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Acute alcohol intoxication and cognitive functioning.

Acute alcohol intoxication produces changes in the cognitive functioning of normal individuals. These changes appear similar prima facie to those exhibited by individuals who sustain prefrontal lobe damage during adulthood. In order to test the validity of this observation, and to control for the confounding effects of expectancy, 72 male subjects were administered a battery of neuropsychological tests, within the context of a balanced-placebo design. Each subject received one of three widely different doses of alcohol. Analysis of the results of the cognitive test battery demonstrated that a high dose of alcohol detrimentally affects a number of functions associated with the prefrontal and temporal lobes, including planning, verbal fluency, memory and complex motor control. Expectancy does not appear to play a significant role in determining this effect. The implications of this pattern of impairment are analyzed and discussed.

Adolescent↗

Protective effect of anti-hypertensive treatment on cognitive function in essential hypertension: analysis of published clinical data.

Hypertension is a risk factor for stroke and may also contribute to the development of vascular cognitive impairment (VCI) and vascular dementia (VaD). Cognitive complications of hypertension and the influence of anti-hypertensive treatment were underestimated until recently. In this paper, trials investigating the effect of anti-hypertensive treatment on cognitive function were evaluated. Analysis of these studies revealed that until approximately 1990-1995 investigations have assessed primarily if anti-hypertensive treatment impaired cognitive function. Only more recent studies have investigated positive effects on cognition of anti-hypertensive medication. Drugs more extensively evaluated were diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, sartanes and Ca(2+) channel blockers. Available studies have confirmed that elevated diastolic blood pressure or pulse pressure and isolated systolic hypertension play an important role in the development of cognitive impairment. Randomized placebo-controlled trials have provided evidence that reduction of hypertension safely and effectively decreases morbidity and mortality rates and cognitive complications of hypertension. Ca(2+) channel blockers and ACE inhibitors have been shown to be effective and probably better than diuretics and beta-blockers on cognitive domains of hypertension. More extensive investigations could contribute to establishing optimal choice and drug dosage for the treatment of cognitive complications of hypertension.

Antihypertensive Agents↗

Serotonin 6 receptor polymorphism in schizophrenia: frequency, age at onset and cognitive function.

The relative abundance of serotonin 6 receptor (5HT6) in some limbic regions and the high affinity of some antipsychotics for 5HT6 suggest that the 5HT6 gene might play a role in the pathogenesis of schizophrenic disorders. A recent study reported an association between a C267T polymorphism of the 5HT6 gene and schizophrenia. In order to test whether the 5HT6 gene plays a role in the pathogenesis of schizophrenic disorders, patients (n = 148) and control subjects (n = 160) were genotyped for 5HT6. We also investigated the relationship between genotypes and patients' age at onset and cognitive function in schizophrenic patients. Cognitive function in the patients was evaluated by the Mini-Mental State Examination (MMSE). The results demonstrated no significant differences in genotype or allele frequencies between controls and patients. In the patient group, age at onset and MMSE score did not differ significantly among the three 5HT6 genotpyes. The results of this study suggest that the 5HT6 C267T polymorphism plays no major role in susceptibility to the development of schizophrenia and is not related to cognitive impairment or age at onset in schizophrenic patients. Further studies of the relation between 5HT6 polymorphism and the symptoms and the therapeutic response in schizophrenic patients may help to elucidate the role of 5HT6 in the pathogenesis of schizophrenia.

Adult↗

The effect of raloxifene on cognitive function in postmenopausal women: a randomized clinical trial.

To determine whether treatment with raloxifene has a beneficial effect on cognitive function in postmenopausal women, 50 postmenopausal women were randomized to receive raloxifene 60 mg, or placebo, for eight weeks. Participants completed pre- and post-treatment assessment of cognitive and psychological function including the Beck Anxiety and Beck Depression inventories, the SF-36 Scale of physical and emotional well-being, five tests of cognitive function including Block Design and Digit Span subtests of the Wechsler Adult Intelligence Scale-III (WAIS-III), the Logical Memory and Paired Associates subtests of the Wechsler Memory Scale-III, and the Digit Cancellation test. Results showed no significant effect attributable to eight weeks of treatment with raloxifene on cognitive, psychological, or health variables.

Aged↗

Effect of a 915-MHz simulated mobile phone signal on cognitive function in man.

