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PubMed1996

Pattern of cerebral blood flow and cognition in patients undergoing chronic haemodialysis treatment.

We studied 20 patients aged 46-69 years (mean 57 years) undergoing long-term haemodialysis (HD) and 20 age- and sex-matched controls with single photon emission tomography (SPET) and 99Tcm-hexamethyl-propyleneamine-oxime to look for regional abnormalities in cerebral blood flow (CBF) and their relation to cognitive dysfunction. Global hemispheric tracer uptake relative to the cerebellum was similar in both groups, but regional over cerebellar activity was significantly reduced in the frontal cortex (85.9 +/- 5.1 vs 90.4 +/- 5.3; P = 0.01) and thalamus (99.2 +/- 8.8 vs 104.9 +/- 8.4; P = 0.05) of the HD patients. Normalization to whole-brain activity also showed the frontal cortex to be hypoactive in the HD patients, while tracer uptake was increased occipitally. These regional differences were not explained by the presence of atrophy or cerebrovascular damage seen on brain magnetic resonance imaging. The HD patients scored significantly worse on cognitive tests such as the Mini Mental State Examination (23 +/- 4 vs 28 +/- 1; P < 0.001) and Mattis Dementia Rating Scale (114 +/- 24 vs 143 +/- 1; P < 0.001). Regional activity ratios did not correlate with cognitive test scores, however. Our results indicate a disturbed pattern of CBF in HD patients, although regional SPET abnormalities did not correspond to the severity of cognitive dysfunction.

Aged↗

PubMed2003

Incipient CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Knowledge of disease expression in young adult NOTCH3 mutation carriers (MCs) is limited. OBJECTIVE: To characterize clinical, neuropsychological, and radiological status in NOTCH3 MCs younger than 35 years. DESIGN: Clinical characterization and blinded survey comparing MCs with non-MCs. SETTING: Referral center. PARTICIPANTS: Individuals younger than 35 years who were at a 50% risk of a NOTCH3 mutation, from our CADASIL database. Thirteen individuals, from 8 families, met the criteria. METHODS: Comprehensive clinical, genetic, neuropsychological, and radiological investigations. Magnetic resonance images were scored according to a standardized white matter hyperintensities rating scale. RESULTS: Six individuals, from 5 families, were MCs. Clinical symptoms consisted of migraine (with aura), stroke, and stroke-like episodes. We did not find evidence for psychiatric disturbances, functional disability, or cognitive dysfunction, compared with non-MCs. Radiologically, a characteristic magnetic resonance imaging lesion pattern emerged for all MCs. This comprised white matter hyperintensities in the anterior temporal lobes, the frontal lobes, and the periventricular frontal caps. CONCLUSIONS: Migraine (with aura) and stroke can present in NOTCH3 MCs younger than 35 years; however, more importantly, physical function and cognition are intact. Possible subtle cognitive dysfunction needs to be assessed in a larger study. White matter hyperintensities on magnetic resonance imaging are characteristic, and are consistently visualized from the age of 21 years and onward. Awareness of the clinical and radiological features of CADASIL in those younger than 35 years should increase early diagnosis and allow for customized counseling of young adults from families with CADASIL.

Adult↗

PubMed1987

Clinical significance of cognitive performance by hypertensive patients.

Fifty-four subjects with uncomplicated essential hypertension and 54 normotensive subjects were compared with regard to a widely employed clinical index of cognitive dysfunction (the Average Impairment Rating) calculated from neuropsychological tests that discriminate between brain-damaged and neurologically normal persons. Hypertensive subjects exhibited lower mean scores on this index when education was ignored, but results were not the same for highly educated and less well educated groups. There were no differences between exceptionally well educated hypertensive and normotensive subjects, but in the less well educated group, hypertensive subjects performed more poorly than normotensive subjects. The percentages of hypertensive and normotensive subjects scoring in a cognitively impaired range on the Average Impairment Rating were low and did not differ for either education group. These data indicate the important role of subtle differences in education level with respect to positive or negative findings for studies comparing hypertensive and normotensive subjects and illustrate the important role of clinical neuropsychological indices of cognitive dysfunction when one wishes to make meaningful inferences regarding cerebral cortical function in hypertensive subjects.

Adult↗

PubMed2001

Corticobasal degeneration.

