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Hypertension and changes of cognitive function in 81-year-old men: a 13-year follow-up of the population study "Men born in 1914", Sweden.

BACKGROUND: The relationship between blood pressure levels and decline of cognition has been discussed previously, but little is known about the confounding effect of lifestyle factors, antihypertensive treatment and disease in the elderly. OBJECTIVE: To examine the association between systolic (SBP) and diastolic (DBP) blood pressure, changes of DBP and SBP and hypertension (HT) on cognitive function, while controlling for confounding factors. DESIGN: A longitudinal cohort study of men born in 1914 and residing in the municipality of Malmö studied at age 68 and 81 years. SETTING: Probands invited to a university clinic. SUBJECTS: One hundred and eighty-six out of 281 invited men still alive in 1995/6 participated in the most recent follow-up. MAIN OUTCOME: Change of the cognitive performance in the verbal (Paired Associates and Synonyms), spatial (Block Design and Benton Visual Retention test) and speed (Digit Symbol Substitution) functions. RESULTS: DBP by tertiles at 68 years, but not HT, was inversely related to verbal, spatial and speed performance at 81 years. Only spatial function was related to SBP at 68 years. The association between DBP and SBP by tertiles, and spatial functions (Block Design and Benton Visual Retention test) remained after controlling for education, marital status, smoking, alcohol and physical activity, and intermediates such as arteriosclerotic manifestations (block design, beta = 0.17; = 0.029) in multiple regression models. A decrease in DBP was likewise related to spatial (beta = 0.16; = 0.049) and speed performance (beta = 0.17; = 0.039) in the same regression model. CONCLUSIONS: Evidence is found to support the hypothesis that hypertension, especially high DBP in late midlife, is associated with a decline in spatial performance of cognitive functions in elderly men.

Aged↗

Nerve growth factor (NGF) in rat brain following long-term barbital treatment: relation to convulsions and cognitive function.

Nerve growth factor (NGF) protein has been implicated in alterations of cognitive function either following brain damage, selective lesions or aging. Groups of rats were given long-term (48 weeks) oral barbital treatment or tap water and following an extended period of abstinence (14 weeks) were tested for spatial learning ability in the Morris swim maze. Following the maze test, they were sacrificed and the NGF content of hippocampal and cortical brain regions were analyzed. Barbital treated rats were divided into convulsing and non-convulsing groups. It was found that there was a slight, significant increase (12%) in NGF content of the hippocampus in convulsing rats. Correlations between maze learning performance, brain weight and NGF in the cortex indicated a significant negative relationship between (a) performance and brain weight on day 1 of testing and (b) NGF content and performance on day 2. These data indicate some involvement of NGF in functions derived from a considerably different animal model to those applied previously.

Animals↗

Cognitive functioning, and behavioral and emotional adjustment in maltreated children post-intervention.

Cognitive functioning and behavioral and emotional adjustment were examined in children who were previously maltreated as preschoolers, had received intervention in a developmentally salient day treatment program, and were either placed in adoptive families or returned to the biological family system. The children were evaluated, on average, four years postintervention. The children in this sample were as emotionally maladjusted as those in a clinical population; they experienced more anxiety and aggression. Additionally, they fared worse than clinical (and nonclinical) norms in terms of self-confidence and the adaptive ability to perceive support from others, and were comparable to the clinical group in their limited ability to reach out to others in the face of problem-resolution skills below a nonclinical level.

Adaptation, Psychological↗

Cognitive function after two doses of cranial irradiation for acute lymphoblastic leukaemia.

The cognitive function of 23 children given cranial irradiation in a dose of 24 Gy was compared with that of 41 given 18 Gy. No significant differences were found in intellectual function or in mean number of intelligence quotient points lost between patients in the two treatment groups. A reduction in the dose of cranial irradiation does not seem to alleviate long term neuropsychological deficits.

Child, Preschool↗

Effect of repetitive TMS and fluoxetine on cognitive function in patients with Parkinson's disease and concurrent depression.

