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Effects of depression and Parkinson's disease on cognitive functioning.

This study compared the performance of Parkinson's disease (PD) patients with and without depression, patients with depression alone, and normal control subjects on a cognitive screening instrument, the Mattis Dementia Rating Scale (DRS) to evaluate the influences of depression and Parkinson's disease on cognition. PD affects overall level of cognitive functioning and, to a lesser extent, DRS Initiation/Perseveration, Construction, and Attention. Diminished memory was primarily related to depression. Treatment of depression may ameliorate aspects of cognitive dysfunction in the PD patient with depression.

Aged↗

Sex differences in material-specific cognitive functions related to language dominance: an intracarotid amobarbital study in left temporal lobe epilepsy.

Population-based studies of material-specific cognitive functions yield evidence of sex differences: women are superior on verbal tasks whereas men are superior on figural and visuo-spatial tasks. Although there is still no direct evidence, these sex differences have been assumed to be related to a different cerebral organisation of language and nonlanguage functions, i.e. language in women is suggested to be more bilaterally organised than in men. We investigated this issue with respect to verbal/nonverbal memory functions in 42 men and 43 women with left temporal lobe epilepsies who all underwent intracarotid amobarbital testing for language dominance. The results indicate that atypical language dominance is not significantly more frequent in women than in men (44% vs 33%). Atypical dominance was related to an onset of epilepsy before puberty and appeared to be a consequence of the left hemisphere pathology rather than being naturally predisposed. Furthermore, women indeed showed the expected advantage with respect to verbal memory, and men showed an advantage in figural memory. With consideration of language dominance, however, the sex difference in verbal memory was observed particularly with atypical dominance, whereas the sex difference in figural memory was observed with left dominance.

Journal Article↗

Estrogen replacement therapy: effects on the cognitive functioning and clinical course of women with Alzheimer's disease.

This study examined the effects of unopposed estrogen replacement therapy (ERT) on the cognition and clinical course of women who have been diagnosed with probable Alzheimer's disease. The records of 99 women diagnosed with probable Alzheimer's disease according to NINCDS-ADRDA criteria, and in some cases autopsy confirmed as well, were analyzed. Depression, education, and age were all considered in the analysis. Results suggest that after an average of four years after symptoms appeared, women on ERT at the time of their diagnoses had similar cognitive functioning compared to those who are not on ERT. There were, however, significant differences in the clinical course of the illness between the two groups, with the non-ERT group reporting more "non-memory" problems as initial symptoms in addition to a having greater degree of overall behavioral deficit in activities of daily living.

Activities of Daily Living↗

Equivalence of two screens of cognitive functioning: the Short Portable Mental Status Questionnaire and the Orientation-Memory-Concentration test.

OBJECTIVE: To determine the equivalence of two screens of cognitive functioning: the Short Portable Mental Status Questionnaire (SPMSQ) and the Orientation-Memory-Concentration (OMC) test. DESIGN: The design was cross-sectional and longitudinal. SETTING: Four rural and one urban county in the Piedmont region of North Carolina (n = 3210). PARTICIPANTS: A stratified random cluster sample (n = 3210) of people 68 years of age and older. MEASUREMENTS: SPMSQ and OMC at the fourth wave of the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE); disability, depression, and death measurements from the fourth through seventh waves of EPESE; demographic characteristics. RESULTS: On the SPMSQ and the OMC (r = .80), 15.3% and 38.4%, respectively, of those tested were rated cognitively impaired. Poorer scores were associated with older age, black race, and less education. These associations were attenuated on the dichotomized SPMSQ but not on the OMC. Both measures predicted disability and depressive symptomatology currently and 3 years hence and death. CONCLUSIONS: The SPMSQ and OMC, although highly correlated, are not equivalent. Association with race and education are greater for the OMC, whereas an association with age exists for both measures. The milder level of impairment identified by the OMC increases predictive capacity.

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Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort.

