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A longitudinal study of cognitive function in elderly persons with subjective memory complaints.

OBJECTIVE: To assess change in cognitive function in elderly individuals with subjective memory loss over a follow-up interval of more than 3 years. DESIGN: Prospective cohort study. SETTING: An outpatient research clinic in aging and dementia at a university hospital. PARTICIPANTS: A convenience sample of 59 healthy, elderly individuals (mean age 68.7 years) with memory complaints but no clinically apparent cognitive dysfunction. MEASUREMENTS: Participants were given a full diagnostic evaluation and were administered a neuropsychological test battery at baseline and follow-up. The cognitive assessment battery included 12 tests of recent memory, immediate memory, language function, visuospatial praxis, and psychomotor speed. Most of the tests had been established to be sensitive to cross-sectional age differences. RESULTS: Of 59 subjects, 54 (91.5%) were successfully followed up an average of 3.4 years later. Between baseline and follow-up, two tests exhibited significant improvement, two tests exhibited significant decline, and the other eight were unaffected. CONCLUSION: Elderly individuals with subjective perceptions of cognitive decrements who fail to provide clear evidence of cognitive impairment upon clinical interview are not at high risk for progressive cognitive deterioration over the subsequent 3- to 4-year interval.

Aged↗

Regulation of brain-derived neurotrophic factor (BDNF) during sleep apnoea treatment.

BACKGROUND: Patients with obstructive sleep apnoea syndrome (OSAS) often display persistent cognitive dysfunction despite effective treatment with continuous positive airway pressure (CPAP). Brain-derived neurotrophic factor (BDNF) is a key mediator of memory and cognition, but its regulation in OSAS and during CPAP treatment is unknown. METHODS: Serum and plasma BDNF concentrations, BDNF secretion by peripheral blood mononuclear cells, and overnight polysomnography were evaluated in 17 men with newly diagnosed OSAS (as defined by a respiratory disturbance index of >10/hour with >70% obstructive events and corresponding daytime symptoms) and 12 healthy control men. In the patients all the parameters were monitored after 1 night and 3 months of CPAP treatment. RESULTS: There was no significant difference in baseline serum BDNF, plasma BDNF, or spontaneous BDNF secretion by peripheral blood mononuclear cells between untreated patients and controls. After 1 night of CPAP treatment there was a steep fall in median serum BDNF (from 18.0 ng/ml to 4.1 ng/ml) and plasma BDNF (from 58.7 pg/ml to 22.0 pg/ml) concentrations. Following 3 months of treatment BDNF concentrations did not return to baseline. In contrast, BDNF secretion was not suppressed by CPAP treatment. CONCLUSIONS: Patients with untreated OSAS have normal serum and plasma BDNF levels. CPAP treatment is associated with a rapid decrease in serum and plasma BDNF levels which may reflect enhanced neuronal demand for BDNF in this condition.

Biomarkers↗

A controlled study of cognitive deficits in children with chronic Lyme disease.

Although neurologic Lyme disease is known to cause cognitive dysfunction in adults, little is known about its long-term sequelae in children. Twenty children with a history of new-onset cognitive complaints after Lyme disease were compared with 20 matched healthy control subjects. Each child was assessed with measures of cognition and psychopathology. Children with Lyme disease had significantly more cognitive and psychiatric disturbances. Cognitive deficits were still found after controlling for anxiety, depression, and fatigue. Lyme disease in children may be accompanied by long-term neuropsychiatric disturbances, resulting in psychosocial and academic impairments. Areas for further study are discussed.

Adolescent↗

[Psychiatric manifestations in dementia: phenomenologic perspectives].