PURPOSE: To examine whether a simulated mobile telephone transmission at 915 MHz has an effect on cognitive function in man. MATERIALS AND METHODS: Thirty-six subjects in two groups were each given two training sessions and then three test sessions in a randomized three-way cross-over design. About 1 W mean power at 915 MHz from a quarter-wave antenna mounted on a physical copy of an analogue phone, as a sine wave, or modulated at 217 Hz with 12.5% duty cycle, or no power, was applied to the left squamous temple region of the subjects while they undertook a series of cognitive function tests lasting approximately 25-30 min. The second group was investigated for sleep, consumption of alcohol and beverages, and any other substances that might affect performance. RESULTS: In both groups, the only test affected was the choice reaction time and this showed as an increase in speed (a decrease in reaction time). There were no changes in word, number or picture recall, or in spatial memory. While an effect of visit-order was evident suggesting a learning effect of repeat tests, the design of the study allowed for this. Additionally, there was no systematic error introduced as a result of consumption of substances or sleep time. CONCLUSIONS: There was evidence of an increase in responsiveness, strongly in the analogue and less in the digital simulation, in choice reaction time. This could be associated with an effect on the angular gyrus that acts as an interface between the visual and speech centres and which lies directly under and on the same side as the antenna. Such an effect could be consistent with mild localized heating, or possibly a non-thermal response, which is nevertheless power-dependent.

Absorption↗

Metabolic syndrome and cognitive function: a population-based follow-up study in elderly women.

OBJECTIVE: To test the hypothesis that metabolic syndrome predicts cognitive impairment, and to examine the association of single metabolic risk factors with cognitive functioning. METHODS: We performed a 12-year follow-up study in a population-based sample of 101 women aged 60-70 years at baseline. Metabolic syndrome was defined by the National Cholesterol Education Program criteria (> or =3 out of 5 risk factors). Global cognitive function was measured by the Mini-Mental State Examination both at baseline and follow-up. A detailed neuropsychological evaluation for memory and cognitive speed was performed at follow-up. RESULTS: The prevalence of metabolic syndrome increased from 13% at baseline to 49% at follow-up (p < 0.001). Women with metabolic syndrome at baseline had a 4.27 (95% confidence interval: 1.02-17.90; p = 0.047) times higher risk of poor memory at follow-up after adjustment for age, education and depression. The increasing number of metabolic risk factors was associated with worsening of memory at follow-up (p = 0.034 for linear trend). Women with low baseline levels of high-density lipoprotein (HDL) cholesterol were more likely to have poor memory at follow-up than those with higher HDL levels (p = 0.028). The risk of having poor memory increased by 46.5% (95% confidence interval: 15-66%; p = 0.008) with 1 SD decrease in HDL cholesterol level. CONCLUSION: In elderly women, metabolic syndrome may be an important contributor to worsening of memory, which is an essential part of mild cognitive impairment.

Aged↗

Atenolol compared with nifedipine: effect on cognitive function and mood in elderly hypertensive patients.

OBJECTIVE: To compare the effects of atenolol and nifedipine on mood and cognitive function in elderly hypertensive patients. DESIGN: Randomized, double-blind, crossover trial. PATIENTS: Thirty-one elderly volunteers (7 women and 4 men) 60 to 81 years of age with mild to moderate hypertension were recruited from the general community and a Veterans Affairs hospital hypertension clinic. Six volunteers withdrew at early phases of the study for reasons unrelated to adverse drug effects. INTERVENTIONS: Participants had 2 weeks of placebo, to 6 weeks of titration with atenolol or nifedipine, and weeks of treatment followed by similar periods with the other drug. MEASUREMENTS: Psychometric tests designed to assess mood and cognitive function. RESULTS: In the group first treated with nifedipine, the summed recall score on the Buschke selective reminding test (a test of verbal learning and memory) decreased by 9.3 words (95% CI, 2.8 to 15.6 words), or 0%, during nifedipine treatment compared with placebo (P = 0.031). The group first treated with atenolol showed no improvement in summed recall scores when results seen during atenolol therapy and placebo administration were compared (P = 0.10); however, this group had an improvement of 16.1 words (CI, 5.6 to 26.5 words), or of 16%, when the atenolol score was compared with the nifedipine score (P = 0.026). In the group first treated with nifedipine, 6 of 11 patients 55%) showed a decrease of 5 words or more during nifedipine therapy compared with placebo, whereas only 1 of the 14 patients (7%) in the group first treated with atenolol showed a similar decrease (P less than 0.01). On the digit symbol test (a psychomotor test), patients treated first with atenolol tended to improve, whereas patients treated first with nifedipine tended to decline. The difference between nifedipine and atenolol, in terms of the change from the score seen during placebo, was 4.3 codings (CI, 0.7 to 7.9 codings) or 10% (P = 0.043). No statistically significant differences were seen between nifedipine and atenolol therapy regarding the other measures of psychomotor ability, sustained attention, motor performance, verbal fluency, or abstract reasoning, and no effects of either drug on mood or psychopathologic symptoms were noted. CONCLUSIONS: Although atenolol and nifedipine are generally free of gross effects on cognition or mood, nifedipine may subtly impair learning and memory in some elderly hypertensive patients.

