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PubMed2005

Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism.

OBJECTIVE: Hypothyroidism is associated with neurocognitive impairment. Sparse data suggest that treatment of hypothyroidism, resulting in a return to euthyroidism, may be associated with only partial recovery of overall neurocognitive functioning. The aim of this study was to assess neurocognitive functioning and well-being in euthyroid patients with primary hypothyroidism on adequate thyroxine (T4) treatment. We also investigated whether serum TSH and thyroid antibodies are determinants of neurocognitive functioning and well-being. DESIGN: We assessed neurocognitive functioning and well-being in 141 patients with primary hypothyroidism. METHODS: Neurocognitive test results and scores on questionnaires measuring well-being of 141 patients were compared with the reference values for these tests as published and used in Dutch clinical neuropsychological practice. Assessment of neurocognitive functioning included tests for cognitive or psychomotor speed, attention, working memory as well as learning and memory. Well-being was measured with the Symptom Check List-90 total score and the Rand 36-item Health Survey subscales for 'mental health' and 'vitality'. RESULTS: Patients showed poor performance on various domains of neurocognitive functioning compared with mean standard reference values, especially on a complex attention task and on verbal memory tests. Levels of well-being were significantly lower for patients compared with those of the general population. Neither serum TSH nor thyroid antibodies were determinants of neurocognitive functioning and well-being. CONCLUSION: The results of this study suggest that neurocognitive functioning as well as psychological well-being may not be completely restored in patients with hypothyroidism, despite T4 treatment.

Adult↗
PubMed2004

Brain transplantation of genetically modified bone marrow stromal cells corrects CNS pathology and cognitive function in MPS VII mice.

Current therapies for lysosomal storage diseases (LSDs), enzyme replacement therapy and bone marrow transplantation are effective for visceral organ pathology of LSD, but their effectiveness for brain involvement in LSDs is still a subject of controversy. As an alternative approach, we transplanted genetically modified bone marrow stromal (BMS) cells to lateral ventricle of newborn mucopolysaccharidosis VII (MPS VII) mice. MPS VII is one of LSDs and caused by deficiency of beta-glucuronidase (GUSB), resulting in accumulation of glycosaminoglycans (GAGs) in brain. At 2 weeks after transplantation, the GUSB enzyme-positive cells were identified in olfactory bulb, striatum and cerebral cortex, and the enzymatic activities in various brain areas increased. The GAGs contents in brain were reduced to near normal level at 4 weeks after transplantation. Although GUSB activity declined to homozygous level after 8 weeks, the reduction of GAGs persisted for 16 weeks. Microscopic examination indicated that the lysosomal distention was not found in treated animal brain. Cognitive function in MPS VII animals as evaluated by Morris Water Maze test in treated mice showed a marked improvement over nontreated animals. Brain transplantation of genetically modified BMS cells appears to be a promising approach to treat diffuse CNS involvement of LSDs.

Animals↗
PubMed1992

[The effect of monotherapy on concentration of selected blood serum hormones and upon cognitive function of children with epilepsy].