BACKGROUND: A few studies have examined change in cognitive performance by diabetes status with disparate results. We examined the 4-year change in cognitive performance among older adults according to glucose tolerance status. METHODS: Three cognitive tests (Mini-Mental State Examination, Verbal Fluency [VF] test, and Trail-Making Test B) were measured 4 years apart in 999 white men and women aged 42 to 89 years, who were enrolled in the Rancho Bernardo Study. Participants were classified with normal (NGT), impaired (IGT) or diabetic glucose tolerance. Sex-specific linear regression models adjusted for age, education, depression score, apolipoprotein E epsilon4 allele, and current estrogen use. We checked for mediation by further adjusting for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels; blood pressure; glycohemoglobin level; and microalbuminuria, retinopathy, stroke, or coronary heart disease. RESULTS: At baseline, mean cognitive function scores did not differ between glucose tolerance groups. Women with diabetes mellitus had a 4-fold increased risk of a major cognitive decline on the VF test after 4 years compared with nondiabetic women. After multivariate adjustment, VF test scores at follow-up for women were 15.2 +/- 0.6 for those with diabetes, 16.7 +/- 0.4 for those with IGT, and 17.2 +/- 0.2 for those with NGT (P =.007). Glycohemoglobin attenuated this effect, but lipid levels, blood pressure, and microvascular or macrovascular disease did not. Performance on Mini-Mental State Examination and Trail-Making Test B did not differ by baseline glucose status. CONCLUSIONS: Elderly white women with diabetes had a more rapid decline in performance on the VF test compared with women with IGT or NGT. Better glucose control might ameliorate this decline.

Adult↗

Impaired cognitive function and compliance with antihypertensive drugs in elderly: the Rotterdam Study.

BACKGROUND: To our knowledge, there are no epidemiologic studies on the association between cognitive impairment and noncompliance with antihypertensive therapy. We studied compliance with antihypertensive treatment in elderly patients with cognitive impairment. METHODS: The Rotterdam Study is a prospective community-based cohort study of 7983 residents > or = 55 years old. We studied 1979 participants in the study who had 2 consecutive Mini Mental State Examination (MMSE) assessments in the period from 1991 to 1996, who did not have dementia at baseline, and who had received 3 or more consecutive antihypertensive prescriptions for at least 6 months. We compared persons with MMSE scores < or = 25 on both assessments to persons with MMSE scores > 25 on both occasions. Compliance was estimated by dividing the number of days the subjects took antihypertensive drugs by the follow-up period in days, and it was expressed as a ratio between 0 and 1. We defined patients as compliant if they had a compliance ratio > or = 0.80 and as noncompliant if they had a compliance ratio < or = 0.50 during the study period. RESULTS: We followed-up on 1573 patients (mean age, 68 years) during an average period of 1609 days. The risk of noncompliance in cognitively impaired elderly subjects was 2.0 (95% confidence interval, 1.4 to 2.8) after adjustment for age, sex, education, income, living situation, and smoking. Stratification by living situation showed that the risk increase predominantly occurred in those who lived alone (odds ratio, 2.9; 95% confidence interval, 1.2 to 7.5). CONCLUSIONS: Cognitive function is an independent predictor of compliance with antihypertensive drugs in elderly patients who are living alone.

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Effects of phenytoin and carbamazepine on cognitive functions in newly diagnosed epileptic patients.

Phenytoin (PT) and carbamazepine (CBZ) are the two most prescribed anticonvulsants in Finland. Their effect on the cognitive functions of 43 newly diagnosed epileptic patients was examined. The medication was randomly assigned. The patients were tested before the medication was started, and after half a year's therapy. In order to estimate the practice effect in repeated testing a control group of 21 volunteers was similarly tested and retested. Both anticonvulsants, PT in particular, decrease the normal practice effect observed in neuropsychological testing. Compared to the CBZ group, patients with PT became somewhat slower, and their visual memory decreased. Within the PT group the motor slowing was more marked in female patients, and in patients having higher PT serum levels. In PT and CBZ groups there was an equal decrease in negative mood i.e. tension, depression, bewilderment and irritability.