Affect↗

Is there a relationship between fat-free soft tissue mass and low cognitive function? Results from a study of 7,105 women.

OBJECTIVES: To test the hypothesis that low fat-free soft tissue mass and cognitive impairment are independently associated. DESIGN: Cross-sectional study. SETTING: Five geographic areas of France. PARTICIPANTS: Seven thousand one hundred five community-dwelling women aged 75 and older recruited from electoral rolls between 1992 and 1994. MEASUREMENTS: Fat-free soft tissue mass, body fat mass, and bone mineral density were measured using dual-energy x-ray absorptiometry. Study participants were assessed for cognitive impairment using the Short Portable Mental Status Questionnaire and divided into two groups according to their scores. Logistic regression models were used to calculate multivariate-adjusted differences in body composition between two groups of subjects according to their cognitive function. RESULTS: After adjustment for confounders, compared with women in the highest quartile of fat-free soft tissue mass, women in the lowest quartile had an odds ratio of 1.43 (95% confidence interval (CI) = 1.07-1.91) for cognitive impairment. Low fat mass was also associated with lower cognitive function, with an odds ratio of 1.35 (95% CI = 1.01-1.79) for the lower quartile of fat mass compared with the highest quartile. There was no association between cognitive impairment and bone mineral density. CONCLUSIONS: This finding supports the hypothesis that low muscle mass is associated with cognitive impairment in older women. These two components represent major causes of frailty and functional decline in older people and could have some common mechanisms. Nevertheless, these results do not predict the causal variable.

Adipose Tissue↗

Change in cognitive function in Alzheimer's disease in African-American and white persons.

Few studies have examined the association of race with change in cognitive function in Alzheimer's disease (AD). We studied the rate of decline in global and specific measures of cognitive function in a cohort of 410 older African-Americans and whites with clinically diagnosed AD. Persons were examined annually for an average of 3.5 years, and follow-up participation among survivors exceeded 90%. In mixed-effects models that controlled for age, gender, education, and premorbid reading activity, African-Americans scored lower than whites at baseline on a composite measure of global cognition and on specific measures of visuoconstruction and naming. However, they experienced less rapid decline in episodic memory (p < 0.01), with similar but not quite significant effects for global cognition (p = 0.06), perceptual speed (p = 0.07) and naming (p = 0.08). The results suggest that the rate of cognitive decline in AD is slower in African-Americans compared with whites, particularly for episodic memory.

Aged↗

The relationship of pain and depression to cognitive function in rheumatoid arthritis patients.

The purpose of this study was to assess the hypothesis that pain and depression negatively impact the cognitive functioning of individuals with rheumatoid arthritis (RA). One hundred twenty-one community-dwelling RA patients (ages 34-84) completed a battery of cognitive tasks and multiple measures of pain and depression. Structural equation modeling techniques were used to assess the relative contributions of pain, depression, and age to cognitive performance. Individuals who performed poorly on cognitive tasks reported more pain and depression and were older than those individuals who performed well on cognitive tasks. Moreover, high levels of pain were associated with depression. Further analyses revealed that depression mediated the relationship between pain and cognition. That is, when depression was entered into the analyses, the previously significant effects of pain on cognition were no longer found. Interestingly, depression still mediated the pain-cognition relationship even after controlling for age. These findings suggest the importance of both pain and depression for understanding cognitive function in RA and may have important implications for treating this disease.

Adult↗

Assessing cognitive function in clinical trials: latest developments and future directions.

Properly developed automated test systems are of value for assessing changes in cognitive function in clinical trials. Besides the other advantages that automation brings to trials, such as increased reliability and utility, it is shown that such systems are also more sensitive to change in cognitive function than traditional nonautomated procedures. Data from a variety of topical areas in drug development are presented to illustrate the added value such techniques have brought. The latest developments in automation include remote testing via the Internet and telephone.

Attention↗

Impact of estrogen use on decline in cognitive function in a representative sample of older community-resident women.