Previous studies show that cognitive functions are more impaired in patients with Parkinson's disease (PD) and depression than in nondepressed PD patients. We compared the cognitive effects of two types of antidepressant treatments in PD patients: fluoxetine (20 mg/day) versus repetitive transcranial magnetic stimulation (rTMS, 15 Hz, 110% above motor threshold, 10 daily sessions) of the left dorsolateral prefrontal cortex. Twenty-five patients with PD and depression were randomly assigned either to Group 1 (active rTMS and placebo medication) or to Group 2 (sham rTMS and fluoxetine). A neuropsychological battery was assessed by a rater blind to treatment arm at baseline and 2 and 8 weeks after treatment. Patients in both groups had a significant improvement of Stroop (colored words and interference card) and Hooper and Wisconsin (perseverative errors) test performances after both treatments. Furthermore, there were no adverse effects after either rTMS or fluoxetine in any neuropsychological test of the cognitive test battery. The results show that rTMS could improve some aspects of cognition in PD patients similar to that of fluoxetine. The mechanisms for this cognitive improvement are unclear, but it is in the context of mood improvement.

Aged↗

[Cognitive functions of children with attention deficit/hyperactivity disorder].

OBJECTIVE: To investigate the features of cognitive function in children with attention deficit/hyperactivity disorder (ADHD). METHODS: Wechsler Intelligence Scale for Children-RC, Wechsler Memory Scale (WMS), Number Cancellation Test, Ravin's Standard Progressive Matrices, and Stroop test were conducted among 60 7 approximately 12-year-old children diagnosed with ADHD and 60 children matched by age, sex, and maternal education level. RESULTS: The verbal intelligence quotient, performance IQ, full scale IQ, verbal comprehension IQ, perceptual organization IQ, and freedom from distractibility IQ of the ADHD CHILDREN were 104 +/- 13, 98 +/- 14, 102 +/- 13, 100 +/- 15, and 102 +/- 15, all less than those of the controls (112 +/- 11, 108 +/- 13, 112 +/- 12, 111 +/- 12, 107 +/- 13, and 116 +/- 13, all P < 0.01). The scores of long-term memory, short-term memory, immediate memory, memory quotient, and reverse digit span in the children with ADHD were 40 +/- 7, 58 +/- 12, 7 +/- 3, 95 +/- 15, and 4.2 +/- 1.7 respectively, all less than those in the controls (49 +/- 5, 63 +/- 10, 8.4 +/- 3.0, 109 +/- 12.5, and 5.0 +/- 1.4 respectively, all P < 0.05). Number cancellation test showed significantly lower total score and higher error rate in ADHD children than in the controls (51.5 and 76.4 VS 77.3 and 38.0, both P = 0.000). In Stroop test, the ADHD children spent more time for all the four parts, had to make more effort to eliminate the interference of word meaning, and made more errors in the C and D parts. The average standard score of Raven's Standard Progressive Matrices was 4.0 +/- 1.5, significantly higher than that in the controls (2.7 +/- 1.2, P = 0.000). CONCLUSION: The levels of intelligence, memory, and attention in ADHD children are lower that those in normal children. ADHD children have deficiency in executive functions, such as selective inhibition, working memory and plan implementation.

Attention Deficit Disorder with Hyperactivity↗

The consequences of treatment and disease in patients with primary CNS non-Hodgkin's lymphoma: cognitive function and performance status. North Central Cancer Treatment Group.

Per protocol, patients with primary CNS non-Hodgkin's lymphoma in an intergroup phase II trial conducted by the North Central Cancer Treatment Group and the Eastern Cooperative Oncology Group had their cognitive functions measured using the Folstein and Folstein Mini-Mental Status Examination (MMSE) and their physical functions measured using the Eastern Cooperative Oncology Group Performance Score (PS) at study entry, at each treatment evaluation, and at quarterly intervals thereafter until disease progression or death. Of the 53 eligible participants who began therapy, 46 (87%) had baseline MMSE scores recorded, 36 (68%) had at least one follow-up MMSE, and 32 (60%) had both, while 52 (98%) had baseline PS, 49 (92%) had at least one follow-up PS, and 48 (91%) had both. Patterns of MMSE and PS values over time were studied in each individual, in the group as a whole, in the 20 patients who completed the study regimen, in the 23 who survived more than a year, and in patients who were classified as nonprogressors at each key evaluation. For each patient, all recorded values were plotted versus time, with dates of disease progression and death included, to look for signs of decline in cognitive or physical function preceding adverse events. Long-term declines in scores of both cognitive and physical function were observed in many treated patients with primary CNS non-Hodgkin's lymphoma. Nearly all patients who were alive more than 52 weeks after study entry had a demonstrable decline in cognitive and physical functionality. Such declines may occur before disease progression is documented; they may also occur in some patients who have long-term follow-up without evidence of disease progression. Declining MMSE and PS was a poor predictor of disease progression. There was no association of PS and toxicity. The data from this study demonstrated the considerable difficulties we encountered conducting an ancillary study such as this within a multicenter clinical trial. Firstly, the test instruments written into the protocol were unable to tell if the declines seen were due to disease, treatment, co-morbidity, or other factors. Secondly, the missing data created difficulties in interpreting outcome.

