunitaria española de adultos con funcionalidad preservada

Our aim was to calculate the ‘Timed Up & Go’ (TUG) normative scores in a Spanish sample composed of functional older adults. The TUG test provides a measure of global ambulation skills and its total score has been successfully related with functionality and other important health variables in older adults. Reliable norms are needed for adults 50 years and older that allow the early identification and intervention in motor disturbances. The study was carried out with adults from Galicia and Valencia living in the community. A total of 314 Spanish community-living participants, aged from 50 to 90 years and functionality preserved were assessed through the implementation of a cross-sectional design. Health, comorbidity, physical activity, cognitive status, functionality measures and TUG test scores were obtained. TUG scores were successfully predicted by age and gender, and significantly correlated with cognitive status and comorbidity. TUG norms were calculated by age-group for women and men. TUG normative scores were below 13s and slightly lower in men. Normative scores for women and men were lower than those proposed in studies carried-out in our context. Our norms showed risk reference scores close to those obtained by meta-analytical procedures.(AU)

Conocer las puntuaciones normativas del test Timed Up & Go (TUG) sobre una muestra de adultos mayores con funcionalidad preservada. El test TUG proporciona una medida global de deambulación, y su puntuación total se ha relaciona con medidas de funcionalidad y otras relacionadas con la salud en las personas mayores. Conviene disponer de valores normativos para adultos a partir de los 50 años que permitan realizar una identificación e intervención tempranas en las dificultades motrices. El estudio se llevó a cabo con personas adultas de Galicia y Valencia que viven en la comunidad. Un total de 314 participantes mayores, de entre 50 y 90 años, que vivían en la comunidad fueron evaluadas implementando un diseño transversal. Se obtuvieron medidas de salud, comorbilidad, actividad física, cognición, funcionalidad, además de las puntuaciones en el test TUG. Edad y género predijeron de modo significativo la puntuación total en el TUG que, además, estableció correlaciones significativas con estatus cognitivo y comorbilidad. Se calcularon los valores normativos para el TUG por grupo de edad para varones y mujeres. Las puntuaciones normativas estuvieron por debajo de los 13s, y fueron ligeramente inferiores en los varones. Las puntuaciones normativas estuvieron, en ambos géneros, por debajo de los valores propuestos en estudios previos realizados con población española. Nuestros valores normativos ofrecen puntuaciones de referencia para la detección de riesgo semejantes a las obtenidas por procedimientos meta-analíticos.(AU)

Relevance of Complaint Severity in Predicting the Progression of Subjective Cognitive Decline and Mild Cognitive Impairment: A Machine Learning Approach.

BACKGROUND: The presence of subjective cognitive complaints (SCCs) is a core criterion for diagnosis of subjective cognitive decline (SCD); however, no standard procedure for distinguishing normative and non-normative SCCs has yet been established. OBJECTIVE: To determine whether differentiation of participants with SCD according to SCC severity improves the validity of the prediction of progression in SCD and MCI and to explore validity metrics for two extreme thresholds of the distribution in scores in a questionnaire on SCCs. METHODS: Two hundred and fifty-three older adults with SCCs participating in the Compostela Aging Study (CompAS) were classified as MCI or SCD at baseline. The participants underwent two follow-up assessments and were classified as cognitively stable or worsened. Severity of SCCs (low and high) in SCD was established by using two different percentiles of the questionnaire score distribution as cut-off points. The validity of these cut-off points for predicting progression using socio-demographic, health, and neuropsychological variables was tested by machine learning (ML) analysis. RESULTS: Severity of SCCs in SCD established considering the 5th percentile as a cut-off point proved to be the best metric for predicting progression. The variables with the main role in conforming the predictive algorithm were those related to memory, cognitive reserve, general health, and the stability of diagnosis over time. CONCLUSION: Moderate to high complainers showed an increased probability of progression in cognitive decline, suggesting the clinical relevance of standard procedures to determine SCC severity. Our findings highlight the important role of the multimodal ML approach in predicting progression.

Normative scores for the Timed Up & Go in a Spanish sample of community-dweller adults with preserved functionality.