The studies included 64 children with newly diagnosed epilepsy, aged from 6 to 15 years of life. In 25 children with partial and secondary generalized seizures monotherapy with carbamazepine was introduced; in 19 children with primary generalized seizures--with phenobarbital, and in patients with both types of seizures--with primidone. Monotherapy was controlled by means of blood serum drug concentration level monitoring; the therapy was successful in all the children. The group did not include patients with mental retardation, and epilepsy was idiopathic. Prior to the institution of treatment, a single determination of blood serum triiodothyronine, thyroxine, TSH, prolactin, cortisol, LH and testosterone was made. Psychological test were carried out employing Wechsler's scale, Bender-Santucci test, rhythmic structures developed by Mira Stambak and test of manual dexterity (card display). In order to evaluate short-term effects of the employed drugs upon the blood serum concentration values of the studied hormones, a repeated determination was made one month after the initiation of therapy. The third determination was made one year after the onset of treatment in order to assess the long-term effects. The effect of drugs upon their cognitive functions was assessed in a follow-up psychological testing performed after one year of therapy. The studies combined with statistical analysis led to a conclusion that after one month of monotherapy there occurred a significant drop in thyroxine concentration levels, still augmented after one year. Patients treated with carbamazepine showed a significant decrease of T3 levels after one month and one year, whereas treatment with phenobarbital and primidone did not result in significant changes of T3 concentration. Yet, T3 and T4 concentration values did not exceed normal limits. No type of monotherapy resulted in significant long-term changes of TSH concentration levels. No clinical signs of hypothyroidism nor goiter were observed in the studied children. After one month of monotherapy with carbamazepine and phenobarbital there was observed a significant increase of prolactin and cortisol levels, which was absent after one year. The values observed did lie within normal limits. No significant changes were observed with respect to the effect of the studied drugs upon blood serum LH and testosterone levels. After a one-year monotherapy with primidone the children revealed a significant improvement of results measured on performance scale and by means of a full Wechsler scale. Carbamazepine and phenobarbital did not affect the intelligence quotient of the studied children.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1996

The effect of cimetidine and ranitidine on cognitive function in postoperative cardiac surgical patients.

OBJECTIVE: To compare the incidence of delirium in postoperative cardiac surgical patients treated with either cimetidine or ranitidine. METHOD: Cardiac surgery patients were randomized to receive either cimetidine or ranitidine postoperatively. Each patient underwent three Mini-Mental Status Examinations (MMSE) and the medical record was reviewed for pertinent past medical history, laboratory data, and evidence of delirium on three occasions: one day preoperatively (before H-2 blocker was given), in the early postoperative period (while receiving the H-2 blocker); usually two days postoperatively on the day of hospital discharge (several days after the H2 blocker had been discontinued). RESULTS: Overall, both groups in the early postoperative period showed a significant decrease in the MMSE score (27.11 +/- 4.44 to 25.38 +/-2.87, mean +/- SD; t = 5.16, p < .0005), which resolved by the time of hospital discharge. There was no significant difference between cimetidine and ranitidine. Both age and preoperative MMSE score were strongly associated with the development of delirium. CONCLUSIONS: We found no significant difference between cimetidine's versus ranitidine's effect upon cognitive functioning in the postoperative cardiac surgical patient. This was true even when controlling for age and length of stay.

Adult↗
PubMed2005

A method for determining the magnitude of change across different cognitive functions in clinical trials: the effects of acute administration of two different doses alprazolam.

While there is no doubt that benzodiazepine administration leads to transient cognitive impairment in healthy adults, the nature and magnitude of such impairment has not been well described. The cognitive effects of a single dose of alprazolam 0.5 and 1 mg were therefore assessed in 36 healthy adults on measures of psychomotor function, visual attention, working memory, planning and learning in a double-blind parallel-groups study. Measures of these different cognitive functions were selected on the basis of their brevity and because they yielded distributions of performance data that were without skew, floor or ceiling effects of range restriction (i.e. normal distributions). With data satisfying the assumptions for parametric analysis, measures of effect size could be computed in addition to significance testing, thus allowing for direct and meaningful comparison between the different performance measures used. Alprazolam 0.5 mg reduced only the speed of attentional performance although the magnitude of this reduction was large (d = 0.8). At 1.0 mg, impairments in psychomotor function, equivalent to that seen for attentional function at the lower dose, were observed. In addition, moderate (d approx = 0.5) impairments in working memory, and learning also became obvious. When considered together, these results suggest that low-dose alprazolam primarily alters visual attentional function. At the higher dose psychomotor functions also become impaired, and it is likely that the combination of these led to the observed moderate impairments in higher level executive and memory processes. The current study also illustrates a method for directly comparing the magnitude of change in cognitive function between measures with different performance metrics.

Adult↗
PubMed2005

Assessment of cognitive function in heart failure patients.