Adult↗

Cognitive function and incidence of stroke in older Mexican Americans.

BACKGROUND: Given the high prevalence of cognitive impairment in older Mexican Americans and limited longitudinal research examining cognitive function in this ethnic group, we conducted a study examining whether cognitive impairment is a risk factor for new onset of stroke among older Mexican Americans. METHODS: We performed a prospective cohort study of 2682 Mexican Americans aged 65 years and older living in the southwestern United States. For subjects with no prior history of stroke and who completed the Mini-Mental State Examination (MMSE) at baseline, stroke incidence was assessed after 2, 5, and 7 years of follow-up. RESULTS: In Cox proportional regression models, MMSE score at baseline predicted risk of incident stroke over a 7-year follow-up period. For the unadjusted model, subjects with an MMSE score of 21 or higher were half as likely to report stroke at follow-up (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.35-0.69; p <.001) compared with those with a score of less than 21. We found similar results after controlling for relevant risk factors for stroke including age, gender, smoking status, education, body mass index, diabetes, heart attack, systolic blood pressure, and depressive symptoms (HR, 0.54; 95% CI, 0.38-0.77; p =.001). Additionally, each 1-point increase in MMSE score was associated with a 5% reduction in risk (HR, 0.95; 95% CI, 0.92-0.99; p =.01). CONCLUSIONS: Increasing MMSE score is associated with a decreasing incidence of stroke in older Mexican Americans. This study highlights the need for a more aggressive focus on identifying and addressing cognitive decline in the Mexican American population.

Aged↗

Effects of pallidotomy and bilateral subthalamic stimulation on cognitive function in Parkinson disease. A controlled comparative study.

Unilateral pallidotomy and bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) have demonstrated a positive effect on motor functions. However, further studies are needed of the unintended cognitive effects accompanying these new surgical procedures. We studied the consequences of unilateral pallidotomy and STN-DBS on cognitive function in a controlled comparative design. Sixteen consecutive PD patients were assessed before and 6 months after unilateral pallidotomy (n = 8) and bilateral STN-DBS (n = 8). The same assessments were performed in a control group of eight non-operated matched PD patients recruited from surgery candidates who refused operation. The neuropsychological battery consisted of test measuring memory, attention, arithmetic, problem solving and language, as well as visuospatial, executive and premotor functions. An analysis of variance (factors time and treatment) was applied. No statistically significant differences were found in the presurgical evaluation of clinical and demographic data for the three treatment groups. The controlled comparison between presurgical and postsurgical performance revealed no significant changes in the cognitive domains tested in the pallidotomy group. The STN-DBS group showed a selective significant worsening of semantic verbal fluency (p = 0.005). This controlled comparative study suggests that neither unilateral pallidotomy nor bilateral STN-DBS have global adverse cognitive consequences, but bilateral STN-DBS may cause a selective decrease in verbal fluency.

Aged↗

Psychiatric, psychosocial, and cognitive functioning of female adolescents with ADHD.