The authors investigated whether postmenopausal estrogen use helps to maintain cognitive function; a brief screen, the Short Portable Mental Status Questionnaire (SPMSQ), was used. Information was gathered from a stratified, random sample of 1,907 African-American and White women (aged 65-100 years) participating in the longitudinal Duke Established Populations for Epidemiologic Studies of the Elderly project carried out in five urban and rural counties of North Carolina. All women were cognitively unimpaired in 1986-1987 and were evaluated 3 and 6 years later. Decline in cognitive function was measured as an increase of two or more errors on the SPMSQ and crossing of an SPMSQ threshold indicative of cognitive impairment. Recency and continuity of estrogen use were measured. Univariate analyses indicated that recent (crude odds ratio = 0.42, 95% confidence interval: 0.21, 0.86) and continuous (crude odds ratio = 0.32, 95% confidence interval: 0.13, 0.81) estrogen use reduced the risk of cognitive decline but not of cognitive impairment. After adjustment for demographic and health characteristics, protective effects became nonsignificant. While postmenopausal use of estrogen may be protective for Alzheimer's disease, current findings based on a brief cognitive screen suggest that it is not protective for cognitive decline related to aging.

Aged↗

Leisure activities and cognitive function in middle age: evidence from the Whitehall II study.

OBJECTIVES: To test the hypothesis of a positive association, independent of social position, between participation in leisure activities and cognitive function in middle age. The nature of this relation is explored by first classifying leisure activities as entailing high or low cognitive effort, and then classifying them as entailing individual or social activities. SETTING: London based office staff (Whitehall II study) in 20 civil service departments at baseline. METHODS: Data are from the fifth wave of data collection (phase 5) of a prospective cohort study, collected through clinical examination and a self administered questionnaire. Firstly, hierarchical multiple regression was used to examine age and socioeconomic status (SES) adjusted effect of each leisure activity on cognition. Then structural equation models were used to examine the effects of two categories of leisure activities-activities entailing high or low cognitive effort and social or individual activities. All analyses are cross sectional. RESULTS: There was an age and SES adjusted association between participation in leisure activities and cognitive function. More specifically, leisure activity entailing high cognitive effort or social interaction was associated with better cognitive ability. CONCLUSIONS: Participation in cognitively complex or social leisure activities has an independent association with adult cognition, suggesting that seeking mental stimulation may have a beneficial effect on cognition in middle age.

Adult↗

Impairment in the cognitive functioning of men with fragile X-associated tremor/ataxia syndrome (FXTAS).

Disorders associated with fragile X syndrome involve a trinucleotide (CGG) repeat expansion in the FMR1 gene. Recently, a progressive movement disorder (fragile X-associated tremor/ataxia syndrome [FXTAS]) has been identified in premutation carriers, persons with 55 to 200 CGG repeats. In addition to ataxia, action tremor, and Parkinsonism, early case reports suggested that FXTAS involves impaired cognition, but the precise nature of the impairment has not been elucidated. In this first, preliminary study of the subject, circumscribed aspects of cognitive functioning were examined in 25 men with FXTAS. Subjects' performance on the cognitive tests was compared with normative data. Scores on two measures of executive cognitive functioning showed a high prevalence of substantial impairment. Capacity for inhibition was severely affected in one-quarter of this highly educated sample; information processing speed was profoundly impaired in most subjects. Although mean verbal and performance IQ scores were not significantly different from the general population, they were quite low given the sample's educational level. Cognitive and functional impairment was greater for men with more CGG repeats, although number of repeats was not associated with age of onset of either tremor or ataxia. The results provide evidence that FXTAS involves marked impairment of executive cognitive abilities.

Aged↗

Cognitive function in hypertensives treated with atenolol or propranolol.

STUDY OBJECTIVE: To test reports that beta blockers, particularly lipophilic forms, impair cognitive function and cause psychiatric disturbances. DESIGN: Randomized, double-blind, controlled crossover trial with eight-week treatment periods. PATIENTS: Sequential sample of 42 male veterans, with untreated diastolic blood pressures (DBP) between 90 and 110 mmHg, aged 35-64 years. INTERVENTIONS: Propranolol-LA, 80-mg tablets, or atenolol, 50-mg tablets, were given daily, incremented by one tablet at weekly intervals until DBP less than or equal to 90 mmHg. Hydrochlorothiazide was added, if necessary. MAIN RESULTS: Repeated-measures ANOVA was performed on all cognitive tests. Cognitive test performance was not affected by beta blocker therapy in seven of nine tests and was enhanced on Trail Making Test. Performance was impaired only on Digit Cancellation. Neither Speilberger's State Trait Anxiety Inventory nor the Beck Depression Inventory was affected by either beta blocker. CONCLUSIONS: Atenolol or propranolol therapy does not impair cognitive function or contribute significantly to psychiatric side effects.