The study of psychiatric manifestations in dementia has long been overshadowed by the more classical manifestations of the disease, such as memory loss and other cognitive deficits. In recent years, however, psychiatric symptoms as part of the demential process have attracted interest and research has become more specific. Clinicians are faced with diagnostic, treatment and management difficulties related to affective or psychotic symptoms, which account for much distress and morbidity. Several studies indicate that the prevalence of psychiatric manifestations in clinical populations of patients suffering from dementia is high: 15% to 30% for hallucinations, 15% to 30% for delusions, ten percent to 20% for major depression and 40% to 50% for depressed mood. These figures tend to confirm the hypothesis that psychiatric features in dementia are neither infrequent nor atypical. Thus, researchers have sought to link psychotic or depressive symptomatology with several clinical characteristics of dementia, namely stage, severity, prognosis or cognitive dysfunction. Some recent studies involving extensive neuropsychological evaluations indicate that subgroups of patients can be defined according to psychiatric criteria, as well as cognitive or neurological criteria. Unfortunately, results are inconsistent. Some of the contradictions in the literature are related to poorly defined terms and symptoms, a lack of reliable operational criteria, absence of validation of instruments and scales and heterogeneity of the populations studied. Ambiguous syndromes, such as pseudodementia, while illustrative of certain clinical situations, have not been helpful in categorizing demented patients. The author suggests that research focused on specific and clearly defined psychiatric symptoms in dementia will better serve our comprehension of mixed syndromes.

Aged↗

Donepezil improved memory in multiple sclerosis in a randomized clinical trial.

OBJECTIVE: To determine the effect of donepezil in treating memory and cognitive dysfunction in multiple sclerosis (MS). METHODS: This single-center double-blind placebo-controlled clinical trial evaluated 69 MS patients with cognitive impairment who were randomly assigned to receive a 24-week treatment course of either donepezil (10 mg daily) or placebo. Patients underwent neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in verbal learning and memory on the Selective Reminding Test (SRT). Secondary outcomes included other tests of cognitive function, patient-reported change in memory, and clinician-reported impression of cognitive change. RESULTS: Donepezil-treated patients showed significant improvement in memory performance on the SRT compared to placebo (p = 0.043). The benefit of donepezil remained significant after controlling for various covariates including age, Expanded Disability Status Scale, baseline SRT score, reading ability, MS subtype, and sex. Donepezil-treated patients did not show significant improvements on other cognitive tests, but were more than twice as likely to report memory improvement than those in the placebo group (p = 0.006). The clinician also reported cognitive improvement in almost twice as many donepezil vs placebo patients (p = 0.036). No serious adverse events related to study medication occurred, although more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams (p = 0.010). CONCLUSIONS: Donepezil improved memory in MS patients with initial cognitive impairment in a single center clinical trial. A larger multicenter investigation of donepezil in MS is warranted in order to more definitively assess the efficacy of this intervention.

Adolescent↗

Altered hierarchy of protective responses against severe hypoglycemia in normal aging in healthy men.

OBJECTIVE: To investigate the effect of normal aging on the protective responses against hypoglycemia, in view of the fact that type II diabetes is primarily a disease of aging, and its treatment is associated with risk of hypoglycemia with cognitive impairment. RESEARCH DESIGN AND METHODS: Plasma glucose was lowered stepwise from 5 to 2.4 mmol/l and restored by manipulation of an infusion of 20% glucose during 220-min intravenous infusion of 1.5 mU.kg-1.min-1 soluble insulin in 14 men; 7 were aged 60-70 years and the other 7 were 22-26 years. Changes in neurohumoral responses, subjective awareness, and choice reaction time were assessed. RESULTS: Hormonal responses were similar in the two groups, but symptoms began earlier in the younger men (at a plasma glucose of 3.6 +/- 0.1 vs. 3.0 +/- 0.2 mmol/l, P = 0.02) and were more intense (P = 0.03). Four-choice reaction time, a measure of psychomotor coordination, deteriorated earlier in the older men (at a plasma glucose of 3.0 +/- 0.1 vs. 2.6 +/- 0.1 mmol/l, P = 0.07) and to a greater degree. The difference between the glucose level for subjective awareness of hypoglycemia and the onset of cognitive dysfunction was lost in the older men (0.0 +/- 0.2 vs. 0.8 +/- 0.1 mmol/l, P < 0.007). CONCLUSIONS: Older men are prone to more severe cognitive impairment during hypoglycemia than younger men and are less likely to experience prior warning symptoms if blood glucose falls. This effect of normal aging may contribute to the risk of severe hypoglycemia in older diabetic patients treated with sulfonylureas and insulin.

