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Cognitive functioning in first-episode schizophrenia.

OBJECTIVE: To compare the cognitive functioning of a sample of patients experiencing their first episode of schizophrenia with that of patients with an established schizophrenia illness. DESIGN: Cross-sectional and longitudinal study. SETTING: The Calgary Early Psychosis Treatment and Prevention Program and an outpatient clinic in a department of psychiatry at a university-affiliated hospital. PARTICIPANTS: One hundred and eleven patients who were experiencing their first episode of schizophrenia and 76 outpatients with an established schizophrenia illness. MEASURES: The Positive and Negative Syndrome Scale for schizophrenia was administered to all subjects to determine levels of positive and negative symptoms. Executive functioning, information processing, visual memory, and immediate and delayed verbal memory were assessed. RESULTS: There were limited differences between the 2 groups in terms of cognitive functioning. Although the first-episode patients demonstrated generally superior scores, their performance was impaired. CONCLUSIONS: These results support the findings of previous studies suggesting that first-episode patients demonstrate cognitive impairments similar to those of patients with an established schizophrenia illness.

Adult↗

The effects of KATP channel modulators on counterregulatory responses and cognitive function during acute controlled hypoglycaemia in healthy men: a pilot study.

AIMS: To examine the effects of agents that alter potassium adenosine triphosphate (KATP) channel activity in beta-cells on cognitive function and counterregulatory hormone responses during acute hypoglycaemia, given the physiological similarities between the pancreatic beta-cell and the hypothalamic glucose-sensitive neurones (GSN) and the widespread distribution of sulphonylurea receptors in neuronal cells throughout the brain. METHODS: Ten healthy males were studied on four occasions and in random order underwent three stepped hypoglycaemic (plasma glucose aims: 3.4, 2.8, 2.4 mmol/l) and one euglycaemic (plasma glucose aim: 5 mmol/l) insulin clamps. Prior to each hypoglycaemic study, volunteers received either 10 mg glibenclamide, or 5 mg/kg diazoxide or placebo orally. Cognitive function, symptom scores and counterregulatory hormone responses were measured at each glycaemic level. RESULTS: There was no statistically significant effect of either drug on the symptoms generated or the counterregulatory hormonal response during hypoglycaemia. However, cognitive function was better preserved during hypoglycaemia in the glibenclamide-treated arm, particularly four-choice reaction time which deteriorated at a plasma glucose 2.5 mmol/l compared with 3.0 mmol/l with diazoxide (P = 0.015) and 2.9 mmol/l with placebo (P = 0.114). CONCLUSIONS: Single doses of pharmacological agents which alter membrane KATP channel activity do not affect the counterregulatory response to hypoglycaemia but may modify cognitive function during cerebral glucopenia. The unexpected effects of glibenclamide on cortical function suggest a novel action of sulphonylureas that warrants further investigation.

Adenosine Triphosphate↗

The influence of growth hormone (GH) substitution on patient-reported outcomes and cognitive functions in GH-deficient patients: a meta-analysis.

OBJECTIVE: The influence of growth hormone (GH) replacement on patient-reported outcomes (i.e., quality of life, health status and well-being) and cognitive functioning in GH-deficient adults is controversial. DESIGN: We carried out a meta-analysis of clinical trials concerning the influence of GH substitution on patient-reported outcomes and cognitive functions (studies were selected from 1985 to 2004). The results of individual studies were combined in a series of meta-analyses using a random effects model. Effects of GH replacement in GH-deficient adults were compared to baseline and/or placebo. RESULTS: Fifteen studies on GH and patient-reported outcomes were included (830 patients, follow-up 3-50 months). Four of these studies also provided data on cognitive functions (85 patients, follow-up 6-12 months). Relative to baseline, GH treatment is found to have a large effect on patient-reported outcomes at 3 months, a medium effect at 6 months and a small effect at 12 months. With respect to the median treatment duration of 6 months placebo appears to be as effective as GH substitution. Cognitive functioning does not improve after 6 months of GH substitution, relative to baseline. CONCLUSION: This meta-analysis provides no evidence that GH improves patient-reported outcomes in GH-deficient patients. As the amount of cognitive data was too limited to allow for comparisons with placebo, from the present meta-analysis no conclusions can be drawn with respect to the impact of GH treatment on cognition.

