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Technology for improving cognitive function. A workshop sponsored by the US Interagency Committee on Disability Research (ICDR): reports from working groups.

The U.S. federal Interagency Committee on Disability Research (ICDR) and its Subcommittee on Technology (IST) sponsored a state of the art workshop on "Technology for Improving Cognitive Function", from 29-30 June 2006 in Washington, D.C. This paper summarizes the content of the working groups charged with providing strategic direction for the future of technology for persons with cognitive disabilities.

Alzheimer Disease↗

Body weight, estrogen and cognitive functioning in Alzheimer's disease: an analysis of the Tacrine Study Group data.

We conducted a retrospective analysis of clinically ascertained Alzheimer's disease subjects, hypothesizing that weight, given its positive relationship to endogenous estrogen levels, would correlate with better cognitive performance among women, but not necessarily men, with this disorder. Baseline (pretreatment) data, collected by the Tacrine Study Group were available from 347 women and 316 men. After controlling for age, duration of dementia, height, and education, we found weight to have a significant, positive relationship with two measures of global cognitive functioning among women. For men, this relationship was smaller and did not reach statistical significance. Post hoc analyses among women found the effect of weight to be independent of concurrent use of estrogen replacement medication. The use of estrogen replacement was independently related to better cognitive performance. Results support the contention that higher body weight - putatively as a reflection of higher levels of endogenous estrogens - has a positive effect on cognitive performance among women with Alzheimer's disease.

Journal Article↗

Recovery of cognitive function soon after stroke: a study of visual neglect, attention span and verbal recall.

Sixty two consecutive patients admitted to hospital and surviving 6 months were tested regularly over the first 3 months after their stroke to plot recovery in three aspects of cognition: visual neglect, assessed using a cancellation task, attention span assessed using digit span, and verbal recall, tested by counting number of words remembered from a list of 10 words. Normative data were collected for the cancellation test. Fifteen patients showed recovery from visual neglect, 10 improvement in attention span and nine improvement in verbal recall. The difficulties of measuring recovery of cognitive function after stroke are discussed.

Adult↗

Cognitive function, cardiovascular reactivity, and behavior in boys at high risk for alcoholism.

Boys (average age = 12.1 years) from families with an extensive history of paternal alcoholism differed from controls of similar age and IQ on measures of cognitive function, cardiovascular reactivity, and parent-rated conduct problems. High-risk boys performed most poorly on neuropsychological tests of frontal lobe function. According to tests of temporal organization and conditional-associate learning, control over working memory was the frontal subfunction primarily affected. A mental arithmetic task also elicited greater heart rate increases and peripheral vasoconstriction among high-risk boys than among controls. After controlling for group status, significant correlations remained between frontal lobe test scores and disruptive behavior and between cardiovascular hyperreactivity and anxiety levels. The possible contribution of these findings to alcohol abuse was discussed.

Adolescent↗

Pre-pubertal growth and cognitive function.

British longitudinal data were used to investigate the association of heights at 22 months and 5 years with a digit recall test at age 10 years. Greater height, particularly at 5 years, was associated with higher scores, suggesting that some exposures influence both growth and capability for cognitive function.

Anthropometry↗

Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels.

BACKGROUND: Many men older than 50 years have bioavailable testosterone levels below the reference range for young adult men. The impact of the decreased androgen levels on cognition and health perception has received little attention. METHODS: Sixty-seven men (mean age 76 +/- 4 years, range 65-87) with bioavailable testosterone levels below 128 ng/dl (lower limit for adult normal range) were randomized to receive transdermal testosterone (2-2.5 mg patches/d) or placebo patches for 1 year. All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones [testosterone, bioavailable testosterone, sex hormone binding globulin (SHBG), estradiol, and estrone], cognitive tests (Digit Symbol, Digit Span, Trailmaking A and B), health perception (Medical Outcome Survey Short-form 36 or SF-36), lower extremity muscle strength and power, and calcium intake. RESULTS: Twenty-three men (34%) withdrew from the study; 44 men completed the trial. Bioavailable testosterone levels increased from 93 +/- 34 (SD) to 162 +/- 100 ng/dl (p <.002) at 12 months in the testosterone group (n = 24) while no change occurred in the control group (n = 20). While there was no change in estradiol levels in either group, estrone levels increased in the testosterone group (28 +/- 7 to 32 +/- 9 pg/dl, p =.017). Scores on the Digit Symbol test improved in both the testosterone and placebo groups. Scores on Trailmaking B improved in men treated with testosterone (p <.005), although the changes were not statistically different from the changes seen in the placebo group. Twelve-month scores on Trailmaking B for the entire group were correlated with 12-month testosterone levels (p =.016). Scores for health perception measured by SF-36 did not change significantly, though scores of mental and general health declined in both groups during the 12-month intervention. Twelve-month bioavailable testosterone scores were directly correlated with scores for physical role (p =.022), vitality (p =.036), and the physical composite score (p =.010). CONCLUSIONS: Transdermal testosterone treatment in men with low bioavailable testosterone levels does not impair and may improve cognitive function. Treatment did not improve health perception but this may have been due to the side effects of skin irritation suggested by similar reactions in both the testosterone and placebo groups.

