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PubMedDate not supplied

Assessment of cognitive function in elderly patients treated with naproxen. A prospective study.

Cognitive functions were assessed in 12 elderly patients prior to and following a three-week therapeutic course of Naproxen, 750 mg/day. Four of the patients deteriorated in one of the four cognitive tests, one of these patients in two tests. However, none of these changes reached statistical significance. Although non-steroidal anti-inflammatory drugs can cause some cognitive alteration in the elderly, this change is mild, and its clinical meaning questioned.

Aged↗
PubMed2004

Nicotine-induced changes in neurotransmitter levels in brain areas associated with cognitive function.

Nicotine, one of the most widespread drugs of abuse, has long been shown to impact areas of the brain involved in addiction and reward. Recent research, however, has begun to explore the positive effects that nicotine may have on learning and memory. The mechanisms by which nicotine interacts with areas of cognitive function are relatively unknown. Therefore, this paper is part of an ongoing study to evaluate regional effects of nicotine enhancement of cognitive function. Nicotine-induced changes in the levels of three neurotransmitters, dopamine (DA), serotonin (5-HT), norepinepherine (NE), their metabolites, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and their precursor, L-DOPA, were evaluated in the ventral and dorsal hippocampus (VH and DH), prefrontal and medial temporal cortex (PFC and MTC), and the ventral tegmental area (VTA) using in vivo microdialysis in awake, freely moving, male Sprague-Dawley rats. The animals were treated with acute nicotine (0.5 mg/kg, s.c.) halfway through the 300-min experimental period. The reuptake blockers, desipramine (100 microM) and fluoxetine (30 microM), were given to increase the levels of NE and 5-HT so that they could be detected. Overall, a nicotine-induced DA increase was found in some areas, and this increase was potentiated by desipramine and fluoxetine. The two DA metabolites, HVA and DOPAC, increased in all the areas throughout the experiments, both with and without the inhibitors, indicating a rapid metabolism of the released DA. The increase in these metabolites was greater than the increase in DA. 5-HT was increased in the DH, MTC, and VTA in the presence of fluoxetine; its metabolite, 5-HIAA, was increased in the presence and absence of fluoxetine. Except in the VTA, NE levels increased to a similar extent with desipramine and fluoxetine. Overall, nicotine appeared to increase the release and turnover of these three neurotransmitters, which was indicated by significant increases in their metabolites. Furthermore, DA, and especially HVA and DOPAC, increased for the 150 min following nicotine administration; 5-HT and NE changes were shorter in duration. As gas chromatography experiments showed that nicotine levels in the brain decreased by 75% after 150 min, this may indicate that DA is more susceptible to lower levels of nicotine than 5-HT or NE. In conclusion, acute nicotine administration caused alterations in the levels of DA, 5-HT, and NE, and in the metabolism of DA and 5-HT, in brain areas that are involved in cognitive processes.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2004

Blood pressure variability and cognitive function in older hypertensives.

Several studies have shown that cerebrovascular organ damage can related not only to average blood pressure (BP) levels, but also to BP variability. The aim of this study was to investigate the relationship between 24 hr BP variability and cognitive function in older hypertensives. Forty older, never treated hypertensives were submitted to 24 hr ambulatory BP monitoring (ABPM) and subdivided, according to the variability of the systolic BP (SBP), in two groups: 23 with higher (> PV) and 17 with lower (< PV) SBP variability, defined as the standard deviation (SD) of the mean 24 hr SBP values and as coefficient of variation (CV). They underwent a cognitive assessment by mini mental state examination (MMSE) and a recording of the brain event-related potentials (ERPs). ERPs record neuronal electric activity when the patients are submitted to frequent and rare acoustic stimuli and must recognize and count rare (target) stimuli. The two groups with statistically different 24 hr SBP variability, did not show significant differences in MMSE scores or in N2 and P300 ERP latencies, thus indicating a lack of difference in the cognitive ability between the two groups. Our results show that cognitive function is not related to 24 hr SBP variability in older hypertensives.