Our aim was to calculate the 'Timed Up & Go' (TUG) normative scores in a Spanish sample composed of functional older adults. The TUG test provides a measure of global ambulation skills and its total score has been successfully related with functionality and other important health variables in older adults. Reliable norms are needed for adults 50 years and older that allow the early identification and intervention in motor disturbances. The study was carried out with adults from Galicia and Valencia living in the community. A total of 314 Spanish community-living participants, aged from 50 to 90 years and functionality preserved were assessed through the implementation of a cross-sectional design. Health, comorbidity, physical activity, cognitive status, functionality measures and TUG test scores were obtained. TUG scores were successfully predicted by age and gender, and significantly correlated with cognitive status and comorbidity. TUG norms were calculated by age-group for women and men. TUG normative scores were below 13s and slightly lower in men. Normative scores for women and men were lower than those proposed in studies carried-out in our context. Our norms showed risk reference scores close to those obtained by meta-analytical procedures.

Changes in visual memory in mild cognitive impairment: a longitudinal study with CANTAB.

BACKGROUND: Mild cognitive impairment (MCI), as a stage in the cognitive continuum between normal ageing and dementia, is mainly characterized by memory impairment. The aims of this study were to examine CANTAB measures of temporal changes of visual memory in MCI and to evaluate the usefulness of the baseline scores for predicting changes in cognitive status. METHODS: The study included 201 participants aged over 50 years with subjective cognitive complaints. Visual memory was assessed with four CANTAB tests [paired associates learning (PAL), delayed matching to sample (DMS), pattern recognition memory (PRM) and spatial span (SSP)] administered at baseline and on two further occasions, with a follow-up interval of 18-24 months. Participants were divided into three groups according to the change in their cognitive status: participants with subjective cognitive complaints who remained stable, MCI participants who remained stable (MCI-Stable) and MCI participants whose cognitive deterioration continued (MCI-Worsened). Linear mixed models were used to model longitudinal changes, with evaluation time as a fixed variable, and multinomial regression models were used to predict changes in cognitive status. RESULTS: Isolated significant effects were obtained for age and group with all CANTAB tests used. Interactions between evaluation time and group were identified in the PAL and DMS tests, indicating different temporal patterns depending on the changes in cognitive status. Regression models also indicated that CANTAB scores were good predictors of changes in cognitive status. CONCLUSIONS: Decline in visual memory measured by PAL and DMS tests can successfully distinguish different types of MCI, and considered together PAL, DMS, PRM and SSP can predict changes in cognitive status.

Prevalence of Cognitive Frailty, Do Psychosocial-Related Factors Matter?

Cognitive frailty (CF) is a topic of growing interest with implications for the study of preventive interventions in aging. Nevertheless, little research has been done to assess the influence of psychosocial variables on the risk of CF. Our objectives were to estimate the prevalence of CF in a Spanish sample and to explore the influence of psychosocial variables in this prevalence. Physical frailty and cognitive, functional, psychosocial, and socio-demographic aspects were assessed in a sample of 285 participants over 60 years. Univariate and multivariate logistic regression models were carried out. A prevalence of 21.8% (95% CI 17.4-26.9) was established when both frail and pre-frail conditions were included, and a prevalence of 3.2% (95% CI 1.7-5.9) if only frail individuals were considered. Age, educational level, profession and psychological well-being variables significantly predicted CF. Frailty and pre-frailty are high-prevalence health conditions in older adults influenced by socio-demographic, socio-educative and affective factors.

Longitudinal Patterns of the Tip-of-the-Tongue Phenomenon in People With Subjective Cognitive Complaints and Mild Cognitive Impairment.

BACKGROUND: The Tip-of-the-Tongue (ToTs) state is considered a universal phenomenon and is a frequent cognitive complaint in old age. Previous cross-sectional studies have found that ToT measures successfully discriminate between cognitively unimpaired adults and adults with Mild Cognitive Impairment (MCI). The aim of this study was to identify longitudinal patterns of ToTs in individuals with subjective complaints and with MCI regarding progress of their cognitive status. METHOD: The study included 193 participants with subjective cognitive complaints (SCC) and 56 participants with MCI who completed a baseline and two follow-up assessments, with an interval of about 18 months between each assessment. Participants were classified into three groups by considering cognitive stability or deterioration from the baseline diagnosis: SCC-stable, MCI-stable and MCI-worsened. Participants performed a ToT task involving recognition and naming of famous people depicted in 50 photographs. Generalized Linear Mixed Models (GLMM) were used to model longitudinal changes in familiarity, feeling of knowing, semantic access, phonological access and verbal fluency. RESULTS: Phonological access differentiated MCI patients, stable and worsened, from adults with SCCs at all evaluation times. Phonological access declined over time in the three groups, without significant interactions between groups and time. DISCUSSION: This study provides the first longitudinal evidence of differences in ToT measures for adults with MCI. The findings indicate that phonological access measures successfully differentiated between the diagnostic groups. However, slopes remain irrespective of the diagnostic group and progression toward more advance stages of cognitive impairment.