Administration, Cutaneous↗

The interaction between mood and cognitive function studied with PET.

BACKGROUND: Experimentally induced depressed mood is a suggested model for retarded depression. We describe the neural response associated with induced mood and the locus of the interaction between systems mediating mood and cognitive function. METHODS: Normal subjects performed a verbal fluency task during induced elated and depressed mood states. Regional cerebral blood flow (rCBF) was measured as an index of neural activity using Positron Emission Tomography (PET). RESULTS: In both elated and depressed mood state rCBF was increased in lateral orbitofrontal cortex, rCBF was also increased in the midbrain in elated mood. In the depressed condition rCBF was decreased in rostral medial prefrontal cortex. Verbal fluency produced an expected increase of rCBF in left dorsolateral prefrontal, inferior frontal and premotor cortex, anterior cingulate and insula cortex bilaterally, the left supramarginal gyrus posteriorly and the thalamus. Activation in the verbal fluency task was attenuated throughout the left prefrontal, premotor and cingulate cortex and thalamus in both elated and depressed mood conditions. An attenuation of anterior cingulate activation was specific to depressed mood. CONCLUSIONS: Alteration of mood is associated with activation of orbitofrontal cortex which may be critical to the experience of emotion. The mood induced modulation of verbal fluency induced activations is consistent with resting state findings of decreased function in these regions in depressed patients. The present data suggest that resting state rCBF profile may represent the modulation of spontaneous activity in this network by a core system that is dysfunctional in depression.

Adolescent↗

Ecological measures of cognitive functioning: a validation study.

Observed cognitive decline in the elderly has been widely reported in the literature. The relation of experimental cognitive ability measures to real-world cognitive competence has been questioned. This research examines the validity of English-language versions of two measures of everyday competency: the Memory in Reality test involving object placement recall and the Coin Test, a money-sorting task. The measures were developed as part of a Swedish epidemiologic study. Validity was evaluated by comparison of these tasks with standard cognitive tests and with a measure of metamemory. It was expected that the ecological measures would have a stronger association with metamemory than the standard tests. Subjects were 93 community-dwelling women, aged 75 and older. The ecological tasks correlated positively with the standard tests, but there were inconsistent relations of both standard and ecological measures with metamemory. The results partly support use of these measures for evaluating everyday functioning.

Activities of Daily Living↗

The effect of working serial night shifts on the cognitive functioning of emergency physicians.

STUDY OBJECTIVE: We sought to determine whether working 5 serial night shifts in the emergency department results in a decline in physician performance as measured with an intelligence test. METHODS: This study compared the cognitive functioning of emergency physicians who worked the day shift (7 AM to 5 pm) with those who worked 5 consecutive night shifts (11 pm to 7 am). The Fluid Scale of the Kaufman Adolescent and Adult Intelligence Test (KAIT) was administered to 16 emergency medicine residents. Half of the residents (group A) were tested while working day shifts, and the other half (group B) were tested after working 5 consecutive night shifts. After a minimum interval of 2 months, the residents were retested in reverse order, with group A tested after working night shifts and group B tested while working day shifts. RESULTS: A total of 16 emergency medicine residents were tested. A paired t test was used to determine whether day-shift KAIT scores are different from night-shift KAIT scores. The mean day-shift KAIT score was 119.1 (SD=7.7), and the mean night-shift KAIT score was 107.2 (SD=10.2). This difference was significant (mean difference=11.9; 95% confidence interval 7.0 to 16.8; P <.001), with the day-shift scores being statistically higher than the night-shift scores. CONCLUSION: Working a series of 5 night shifts results in a substantial decline in cognitive performance in physicians working in the ED.