Adult↗

Cognitive function in elderly people is influenced by vitamin E status.

The aim of this study was to examine associations between vitamin E status and cognitive performance in elderly people. The study subjects were a group of 34 men and 86 women, aged 65-91 y, who were free of significant cognitive impairment. Dietary intake was monitored using a "weighed food record" for 5 consecutive days including a Sunday. Serum levels of alpha-tocopherol and cholesterol were determined by HPLC and colorimetric methods, respectively. The cognitive capacity of subjects was tested using the Pfeiffer's Mental Status Questionnaire (PMSQ). Subjects with vitamin E intakes lower than 50% of those recommended had higher PMSQ scores, demonstrating a greater number of errors in comparison to participants with a greater intake of the vitamin (0.91 +/- 1.22 vs. 0.47 +/- 0.60, respectively, P < 0.05). Subjects who made no errors in the PMSQ test had significantly higher serum alpha-tocopherol concentrations (19.7 +/- 8.6 micromol/L in men and 20.0 +/- 8.4 micromol/L in women) and alpha-tocopherol/cholesterol ratios (3.5 +/- 2.0 micromol/mmol in men 2.9 +/- 1.4 micromol/mmol in women) compared with those who made errors (alpha-tocopherol 15.1 +/- 5.6 micromol/L in men and 14.9 +/- 6.1 micromol/L in women; alpha-tocopherol/cholesterol ratio 2.4 +/- 0.8 and 2.3 +/- 1.3 micromol/mmol in men and women, respectively). This study shows there to be a relationship between vitamin E status and cognitive function, and that vitamin E status could be improved in this population of elderly individuals.

Aged↗

Cognitive function in middle-aged snorers and controls: role of excessive daytime somnolence and sleep-related hypoxic events.

Association of snoring and cognitive function was studied in 46 habitually snoring men ages 41-52 years, and 60 occasionally or never-snoring control male subjects of the same age group. Sleep recordings with monitoring of apneas and hypopneas were made with the static-charge sensitive bed method. Blood oxygen saturation was measured with an oximeter and the snoring sounds were recorded with a microphone after clinical and neuropsychological assessment. A questionnaire with items on excessive daytime somnolence (EDS), sleep, and snoring quality was also used. EDS (as measured by items on the questionnaire) associated with tests requiring concentration, memory retention, and verbal and spatial skills in the habitual snorers group. The number of oxygen desaturation episodes exceeding 4% associated with defective delayed Recall of Logical Stories of the Wechsler Memory Scale and with spatial orientation (Clock test) in the habitual snorers' group even after adjusting for age and obesity.

Adult↗

Association of a serotonin receptor 2A gene polymorphism with cognitive functions in patients with schizophrenia.

The aim of this study was to investigate the association between the T102C polymorphism on the 5HT2A gene and cognitive function as well as clinical manifestations in patients with schizophrenia. Eighty-two outpatients with schizophrenia participated in this study. The Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of each patient's symptoms. In order to evaluate their short-term attention capacity, a Digit Span Test was used. The Continuous Performance Test (CPT) was used to test the sustained attention span of each of the subjects. Cognitive flexibility was measured with the Wisconsin Card Sorting Test (WCST). The polymorphism of the 5-HT2A gene at codon 102 (T/C) was genotyped by sequence specific polymerase chain reaction. The T allele at codon 102 correlated with a lower hit rate and more commission errors in the CPT and patients with the heterogeneous genotype (TC) had more commission errors than those who were of homogeneous type (CC or TT). Patients with the TC genotype also had significantly fewer correct responses in the WCST compared to those who were type CC or TT. No relationship was found to exist between the C allele and cognitive variables. There was also no relationship established between the codon 102 polymorphism and clinical parameters. These findings suggest that the TC genotype might be related to certain cognitive impairments in patients with schizophrenia.

Adult↗

Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers.