Aged↗
PubMedDate not supplied

Determinants of quantitative spectral electroencephalography in early Alzheimer's disease: cognitive function, regional cerebral blood flow, and computed tomography.

Electroencephalography (EEG) bands may have different clinical or physiological correlates at initial diagnosis of Alzheimer's disease (AD). We studied 163 consecutive patients with probable (n = 105) and possible (n = 58) AD with measurements of cognitive function (CAMCOG), regional cerebral blood flow (rCBF) with single photon emission computed tomography using technetium-99m-labeled hexamethylpropylene amine oxime, and computed tomography (CT). Lower CAMCOG scores were significantly and most strongly associated with lower parieto-occipital and fronto-central alpha power. In a separate analysis of cognitive domains, disturbances in language, praxis, attention, and abstraction were also significantly and most consistently related to decrease in alpha power. Presence of cortical atrophy as measured on CT showed some statistically significant relations with EEG bands, but these associations were not consistent. Lower temporal and parietal rCBF were significantly related to lower parieto-occipital alpha activity. Presence of leukoaraiosis was significantly associated with lower beta values, but also with higher absolute theta and delta activity. The results suggest that alpha on EEG is most closely linked to cognitive function and rCBF, while beta and theta activity more likely reflect lower cortical or subcortical changes. Our study thus provides evidence that the EEG bands reflect differential pathophysiologic changes in AD.

Aged↗
PubMed1996

The effects of antihypertensive treatment on cognitive function: results from the HOPE study.

OBJECTIVES: Hypertension is associated with impaired cognition, but it is unclear whether this impairment is reversible. We sought to evaluate the effect of blood pressure reduction on cognition. DESIGN: A randomized, double-blind trial. SETTING: A single center, with assessments in subjects' domiciles. PARTICIPANTS: Community-screened subjects more than 69 years of age who had median diastolic pressures > 99 mm Hg and systolic pressures > 159 mm Hg or diastolic > 85 mm Hg and systolic > 179 mm Hg with Mini-Mental State Examination scores of 20 to 28. Subjects had not previously received antihypertensive treatment. INTERVENTION: Captopril 12.5 mg twice daily or bendrofluazide 2.5 mg daily for 24 weeks, preceded by a 2-week placebo phase. MEASUREMENTS: Cognition was evaluated by a psychometric test battery comprising Immediate and Delayed Logical Memory, Paired Associates recall, Raven's Progressive Matrices, Halstead Reitan Trail Making A, and the Anomalous Sentences Repetition Test. RESULTS: Eighty-one subjects (28 male, 53 female) were treated (41 captopril, 40 bendrofluazide). At entry, mean age was 76.1 years (range 70-84), mean blood pressure was 191 (160-230) mm Hg systolic, 101 (88-110) mm Hg diastolic, and mean MMSE score 26.1. A total of 69 subjects completed the trial. The 25th, 50th, and 75th percentiles of the difference between pretreatment and Week 24 blood pressures wer 15 mm Hg, 35 mm Hg, and 50 mm Hg (systolic) and 5 mm Hg, 10 mm Hg, and 19 mm Hg (diastolic). There were no significant differences in any psychometric test between captopril and bendrofluazide. The 19 subjects in the quartile that lowered their diastolic blood pressure most ( > or = 19 mm Hg) had improved scores on Anomalous Sentences (P = .012) and Paired Associates (P = .044) compared to the 19 subjects in the least blood pressure responsive quartile (fall < or = 5 mm Hg)s. CONCLUSION: The treatment of hypertension is not hazardous to cognitive function in older people with pre-existing cognitive impairment. Long-term adequate blood pressure control may reverse cognitive impairment associated with pre-existing hypertension.

Aged↗
PubMed2000

Cognitive function of patients with nasopharyngeal carcinoma with and without temporal lobe radionecrosis.