Cognition↗

Improvement of cognitive function in schizophrenic patients receiving clozapine or zotepine: results from a double-blind study.

Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia and the cognitive dysfunction associated with the disease. While clozapine has been shown to be effective in this respect, no data are available on zotepine. We report on a double-blind randomized study designed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia. Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity. Passage time, route, and motor errors were evaluated. 25 schizophrenic (DSM-IIIR) patients were included in each group. After washout, they were randomized on zotepine or clozapine and given up to 450 mg of substance each. Patients were followed for six weeks and evaluated weekly. We report on a subsample of 26 patients matched for baseline BPRS, SANS, and age. 13 matched healthy persons were recruited as controls. ANOVA with group and course over time as factors was used for analysis. Both clozapine and zotepine achieved a highly significant decrease in overall symptoms (BPRS) and negative symptoms (SANS). Zotepine and clozapine were equally effective. In the maze tests, motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a "trait" marker. In passage time and maze route, schizophrenics performed worse than controls. An improvement by medication was evident in both medication groups, but was more pronounced in the zotepine-treated group. The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia. The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction, confirming this substance's value as an atypical antipsychotic.

Adult↗

Assessment of cognitive functioning of methadone-maintenance patients: impact of adult ADHD and current cocaine dependence.

The purpose of this study was to determine if methadone-maintained patients (MMP) with cocaine dependence (CD) and/or adult Attention Deficit Hyperactivity Disorder (ADHD) exhibited compounded cognitive dysfunction associated with their poly-substance use and/or co-morbid psychiatric diagnoses. The sample consisted of 79 MMP (59% male, 51% Caucasian), maintained on methadone doses ranging from 40-130 mg/day, who were placed into one of four diagnostic categories: (1) a control group (no ADHD, no CD) (n = 24), (2) CD alone (n = 18), (3)ADHDalone (n = 18), and (4)ADHD+ CD(n = 19). The California Computerized Assessment Package (CalCAP) was administered to assess cognitive functioning requiring focused and sustained attention in a standardized fashion. There were no group differences on Simple Reaction tasks. Compared to the control group, the ADHD+ CD group was slower and less accurate on 33% of the Choice Reaction (CR) tasks. Specifically, individuals in the ADHD + CD group and the ADHD alone group performed significantly worse on tasks measuring attention and psychomotor responding. These tasks are associated with broader cognitive skills in working memory, language discrimination and flexibility of cognitive sets that may have implications for treatment outcome. Diagnostic services capable of identifying cognitive deficits among MMP with ADHD and/or CD are needed to maximize the likelihood of treatment success and to serve as an indicator for the efficacy of therapeutic approaches.

Adult↗

Dietary fat intake is associated with psychosocial and cognitive functioning of school-aged children in the United States.

Using cross-sectional data from the Third National Health and Nutrition Survey, 1988-1994, we examined whether dietary fat intake is associated with cognitive and psychosocial functioning in school-aged children. Based upon 24-h diet recall interviews, dietary intakes of total fat, SFA, monounsaturated fatty, PUFAs, and cholesterol were estimated in 3666 participants aged 6 to 16 y. Psychosocial functioning was evaluated in interviews of each child's mother. Cognitive functioning was measured using achievement and intelligence tests. Overall, total fat and saturated fat were unrelated to measures of cognitive and psychosocial functioning. Compared with equivalent energy intake from saturated fat or carbohydrate, each 5% increase in energy intake from PUFAs was associated with lower risks of poor performance on the digit span test (replacing SFA, OR = 0.58, 95% CI = 0.37-0.91; replacing carbohydrate, OR = 0.61, 95% CI = 0.43-0.88). Cholesterol intake was associated with an increased risk of poor performance on the digit span test (OR = 1.25, 95% CI = 1.11-1.42 for each 100-mg increment intake of cholesterol). The associations were independent of socioeconomic status, maternal education and marital status, and children's nutrition status and were consistent across different methods of energy adjustment in regression models. We conclude that high intake of PUFAs may contribute to an improved performance on the digit span test. In contrast, increased intake of cholesterol may be associated with a poorer performance.