BACKGROUND: Recent research on schizophrenia indicates that cognitive deficits in this illness are important predictors of functional outcome, highlighting the need for treatments that have a positive impact on cognitive function. Here we explore the hypothesis that acute administration of d-amphetamine can improve cognitive function in individuals with schizophrenia who are well-treated with typical antipsychotics, as well as in healthy controls performing under dual task conditions designed to elicit performance deficits analogous to those found in schizophrenia. METHODS: Ten individuals with schizophrenia taking haldol or prolixin and 22 healthy controls performed spatial working memory, language production, and Stroop tasks under both placebo and 0.25 mg/kg of D-amphetamine. RESULTS: D-Amphetamine improved reactions times on the spatial working memory and Stroop tasks for both individuals with schizophrenia and controls, and improved working memory accuracy in schizophrenia. In addition, D-amphetamine improved language production for both individuals with schizophrenia and controls. CONCLUSIONS: These results provide support for the hypothesis that the adjunctive administration of dopamine agonist can improve cognitive in individuals with schizophrenia taking typical antipsychotics. The results are discussed in terms of their implications for understanding the nature of working memory deficits in schizophrenia, and potential future avenues for cognitive enhancement in this illness.

Adult↗

Cognitive function in hepatitis C patients with advanced fibrosis enrolled in the HALT-C trial.

BACKGROUND/AIMS: Prior studies have demonstrated neuropsychological abnormalities in chronic hepatitis C (CHC) patients even with mild fibrosis. The aim of this study was to determine the frequency, type, and severity of cognitive impairment in a large group of CHC patients with advanced fibrosis. METHODS: Ten validated neuropsychological tests were administered to 201 CHC patients. Standard scores for individual tests were calculated using normative population data that controlled for age, gender, and/or education. Lifetime psychiatric history, alcohol consumption, and mood status were also determined. RESULTS: 33% of patients met criteria for cognitive impairment (i.e. standard score <40 on at least 4 tests). Mild impairment in verbal recall and working memory were noted with other domains remaining intact. Liver disease severity and lifetime psychiatric/substance abuse history did not correlate with group mean cognitive test results or the presence of cognitive impairment. In contrast, IQ and depression scores were significant and independent predictors of cognitive impairment (ROC = 0.84). CONCLUSIONS: 33% of patients entering the HALT-C trial have evidence of a mild, non-focal subcortical processing deficit which was highly correlated with IQ, education, and occupation. Future studies of cognitive function in CHC patients should control for general cognitive ability.

Affect↗

Relationships among age, exercise, health, and cognitive function in a British sample.

This study was designed to evaluate the association of age, self-rated health, and walking activity with four measures of cognitive functioning in 6,979 men and women (age range: 18-94 years) randomly selected from British electoral registers. Assessments included a face-to-face interview regarding health and health beliefs as well as cognitive testing (including simple reaction time [SRT] and choice reaction time [CRT]. Hierarchical regression analyses indicated that faster reaction time (RT) speed was associated with both younger age and better self-rated health. There were also significant interactions of Age by Self-Rated Health and of Health Rating by Walking Activity for CRT, as well as an interaction of Age by Walking Activity for both SRT and CRT. Exercise and health may have an interactive effect on RT speed, and both exercise and health may modify age-related changes in RT.

Adolescent↗

Are changes in cognitive functioning in older adults related to changes in subjective complaints?

In many areas of intellectual functioning, age-related declines in older adults' performance and increases in subjective complaints about intellectual performance are observed. However, the literature mostly reports very low relations between functioning and respective complaints. This finding could be the consequence of examining the relation between subjective complaints and the perceived level of functioning. If, however, persons are sensitive to relative changes in performance, they might base their subjective judgment on changes in the level of cognitive functioning. With 202 subjects (mean age=63 years) and two measurements, the authors examine (a) the relation between functioning and complaints at each measurement point, and (b) the relation between changes in functioning and changes in complaints between the measurement points with latent difference variables. The results indicate that there is no relation between level of functioning and level of complaints, but that there is a substantial relation between changes in functioning and complaints.

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Pregnenolone sulfate and aging of cognitive functions: behavioral, neurochemical, and morphological investigations.