Adolescent↗

Structured treatment and teaching of patients with Type 2 diabetes mellitus and impaired cognitive function--the DICOF trial.

BACKGROUND: Patient education is integral part of any diabetes therapy in Germany, but elderly patients are not able to follow the variety of topics comprising standard treatment and teaching programmes (TTP), primarily due to impaired neuropsychological function. This leads to deficits in diabetes knowledge and hindered ability for diabetes self-management. AIM: To evaluate structured TTP for geriatric patients with impaired cognitive function. PATIENTS AND METHODS: A neuropsychological examination was performed on all patients over 54 years [n=102, age 68.6 +/- 8.7 years, diabetes duration 10.3 (0.03-35.4) years, HbA1c 10.3 +/- 1.7% (HPLC, Diamat, NR 4.5-6.3%), cognitive function 87.7 +/- 12.3 IQ points] who took part in TTP for insulin therapy. Patients with impaired cognitive function participated either in the standard TTP of Berger [n = 35, age 67.6 +/- 8.9 years, diabetes duration 9.9 (0.04-35.4) years, HbA1c 10.3 +/- 2.0%] or in the specialized structured geriatric DICOF-TTP [n=33, age 70.4 +/- 8.2 years, diabetes duration 10.4 (0.03-24.9) years, HbA1c 10.7 +/- 1.8%]. RESULTS: After TTP there were no differences in knowledge and ability for diabetes self-management (standard/DICOF: knowledge 11.0 +/- 2.6 vs. 12.2 +/- 2.7 points, P = 0.11; handling 14.9 +/- 3.3 vs. 15.9 +/- 2.5 points, P = 0.18). However, patients who took part in the DICOF programme showed better scores in satisfaction with the education programme [standard/DICOF 44.7 (31-57) vs. 52.5 (45-59) points, P < 0.001]. Six months later the DICOF participants showed better results regarding diabetes self-management (standard/DICOF: handling 12.5 +/- 4.1 vs. 15.9 +/- 3.1 points, P = 0.001). Both groups showed HbA1c decrease (8.3 +/- 1.4 vs. 8.5 +/- 1.3%, P=0.62) and similar incidence of acute complications. CONCLUSIONS: Elderly patients with impaired cognitive function should take part in specialized structured TTP. This leads to both better satisfaction with the education programme and an improved ability for diabetes self-management.

Aged↗

Personality and self-report of cognitive functioning.

We examined the relationship of trait personality dimensions (negative affectivity and positive affectivity) on self-report of cognitive functioning. Ninety-six subjects who were screened to be without evidence of psychiatric or neurologic disorder, and who had previously completed the Tellegen Differential Personality Questionnaire (mean interval = 2 years) were sent a self-report questionnaire of cognitive functioning (MASQ). As predicted, negative affectivity (NA) was more strongly related to self-appraisal of cognitive functioning than was positive affectivity (PA); subjects with higher NA scores acknowledged more cognitive difficulties. Negative affectivity was also a stronger predictor of cognitive self-report than was self-report of current sad mood state. The implications of these findings for the examination of self-appraisal and accuracy of self-report are discussed.

Journal Article↗

Cognitive function and assessment of lung function in the elderly.

The feasibility of spirometry or respiratory impedance measurements for assessing lung function in the elderly was compared in 208 institutionalized patients with various degrees of cognitive function impairment. Respiratory impedance was determined by the forced oscillation technique. Cognitive function was assessed by the score for the mini-mental state (MMS) examination. Of the 208 patients, 126 had severe cognitive impairment (MMS < or = 17), 36 had mild impairment (18 < or = MMS < or = 23), and 46 had no impairment (MMS > or = 24). Of the 208 patients, respiratory impedance measurements were possible in 159, whereas in only 85 was spirometry possible. The overall difference between the feasibility rates for the spirometric and respiratory impedance measurements was highly significant (chi 2 = 71.4; p < 10(-6)). The difference between the feasibility rates for the two techniques was higher in the group of subjects with severe cognitive impairment than in the groups with mild impairment and no impairment, respectively. Among the 84 patients able to complete both tests, significant correlations were found between the spirometric and respiratory impedance measurements. These results indicate that respiratory impedance measurement seems a more useful tool than spirometry for assessing lung function in elderly patients whenever cognitive function is impaired.