Adolescent↗

Effect of levodopa on cognitive function in Parkinson's disease with and without dementia and dementia with Lewy bodies.

BACKGROUND: Levodopa (L-dopa) is the gold standard treatment for Parkinson's disease, but a lack of clear efficacy combined with a perceived liability to neuropsychiatric side effects has limited L-dopa use in patients with parkinsonism and dementia. Therefore, the effect of L-dopa on the cognitive profile of dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is unclear. AIM: To ascertain the acute and long-term effects of L-dopa on aspects of attention and cognition in patients with DLB and PDD, and to compare these with the effects in Parkinson's disease. METHOD: Baseline cognitive and motor function was assessed off L-dopa in patients with Parkinson's disease (n = 22), PDD (n = 27) and DLB (n = 11) using standard "bedside" measures and a computerised programme detecting reaction times and accuracy. All patients then underwent an acute L-dopa challenge with subsequent subjective and objective analysis of alertness, verbal recall, reaction times and accuracy. The same parameters were measured after 3 months on L-dopa to assess the prolonged effect. RESULTS: Acute L-dopa challenge considerably improved motor function and subjective alertness in all patients without compromising either reaction times or accuracy, but increased fluctuations were noted in both groups with dementia. Neuropsychiatric scores improved in patients with Parkinson's disease both with and without dementia on L-dopa at 3 months. Although patients with Parkinson's disease also had better mean global cognitive function at this time, mean verbal attention and memory deteriorated, and patients with PDD had slower reaction times in some tests. No patient had a marked deterioration over this time. Patients with DLB did not experience any adverse cognitive or neuropsychiatric effects after 3 months of L-dopa treatment. CONCLUSION: The use of L-dopa in patients with parkinsonism with dementia does not adversely affect cognitive function.

Aged↗

Schizophrenia and cognitive function.

Schizophrenia is often associated with cognitive deficits, particularly within the domains of memory and language. Specific cognitive deficits have recently been linked to psychotic phenomena, including verbal hallucinations and disorganized speech. Impairments of working and semantic memory are primarily due to dysfunction of the frontal cortex, temporal cortex, and hippocampus. Cognitive skills in schizophrenia predict social functioning and may serve as outcome measures in the development of effective treatment strategies.

Brain Mapping↗

Correlational analysis of MicroCog: Assessment of Cognitive Functioning with the Wechsler Adult Intelligence Scale-III for a clinical sample of veterans.

With rapid advances in technology and an emphasis in efficiency in psychological testing, there is a need to investigate the relation between a computerized cognitive examination and a traditional individually administered intelligence test. The current study provided correlations of intelligence scores from MicroCog: Assessment of Cognitive Functioning and intelligence scores from WAIS-III. MicroCog is a single computerized test measuring intelligence and the WAIS-III is a single traditionally administered test measuring intelligence. The study included 30 participants referred for psychological testing at a Veterans Medical Center in Tennessee as part of the standard intake process. Half of the participants were administered MicroCog first and half the WAIS-III first. Analysis indicated scores on the two tests were positively correlated. Index scores measuring similar constructs also were positively correlated. However, MicroCog was significantly more difficult than the WAIS-III in that scores were, on average, lower on MicroCog.

Adult↗

Brain metabolites and cognitive function among older depressed and healthy individuals using 2D MR spectroscopy.

Brain metabolites of choline (Ch) and myo-Inisotol (mI) have been reported as elevated among geriatric depressed patients. Two-dimensional (2D) magnetic resonance spectroscopy (MRS) provides estimates of Ch, mI, and creatine (Cr) similar to one-dimensional MRS, and it also estimates the resonances of the Ch-containing compounds of phosphoethanolamine (Pe) and phosphocholine (PCh). In this cross-sectional geriatric study, 14 depressed patients and 14 healthy volunteers who were comparable in age, gender, education, comorbid medical burden, and Mini-Mental State Examination (MMSE) scores completed 2D MRS and a neurocognitive battery. A voxel in the left dorsolateral cortex, which was comprised of approximately 60% white matter, was used to estimate the CR ratios of Ch, PCh, Pe, and mI. Composite scores for cognitive function were developed for verbal learning, recall, recognition, executive function, hypothesis generation, and processing speed. Among nondepressed subjects, cognition was positively correlated with Ch/Cr and mI/Cr and negatively correlated with PCh/Cr in four domains of verbal learning, recognition, recall, and hypothesis generation. In contrast, depressed patients did not have consistent relationships between Ch/Cr, mI/Cr, and PCh/Cr and cognition. There was a significant difference in the overall pattern of associations between the four metabolites and verbal learning and processing speed in depressed patients compared to healthy controls. The attenuated relationship between metabolites and specific cognitive domains in patients with late-life MDD suggests that the level of cognitive performance observed during depressive episodes may be associated with changes in biochemistry within the frontostriatal neuronal circuitry.