OBJECTIVE: To characterize the psychiatric, psychosocial, and cognitive functioning of female adolescents with attention-deficit/hyperactivity disorder (ADHD) in comparison with female controls and males with ADHD. Female controls were also compared with male controls to verify gender differences in a nonclinical sample. METHOD: One hundred seven adolescents from Southern Ontario aged 13 to 16 were included: 24 females with ADHD, 35 males with ADHD, 28 control females, and 20 control males. All were assessed with semistructured interviews, questionnaires, and tests of achievement and intellectual functioning. RESULTS: After controlling for parental education and estimated Full Scale IQ, females with ADHD were more impaired than control females in depression, anxiety, distress, teacher relationships, stress, attributional styles, and locus of control and on all cognitive and achievement measures. Females with ADHD were more impaired than males with ADHD in self-reported anxiety, distress, depression, locus of control, and vocabulary scores. These group differences were confirmed by higher ratings by parents and teachers in symptoms of psychopathology. Males with ADHD were more impaired in processing speed. Some gender differences (locus of control and vocabulary scores) were eliminated when controlling for ADHD severity. The absence of any differences between male and female controls indicates gender differences were specific to the clinical groups. CONCLUSION: Females with ADHD are at high risk for more psychological impairment than both males with ADHD and control females. The identified psychosocial problems point to areas for intervention.

Achievement↗

A prospective controlled study of cognitive function during an amateur boxing tournament.

BACKGROUND: Few studies have reported acute postbout cognitive function in amateur boxers, and none have documented the effects of repeated boxing bouts within a short time frame. OBJECTIVE: To determine whether participation in a 7-day amateur boxing tournament is associated with acute deterioration in cognitive test performance. METHODS: A prospective study was done of 82 collegiate amateur boxers participating in a 7-day single elimination tournament and a group of 30 matched nonboxing control participants. No participants had a history of recent concussion or past history of brain injury. For boxers, cognitive assessment using a computerized test battery was performed before the tournament and within 2 hours of completing each bout. Tests of simple and choice reaction time, working memory, and learning were administered. Analysis of variance was conducted to compare the serial performance of control participants with that of boxers participating in one, two, and three bouts. RESULTS: The 82 boxers fought 159 times. Cognitive testing was performed after 142 of these bouts. On simple reaction time, choice reaction time, and working memory tasks, the serial performance of boxers participating in three bouts (n = 22) was equivalent to that of boxers participating in two bouts (n = 22) and one bout (n = 32) and to nonboxing control participants (n = 30). An improvement in performance was observed on the learning task in boxers participating in three bouts. Boxers whose bout was stopped by the referee (n = 7) displayed significant slowing in simple and choice reaction time. CONCLUSIONS: With the exception of boxers whose contest is stopped by the referee, amateur boxers participating in multiple bouts during a 7-day tournament display no evidence of cognitive dysfunction in the immediate postbout period.

Adult↗

Interaction of atherosclerosis and inflammation in elderly subjects with poor cognitive function.

OBJECTIVE: To test the hypothesis that a pro-inflammatory response is associated with cognitive impairment among individuals with cardiovascular disease. METHOD: All 85-year-old inhabitants of Leiden (n = 599) were visited at their place of residence. A history of cardiovascular disease and an EKG were used as indicators of atherosclerosis. Production of the pro-inflammatory cytokine tumor necrosis factor-alpha and the anti-inflammatory cytokine interleukin-10 was assessed in a whole-blood assay using lipopolysaccharide as a stimulus. Global cognitive functioning was determined with the Mini-Mental State Examination (MMSE); attention, cognitive speed, and memory were determined with four neuropsychological tests; and a history of dementia was obtained. RESULTS: In subjects with cardiovascular disease, median MMSE scores were lower in those with a pro-inflammatory response when compared with those with an anti-inflammatory response (p = 0.02). Similar associations were found for the Stroop Test, measuring attention (p < 0.01), the Coding Test measuring cognitive speed (p = 0.02), the Word Learning Test measuring memory (p < 0.01), and the presence of dementia (p = 0.04). The associations remained unaltered after adjustments for possible confounders such as gender, level of education, use of nonsteroidal anti-inflammatory drugs, use of cardiovascular drugs, and cardiovascular risk factors. In contrast, outcomes of the cognitive tests and presence of dementia were not dependent on the inflammatory response when cardiovascular disease was absent. CONCLUSION: The combination of cardiovascular disease and a pro-inflammatory cytokine response may be associated with cognitive impairment and dementia.