BACKGROUND: Research on the cognitive capacity of heart failure patients is limited, with a paucity of benchmark information available for this population. It is highly likely that cognitive deficits affect patients' understanding of disease and treatment requirements, as well as limiting their functional capacity and ability to implement treatment plans, and undertake self-care. AIMS: The purpose of this study was to establish a comprehensive neurocognitive profile of the heart failure patient through systematic neurocognitive assessment and to determine whether an association existed between severity of heart failure and cognitive abilities. METHODS: Thirty-eight patients were recruited from the heart failure patient databases of two metropolitan hospitals in Melbourne, Australia. Participants were individually assessed using four standardised, internationally recognised neuropsychological tests that examined current and premorbid intelligence, memory and executive functioning. RESULTS: Although there was no significant decline from premorbid general intellectual function, other specific areas of deficit, including impaired memory and executive functioning, were identified. There were no significant correlations between heart failure severity and the neurocognitive measures used. CONCLUSION: The results support the need to recognise cognitive impairment in people with heart failure and to develop an abbreviated method of assessing cognitive function that can be easily implemented in the clinical setting. Identifying cognitive deficits in this population will be useful in guiding the content and nature of treatment plans to maximise adherence and minimise worsening of heart failure symptoms.

Activities of Daily Living↗
PubMed2000

Differential preservation of cognitive functions in geriatric patients with lifelong chronic schizophrenia: less impairment in reading compared with other skill areas.

BACKGROUND: Our study examined the differential performance of cognitive skills in geriatric, cognitively impaired schizophrenic patients (n = 165) with a lengthy course of institutional stay and a poor overall functional outcome. Their relative deficits were compared with a sample of healthy elderly individuals. METHODS: Schizophrenic patients were matched one-to-one with healthy individuals of the same age and education and compared on a number of measures of cognitive functioning. The schizophrenic patients' old-learning performance was also compared with their educational level only. RESULTS: Mini-Mental State Examination (Folstein et al 1975) scores of the patients were in the moderately demented range (M = 20.36), and these patients underperformed healthy control subjects by more than 1 to slightly less than 3 standard deviations on measures of memory, praxis, and verbal skills. Wide Range Achievement Test-Revised word-recognition reading scores were found to be at the 10th-grade level, although the patients on average had completed 11 years of formal education. CONCLUSIONS: These results suggest that even in schizophrenic patients with significant cognitive impairment, reading scores are relatively consistent with educational attainment. These data indicate that poor performance on measures of cognitive functioning in this population does not necessarily occur on measures of old learning.

Aged↗
PubMed1997

Emergence of a powerful connection between sensory and cognitive functions across the adult life span: a new window to the study of cognitive aging?

Six hundred eighty seven individuals ages 25-103 years were studied cross-sectionally to examine the relationship between measures of sensory functioning (visual and auditory acuity) and intelligence (14 cognitive tasks representing a 5-factor space of psychometric intelligence). As predicted, the average proportion of individual differences in intellectual functioning connected to sensory functioning increased from 11% in adulthood (25-69 years) to 31% in old age (70-103 years). However, the link between fluid intellectual abilities and sensory functioning, albeit of different size, displayed a similarly high connection to age in both age groups. Several explanations are discussed, including a "common cause" hypothesis. In this vein, we argue that the increase in the age-associated link between sensory and intellectual functioning may reflect brain aging and that the search for explanations of cognitive aging phenomena would benefit from attending to factors that are shared between the 2 domains.

Adult↗
PubMed2002

Functional, cognitive and behavioral effects of donepezil in patients with moderate Alzheimer's disease.