Corticobasal degeneration (CBG) is an increasingly recognized neurodegenerative disease with both motor and cognitive dysfunction. The diagnosis is probably underestimated because of the heterogeneity of clinical features, overlap with symptoms, and pathologic findings of other neurodegenerative diseases. The most characteristic initial motor symptoms are akinesia, rigidity, and apraxia. Dystonia and alien limb phenomena are frequently observed. There is often a parkinsonian picture with failure or lack of efficacy of dopaminergic medical therapy. Cognitive decline, prompting the diagnosis of dementia, may be the most common presentation of CBD that is misdiagnosed. Pathology is characterized by an asymmetric frontoparietal neuronal loss and gliosis with ballooned, achromatic cortical neurons, nigral degeneration, and variable subcortical involvement. Neuroimaging and electrophysiologic studies may help with the diagnosis but are not specific. Treatment is primarily symptomatic and minimally effective, especially after the first several years of symptoms. CBD should be considered in the differential diagnosis of patients with motor and cognitive dysfunction presenting with cortical and subcortical features. Further studies to elucidate molecular abnormalities and biological markers associated with CBD are needed to improve clinical diagnosis and treatment of patients with this disorder.

Basal Ganglia↗

PubMed1987

Concurrent validity of a stress-vulnerability model of suicidal ideation and behavior: a follow-up study.

A follow-up study to test the concurrent validity of a stress-vulnerability model of suicidal ideation and behavior was conducted. A total of 202 college students (139 females, 63 males) completed self-report measures of life stress, loneliness, depression, dysfunctional cognitions, reasons for living, hopelessness, current suicide ideation, and predictions of future suicide probability. The results of a multiple-regression analysis indicated that 30% of the variation in suicide ideation scores could be accounted for by the linear combination of negative life stress, depression, loneliness, and few reasons for living. The linear combination of current suicide ideation, hopelessness, dysfunctional cognitions, and few reasons for living explained 56% of the variance in self-predicted future suicide probability. The results are interpreted as being supportive of the proposed model.

Adult↗

PubMed1995

Cognitive effects after epidural vs general anesthesia in older adults. A randomized trial.

OBJECTIVE: To compare the effect of epidural vs general anesthesia on the incidence of long-term cognitive dysfunction after total knee replacement surgery in older adults. DESIGN: Randomized controlled clinical trial. SETTING: Orthopedic specialty academic hospital. PATIENTS: A total of 262 patients undergoing elective primary total knee replacement with a median age of 69 years; 70% women. INTERVENTION: Random assignment to either epidural or general anesthesia. MAIN OUTCOME MEASURES: A thorough neuropsychological assessment was performed preoperatively and repeated at 1 week and 6 months postoperatively. Cognitive outcome was assessed by within-patient change on 10 tests of memory, psychomotor, and language skills. Prospective standardized surveillance for cardiovascular complications was performed to allow simultaneous assessment of anesthetic effects on cognitive and cardiovascular outcomes. RESULTS: The two groups were similar at baseline in terms of age, sex, comorbidity, and cognitive function. There were no significant differences between the epidural and general anesthesia groups in within-subject change from baseline on any of the 10 cognitive test results at either 1 week or 6 months. Overall, 5% of patients showed a long-term clinically significant deterioration in cognitive function. There was no difference between the anesthesia groups in the incidence of major cardiovascular complications (3% overall). CONCLUSIONS: The type of anesthesia, general or epidural, does not affect the magnitude or pattern of postoperative cognitive dysfunction or the incidence of major cardiovascular complications in older adults undergoing elective total knee replacement. This is the largest trial of the effects of general vs regional anesthesia on cerebral function reported to date, with more than 99% power to detect a clinically significant difference on any of the neuropsychological tests.

Aged↗

PubMed1991

Cognitive functions of epileptic patients on monotherapy with phenobarbitone and healthy controls.

Quantitative measurements have indicated that heredity, cerebral damage, psycho-social aspects, ictal and inter-ictal phenomena and antiepileptic drugs may interfere in the cognitive dysfunction of epileptic patients. In the present study objective methods included immediate and late recall and recognition of pictures, Stroop test and auditory selection. Twenty patients with symptomatic localized epilepsy aged 17-52 years (27 +/- 10, mean +/- sd) were compared to age and socially matched healthy controls. Patients were on therapeutic serum concentrations (25 +/- 12 mu/ml) of phenobarbitone and had active epilepsy with 1.94 generalized tonic-clonic, 0.85 simple partial and 6.28 complex partial seizures monthly (means). Patients performed worse than controls in all 6 tests (p less than 0.05 to p less than 0.001), indicating a generalized cognitive deficit related to seizures and/or barbiturate therapy. We suggest further studies should be carried out in populations with uniform monotherapeutic regimens and epileptic syndromes in order to isolate factors related to the cognitive dysfunction of epileptic patients.