Neurosteroids are a subclass of steroids that can be synthesized in the central nervous system independently of peripheral sources. Several neurosteroids influence cognitive functions. Indeed, in senescent animals we have previously demonstrated a significant correlation between the cerebral concentration of pregnenolone sulfate (PREG-S) and cognitive performance. Indeed, rats with memory impairments exhibited low PREG-S concentrations compared to animals with correct memory performance. Furthermore, these memory deficits can be reversed by intracerebral infusions of PREG-S. Neurotransmitter systems modulated by this neurosteroid were unknown until our recent report of an enhancement of acetylcholine (ACh) release in basolateral amygdala, cortex, and hippocampus induced by central administrations of PREG-S. Central ACh neurotransmission is involved in the regulation of memory processes and is affected in normal aging and in human neurodegenerative pathologies like Alzheimer's disease. ACh neurotransmission is also involved in the modulation of sleep-wakefulness cycle and relationships between paradoxical sleep and memory are well documented in the literature. PREG-S infused at the level of ACh cell bodies induces a dramatic increase of paradoxical sleep in young animals. Cognitive dysfunctions, particularly those observed in Alzheimer's disease, have also been related to alterations of cerebral plasticity. Among these mechanisms, neurogenesis has been recently studied. Preliminary data suggest that PREG-S central infusions dramatically increase neurogenesis. Taken together these data suggest that PREG-S can influence cognitive processes, particularly in senescent subjects, through a modulation of ACh neurotransmission associated with paradoxical sleep modifications; furthermore our recent data suggest a role for neurosteroids in the modulation of hippocampal neurogenesis.

Aging↗

CGP 11.952: an experimental benzodiazepine derivative. Effects on cognitive functioning in patients with epilepsy.

1. In two open studies using patients with intractable epilepsy, the effects of CGP 11.952, a triazolyl benzophenone, on cognitive functioning were assessed by means of a computerized neuropsychological battery. 2. In the first study CGP 11.952 turned out to have a positive effect on information processing speed, perceptual sensitivity and preciseness of responses. 3. Negative effects were found on reaction time. 4. In the second study this latter effect was less clear. 5. A striking result was the less negative effect on memory consolidation under influence of CGP 11.952 in comparison with other benzodiazepines.

Adolescent↗

Dose-related impact of alcohol consumption on cognitive function in advanced age: results of a multicenter survey.

BACKGROUND: Moderate alcohol consumption has been associated in several studies with decreased risk of cardiovascular and cerebrovascular events; however, available data on the effects of alcohol intake on cognitive functioning are conflicting. We assessed the association between alcohol consumption and cognitive impairment in a series of older subjects enrolled in a multicenter pharmacoepidemiology survey. METHODS: The association between average alcoholic intake and cognitive performance was assessed in 15,807 patients admitted to participating centers during the survey periods. Demographic variables, comorbid conditions, medications, and objective tests that were associated with cognitive impairment (as indicated by a Hodkinson Abbreviated Mental Test score <7) in separate logistical regression models were examined as potential confounders in a summary model. RESULTS: Cognitive impairment was detected in 1693 (19%) of 8755 drinkers and 2008 (29%) of 7052 nondrinkers (Fisher's exact test, p < 0.0001). After adjusting for potential confounders, alcohol consumption was associated with decreased probability of cognitive impairment (odds ratio, 0.75; 95% confidence interval, 0.66-0.85). The relationship between drinking level and cognitive dysfunction was nonlinear, because the probability of cognitive impairment was decreased for moderate alcohol use as compared with abstinence, but it was increased for daily consumption exceeding one wine-equivalent liter among men and 0.5 liter among women. This nonlinear association persisted when cerebrovascular and Alzheimer's disease were considered separately. CONCLUSIONS: Alcohol abuse is associated with increased prevalence of cognitive dysfunction among older subjects; however, a daily alcohol consumption of less than 40 g for women and 80 g or less for men might be associated with a decreased probability of cognitive impairment. This possible protective effect of alcohol consumption should be further assessed by prospective studies.

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