BACKGROUND: Radiotherapy is the primary treatment for nasopharyngeal carcinoma, and temporal lobe necrosis is observed in about 7% of patients after radiotherapy. Although some studies reported that these patients demonstrated cognitive impairment after radiotherapy, it is still unclear if the cognitive deficits are related to the radiation exposure or the radiation-induced necrosis. OBJECTIVE: To compare the cognitive function of patients with and without temporal lobe necrosis after radiotherapy for nasopharyngeal carcinoma. METHODS: A comprehensive neuropsychological battery was administered to 53 patients with nasopharyngeal carcinoma who had completed their radiotherapy at least 1 year previously. As evidenced by magnetic resonance imaging, 31 patients developed necrosis after treatment. Thirty-one age- and education-matched individuals were recruited as normal control subjects. RESULTS: Whereas the performance of patients without temporal lobe necrosis was similar to that of normal control subjects, patients with temporal lobe necrosis demonstrated significant impairment on tests of verbal (P<.001) and visual memory (range, P<.001 to P =.03), language (range, P<.001 to P =.01), motor ability (P =.02), planning (P =.02), cognitive ability (P =.007), and abstract thinking (range, P =.009 to P =.04). However, the performance of patients with necrosis on tests of general intelligence (range, P =.08 to P =.15), attention (range, P =.06 to P =.55), and visual abilities (range, P =.06 to P =.47) was not significantly different from that of normal control subjects and patients without necrosis. CONCLUSIONS: Radiotherapy for nasopharyngeal carcinoma seemed to have adverse but insignificant effects on the cognitive functions of the patients. However, for patients who developed temporal lobe necrosis after radiotherapy, memory, language, motor ability, and executive functions were significantly impaired, although their general intelligence remained relatively intact.

Cognition Disorders↗
PubMed1996

Cognitive functions of the basal forebrain cholinergic system in monkeys: memory or attention?

The cholinergic hypothesis of memory dysfunction originally proposed that dysfunction of cholinergic neurons in the basal forebrain cholinergic system (BFCS) may be responsible for the memory deficits associated with aging and Alzheimer's disease (AD). This hypothesis directed focus on the BFCS in experimental animal models of AD. In contrast to numerous studies in rodents, fewer investigations have been conducted in monkeys with BFCS lesions. The medical septal nucleus/nucleus of the diagonal band of Broca (MS/NDBB) and the nucleus basalis of Meynert (NBM) may be involved in different cognitive functions in monkeys. Although few investigations have specifically addressed the issue of cognitive functions of the MS/NDBB in monkeys, there is some indication that these regions may be important for memory. In contrast, lesions of the NBM do not consistently disrupt mnemonic functions in monkeys. Recent electrophysiological and lesion studies of monkeys indicate that the NBM may play a more important role in attention functions, impairments of which are an early and significant feature of patients with AD.

Animals↗
PubMed2006

Diurnal cycle of salivary cortisol in older adult men and women with subjective complaints of memory deficits and/or depressive symptoms: relation to cognitive functioning.

In populations of young and older adults, it has been shown that individuals may be categorized into one of three diurnal subgroups when salivary cortisol levels are assessed over a 2-day period and compared for their consistency across days: a typical subgroup, a flat subgroup, and an inconsistent subgroup. Interestingly, recent studies have reported that the typical subgroup represents the majority of the young and older adult population, a finding that is difficult to reconcile with previous studies showing increased cortisol levels in older adults with depression or cognitive impairments. In order to assess whether a typical diurnal cortisol profile is representative across different subgroups of older adults, we assessed diurnal cortisol cycle representation in a sample of older adults with subjective complaints of depression and/or memory problems. Furthermore, given the robust relationship between cortisol and cognitive function, the present study examined the association between the three diurnal subgroups and cognitive performance. Forty-two older individuals were recruited on the basis of reporting subjective complaints of either memory problems and/or depressive mood. Participants were asked to sample their saliva over a 2-day period and were then asked to undergo a neuropsychological evaluation that taps into short-term memory, declarative memory and language. The results showed that 69% of the sample presented a Flat cycle of salivary cortisol over a 2-day period while 19% presented an inconsistent pattern and 12% presented a typical pattern. Participants in the flat subgroup were significantly impaired on letter verbal fluency. Furthermore, a relationship was found between diurnal cortisol subgroup representation and subjective complaint profile. These findings show that older adults with complaints of memory problems and/or depressive symptoms do not present the typical profile of the diurnal cortisol cycle, and they provide a preliminary view of how diurnal cortisol profile relates to cognitive function during human aging.