Adult↗

Tranquilizers, stimulants, and enhancers of cognition.

For patients with cognitive dysfunction, the appropriate use of neurotransmitter specific medication may permit independent living. This article examines a variety of tranquilizers, stimulants, and enhancers of cognition and evaluates which may be most effective given their side effect profiles.

Anti-Anxiety Agents↗

A study of P300-event related evoked potential in the patients of major depression.

Many studies involving various electrophysiological parameters have been conducted in psychiatric disorders like schizophrenia and dementia to assess their cognitive dysfunctions. Not much reports are available in major depression. The present study was conducted in 20 patients of major depression to evaluate their cognitive functions in terms of P300. P300 or P3 wave of auditory event related evoked potentials (ERPs) is usually seen around 300 msec of presenting of target stimulus, if the subject is responding to it. Auditory ERPs were recorded using the standard 'odd ball' paradigm. The latencies of various components of ERPs N1, N2, P1, P2, and P3 were recorded and compared with those of 20 normal age and sex matched controls. The latency of P300 was found to be significantly delayed in cases of major depression as compared to that of controls. Other waves were also delayed in cases of depression but the difference was not statistically significant. Our results suggest that P300 latency is longer in the patients of major depression disorders which could be due to constitutive altered 'cognitive neuronal pool' or a neurotransmitter/neuropeptide imbalance. Further studies involving larger populations are required to elucidate the diagnostic and predictive role of latency of P300 in the cases of depression.

Adult↗

Performance of normal Nigerian students on the mini-mental state examination.

BACKGROUND: Cognitive dysfunction is a feature of many diseases and the impact is especially relevant in the young. While there are many sophisticated tests of cognitive function, the shorter Mini Mental State examination (MMSE) is the most widely used screening test. In Nigeria where cognitive function is not routinely assessed in the management of cases, the MMSE is probably the most practical test of cognitive function to be promoted. This is because it is easy to administer and to interpret. There is however a need to define the performance of normal Nigerian subjects on the MMSE to make its use more relevant. METHODOLOGY: Seventy normal adolescents attending a secondary school in Ibadan, Nigeria, were administered the MMSE. Excluded were subjects with a history of mental impairment or medical disorders known to influence cognitive function. All subjects were tested only once. RESULTS: Normal MMSE scores were obtained by 88.6% of subjects while 11.4% of the subjects were found to be mildly or moderately cognitively impaired. More than 55% of the subjects did not obtain full scores with test of orientation in place while 30% and 34.3% respectively did not obtain full scores with tests of orientation in time and of attention respectively. Males and females performed equally with regard to the test items except for a non-statistically significant better performance of the females with test of three-item recall (p = 0.09). CONCLUSION: Abnormalities on the MMSE in Nigerians should be interpreted with caution as more than 10% of subjects may have abnormal scores. Tests of orientation and of attention are particularly likely to indicate abnormal cognitive function even in subjects with overall scores in the normal range. There may be a need to modify the MMSE to make it more applicable to young Nigerian subjects.

Adolescent↗

Cognitive and emotional impairment in obstructive sleep apnea syndrome.