Cognitive reserve and working memory in cognitive performance of adults with subjective cognitive complaints: longitudinal structural equation modeling.

OBJECTIVE: To study the influence of cognitive reserve (CR) on cognitive performance of individuals with subjective cognitive complaints (SCCs) within a period of 36 months. DESIGN: We used a general linear model repeated measures procedure to analyze the differences in performance between three assessments. We used a longitudinal structural equation modeling to analyze the relationship between CR and cognitive performance at baseline and at two follow-up assessments. SETTING: Participants with SCCs were recruited and assessed in primary care health centers. PARTICIPANTS: A total of 212 participants older than 50 years with SCCs. MEASUREMENTS: Cognitive reserve data were collected with an ad hoc questionnaire administered to the subjects in an interview. General cognitive performance (GCP), episodic memory (EM), and working memory (WM) have been evaluated. The Mini-Mental State Examination and the total score of Spanish version of the Cambridge Cognitive Examination evaluated the GCP. Episodic memory was assessed with the Spanish version of the California Verbal Learning. Working memory was evaluated by the counting span task and the listening span task. RESULTS: The satisfactory fit of the proposed model confirmed the direct effects of CR on WM and GCP at baseline, as well as indirect effects on EM and WM at first and second follow-up. Indirect effects of CR on other cognitive constructs via WM were observed over time. CONCLUSION: The proposed model is useful for measuring the influence of CR on cognitive performance over time. Cognitive response acquired throughout life may influence cognitive performance in old age and prevent cognitive deterioration, thus increasing processing resources via WM.

Does the neuropsychiatric inventory predict progression from mild cognitive impairment to dementia? A systematic review and meta-analysis.

BACKGROUND: Neuropsychiatric Symptoms (NPS) are common in Mild Cognitive Impairment (MCI). The Neuropsychiatric Inventory (NPI) and its shorter version, the Neuropsychiatric Inventory Questionnaire (NPI-Q), are the most common measures to assess NPS. Our objective was to determine if NPI/NPI-Q ratings predict conversion from MCI to dementia. METHODS: Empirical longitudinal studies published in English or Spanish, concerned with the role of NPS as a risk factor for conversion from MCI to dementia, with a diagnosis of MCI following clinical criteria, that reported NPI/NPI-Q total score in converters versus non-converters, were included. Random effects models were used, and heterogeneity was explored with stratification and a random-effects meta-regression. The overall conversion rate and the standardized mean difference (SMD) for evolution, as a function of NPI/NPI-Q scores, were calculated. RESULTS: The overall conversion rate was 35 %. Mean NPI/NPI-Q ratings were higher in converters versus in non-converters, with the overall SMD approaching significance. Heterogeneity was observed in studies of more than two years of follow-up and in a study with a mean age of more than 80 years. This heterogeneity concerned the size, not the direction of the difference. CONCLUSIONS: Our results suggest that NPI/NPI-Q ratings are associated with conversion from MCI to dementia.

Does Empirically Derived Classification of Individuals with Subjective Cognitive Complaints Predict Dementia?

(1) Background: Early identification of mild cognitive impairment (MCI) in people reporting subjective cognitive complaints (SCC) and the study of progression of cognitive decline are important issues in dementia research. This paper examines whether empirically derived procedures predict progression from MCI to dementia. (2) Methods: At baseline, 192 participants with SCC were diagnosed according to clinical criteria as cognitively unimpaired (70), single-domain amnestic MCI (65), multiple-domain amnestic MCI (33) and multiple-domain non-amnestic MCI (24). A two-stage hierarchical cluster analysis was performed for empirical classification. Categorical regression analysis was then used to assess the predictive value of the clusters obtained. Participants were re-assessed after 36 months. (3) Results: Participants were grouped into four empirically derived clusters: Cluster 1, similar to multiple-domain amnestic MCI; Cluster 2, characterized by subjective cognitive decline (SCD) but with low scores in language and working memory; Cluster 3, with specific deterioration in episodic memory, similar to single-domain amnestic MCI; and Cluster 4, with SCD but with scores above the mean in all domains. The majority of participants who progressed to dementia were included in Cluster 1. (4) Conclusions: Cluster analysis differentiated between MCI and SCD in a sample of people with SCC and empirical criteria were more closely associated with progression to dementia than standard criteria.

Using an Overlapping Time Interval Strategy to Study Diagnostic Instability in Mild Cognitive Impairment Subtypes.