Aged↗

Cognitive function and endogenous sex hormones in older women.

OBJECTIVE: To determine if endogenous hormone levels predict cognitive function in older women. DESIGN: A longitudinal, population-based study. SETTING: Rancho Bernardo, California PARTICIPANTS: A total of 393 community-dwelling women aged 55 to 89 years who were not using replacement estrogen. METHODS: Between 1984 and 1987, sera were collected for measurement of total and bioavailable testosterone, total and bioavailable estradiol, and estrone. Between 1988 and 1991, 12 standard neuropsychological tests were administered, including two items from the Blessed Information-Memory-Concentration Test, three measures of retrieval from the Buschke-Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini-Mental State Examination (MMSE) with individual analysis of the Serial 7's and the "World" Backwards components, and the Trail-Making Test part B (Trails B). The association between the five hormones and the 12 cognitive function tests was tested in age- and education-adjusted analyses using linear regression, partial correlation, quintile and categorical analyses. RESULTS: Women with better MMSE scores (>23) had significantly higher adjusted mean total and bioavailable testosterone levels (P = .009; P = .02, respectively). Using linear regression, the mean total testosterone was significantly associated with better performance on the World component of the MMSE (b = .12; P = .08). With regard to estrogen, the only statistically significant (P = .02) association was better performance on one test in women with very low levels of estradiol. CONCLUSIONS: In these older women, higher endogenous estrogen levels were not associated with significantly better performance on any cognitive function test. In contrast, higher levels of testosterone predicted better categorical performance on the MMSE and the World component of the MMSE. These novel findings warrant further research.

Age Factors↗

Gender-specific effects of the catechol-O-methyltransferase Val108/158Met polymorphism on cognitive function in children.

OBJECTIVE: The study aimed to determine the cognitive effect of the Val108/158Met polymorphism in the catechol-O-methyltransferase (COMT) gene in children before and during puberty. This polymorphism affects cognitive function in healthy adults and may contribute to risk for schizophrenia. METHOD: COMT genotype was determined for 8,707 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), a geographically defined general population cohort of children born between April 1, 1991, and Dec. 31, 1992, in the southwest of England. Fourteen measures of cognitive function--including working memory, verbal and motor inhibition, attentional control, and IQ--were assessed at ages 8 and 10 years. Any pubertal development at age 9 years was reported by parents. Effects of COMT genotype on cognition and interactions with gender and puberty were assessed using general linear models. RESULTS: In boys, genotype significantly affected executive function and explained up to 10 points normal variation in verbal IQ. The effects on IQ were significantly greater in pubertal than in prepubertal boys. In girls, there were no significant effects of genotype on cognition. CONCLUSIONS: This common polymorphism may be one of the genes of small effect that contribute to normal variation in IQ. The gender-specific nature of the effect and its possible interaction with puberty may be relevant to both normal cognitive and brain development and to abnormal development in disorders such as schizophrenia.

Adolescent↗

Cognitive functioning in patients with cerebral aneurysms measured with the mini mental state examination and the telephone interview for cognitive status.

BACKGROUND: Clinicians and researchers use brief instruments, such as the Mini Mental State Examination (MMSE) and the Telephone Interview for Cognitive Status (TICS), to measure cognitive functioning in patients with cerebral aneurysms. MMSE and TICS scores are often dichotomized to classify patients as cognitively impaired or not. Frequently, after an initial MMSE face-to-face evaluation, the TICS is used for follow-up assessments by telephone. METHODS: A cross-sectional cohort of patients with cerebral aneurysms completed the MMSE at baseline and the MMSE or TICS at the 12-month follow-up examination. Multivariate logistic regression adjusting for demographics was used to model cognitive impairment. MMSE and TICS results were compared using the MMSE as the "gold standard." RESULTS: Eleven out of 171 (6%) patients had baseline MMSE scores less than 24, indicating cognitive impairment. Multivariate analysis showed that a history of subarachnoid hemorrhage was associated with cognitive impairment measured with the MMSE (odds ratio, 13.9; P = 0.021; C statistic = 0.87); there was no relationship between subarachnoid hemorrhage or treatment and TICS cognitive impairment (i.e., score < 27). In patients without recent or interim invasive interventions that might affect cognition (n = 65), raw baseline MMSE and 12-month TICS scores had fair correlations (r = 0.30, P = 0.015); however, dichotomized scores had poor agreement, and TICS sensitivity and positive predictive value was 0% compared with the MMSE. CONCLUSION: The MMSE may be more sensitive than the TICS to the effects of subarachnoid hemorrhage on cognitive functioning. Raw MMSE and TICS scores are well correlated, but dichotomized MMSE and TICS scores are probably not interchangeable in this patient population.