Adolescent↗

PubMed2004

CPAP-therapy effectively lowers serum homocysteine in obstructive sleep apnea syndrome.

Assessment of serum total homocysteine (tHcy) in patients with obstructive sleep apnea (OSA) syndrome is highly relevant since both are strongly associated with stroke and cognitive dysfunction. Seven of 16 untreated OSA patients showed tHcy levels exceeding 11.7 micromol/l. The circadian pattern of serum tHcy in untreated and treated patients (p < 0.001) implied a diagnostic impact of blood sampling time. Treatment with continuous positive airway pressure (CPAP) effectively lowered tHcy levels in patients by about 30% (p < 0.005) and thus probably the (hyper)homocysteinemia-related cognitive dysfunction and the risk for cardio-/cerebrovascular diseases.

Chromatography, High Pressure Liquid↗

PubMed1999

[Neuropsychological aspects of dementia diagnosis].

In the interdisciplinary diagnostics of dementia neuropsychology is applied in early detection, in differential diagnostics and in progressive course assessment. With standardized neuropsychological testing severity and nature of cognitive dysfunction is assessed. In particular memory disorders, aphasia, apraxia, agnosia and disorders of executive functions are assessed by these methods. In early stage of Alzheimer's Disease episodic and semantic memory as well as certain language functions are affected. Apractic and agnostic disorders often appear only in the later course of the disease. Depending on localization and nature of lesion cognitive dysfunction patterns tend to be more lateralized in vascular dementia (e.g. aphasic, apractic or visual-constructive disorders). In the various forms of fronto-temporal dementia executive functions and/or personality are mainly affected.

Aged↗

PubMed2006

Stereotypy in schizophrenia.

OBJECTIVES: In schizophrenia, stereotypy is observed, a symptom characterized by repetitive, functionless motor behaviour. Whereas cognitive dysfunctioning is known to remain stable throughout the illness, less is known about the course of the motor symptoms. The Zeigeversuch [Mittenecker, E., 1953. Perseveration und Persönlichkeit: 1. Teil: experimentelle Untersuchungen. Z. Exp. Angew. Psychol. 1, 5-31], which entails the generation of a random sequence of button presses, was claimed to capture stereotypy. We used a newly designed computerized version of the Zeigeversuch, the Stereotypy Test Apparatus (STA) to evaluate the evolution of STA performance through the course of the illness. METHODS: To assess stereotyped and perseverative behaviour, 58 schizophrenic inpatients and 48 healthy controls performed the STA and the Wisconsin Card Sorting Test (WCST), respectively, as well as several other traditional neuropsychological tests and the Symbol Digit Substitution Test (SDST) on a writing digitizer. RESULTS: The STA correlated only weakly with the WCST and SDST measures but not with the cognitive or motor slowing on the SDST, nor with the other cognitive measures. Stereotyped and perseverative idiosyncrasies both seem to increase in the course of the illness, in contrast with other cognitive dysfunctions. However, whereas perseveration is already present in the early stages of the illness, stereotyped behaviour only manifests itself in the later stages of schizophrenia. Failure of cognitive inhibition may result in an activation of prepotent stereotyped responses captured by the STA.

Adult↗

PubMed2005

Atypical diabetes associated with inclusion formation in the R6/2 mouse model of Huntington's disease is not improved by treatment with hypoglycaemic agents.

The R6/2 transgenic mouse model of Huntington's disease (HD) develops a progressive neurological phenotype that involves severe motor and cognitive dysfunctions. Although not a cardinal sign, diabetes has been described in R6/2 mice. It is not clear, however, whether the diabetes contributes to the HD-like phenotype of R6/2 mice. In our study we found that the severity of diabetes in R6/2 mice was associated with the progressive formation of ubiquinated inclusions in pancreatic beta cells. Diabetes is dissociated from early motor and cognitive dysfunctions and did not correlate with motor impairment and survival of R6/2 mice. However, chronic behavioural testing (at a level higher than that which is reported to improve several aspects of the R6/2 phenotype) exacerbated the onset of diabetes. Pharmacological treatment of the diabetes was attempted using two oral hypoglycaemic agents commonly used by diabetics. The mice responded acutely to glibenclamide (which induces exocytosis of insulin) but not to rosiglitazone (which induces sensitization to insulin). This supports the suggestion that the diabetes in R6/2 mice is caused by an impairment in insulin release rather than insulin insensitivity. However, chronic treatment with these hypoglycaemic agents had no effect on either the course of the diabetes or the disease in R6/2 mice.