Aged↗

Infant motor development and adult cognitive functions in schizophrenia.

BACKGROUND: Childhood neuromotor dysfunction is a risk factor for schizophrenia, a disorder in which cognitive deficits are prominent. The relationship between early neurodevelopment and adult cognition in schizophrenia remains unclear. METHODS: We examined the associations between infant motor development and adult cognitive functions in schizophrenia (n = 61) and the general population (n = 104) in a sample drawn from the The Northern Finland 1966 Birth Cohort. Data on ages of learning to stand and walk with or without support were obtained at age 12 months by health visitor assessment. Neurocognitive measures at age 33-35 included executive function, verbal and visual episodic memory, and visuo-spatial working memory. RESULTS: The schizophrenia group achieved neuromotor milestones later and performed significantly worse than the control group on all measures of cognition. In pooled analyses there were associations between infant motor development and adult cognition in the domains of executive function, verbal learning and visuospatial working memory, but not in visual object learning. The pattern of associations between development and cognition was similar in schizophrenia and the general population. CONCLUSIONS: These findings are consistent with the hypothesis that in schizophrenia mild infant motor developmental delay and adult cognitive deficits (at least in some domains) are age dependent manifestations of the same underlying neural process. Thus, they may be better considered as part of a single longitudinal syndrome.

Adult↗

Cognitive function in multiple sclerosis and its relation to functional abilities.

The performance of patients with multiple sclerosis (MS) on selected neuropsychologic tests was examined to ascertain the applicability of such examinations to diagnosis. Twenty-four patients with definite or probable MS, and sixteen age- and education-matched control subjects were given a battery of tests to assess intellectual functions. The results indicate that the MS patients had cognitive impairment. Severity of disability was not significantly correlated with cognitive impairment. Impaired cognitive functioning, which is often not detected through routine examination, may occur in the disease. These deficits may represent manifestations of otherwise undetectable plaques in the subcortical white matter.

Adult↗

Effect of a change in drinking pattern on the cognitive function of female social drinkers.

The relationship between social drinking patterns and sober cognitive performance was evaluated, and the effects of a change in alcohol consumption on cognitive function were measured. Sixty female drinkers were randomly assigned either to abstain for 3 weeks or to continue to drink as usual; 25 female abstainers served as a comparison group. Subjects' drinking patterns during the last 6 months were assessed, and a battery of cognitive tests was administered both before and after the 3-week interval. Results indicated that cognitive performance at baseline was not inversely correlated with either the quantity or the frequency of drinking over the last 6 months. Furthermore, the abstinence manipulation did not result in differential improvement on any of the tests between the subjects who abstained and the subjects who continued to drink. Thus, recent drinking practices were not related to cognitive test performance in this sample of female social drinkers.

Adolescent↗

Long-term effects of migraine on cognitive function: a population-based study of Danish twins.

OBJECTIVE: To investigate the cognitive functioning of migraineurs vs nonmigraineurs in a large population-based sample of middle-aged twins where headache diagnoses were established by neurologists. METHODS: Twins identified through the population-based Danish Twin Registry participated in face-to-face structured interviews, which included cognitive tests and two previously validated questions screening for migraine. Twins who screened positive for migraine and their co-twins were invited to participate in a telephone-based interview conducted by neurologists, who established headache diagnoses according to the International Headache Society criteria. Cognitive scores on fluency, digit span, delayed word recall, and symbol digit substitution test were compared between migraineurs and nonmigraineurs. Comparisons within monozygotic and dizygotic same sex twin pairs discordant for migraine were also performed. RESULTS: Of the 1,789 twins who were eligible for inclusion in the present study, 1,393 (77.8%) were interviewed. A diagnosis of migraine was established in 536 twins (migraine without aura n = 347; migraine with aura n = 157). Average scores on cognitive tests in twins with migraine or one of the migraine subtypes did not differ from those of nonmigraineurs in any of the tests. Comparisons within twin pairs discordant for migraine produced highly comparable results. Adjustment for possible confounders and stratification by cumulated number of lifetime attacks did not influence the results. CONCLUSIONS: A lifetime diagnosis of migraine was not associated with cognitive deficits in middle-aged subjects.