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PubMed2000

Perioperative temporal profile of cognitive function in elderly patients undergoing hip surgery.

To test the hypothesis that elderly patients who have surgery for femoral neck fractures may have delirium not only after surgery but before surgery, we prospectively investigated the perioperative temporal profile of cognitive function in such patients. We performed the Abbreviated Mental Test (AMT) six times in each patient (on the day of admission, 3 days after admission, on the day before surgery, 2 days after surgery, 7 days after surgery, and on the day of discharge). Patients were given no premedication and were anesthetized with spinal anesthesia using 0.2% hypobaric tetracaine. Of the 68 patients who were admitted because of a diagnosis of fractured neck of the femur and were scheduled to have surgery, 27 patients were subjected to analysis. Four and three patients showed a significant decrease (3 or more points) in AMT score 2 and 7 days after surgery, respectively. We conclude that surgery may have a stronger impact on cognitive function than environmental change shortly after admission in elderly patients with femoral neck fractures.

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PubMed1999

Association of early childhood diarrhea and cryptosporidiosis with impaired physical fitness and cognitive function four-seven years later in a poor urban community in northeast Brazil.

To determine potential, long-term deficits associated with early childhood diarrhea and parasitic infections, we studied the physical fitness (by the Harvard Step Test) and cognitive function (by standardized tests noted below) of 26 children who had complete surveillance for diarrhea in their first 2 years of life and who had continued surveillance until 6-9 years of age in a poor urban community (favela) in Fortaleza in northeast Brazil. Early childhood diarrhea at 0-2 years of age correlated with reduced fitness by the Harvard Step Test at 6-9 years of age (P = 0.03) even after controlling for anthropometric and muscle area effects, anemia, intestinal helminths, Giardia infections, respiratory illnesses, and socioeconomic variables. Early childhood cryptosporidial infections (6 with diarrhea and 3 without diarrhea) were also associated with reduced fitness at 6-9 year of age, even when controlling for current nutritional status. Early diarrhea did not correlate with activity scores (P = 0.697), and early diarrhea remained significantly correlated with fitness scores (P = 0.035) after controlling for activity scores. Early diarrhea burdens also correlated in pilot studies with impaired cognitive function using a McCarthy Draw-A-Design (P = 0.01; P = 0.017 when controlling for early helminth infections), Wechsler Intelligence Scale for Children coding tasks (P = 0.031), and backward digit span tests (P = 0.045). These findings document for the first time a potentially substantial impact of early childhood diarrhea and cryptosporidial infections on subsequent functional status. If confirmed, these findings have major implications for calculations of global disability adjusted life years and for the importance and potential cost effectiveness of targeted interventions for early childhood diarrhea.

Animals↗
PubMed2005

Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as measured by attentional set shifting capability.