OBJECTIVE: To evaluate the emotional and cognitive status in patients with obstructive sleep apnea syndrome (OSAS), using neuropsychological tests and evoked-related potential (P3). METHODS: Sixteen patients diagnosed of OSAS were tested by Hamilton rating scale for anxiety (HRSA) and Hamilton rating scale for depression (HRSD). Other three groups, OSAS patient group (n = 21), snoring group (n = 21), and control group (n = 21), were administered polysomnography (PSG), auditory evoked event-related potential (P3), and clinic memory test. The results were analyzed using general linear model (GLM) analysis and Post Hoc test. RESULTS: Twelve OSAS patients' scores of HRSA and HRSD were beyond the normal range, 26.42 +/- 4.48 and 22.08 +/- 3.97 respectively. The auditory P3 latency in OSAS group was 363.1 +/- 22.9 ms (Fz), 368.57 +/- 28.03 ms (Cz), in snoring group 336.57 +/- 31.08 ms (Fz), 339.81 +/- 31.76 ms (Cz), in control group 340.8 +/- 28.7 ms (Fz), 338.29 +/- 29.21 ms (Cz). There were significant differences between OSAS group and snoring group, as well as control group (P < 0.05). No significant difference was seen between snoring group and control group. No significant difference was noted in P3 amplitude among three groups. Memory quotient (MQ) reduced in snoring group compared with control group. CONCLUSIONS: Emotional disturbances are common clinical features in OSAS patients. Abnormal auditory P3 latency indicates the cognitive dysfunction in OSAS patients. Nocturnal hypoxaemia may play an important role on it. Snorers should be monitored because of the tendency to develop cognitive impairment.

Adult↗

Immunomodulatory agents for the treatment of relapsing multiple sclerosis: a systematic review.

BACKGROUND: Within the past 10 years, several immunomodulatory agents (IMAs) have become available for the treatment of relapsing multiple sclerosis (MS), making therapeutic decisions more complex. We performed a systematic review of the literature to assess the efficacy and safety of these agents on physical, inflammatory, and cognitive measures of disease activity. METHODS: We identified relevant studies by searching electronic databases (MEDLINE and Current Contents) from January 1, 1993, through August 31, 2001. We included English-language reports of data from phase 3 trials of interferon beta-1b (Betaseron), 2 preparations of interferon beta-1a (Avonex and Rebif), or glatiramer acetate (Copaxone) for the treatment of relapsing MS. RESULTS: Twenty-one studies met explicit inclusion criteria. Comparison of study results indicated no differences among IMAs regarding their efficacy on relapse-related measures. Interferon beta-1a significantly reduced disability progression, whereas no significant effect of glatiramer acetate or interferon beta-1b on disability progression was seen. On inflammatory measures, all of the IMAs showed reductions in the burden of disease (T2-weighted lesions) to varying degrees. Interferon beta and glatiramer acetate reduced new lesion activity; however, interferon beta had a more profound effect. One interferon beta-1a preparation (Avonex) appeared to reduce brain atrophy, whereas glatiramer acetate showed an effect in 1 of 2 studies. Only Avonex demonstrated efficacy in slowing progression of cognitive dysfunction. CONCLUSIONS: Data show that the IMAs have similar effects on several physical and inflammatory measures. In addition, Avonex has demonstrated efficacy in slowing cognitive progression in relapsing MS. One disadvantage of interferon beta is the possibility of immunogenicity, which may occur more often with subcutaneous administration. The IMAs have similar safety and tolerability profiles.

Adjuvants, Immunologic↗

Cognitive function in recent-onset demyelinating diseases.

To determine cognitive disturbances in recent demyelinating disease, we studied 21 patients with definite or probable multiple sclerosis (MS) of less than two years' duration and nine patients with recently isolated optic neuritis. None had any clinical or social evidence of cognitive impairment. Mild to moderate cognitive impairment. Mild to moderate cognitive impairment was present in 18 (60%) of 30 cases, affecting visual and/or verbal efficiency. These abnormalities were statistically significant when compared with the results of a control group of 29 patients. There was no correlation with a depressive status, between the presence of cognitive impairment and either the degree of handicap or the activity of the disease. The frequency of cognitive dysfunction (60%) appears to be comparable to that reported in other series in which MS evolution is over ten years. The natural history of cognitive functions in MS has to be identified. Neuropsychologic tests could be useful in the diagnosis of monosymptomatic or paucisymptomatic forms of MS (ie, visual or medullary).

Adult↗

Practice, learning, and the likelihood of making an error: how task experience shapes physiological response in patients with schizophrenia.