Administration, Oral↗

PubMed2006

Side-effects of chemotherapy and quality of life in ovarian and breast cancer patients.

PURPOSE OF REVIEW: Women diagnosed with ovarian cancer or breast cancer often face aggressive chemotherapy involving multiple treatment regimens. These treatments may be associated with significant side-effects that adversely impact patient quality of life. In this review, we will highlight recent research on side-effects of chemotherapy and the quality-of-life concerns of women with ovarian and breast cancer. RECENT FINDINGS: Adjuvant chemotherapy has demonstrated efficacy in the management of ovarian and breast cancers. In addition to physical side-effects, a subset of women receiving chemotherapy will experience significant cognitive dysfunction that adversely affects their perceived quality of life. Variables including disease response, treatment indication and extent of the patient's social support also influence quality-of-life ratings. SUMMARY: Although prolongation of survival remains the primary goal of chemotherapy, the palliation of symptoms and preservation of quality of life are also important treatment considerations. Chemotherapy may be associated with nausea, vomiting, hair loss, cognitive dysfunction, fatigue, changes in sexual functioning and reductions in quality-of-life ratings. Although rare to date, prospective, randomized, longitudinal studies that incorporate a pre-treatment assessment of symptom burden and perceived quality of life are necessary to define the severity and pattern of treatment-related change and subsequently guide intervention strategies. In some cases, quality-of-life issues may help to guide patient-care decisions.

Antineoplastic Agents↗

PubMed2003

Sex differences in genetic risk for dementia.

We used two Swedish twin samples to test whether women are at greater risk than men of developing dementia and whether there are sex differences in mechanisms underlying dementia and cognitive dysfunction. Dementia analyses found no sex differences in incidence of dementia or Alzheimer's disease among initially intact participants followed longitudinally. Twin analyses indicated a substantial genetic influence on liability to incident dementia. Although sex differences in model parameters were not statistically significant, for women but not men an equally attractive model included genetic influence due to both additive effects and dominance or epistasis. In the cognitive dysfunction analyses, results from a sex limitation model raise the possibility that either different genes or different environments have a role for men and women. We conclude that women are not at higher risk of developing dementia, but there is a hint that different genetic processes may be involved for women than for men.

Alzheimer Disease↗

PubMed2002

Neuron loss after coronary artery bypass detected by SPECT estimation of benzodiazepine receptors.

BACKGROUND: Cerebral dysfunction is common after cardiac surgery and probably related to embolic phenomena, but the etiological mechanisms have not been elucidated. The aim of this study was to assess whether a possible neuron loss could be detected by single photon emission computer tomography (SPECT) estimation of benzodiazepine receptor density. In addition, we correlated the findings with neuropsychological test results. METHODS: We included 15 elderly patients undergoing coronary artery bypass surgery. Neuropsychological testing was performed before surgery and postoperatively at discharge from hospital and after 3 months using a neuropsychological test battery. SPECT was performed before surgery and after 3 months using the iomazenil bolus/infusion technique, and the benzodiazepine receptor density was calculated for the frontal, parietal, temporal, and occipital cortex. RESULTS: Cognitive dysfunction was found in 46.7% at discharge from hospital and in 6.7% after 3 months. A significant decrease in the estimated density of neurons was found in the frontal cortex, but no significant correlation was found between cognitive dysfunction and SPECT findings. CONCLUSIONS: Neuron loss was detectable in the frontal cortex, but the decrease did not correlate with neuropsychological test results.

Aged↗

PubMed1994

Binge eating disorder, weight cycling, and psychopathology.