Age Factors↗

Cognitive functioning in schizophrenia: a consensus statement on its role in the definition and evaluation of effective treatments for the illness.

BACKGROUND: Truly effective treatments for schizophrenia require much more than clinical efficacy. Symptom improvement is all that is required to demonstrate clinical efficacy. However, for a treatment to be effective in a wide-ranging manner, improvement in various life domains, such as social functioning, independent living, and employment, should also be found. Thus, a much wider range of improvements, not widely produced by previous treatments, is required to take treatment for schizophrenia to a new level of effectiveness. CONSENSUS PROCESS: A teleconference consensus meeting was held with the bylined authors on December 10, 2002, to explore the factors that hinder the most effective treatments for schizophrenia. We argue that a possible unifying factor underlying these apparently disparate domains of effective treatment is cognitive functioning, which is impaired in people with schizophrenia. Treatment of cognitive dysfunction may have a central role in increasing the breadth of effective treatment for schizophrenia. CONCLUSIONS: Novel antipsychotics and specific cognitive-enhancing medications have preliminarily been shown to have cognitive benefits that might lead to broader effectiveness of treatments, eventually reflected in improvements in the daily lives of patients. These treatments may have their greatest impact when combined with focused psychological interventions. While the research to date does not provide a large number of successes, this area will be one of considerable research interest for the next decade, with developments likely to be very important to clinicians treating patients with schizophrenia.

Antipsychotic Agents↗

The serotonin1A receptor partial agonist S15535 [4-(benzodioxan-5-yl)1-(indan-2-yl)piperazine] enhances cholinergic transmission and cognitive function in rodents: a combined neurochemical and behavioral analysis.

These studies examined the influence of the selective 5-hydroxytryptamine (serotonin) (5-HT)(1A) receptor partial agonist S15535 [4-(benzodioxan-5-yl)1-(indan-2-yl)piperazine] upon cholinergic transmission and cognitive function in rodents. In the absence of acetylcholinesterase inhibitors, S15535 dose-dependently (0.04-5.0 mg/kg s.c.) elevated dialysis levels of acetylcholine in the frontal cortex and dorsal hippocampus of freely moving rats. In the cortex, the selective 5-HT(1A) receptor antagonist WAY100,635 [(N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide) fumarate] dose-dependently (0.0025-0.63) blocked this action of S15535. By contrast, in dorsal hippocampus, WAY100,635 mimicked the induction of acetylcholine release by S15535. In a social recognition paradigm, S15535 dose-dependently (0.16-10.0) improved retention, an action blocked by WAY100,635 (0.16), which was ineffective alone. Furthermore, S15535 dose-dependently (0.04-2.5) and WAY100,635 reversibly abolished amnesic properties of the muscarinic antagonist scopolamine (0.63) in this procedure. Cognitive deficits provoked by scopolamine in autoshaping and Morris water-maze procedures were likewise blocked by S15535 at doses of 0.63 to 10.0 and 0.16 to 2.5, respectively. In a two-platform spatial discrimination task, in which S15535 similarly abrogates cognitive deficits elicited by scopolamine, injection of S15535 (1.0 and 10.0 microg) into dorsal hippocampus blocked amnesic effects of the 5-HT(1A) agonist 8-hydroxy-2-dipropylaminotetralin (0.5 microg). Finally, S15535 (0.16-0.63) improved performance in a spatial, delayed nonmatching to sample model in mice, and in an operant delayed nonmatching to sample model in old rats, S15535 (1.25-5.0 mg/kg p.o.) increased response accuracy and reduced latency to respond. In conclusion, S15535 reinforces frontocortical and hippocampal release of acetylcholine and displays a broad-based pattern of procognitive properties. Its actions involve both blockade of postsynaptic 5-HT(1A) receptors and engagement of 5-HT(1A) autoreceptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