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PubMed1995

Sensory- and memory-mediated olfactory dysfunction in Huntington's disease.

Neuropathology in Huntington's disease (HD) known to project to areas that process olfactory information raises the questions of which olfactory function, if any, is most affected in HD, and how to explain such dysfunction in terms of olfactory sensitivity and cognition. These questions were studied by comparing HD patients and controls (matched for age, gender, and education) on absolute detection, intensity discrimination, quality discrimination, short-term recognition memory, and lexical- and picture-based identification for odor. Taste or vision were used as comparison modalities. The results suggest that whereas odor-recognition memory is not affected in patients with HD, these patients have impaired olfactory functioning with respect to absolute detection, intensity discrimination, quality discrimination, and identification. The three latter impairments were significantly explained by poor detection sensitivity. Odor identification was the function most affected.

Adult↗
PubMed2001

Placebo expectancy effects in the relationship between glucose and cognition.

The present study investigated the extent of expectancy in the ability of glucose to affect cognitive performance. Using a within-subjects design, subjects (n 26) completed four experimental sessions (in counterbalanced order and after an initial practice session) during which they were given a 500 ml drink 30 min prior to completing a cognitive assessment battery. In addition, all subjects completed a baseline practice session during which they were given no drink. During two of the sessions, subjects were given a drink containing 50 g glucose and on the other two they were given a drink containing aspartame. A balanced placebo design was used, such that for half the sessions subjects were accurately informed as to the content of the drink (glucose or aspartame), whereas in the other two sessions they were misinformed as to the content of the drink. The task battery comprised a 6 min visual analogue of the Bakan vigilance task, an immediate verbal free-recall task, an immediate verbal recognition memory task and a measure of motor speed (two-finger tapping). Blood glucose and self-reported mood were also recorded at several time points during each session. Glucose administration was found to improve recognition memory times, in direct contrast to previous findings in the literature. Glucose administration also improved performance on the Bakan task (relative to the control drink), but only in sessions where subjects were informed that they would receive glucose and not when they were told that they would receive aspartame. There were no effects either of the nature of the drink or expectancy on the other measures. These results are interpreted in terms of there being some contribution of expectancy concerning the positive effects of glucose on cognition in studies which have not used an equi-sweet dose of aspartame as a control drink.

Adolescent↗
PubMed1993

Visual evoked potentials and visual processing in stimulant drug-exposed infants.

Prenatal exposure to cocaine and amphetamines has been associated with many adverse effects in infants, including neurological abnormalities. Recent evidence shows that the visual system may be useful in infancy to evaluate neurological functioning. Visual evoked potentials (VEPs) and visual recognition memory testing were carried out on eight infants with prenatal drug-exposure and eight controls, matched for ethnicity and socio-economic status. The drug-exposed infants performed significantly worse on the visual recognition test. However, there were no differences between groups on VEP testing and no correlations between tests. The results suggest that the difficulties found in visual recognition memory of drug-exposed infants are not related to neurological maturity, as measured by VEPs.

Amphetamines↗
PubMed2006

Profile of executive and memory function associated with amphetamine and opiate dependence.

Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetamine-dependent individuals, opiate-dependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants were administered the Tower of London (TOL) planning task and the 3D-IDED attentional set-shifting task to assess executive function, and Paired Associates Learning and Delayed Pattern Recognition Memory tasks to assess visual memory function. The three groups of substance users showed significant impairments on TOL planning, Pattern Recognition Memory and Paired Associates Learning. Current amphetamine users displayed a greater degree of impairment than current opiate users. Consistent with previous research showing that healthy men are performing better on visuo-spatial tests than women, our male controls remembered significantly more paired associates than their female counterparts. This relationship was reversed in drug users. While performance of female drug users was normal, male drug users showed significant impairment compared to both their female counterparts and male controls. There was no difference in performance between current and former drug users. Neither years of drug abuse nor years of drug abstinence were associated with performance. Chronic drug users display pronounced neuropsychological impairment in the domains of executive and memory function. Impairment persists after several years of drug abstinence and may reflect neuropathology in frontal and temporal cortices.

Adult↗
PubMed1996

The effect of lorazepam on memory and event-related potentials in heavy and light social drinkers.

To investigate the effects of heavy social drinking on sober cognitive processing, event-related potentials were recorded from 13 heavy social drinkers and 13 light social drinkers in the presence and absence of a pharmacological challenge (i.e., lorazepam). Event-related potentials were elicited by a task requiring continuous recognition memory for visually presented words. The heavy social drinkers exhibited shorter P2 latencies than the light social drinkers and decreased P300 latencies to correctly identified "old" words (i.e., words presented previously in the task) versus "new" words. Lorazepam increased motor reaction time to correctly identified old words and produced a deficit in recognition memory only in the light social drinkers. Light social drinkers had an increased P300 latency and a larger P300 amplitude to new words in the lorazepam treatment. The differences in cognitive functioning evident between heavy and light social drinkers were reflected in event-related potential deviations and appear to indicate a tolerance in heavy social drinkers to the effects of lorazepam.