Aged↗

Cognitive function and social abilities in patients with schizophrenia: relationship with atypical antipsychotics.

Although atypical antipsychotics have been associated with improvements in cognitive function in schizophrenia, the neurochemical basis for such effects is not well understood. Candidate neurotransmitter systems primarily involve dopamine and serotonin. The current study explored this issue by examining the cognitive abilities, social function and quality of life in patients with schizophrenia who were medicated with atypical antipsychotics. Comparisons were done for matched schizophrenia patients who were on antipsychotics with (i) an affinity for multiple receptors (olanzapine, clozapine, quetiapine) versus those that have preferential affinity for dopamine receptors (risperidone, amisulpride); and patients on medication with (ii) a high affinity for serotonin (5HT-2A) receptors (risperidone, olanzapine, clozapine) versus those with a low (or no) affinity for 5HT-2A receptors (quetiapine, amisulpride). No differences emerged between groups on any cognitive or social variable when the groups were compared for the dopaminergic properties of antipsychotic medication. By contrast, differences did emerge when patients were compared on the 5HT-2A affinity of their antipsychotic medications. Patients on low 5HT-2A-affinity antipsychotics exhibited a better performance on a measure of selective attention and adjustment to living. These findings accord with the notion that serotonergic mechanisms are important determinants of both the cognitive and the social effects of the atypical antipsychotics.

Adult↗

Nicotinic-antipsychotic drug interactions and cognitive function.

In summary, neuronal nicotinic systems are important for a variety of aspects of cognitive function impacted by antipsychotic drugs. It has been demonstrated that antipsychotic drugs have memory and attentional impairing effects when given to unimpaired subjects. Nicotine can reduce some of these impairments, but antipsychotic drug administration can also attenuate nicotine effects. We have found that nicotinic agonists selective for alpha7 and alpha4beta2 receptor subtypes significantly improve learning and memory. Serotonergic actions of antipsychotic drugs may decrease efficacy of nicotinic co-treatments. When the antipsychotic drug clozapine and nicotine are administered to subjects with cognitive impairments caused by NMDA glutamate receptor blockade or hippocampal dysfunction they can significantly attenuate the attentional and memory impairments. Nicotine has been shown in our studies to reverse the memory impairment caused by acute clozapine-induced memory improvement. Acute risperidone and haloperidol has been shown to attenuate nicotine-induced memory improvement. We have determined the role of hippocampal alpha7 and alpha4beta2 nicotinic receptors in the neural basis of nicotinic antipsychotic interactions. Local acute and chronic hippocampal infusion of either nicotinic alpha7 or alpha4beta2 antagonists cause significant spatial working memory impairment. Chronic hippocampal nicotinic antagonist infusions have served as a model of persistent decreases in nicotinic receptor level seen in schizophrenia and Alzheimer's disease. Clozapine attenuated the memory deficit caused by chronic suppression of hippocampal alpha4beta2 receptors while the amnestic effects of clozapine were potentiated by chronic suppression of hippocampal alpha7 receptors. Nicotinic co-treatment may be a useful adjunct in the treatment of schizophrenia, to attenuate cognitive impairment of schizophrenia. Nicotine as well as selective nicotinic alpha7 and alpha4beta2 receptor agonists significantly improve working memory and attentional function. Nicotine treatment was found to be effective in attenuating the attentional and memory impairments caused by the psychototmimetic NMDA antagonist dizocilpine (MK-801), a model of the cognitive impairment of schizophrenia. Studies of the interactions of antipsychotic drugs with nicotinic agents provided quite useful information concerning possible co-treatment of people with schizophrenia with nicotinic therapy. Nicotine was found to significantly attenuate the memory impairments caused by the antipsychotic drugs clozapine and olanzapine. Interestingly, nicotine-induced cognitive improvement was significantly attenuated by the antipsychotic drug clozapine. One of the principal effects of clozapine is to block 5HT2 receptors. Ketanserin a 5HT2 antagonist significantly attenuated nicotine-induced improvements in attention and memory. Thus it appears that antipsychotic drugs with actions blocking 5HT2 receptors may limit the efficacy of nicotinic co-treatments for cognitive enhancement.

Animals↗