Adult↗

Socioeconomic position in early life, birth weight, childhood cognitive function, and adult mortality. A longitudinal study of Danish men born in 1953.

OBJECTIVE: To examine the relation between socioeconomic position in early life and mortality in young adulthood, taking birth weight and childhood cognitive function into account. DESIGN: A longitudinal study with record linkage to the Civil Registration System and Cause of Death Registry. The data were analysed using Cox regression. SETTING: The metropolitan area of Copenhagen, Denmark. SUBJECTS: 7493 male singletons born in 1953, who completed a questionnaire with various cognitive measures, in school at age 12 years, and for whom birth certificates with data on birth and parental characteristics had been traced manually in 1965. This population was followed up from April 1968 to January 2002 for information on mortality. MAIN OUTCOME MEASURES: Mortality from all causes, cardiovascular diseases, and violent deaths. RESULTS: Men whose fathers were working class or of unknown social class at time of birth had higher mortality rates compared with those whose fathers were high/middle class: hazard ratio 1.39 (95% CI 1.15 to 1.67) and 2.04 (95% CI 1.48 to 2.83) respectively. Birth weight and childhood cognitive function were both related to father's social class and inversely associated with all cause mortality. The association between father's social class and mortality attenuated (HR(working class)1.30 (1.08 to 1.56); HR(unknown class)1.81 (1.30 to 2.52)) after control for birth weight and cognitive function. Mortality from cardiovascular diseases and violent deaths was also significantly higher among men with fathers from the lower social classes. CONCLUSION: The inverse association between father's social class at time of birth and early adult mortality remains, however somewhat attenuated, after adjustment for birth weight and cognitive function.

Adolescent↗

Modality dependent changes in event-related potentials correlate with specific cognitive functions in nondemented patients with Parkinson's disease.

The relationship between event-related potentials (ERPs) and cognitive functioning was studied in patients with Parkinson's Disease (PD) but without dementia. Auditory and visual stimuli were used; 30 subjects participated in the auditory study and 20 in the visual study. Patient groups did not differ with respect to gender, age, education, illness duration, and level of cognitive functioning. Visual stimuli were 2.3 cpd sinusoidal grating patterns randomly presented in an oddball paradigm (oblique vs. vertical spatial orientation). Auditory stimuli were tones presented at 70 dB SPL at a rate of 1.1/second, also using the oddball paradigm (1.5K vs. 1K tones). All patients were given neuropsychological tests to measure verbal fluency, memory, visual spatial perception, and abstract reasoning. P300 and N200 abnormalities correlated with a number of these measures, such that longer ERP latencies were related to lower scores on tests of cognitive functioning. Patterns of results suggest that auditory and visual ERPs correlate with different subsets of neuropsychological functions in nondemented PD patients and that N200 may provide a new metric for clinical use.

Cognition↗

Homocysteine and cognitive function in the elderly: the Rotterdam Scan Study.

BACKGROUND: Elevated plasma total homocysteine (tHcy) concentrations are associated with AD and vascular dementia, but the relation with cognitive performance in nondemented elderly people is not known. OBJECTIVE: To examine the association of tHcy and cognitive function in the elderly, and assess whether this may be mediated by structural brain changes on MRI. METHODS: The Rotterdam Scan Study is a population-based study of 1,077 nondemented elderly. Cognitive performance was assessed, and compound scores were constructed for psychomotor speed, memory function, and global cognitive function. Cerebral infarcts, white matter lesions, and generalized brain atrophy were measured on MRI. The cross-sectional relationship between tHcy levels and neuropsychological test scores was assessed by multiple regression. RESULTS: Mean tHcy level was 11.5 micro mol/L (SD 4.1). Increasing tHcy levels were associated with lower scores for psychomotor speed, memory function, and global cognitive function, and this was largely due to the association with tHcy levels in the upper quintile (>14 micro mol/L). Adjusted differences between test scores of participants in the upper quintile as compared with the lower four quintiles of tHcy were -0.26 (95% CI: -0.37; -0.14) for psychomotor speed, -0.13 (95% CI: -0.27; 0.01) for memory function, and -0.20 (95% CI: -0.30; -0.11) for global cognitive function. These associations were not mediated by structural brain changes on MRI. CONCLUSION: Elevated tHcy levels are associated with decreased cognitive performance in nondemented elderly people, and the relation was most marked for psychomotor speed. This association was independent of structural brain changes on MRI.