RATIONALE: Behavioral and functional neuroimaging research has extensively documented the ways in which people with schizophrenia perform poorly on cognitive tasks and exhibit abnormal brain activity patterns when engaged in those tasks, even when their performance is adjusted to become similar to that of healthy controls. There is, however, substantial diversity in the way this syndrome limits a person's ability to learn and acquire skills. This review considers how functional imaging has helped improve our understanding of learning, practice, and error detection in persons with schizophrenia. OBJECTIVES: Positron Emission Tomography and functional magnetic resonance studies are reviewed with particular attention to the roles of these methods and interventions in understanding the biological substrates of cognitive dysfunction in schizophrenic patients. This is done with particular attention to the question of how brain regions change in response to motor, perceptual, and cognitive training interventions. RESULTS: Investigators agree that the prefrontal cortex, anterior cingulate cortex, and hippocampus are impaired in most persons with schizophrenia. Imaging studies with healthy controls support multiple models of biological change elicited by learning and practice. Application of these methods to patients with schizophrenia is in an early stage. CONCLUSIONS: A person's response to perceptual, motor, and cognitive training may help pharmacologists and clinicians better interpret medication treatment studies in this diverse population.

Behavior Therapy↗

Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: relevance to Alzheimer's disease.

Aging and age-related disorders such as Alzheimer's disease (AD) are usually accompanied by oxidative stress as one of the main mechanisms contributing to neurodegeneration and cognitive decline. Aging canines develop cognitive dysfunction and neuropathology similar to those seen in humans, and the use of antioxidants results in reductions in oxidative damage and in improvement in cognitive function in this canine model of human aging. In the present study, the effect of a long-term treatment with an antioxidant-fortified diet and a program of behavioral enrichment on oxidative damage was studied in aged canines. To identify the neurobiological mechanisms underlying these treatment effects, the parietal cortex from 23 beagle dogs (8.1-12.4 years) were treated for 2.8 years in one of four treatment groups: i.e., control food-control behavioral enrichment (CC); control food-behavioral enrichment (CE); antioxidant food-control behavioral enrichment (CA); enriched environment-antioxidant-fortified food (EA). We analyzed the levels of the oxidative stress biomarkers, i.e., protein carbonyls, 3-nitrotyrosine (3-NT), and the lipid peroxidation product, 4-hydroxynonenal (HNE), and observed a decrease in their levels on all treatments when compared to control, with the most significant effects found in the combined treatment, EA. Since EA treatment was most effective, we also carried out a comparative proteomics study to identify specific brain proteins that were differentially expressed and used a parallel redox proteomics approach to identify specific brain proteins that were less oxidized following EA. The specific protein carbonyl levels of glutamate dehydrogenase [NAD (P)], glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alpha-enolase, neurofilament triplet L protein, glutathione-S-transferase (GST) and fascin actin bundling protein were significantly reduced in brain of EA-treated dogs compared to control. We also observed significant increases in expression of Cu/Zn superoxide dismutase, fructose-bisphosphate aldolase C, creatine kinase, glutamate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The increased expression of these proteins and in particular Cu/Zn SOD correlated with improved cognitive function. In addition, there was a significant increase in the enzymatic activities of glutathione-S-transferase (GST) and total superoxide dismutase (SOD), and significant increase in the protein levels of heme oxygenase (HO-1) in EA treated dogs compared to control. These findings suggest that the combined treatment reduces the levels of oxidative damage and improves the antioxidant reserve systems in the aging canine brain, and may contribute to improvements in learning and memory. These observations provide insights into a possible neurobiological mechanism underlying the effects of the combined treatment. These results support the combination treatments as a possible therapeutic approach that could be translated to the aging human population who are at risk for age-related neurodegenerative disorders, including Alzheimer's disease.

Aldehydes↗

Coping and cognition in schizophrenia and depression.