OBJECTIVE: To investigate the efficacy and safety of donepezil in a subgroup of patients with Alzheimer's disease (AD) of moderate severity from a previous trial. METHODS: Two hundred and seven patients with moderate AD (standardized Mini-Mental State Examination [sMMSE] score 10-17) were randomized to treatment in this 24-week, double-blind, placebo-controlled trial. Patents received either donepezil, 5 mg/day for the first 28 days and 10 mg/day thereafter according to the clinician's judgement (n = 102), or placebo (n = 105). The primary outcome measure was the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC-plus) at week 24 using a last observation carried forward (LOCF) analysis. RESULTS: Baseline patient demographics were similar between treatment groups. Mean age was 74.3 years (range 48-92). Least-squares (LS) mean sMMSE scores at baseline were 13.6 +/- 0.3 for the donepezil group and 13.9 +/- 0.3 for the placebo group. LS mean CIBIC-plus scores for donepezil-treated patients were improved from, or close to, baseline severity at all visits, and were significantly different from placebo at weeks 8, 12, 18, and 24 (week 24 LOCF mean difference = 0.53, p = 0.0003). LS mean change from baseline scores on the sMMSE and Severe Impairment Battery (SIB) for the donepezil group improved throughout the study, and were significantly different from placebo at each visit for the sMMSE (week 24 LOCF mean difference = 2.06, p = 0.0002) and from week 8 for the SIB (week 24 LOCF mean difference = -4.44, p = 0.0026). LS mean change scores on the Disability Assessment for Dementia remained at or above baseline levels throughout the study for the donepezil group, while the placebo group showed a steady decline; treatment differences were significant at each visit (week 24 LOCF mean difference = -9.25, p < 0.0001). LS mean change scores on the Neuropsychiatric Inventory 12-item total improved throughout the study for the donepezil group and were significantly different from placebo at weeks 4 and 24 (week 24 LOCF mean difference = 5.92, p = 0.0022). Eighty-one per cent of donepezil-treated and 89% of placebo-treated patients completed the trial, with 9% and 5%, respectively, discontinuing due to adverse events (AEs). Eighty-two per cent of donepezil-treated and 80% of placebo-treated patients experienced AEs, the majority of which were rated mild in severity and, in general, were similar between treatment groups. CONCLUSION: The significant treatment responses observed with donepezil in these patients reinforce the findings from earlier studies that show donepezil to have important benefits, compared wih placebo, across functional, cognitive, and behavioral symptoms, with good tolerability, in patients with AD of moderate severity.

Activities of Daily Living↗
PubMedDate not supplied

Clock drawing task, mini-mental state examination and cognitive-functional independence measure: relation to functional outcome of stroke patients.

The use of reliable and valid brief cognitive screening instrument for selecting the appropriate candidates for stroke rehabilitation is crucial. Clinicians often face the question which test should be preferred, that will best correlate with functional outcome. The objective of this study was to compare the clock drawing task with other cognitive tests used for the evaluation of discharge functional outcome in elderly stroke patients. We conducted a retrospective chart study including 151 consecutive patients, admitted for inpatient comprehensive rehabilitation following acute stroke. The clock drawing task (CDT), mini-mental state examination (MMSE) and the cognitive-functional independence measure (cognFIM) were used to assess the cognitive status. Functional status outcome was evaluated by the functional independence measure (FIM), using absolute and relative parameters of efficacy and efficiency. Correlation coefficients (Pearson correlation) between the three cognitive tests resulted in r-values ranging from 0.51 to 0.59 (P<0.001). All three tests correlated significantly with motor outcomes. MMSE did not confer additive value to CDT. It is concluded that CDT is similar to mini-mental and both are somewhat better than cognFIM with respect to the evaluation of functional status outcome following stroke. The correlations between the tests as well as the simplicity of administration favor the use of either CDT or MMSE in the initial assessment of elderly stroke patients.

Journal Article↗
PubMed2005

Cognitive functioning in post-polio patients with and without general fatigue.