Aged↗

Hypertension and cognitive functioning among the elderly: an overview.

This paper reviews the longitudinal studies in which the association between hypertension and cognitive functioning has been explored. The findings of these studies are far from being consistent: positive, adverse, or no relationships between cognitive performance and blood pressure have been reported. In some studies, cognitive functioning was related only to systolic blood pressure, whereas in others, it was related to diastolic blood pressure alone. Most probably, the inconsistency is due to the variability in research design, the measures employed, and data management. Some of the main methodological issues are the wide range in the age of the subjects and the variability in hypertension at baseline. Length of exposure to hypertension was rarely considered, and the search for the possible effects of the different antihypertensive treatments on cognitive ability is in its infancy. Many studies seek to identify cognitively impaired elderly and do not distinguish between the different types of dementia or the different cognitive domains. Thus, the possibility that hypertension affects specific cognitive functions has not been explored. The use of subdivisions of blood pressure values may have obscured nonlinear relationship. Nevertheless, the pattern that emerges is that midlife hypertension enhances cognitive impairment later in life, but at old age, mild hypertension may increase cognitive performance. Directions for future research to further elucidate the complex relationship between age, blood pressure, and cognition are discussed.

Aged↗

Longitudinal study of cognitive function in first-episode and recent-onset schizophrenia.

OBJECTIVE: Whether cognitive function in schizophrenia deteriorates, improves, or remains stable is a crucial question. Few studies have examined the longitudinal stability of cognitive function and the relationship between cognitive performance and clinical symptoms over time in a cohort of well-treated patients with schizophrenia. METHOD: In the present study, 54 patients with first-episode and recent-onset schizophrenia completed a comprehensive cognitive test battery and were rated on symptom measures at index hospitalization and again after 5 years. RESULTS: Performance IQ and full-scale IQ significantly improved, whereas verbal IQ did not change. Group performance improved on some of the neuropsychological tests, including the Circle A letter-cancellation task, free recall of logical memory test score, and the Wisconsin Card Sorting Test. Mean finger-tapping performance worsened over time, whereas performance on other neuropsychological tests did not change. Negative, psychotic, and disorganized symptoms significantly improved over the time period. Changes in negative symptoms were correlated with performance changes in verbal IQ and full-scale IQ but not performance IQ. Improvement in verbal cognition was observed when negative symptoms improved. Psychotic and disorganized symptom dimensions were not correlated with any IQ measure. CONCLUSIONS: These results indicate that in a cohort of young patients receiving neuroleptic treatment early in their illness, cognitive performance does not deteriorate--and may improve. Only one of the three symptom dimensions--negative--was associated with change in cognitive performance. This study supports the view that negative symptoms are associated with a poor long-term cognitive outcome and may be closely related to the primary cognitive deficit in schizophrenia.

Adult↗

Effect of naloxone on cognitive function in vascular dementia in rats.