The brain noradrenergic system is thought to facilitate neuronal processes that promote behavioral activation, alertness, and attention. One region in which norepinephrine may exert such effects is the medial prefrontal cortex, which has been implicated in many cognitive functions including arousal, attention, motivation, working memory, response inhibition, and behavioral flexibility. The present study addressed the modulatory influence of noradrenergic neurotransmission in medial prefrontal cortex on cognitive function in rats, as measured by performance in an attentional set shifting task. In experiment 1, we tested effects of increasing and decreasing brain noradrenergic neurotransmission by systemic administration of the alpha2-adrenergic autoreceptor antagonist and agonist drugs, atipamezole and clonidine, respectively. Atipamezole pretreatment significantly improved performance on the stages of the attentional task requiring an extradimensional shift in attention, and those involving stimulus reversals, whereas clonidine had no effect at any stage. In experiment 2, we then tested effects of microinjecting alpha1- or beta-adrenergic receptor antagonists into medial prefrontal cortex on the enhancement of performance on the extradimensional task produced by atipamezole. The atipamezole-induced enhancement of performance on the extradimensional set shifting task was blocked by alpha1-, but not beta-adrenergic receptor antagonists in medial prefrontal cortex. Neither antagonist alone had any effect on extradimensional set shift performance in the absence of atipamezole-induced enhancement. These results indicate that elevating noradrenergic activity at alpha1-receptors in medial prefrontal cortex facilitates cognitive performance of rats in an attentional set-shifting task, which may contribute to the role of norepinephrine in behavioral state changes such as arousal, or to the beneficial cognitive effects of psychotherapeutic drugs that target noradrenergic neurotransmission.

Adrenergic alpha-Agonists↗
PubMed2006

Dopamine transporters and cognitive function in methamphetamine abuser after a short abstinence: A SPECT study.

The purpose of this study was to examine the change of dopamine transporters (DAT) binding in methamphetamine (METH) abusers in a two-week period of abstinence and its association with cognitive function. Seven healthy subjects and seven METH abusers were recruited. At baseline conditions, the values of specific uptake ratio (SUR) of DAT binding measured by single photon emission computed tomography were lower in METH abusers than in controls. After a two-week period of abstinence, DAT binding was partially recovered and there were no statistic differences in SUR between METH abusers and controls. There was a borderline correlation between the changes of DAT binding in the right, but not the left, striatum and the %Error of Wisconsin Card Sorting Test. These findings indicate that DAT binding in METH abusers can be reversed in a short period of abstinence. The recovery of DAT binding was asymmetric and possibly parallel with the improvement of cognitive function.

Adult↗
PubMed2005

The effects of immediate-release morphine on cognitive functioning in patients receiving chronic opioid therapy in palliative care.

Morphine and other potent opioids are frequently used in palliative care and pain management. When sustained-release (SR) opioids do not provide adequate background analgesia, additional immediate-release (IR) opioid (e.g. short-acting morphine) may be required to alleviate breakthrough or episodic pain. Despite the frequent use of IR morphine on top of SR opioids, little is known about the effects of such treatment on patients' everyday cognitive functioning. This study therefore used a double-blind, placebo-controlled, cross-over design to assess cognitive functioning in 14 patients receiving palliative care. All patients were taking SR opioid preparations and required <or=2 doses of IR morphine/day. Performance on cognitive measures (as well as subjective measures of pain and mood) after a dose of IR morphine was compared with placebo. Patients experienced significantly more pain-reduction following IR morphine (P=0.03), while other measures of subjective drug effects (e.g. sedation) were largely unaffected. Patients displayed anterograde memory impairment after IR morphine relative to placebo (P=0.003). Intriguingly, patients also had significant 'retrograde' memory impairment: delayed recall of verbal information presented before IR morphine also declined (P=0.024). In addition, IR morphine reduced performance on a complex tracking task (Reitan's trails B; P=0.03) whilst enhancing it on a simpler tracking task (Reitan's trails A; P=0.03). In conclusion, this study suggests that IR morphine, when taken on top of a SR opioid, produces transient anterograde and retrograde memory impairments and a decrement in two-target tracking. These impairments may impact negatively on patients' everyday functioning.

Affect↗
PubMed2005

Role of circulating androgen levels in effects of apoE4 on cognitive function.