OBJECTIVE AND DESIGN: This study examined 2 main hypotheses. First, whether patients with post-polio suffering from general fatigue (n=10) demonstrate cognitive deficits compared with patients with post-polio without general fatigue (n=10). Secondly, by systematically varied test order administration we examined whether such differences varied as a function of increasing cognitive load during cognitive testing. SUBJECTS: Twenty patients diagnosed with post-polio syndrome, 10 with general fatigue and 10 without fatigue. RESULTS: Neither of the 2 hypotheses were confirmed. The group with general fatigue reported elevated levels of depression. However, no systematic association between level of depression and cognitive performance could be detected. CONCLUSION: The results of this study provide no evidence that general fatigue or cognitive load affects cognitive functioning in post-polio.

Adult↗
PubMed2002

Expression analysis of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry syndrome, is prominently expressed in brain structures essential for cognitive function and learning.

Coffin-Lowry syndrome (CLS) is characterized by cognitive impairment, characteristic facial and digital findings and skeletal anomalies. The gene implicated in CLS encodes RSK2, a serine/threonine kinase acting in the Ras/MAPK signalling pathway. In humans, RSK2 belongs to a family of four highly homologous proteins (RSK1-RSK4), encoded by distinct genes. RSK2 mutations in CLS patients are extremely heterogeneous. No consistent relationship between specific mutations and the severity of the disease or the expression of uncommon features has been established. Together, the data suggest an influence of environmental and/or other genetic components on the presentation of the disease. Obvious modifying genes include those encoding other RSK family members. In this study we have determined the expression of RSK1, 2 and 3 genes in various human tissues, during mouse embryogenesis and in mouse brain. The three RSK mRNAs were expressed in all human tissues and brain regions tested, supporting functional redundancy. However, tissue specific variations in levels suggest that they may also serve specific roles. The mouse Rsk3 gene was prominently expressed in the developing neural and sensory tissues, whereas Rsk1 gene expression was the strongest in various other tissues with high proliferative activity, suggesting distinct roles during development. In adult mouse brain, the highest levels of Rsk2 expression were observed in regions with high synaptic activity, including the neocortex, the hippocampus and Purkinje cells. These structures are essential components in cognitive function and learning. Based on the expression levels, our results suggest that in these areas, the Rsk1 and Rsk3 genes may not be able to fully compensate for a lack of Rsk2 function.

Animals↗
PubMed2007

Cognitive functioning in healthy older adults aged 64-81: a cohort study into the effects of age, sex, and education.

The objective of this study was to determine a possible differential effect of age, education, and sex on cognitive speed, verbal memory, executive functioning, and verbal fluency in healthy older adults. A group of 578 healthy participants in the age range of 64-81 was recruited from a large population study of healthy adults (Maastricht Aging Study). Even in healthy individuals in this restricted age range, there is a clear, age-related decrease in performance on executive functioning, verbal fluency, verbal memory, and cognitive speed tasks. The capacity to inhibit information is affected most. Education had a substantial effect on cognitive functioning: participants with a middle or high level of education performed better on cognitive tests than did participants with a low level of education. Women performed better than men on verbal memory tasks. Therefore, education and sex must be taken into account when examining an older individual's cognitive performance.

Aged↗
PubMed2006

Molecular imaging of the dopaminergic system and its association with human cognitive function.

Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) has recently been used to examine dopamine (DA) function and its relationship with cognition in human subjects. This article will review PET and SPECT studies that have explored the relationship between cognitive processes and components of the DA system (pre-, intra-, and postsynaptic) in healthy and patient populations such as Parkinson's disease (PD), schizophrenia, Huntington's disease, and aging. It is demonstrated that DA activity modulates a range of frontal executive-type cognitive processes such as working memory, attentional functioning, and sequential organization, and alterations of DA within the fronto-striato-thalamic circuits might contribute to the cognitive impairments observed in PD, schizophrenia, and normal aging. Although associations between DA and cognitive measures need to be considered within the context of fronto-striato-thalamic circuitry, it is suggested that striatal (especially caudate) DA activity, particularly via D2 receptors, might be important for response inhibition, temporal organization of material, and motor performance, whereas cortical DA transmission via D1 receptors might be important for maintaining and representing on-going behavior.