(1) Background: Mild cognitive impairment (MCI) is a diagnostic label in which stability is typically low. The aim of this study was to examine temporal changes in the diagnosis of MCI subtypes by using an overlapping-time strategy; (2) Methods: The study included 435 participants aged over 50 years with subjective cognitive complaints and who completed at least one follow-up evaluation. The probability of transition was estimated using Bayesian odds ratios; (3) Results: Within the different time intervals, the controls with subjective cognitive complaints represented the largest proportion of participants, followed by sda-MCI at baseline and in the first five intervals of the follow-up, but not in the last eight intervals. The odds ratios indicated higher odds of conversion to dementia in sda-MCI and mda-MCI groups relative to na-MCI (e.g., interval 9-15 months-sda-MCI OR = 9 and mda-MCI OR = 3.36; interval 27-33-sda-MCI OR = 16 and mda-MCI = 5.06; interval 42-48-sda-MCI OR = 8.16 and mda-MCI = 3.45; interval 45-51-sda-MCI OR = 3.31 and mda-MCI = 1); (4) Conclusions: Notable patterns of instability consistent with the current literature were observed. The limitations of a prospective approach in the study of MCI transitions are discussed.

Lenguaje en la Enfermedad de Parkinson. Retos para la Logopedia / Language in Parkinson's disease. Challenges for speech therapy

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Machine learning approaches to studying the role of cognitive reserve in conversion from mild cognitive impairment to dementia.

OBJECTIVES: The overall aim of the present study was to explore the role of cognitive reserve (CR) in the conversion from mild cognitive impairment (MCI) to dementia. We used traditional and machine learning (ML) techniques to compare converter and nonconverter participants. We also discuss the predictive value of CR proxies in relation to the ML model performance. METHODS: In total, 169 participants completed the longitudinal study. Participants were divided into a control group and three MCI subgroups, according to the Petersen criteria for diagnosis. Information about the participants was compared using nine ML classification techniques. Seven relevant performance metrics were computed in order to evaluate the accuracy of prediction regarding converter and nonconverter participants. RESULTS: ML algorithms applied to socio-demographic, basic health, and CR proxy data enabled prediction of conversion to dementia. The best performing models were the gradient boosting classifier (accuracy (ACC) = 0.93; F1 = 0.86, and Cohen κ = 0.82) and random forest classifier (ACC = 0.92; F1 = 0.79, and Cohen κ = 0.71). Use of ML techniques corroborated the protective role of CR as a mediator of conversion to dementia, whereby participants with more years of education and higher vocabulary scores survived longer without developing dementia. CONCLUSIONS: We used ML approaches to explore the role of CR in conversion from MCI to dementia. The findings indicate the potential value of ML algorithms for detecting risk of conversion to dementia in cognitive aging and CR studies. Further research is required to develop an ML-based procedure that can be used to make robust predictions.

Assessing mild behavioral impairment with the mild behavioral impairment checklist in people with subjective cognitive decline.

ABSTRACTObjectives:To estimate the prevalence of Mild Behavioral Impairment (MBI) in people with Subjective Cognitive Decline (SCD), and validate the Mild Behavioral Impairment Checklist (MBI-C) with respect to score distribution, sensitivity, specificity, and utility for MBI diagnosis, as well as correlation with other neuropsychological tests. DESIGN: Correlational study with a convenience sampling. Descriptive, logistic regression, ROC curve, and bivariate correlations analyses were performed. SETTING: Primary care health centers. PARTICIPANTS: 127 patients with SCD. MEASUREMENTS: An extensive evaluation, including Questionnaire for Subjective Memory Complaints, Mini-Mental State Examination, Cambridge Cognitive Assessment-Revised, Neuropsychiatric Inventory-Questionnaire (NPI-Q), the Geriatric Depression Scale-15 items (GDS-15), the Lawton and Brody Index and the MBI-C, which was administered by phone to participants' informants. RESULTS: MBI prevalence was 5.8% in those with SCD. The total MBI-C scoring was low and differentiated people with MBI at a cut-off point of 8.5 (optimizing sensitivity and specificity). MBI-C total scoring correlated positively with NPI-Q, Questionnaire for Subjective Cognitive Complaints (QSCC) from the informant and GDS-15. CONCLUSIONS: The phone administration of the MBI-C is useful for detecting MBI in people with SCD. The prevalence of MBI in SCD was low. The MBI-C detected subtle Neuropsychiatric symptoms (NPS) that were correlated with scores on the NPI-Q, depressive symptomatology (GDS-15), and memory performance perceived by their relatives (QSCC). Next steps are to determine the predictive utility of MBI in SCD, and its relation to incident cognitive decline over time.