This study examined differences among a total of 70 obese binge eaters, nonbingers, and problem eaters in depression, cognitive function, weight- and eating-related disturbances, and weight cycling. Subjects diagnosed with binge eating disorder (BED) scored significantly higher on depression and on several measures of cognitive dysfunction than did subjects in the other two groups. In addition, they reported significantly greater preoccupation with thinness and feelings of ineffectiveness, as well as a greater likelihood of eating in response to negative emotions. No relationship, however, was found between binge eating and weight cycling. Comparison of subjects identified as low- and high-weight cyclers revealed no significant differences between these two groups on depression, cognitive dysfunction, or the majority of the other measures of weight- and eating-related disturbance. The findings are discussed in terms of the implications for treating persons with BED and/or a history of weight cycling.

Adaptation, Psychological↗

PubMed2004

Serotonin and stress: protective or malevolent actions in the biobehavioral response to repeated trauma?

Structural hippocampus and prefrontal cortex changes occur in patients with posttraumatic stress disorder (PTSD) that appears correlated with cognitive dysfunction. In these brain regions, serotonin (5HT) plays a prominent role in symptom presentation and treatment of PTSD. However, 5HT is both anxiogenic and anxiolytic, and while 5HT reuptake inhibitors are effective in treatment, the role of 5HT in the development of PTSD remains uncertain. Using a model of repeated trauma in rats, we observed significant spatial memory impairment together with significantly increased 5HT(1A) receptor density (B(max)), decreased 5HT(1A) receptor affinity (K(d)), and significantly increased 5HT(2A) receptor affinity on day 7 poststress. The serotonergic agent fluoxetine (FLX; 10 mg/kg/d ip) administered 1 week before stress and continuing throughout the stress procedure, but not the 5HT depleter p-chloro-phenylalanine (PCPA; 300/100/50 mg/kg/d ip), prevented stress-induced cognitive dysfunction. PCPA, however, reversed stress-induced hippocampal 5HT(1A) receptor affinity changes, with FLX narrowly missing significance. Neither drug reversed stress effects on 5HT(2A) receptor affinity. Thus, 5HT plays an important part in the cognitive-behavioral changes evoked by repeated trauma. That raised 5HT activity may mediate hippocampal 5HT(1A) receptor changes evoked by stress suggests a bidirectional role for 5HT in the development of PTSD.

Animals↗

PubMed2006

Daily consumption of green tea catechin delays memory regression in aged mice.

Almost all elderly people show brain atrophy and cognitive dysfunction, even if they are saved from illness, such as cardiac disease, malignancy and diabetes. Prevention or delay of brain senescence would therefore enhance the quality of life for older persons. Because oxidative stress has been implicated in brain senescence, we investigated the effects of green tea catechin (GT-catechin), a potential antioxidant, in senescence-accelerated (SAMP10) mice. The mouse is a model of brain senescence with short life span, cerebral atrophy and cognitive dysfunction. Mice were fed water containing 0.02% GT-catechin from 1- to 15-month-old. The mean dose was about 35 mg/kg/day. We found that daily consumption of GT-catechin prevented memory regression and DNA oxidative damage in these mice. GT-catechin did not prolong the lifetime of SAMP10 mice, but it did delay brain senescence. These findings suggest that continued intake of GT-catechin might promote healthy ageing of the brain in older persons.

Aging↗

PubMed2002

Perseveration in schizophrenia: failure to generate a plan and relationship with the psychomotor poverty subsyndrome.

Although perseveration in the Wisconsin Card Sorting Test (WCST) has been studied extensively in schizophrenia, the underlying cognitive dysfunctions are not yet clear. In schizophrenia, perseveration has been found to relate to frontal and striatal abnormalities. Therefore, both a failure to generate a plan as seen in patients with frontal abnormalities, or a failure to execute a plan as observed in Parkinson patients, who suffer primarily from striatal abnormalities, could explain perseveration in schizophrenia. The aim of the present study was to distinguish between these two cognitive dysfunctions, which are described by Frith in his routes-to-action model. The main difference between these dysfunctions is the ability to use external guidance. In the present study, 39 schizophrenic patients and 36 healthy controls were assessed with the California Verbal Learning Test (CVLT) and the WCST, in which use of external guidance can be measured, and with the Positive and Negative Syndrome Scale (PANSS) to determine the relationship with symptomatology. The results showed that half of the schizophrenic patients showed perseveration, which could be explained by a failure to generate a plan and was related to the psychomotor poverty subsyndrome. No evidence was found for a failure to execute a plan. Type of antipsychotic medication used (atypical vs. typical) proved not relevant. The results are discussed in the light of evidence for involvement of the dorsolateral prefrontal cortex in perseveration in schizophrenia.

Adult↗