Brain↗
PubMed2002

Intrathecal methotrexate affects cognitive function in children with medulloblastoma.

BACKGROUND: Cognitive impairment occurs after malignant brain tumor treatment in children, following brain radiotherapy and systemic and intrathecal chemotherapy. OBJECTIVES: 1) To compare two groups of children who underwent surgery for cerebellar medulloblastoma with their cousins and siblings, assessing intelligence, executive function, attention, visual perception, and short-term memory. Both groups were treated with the same combined radiotherapy-chemotherapy, but differed in that only one group received intrathecal methotrexate (MTX+). 2) To relate these measures to MRI findings (leukomalacia). RESULTS: The two groups performed worse than their control subjects in all tests. The MTX+ group younger than 10 years performed significantly worse in all tests, particularly executive ones. The group older than 10 years performed significantly worse only in short-term memory. Younger patients without MTX performed significantly worse than controls only in some neuropsychological measures; there were no differences between older patients and control subjects. Only in the MTX+ group was there a direct correlation between extent of leukomalacia and performance in some tests. CONCLUSIONS: The administration of intrathecal methotrexate to children with medulloblastoma worsens the cognitive deficits induced by chemotherapy and radiotherapy. The use of intrathecal methotrexate in the treatment of medulloblastoma and other malignancies should be reassessed.

Adolescent↗
PubMed1997

Frontal lobe-related cognitive functions in patients with sleep apnea syndrome before and after treatment.

Impairments of cognitive executive functions has been previously suspected to occur in Sleep Apnea Syndrome (SAS), as suggested by some neuropsychological studies. However such functions have not been assessed directly. In the present study, ten patients with SAS were evaluated with various focused frontal lobe-related tests in comparison with ten matched normal controls. Such tasks explored attention, short term memory spans, learning abilities, planning and programming capacities, categorizing activities and verbal fluency. Patients were found with a significant decreased ability to initiate new mental processes and to inhibit automatic ones in conjunction with a tendency for perseverative errors. They were also affected with deficits of verbal and visual learning abilities and they had reduced spans. Patients were submitted to continuous positive airway pressure (CPAP) and further reevaluated after 4-6 months of treatment. Patients were found to have normalized most of their cognitive executive and learning disabilities, except for all the short-term memory tests which remained unchanged. These findings are discussed in light of data from the literature concerning cognitive impairments described for patients with isolated daytime sleepiness versus hypoxemia, as illustrated in other pathological or physiological circumstances. The contribution of frontal lobe-related systems in short-term memory functions is also taken into account.

Adult↗
PubMed2005

Childhood-onset growth hormone deficiency, cognitive function and brain N-acetylaspartate.

Cognitive deficits have been reported in adults with childhood-onset growth hormone (GH) deficiency. We evaluated cognitive deficits simultaneously with parameters for neuronal integrity using (1)H magnetic resonance spectroscopy (MRS) in a cross-sectional design. We studied 11 adults (mean age 24.5 years) with childhood-onset GH deficiency, which persisted after reaching final height. All subjects were evaluated after interruption of GH supplementation for at least 3 months. We performed neuropsychological assessment (NPA) using tests evaluating memory, mental processing speed, reading ability and executive functioning. MRS was used to assess brain N-acetylaspartate (NAA)/choline ratios. Data were compared with an age-, sex- and education-matched control group (n=9, mean age 27.3 years). NPA demonstrated attenuated performance of the patients in the delayed verbal memory recall score (P<0.05) and the trail making A test (P<0.05), a measure of planning of behavior, processing speed and attention. Other neuropsychological tests were not affected. NAA/choline ratios were significantly reduced (P<0.01) in GH deficient subjects. Specific cognitive defects indicating affected memory and attention were found in patients with childhood-onset GH deficiency. These defects occur simultaneously with reduced neuronal integrity.

Adolescent↗