Analysis of Variance↗

Association of atrial fibrillation and focal neurologic deficits with impaired cognitive function in hospitalized patients >or=65 years of age.

Atrial fibrillation (AF) is a risk factor for cerebrovascular diseases and can manifest as impaired cognitive function (ICF). ICF may be accompanied by various focal neurologic deficits (FNDs). This study evaluated cognitive function and the risk for ICF in patients aged >or=65 years hospitalized for any reason and grouped according to the presence of AF and/or FNDs. Data on 2,314 conscious patients aged >or=65 years (1,506 women) were analyzed. Physical examination, electrocardiography at rest, and the Mini-Mental State Examination were performed at admission. The median Mini-Mental State Examination score was 25 in patients without AF or FNDs (63.4%), 23 in those with AF alone (23.6%), 21 in those with FNDs alone (8.9%), and 18 in those with AF and FNDs (4.1%). On multivariate logistic regression (adjusted for age and gender), the risk for ICF was increased in patients with AF alone (p <0.0001), in those with FNDs alone (p <0.0001), and in those with AF and FNDs (p <0.0001). In conclusion, hospitalized patients aged >or=65 years with AF and/or FNDs at admission are at increased risk for ICF. The influences of AF and FNDs on the risk for ICF are independent of each other.

Age Factors↗

A genotype of exceptional longevity is associated with preservation of cognitive function.

OBJECTIVE: To test whether cholesterol ester transfer protein (CETP) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. METHODS: We studied Ashkenazi Jews with exceptional longevity (n = 158; age 99.2 +/- 0.3 years) for the associations of CETP VV genotype and lipoprotein phenotype, using the Mini-Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort, we studied subjects from the Einstein Aging Study (EAS) for associations between CETP VV and cognitive impairment. RESULTS: Subjects with MMSE > 25 were twice as likely to have the CETP VV genotype (29% vs 14%, p = 0.02), and those with the VV genotype were more likely (61% vs 30%, p = 0.02) to have MMSE > 25. Subjects with the VV genotype had lower levels of CETP (1.73 +/- 0.11 vs 2.12 +/- 0.10 mug/mL, p = 0.01), higher high-density lipoprotein (HDL) levels (p = 0.02), and larger lipoprotein particles (p = 0.03). In the EAS cohort, an approximately fivefold increase in the VV genotype (21% vs 4%, p = 0.02), higher HDL levels, and larger lipoprotein particle sizes were associated with less dementia and improved memory. CONCLUSIONS: Using two independent cohorts, we implicate the longevity CETP gene as a modulator of age-related cognitive function. A specific CETP genotype is associated with lower CETP levels and a favorable lipoprotein profile. It has not been determined whether modulation of this gene prevents age-related decline or AD.

Age Distribution↗

Cognitive function in unaffected twins discordant for affective disorder.

BACKGROUND: Patients may present with cognitive impairment in the euthymic phase of affective disorder, but it is unclear whether the impairment is prevalent before onset of the illness. The aim of the present study was to examine the hypothesis that genetic liability to affective disorder is associated with cognitive impairment. METHOD: In a cross-sectional high-risk case-control study, healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. Cognitive performance of 203 High-Risk and Low-Risk twins was compared. RESULTS: Healthy twins discordant for unipolar disorder showed lower performance on almost all measures of cognitive function: selective and sustained attention, executive function, language processing and working and declarative memory, and also after adjustment for demographic variables, subclinical symptoms and minor psychopathology. Healthy twins discordant for bipolar disorder showed lower performance on tests measuring episodic and working memory, also after adjustment for the above-mentioned covariables. The discrete cognitive impairment found seemed to be related to genetic liability, as the MZ High-Risk twins showed significant impairment on selective and sustained attention, executive function, language processing and working and declarative memory, whereas the DZ High-Risk twins presented with significantly lower scores only on language processing and episodic memory. CONCLUSIONS: The hypothesis that discrete cognitive impairment is present before the onset of the affective disorder and is genetically transmitted was supported. Thus, cognitive function may be a candidate endophenotype for affective disorders.

Adult↗