BACKGROUND & OBJECTIVES: The endogenous opioid system plays an important role in cognitive functions and may also contribute to the progression of some kind of dementia. Naloxone has been shown to exert beneficial effects on memory deficits in patients with senile dementia and reverse some of the effects induced by endogeneous opioids. We therefore investigated the effects of naloxone on cognitive function in rats with vascular dementia (VD). METHODS: Vascular dementia was established by permanent occlusion of the common carotid arteries. Rats were divided into three groups viz., sham-operated controls, naloxone treated VD rats (naloxone 0.8 mg/kg, i.p. daily for 7 days), and nontreated VD rats. The Morris water maze test was performed to study spatial learning and memory. The extracellular recording technique was used to record long-term potentiation (LTP) of the Schaffer collateral-CA1 synapse in the rat hippocampal slices. RESULTS: In the hidden platform trials, escape latencies of the naloxone treated VD rats were significantly shorter than that of the nontreated VD rats (P < 0.001). In the probe trials, the number of enteries in the target area of the naloxone treated VD rats (8.36 +/- 1.38 times/min) were more than that of the nontreated VD rats (4.64 +/- 1.73 times/min) (P < 0.01). The magnitudes of LTP recorded in the CA1 pyramidal neurons of the naloxone treated VD rats were significantly augmented when compared to the nontreated VD rats (P < 0.05). INTERPRETATION & CONCLUSION: Naloxone could facilitate spatial learning and memory and enhance LTP in the CA1 region of hippocampus in rats with VD. It is postulated that naloxone might exert beneficial effects on cognitive function in VD in rats by modulating the synaptic plasticity in the hippocampal neuronal network.

Animals↗

Effects of antihypertensive drugs on cognitive function in adolescents.

The effects of clonidine and hydrochlorothiazide on cognitive function were studied in hypertensive adolescents requiring pharmacologic therapy for blood pressure control. Twenty-four adolescents with persistent blood pressure elevation (greater than 95th%) on placebo were randomized double blind to clonidine or hydrochlorothiazide treatment. A battery of cognitive tests were performed during the placebo phase and after 16 weeks of active therapy. Antihypertensive therapy resulted in significant blood pressure reduction (p less than .01). A slight interactive effect was observed in arithmetic performance (p less than .05). All other parameters of cognitive function were not affected by either treatment.

Adolescent↗

Histamine2 receptor antagonist use and decline in cognitive function among community dwelling elderly.

PURPOSE: Previous studies have reported mixed results regarding the use of histamine(2) receptor antagonist use and cognitive function. This study evaluated the relationship between the use of histamine(2) receptor antagonists and cognitive decline among community dwelling elderly. METHODS: This cohort study included 2082 subjects from the Duke Established Populations for Epidemiologic Studies of the Elderly who were not cognitively impaired at baseline (1989/90). Histamine(2) receptor antagonist use was determined during in-home interviews. Cognitive function was assessed at 3 and 7 years after baseline by two measures: (1) incident cognitive impairment defined by the short portable mental status questionnaire (SPMSQ); and (2) cognitive decline (increase in two or more SPMSQ errors). Analyzes used multivariable discrete-time hazard models with weighted data adjusted for sampling design and controlled for demographic, health behavior characteristics and health status. RESULTS: At baseline, nearly 5% of participants used a histamine(2) receptor antagonist. During follow-up, incident cognitive impairment occurred in 24.0%, whereas 34.5% increased by two or more errors on the SPMSQ. In multivariable models, current histamine(2) receptor antagonist users compared to never users had a higher risk for cognitive impairment (Adj. RR 1.51; 95%CI 0.93-2.47) and for decline in performance (increase of two or more errors) on the SPMSQ (Adj. RR 1.24; 95%CI 0.74-2.08). A nonsignificant increased risk of cognitive impairment and decline with either higher dose or short-term use was found whereas a nonsignificant protective effect on cognitive decline with current long-term use was seen. CONCLUSIONS: These results suggest no beneficial effects, and perhaps a detrimental effect, of histamine(2) receptor antagonist use on cognitive function in community dwelling elderly.

Aged↗

Growth hormone, insulin-like growth factor I and cognitive function in adults.

This review focuses on the possible contribution of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis to cognitive function. Binding sites for GH and IGF-I are found in various areas of the brain. Their distribution suggests that GH and IGF-I contribute to the function of the hippocampus, a brain structure important for the maintenance of cognitive functions such as learning and memory. Evidence for cognitive deficits in GH-deficient individuals has been found in various studies, some of which have shown that these deficits can be reversed by GH substitution therapy. In addition to examining conditions of GH deficiency, this article reviews studies evaluating the correlation between the cognitive deficits associated with ageing and age-related decreases in GH or IGF-I secretion. Based on the available data, one might hypothesize that relative GH or IGF-I deficiency could contribute to the deterioration of cognitive functions observed in the elderly.

Adult↗