We examined the stable relations between coping style and cognitive function in schizophrenic and depressed patients and in patient and normal controls on two test occasions. The results show that a poor self-report of coping style is independent of psychiatric diagnosis, but there are associations with both subjective and objective cognitive malaise. Poor cognitive task performance is associated with a dependent coping style, perhaps pointing to a "giving-up" attitude. Subjective cognitive dysfunction and high levels of mental effort during task performance are associated with an avoidant coping style and with worrying, which suggest failing compensatory cognitive strategies as a causal mechanism of this coping dimension.

Adaptation, Psychological↗

Effect of asymptomatic carotid artery disease on cognitive outcome after cardiopulmonary bypass.

This prospective study reinvestigates the effect of asymptomatic carotid artery disease on the cognitive outcome after cardiopulmonary bypass (CPB) (Harrison et al., 1989). Patients (N = 104) scheduled for cardiac surgery using CPB were classified in one of two groups based on the results of a preoperative duplex B mode Doppler scan of the internal carotid arteries. All patients received a neuropsychological examination before surgery, 8 days after surgery, and 6 months after surgery (n = 79). When group data are considered, patients showed evidence of selective cognitive dysfunction early after surgery. These dysfunctions were resolved by the sixth postoperative month. We found no indications that the presence of asymptomatic carotid artery disease increased the incidence of cognitive disturbances after CPB or differentially affected the postoperative performance. We conclude that mild to moderate asymptomatic carotid artery disease does not appear to play a major role in the genesis of postoperative neuropsychological sequelae.

Aged↗

Negative cognitions and attributional style in depressed adolescents: an examination of stability and specificity.

Despite recent findings that the prevalence of unipolar depression is as high in adolescents as it is in adults, relatively little is known about the applicability of cognitive theories of depression to adolescents. The present study examined the nature, specificity, and stability of cognitive dysfunction in male and female depressed, remitted, and psychiatric control adolescents. Factor analysis of a diverse set of measures yielded two factors, labelled Negative Cognitions and Attributional Style. Scores on both these factors were related to a current diagnosis of depression. Results also indicated that there may not be complete recovery of cognitive functioning (or of depressed mood) with diagnostic remission of depression. Finally, whereas elevated scores on the Negative Cognitions factor appeared to be specific to depression, the depressed and psychiatric control adolescents did not differ with respect to their scores on the Attributional Style factor.

Adolescent↗

Assessment of CNS effects of antiepileptic drugs by using quantitative EEG measures.

PURPOSE: Antiepileptic drugs (AEDs) can be associated with adverse neurologic effects including cognitive dysfunction. Objective methods for recognizing AED effects on the brain could be valuable for long-term management. We compared quantitative EEG measures and cognitive tests in a group of patients beginning or ending AED therapy. METHODS: Subjects included 20 patients beginning AED therapy (AEDon), 12 patients stopping AED therapy (AEDoff), 33 patient controls receiving stable AED therapy (AEDco), and 73 healthy controls (Nco). All subjects underwent structured EEG recording and a cognitive test battery before change in AED dose and again 12-16 weeks later, >or=4 weeks after the last dose change. Four occipital EEG measures (peak frequency, median frequency, relative theta and delta power) were analyzed. Cognitive test changes were scored by using test-retest regression equations based on the Nco subjects. Wilcoxon tests were used for two-group comparisons. RESULTS: AEDons had a significant decrease, and AEDoffs, a significant increase in the peak frequency of the EEG rhythm, as compared with controls. Results for median frequency and theta power were similar. Change in the EEG peak frequency correlated with an aggregate cognitive change measure (r2= 0.71; p < 0.001), individual cognitive measures, and subjective complaints. Of the combined AEDon/AEDoff patients, 58% exceeded the 95% confidence interval for test-retest change in EEG peak frequency. CONCLUSIONS: Quantitative measures derived from the occipital EEG are sensitive to AEDs and correlate with AED-related cognitive effects and subjective complaints. Although this correlation does not indicate a direct relation, quantified EEG may be a practical measure of AED impact on the brain.

Acoustic Stimulation↗