Compared with apoE2 and E3, apoE4 increases the risk of cognitive impairments and of developing Alzheimer's disease (AD). ApoE4 interacts with female sex, further increasing AD risk. Previously, we showed that female Apoe-/- mice are more susceptible to apoE4-induced cognitive deficits than male mice. Androgens protect against these deficits and apoE4 male mice are more sensitive to acute blockade of androgen receptors than apoE3 male mice. To determine the chronic effects of reduced circulating androgen levels on susceptibility to the effects of apoE4 on cognitive function in males, we castrated and sham-castrated apoE4, apoE3, and Apoe-/- male mice and behaviorally compared them 3 months later. Castration impaired novel location recognition in apoE4, but not apoE3 or Apoe-/-, mice. In contrast, castration impaired novel object recognition and spatial memory retention in the water maze in Apoe-/-, but not apoE3 or apoE4, mice. On the contrary, castrated, but not sham-castrated, apoE4 mice showed improved acquisition over the first two hidden platform sessions and spatial memory retention in the first probe trial. While apoE3 and Apoe-/- mice increased their exploratory times with the objects in the trial with the novel object, apoE4 mice did not. ApoE4 mice required more trials than apoE3 or Apoe-/- mice to reach criterion during passive avoidance training, but castration did not modulate passive avoidance learning or memory. Thus, androgens have differential roles in object recognition and spatial learning and memory in the water maze, depending on whether or not apoE4 is present.

Analysis of Variance↗
PubMed2001

Single and Dual Pathologies of the Temporal Lobe: Effects on Cognitive Function in Children with Epilepsy.

The neuropathologies associated with temporal lobe epilepsy (TLE) are heterogeneous. The performance of 61 children with single pathology of hippocampal sclerosis (HS), temporal lobe tumor, or cortical dysplasia (CD) or dual pathology of HS + tumor or HS + CD was examined on measures of intelligence, language, memory, and executive function. Children with single pathologies performed significantly better than did children with HS + CD on all standardized measures of IQ. Children with tumors performed significantly better than children with dual pathology on receptive vocabulary. These results support prior research of an association between neuropathology and cognitive function in children with epilepsy and extend the findings to include additional neuropathologies and measures of cognitive functioning.

Journal Article↗
PubMed1989

Cortical DC-potentials as electrophysiological correlates of hemispheric dominance of higher cognitive functions.

Cortical activation during cognitive processing was assessed with a new, noninvasive electrophysiological method: Cortical DC-potentials were recorded from frontal, central, temporal and parietal electrode positions on the scalps of 150 normal adult subjects while they performed cognitive tasks involving language, calculation, music and spatial vision. During the 10-s registration period, shifts in DC-potentials were analyzed with reference to a baseline 3-s preperiod. 15-30 trials were averaged. A lateralized preponderance of negativity by more than 3 microV was used as the criterion of hemispheric dominance. Language tasks caused left-sided lateralization in 76% of the right-handers (n = 80), bilaterally equal surface negativity in 15% and right-sided lateralization in 9%. During the same tasks, 22% of the left-handers (n = 45) had right-sided lateralization. Calculation tasks produced left-sided lateralization in 65% of the right-handers and left-handers. Music tasks caused more right-sided (53%) than left-sided (39%) lateralization dependent on musical training. Visuospatial processing yielded a right temporoparietal lateralization in 77%.

Adolescent↗
PubMed1996

Effect of long-term glycemic control on cognitive function.

OBJECTIVE: To investigate the relationship between recurrent hypoglycemia and cognitive impairment in insulin-dependent diabetic patients. RESEARCH DESIGN AND METHODS: Seventy patients who were diagnosed as diabetic at age 18 years or older, were under 55 years old, and had no condition likely to affect cognitive abilities were recruited from a diabetic register. Patients were interviewed to obtain information on the frequency of major and minor hypoglycemia. Their cognitive abilities were assessed on tests of premorbid intelligence, current intelligence, reaction time, concentration, memory, and information processing. RESULTS: There was a significant correlation between the apparent decline in intelligence, expressed as the discrepancy between the estimated premorbid and the actual performance intelligence quotient, and the frequency of major hypoglycemic attacks (rs = -0.30; P < 0.01). Comparison of patients with and without recurrent hypoglycemia showed few significant differences in cognitive ability. CONCLUSIONS: Results support previous work that suggests that major hypoglycemic attacks have a significant effect on some aspects of cognitive function, but the clinical importance of this finding remains to be determined.

Adult↗