Adult↗
PubMed2000

Alcohol, dementia, and Alzheimer's disease: comparison of neuropsychological profiles.

Thirty-nine detoxified elderly alcoholics (mean age = 65.85) completed a comprehensive assessment designed to identify individuals meeting DSM-IV criteria for alcohol-related dementia. Ten subjects meeting criteria (mean age = 69.8; mean Mini-Mental State Examination [MMSE] = 25.1) were compared to the 29 nondemented alcoholics (mean age = 64.5; mean MMSE = 27.8), 9 patients with Alzheimer's disease (mean age = 73.4; mean MMSE = 22.3), and 15 control subjects (mean age = 70.8; mean MMSE = 28). Comparison of neuropsychological test scores revealed several statistically significant differences. Furthermore, the overall pattern of test performance between the two demented groups was different. Alzheimer's patients were more impaired on confrontation naming, recognition memory, animal fluency, and orientation. Alcohol dementia subjects were more impaired than controls on initial letter fluency, fine motor control, and free recall. However, alcohol dementia subjects did not differ from controls on tests of verbal recognition memory. This study suggests that it is possible to clinically differentiate the cognitive deficits of alcohol-related dementia from typical Alzheimer's disease. However, the results are preliminary and are based on small sample sizes so should be interpreted with caution.

Aged↗
PubMed2003

Motivation and neuropsychological test performance following mild head injury.

Effect of motivation on neuropsychological test performance in mild head injury was assessed. Motivation was measured using the Portland Digit RecognitionTest. Three groups were compared: (a) mildhead injury, financial incentives, good motivation; (b) mild head injury, financial incentives, poor motivation; (c) moderate/severe head injury, good motivation. The neuropsychological battery included measures of sensory function, motor function, attention, intelligence, abstract reasoning, and memory. Mild head injury well motivated patients performed significantly better than the other two groups on some tests. Mild head injury poorly motivated individuals and moderate-severe head injury patients were indistinguishable on many tests. Consistent with previous reports, tactile sensory (finger recognition and Fingertip Number Writing Perception) and recognition memory (Rey Auditory Verbal Learning) tasks were identified as clinically useful measures of poor motivation. On these measures mild head injury well motivated examinees performed no better than moderate-severe patients, with both groups superior to mild head injury poorly motivated examinees. Sensitivity and specificity data are reported. Our measures of tactile sensation and verbal recognition memory were more affected by motivation than by the severity of head injury.

Adolescent↗
PubMed2000

Behavioral deficits in APP(V717F) transgenic mice deficient for the apolipoprotein E gene.

Both the beta-amyloid precursor protein (APP) and the apoliprotein E (apoE) genes are involved in the pathogenesis of Alzheimer's disease (AD). We previously showed that mice over-expressing a human mutated form of APP (APP(V717F)) display age-dependent recognition memory deficits associated with the progression of amyloid deposition. Here, we asked whether 10- to 12-month-old APP(V717F) mice lacking the apoE gene, which do not present obvious amyloid deposition, differ from APP(V717F) mice in the object recognition task. The recognition performance is decreased in both transgenic mouse groups compared to control groups. Moreover, some behavioral disturbances displayed by APP mice lacking apoE are even more pronounced than those of APP mice expressing apoE. Our results suggest that the recognition memory deficits are related to high levels of soluble Abeta rather than to amyloid deposits.

Amyloid↗
PubMed1991

Longitudinal application of cognitive function measures in a defined population of community-dwelling elders.

The nature and extent of possible age-related changes in cognitive function have primarily been examined in nonrandom samples, and have not been well described in population-based studies. We examined longitudinal changes in performance on a mental status examination and recall and recognition memory tests in a population-based (n = 1953) study of community-dwelling elders. Advanced age was associated with poorer performance on all tests and more rapid decline longitudinally on the mental status and recall and recognition memory tests. Less-educated persons performed more poorly. Lower levels of educational attainment were predictive of more rapid declines on the mental status examination and recall memory test among women. Subsequent survivorship was associated with preserved performance on the mental status and recall memory tests. These findings suggest that there are age-associated changes in cognitive function, and have implications for population-based studies of cognitive function and survey research in general.

Age Factors↗
PubMed1995

Main neurodevelopmental study of Seychellois children following in utero exposure to methylmercury from a maternal fish diet: outcome at six months.

Methylmercury (MeHg) is a human neurotoxin to which the developing fetal brain is especially sensitive. The lowest dose of MeHg that impairs neurodevelopment in the human fetus is not known. The Seychelles Child Development Study (SCDS) is testing the hypothesis that fetal MeHg exposure from a maternal diet high in oceanic fish is related to child neurodevelopmental outcomes. Fish is the major protein source in the Republic of Seychelles, where a cohort of 779 mother-infant pairs was enrolled in a prospective longitudinal study. Maternal total hair mercury values during pregnancy were determined by cold vapor atomic absorption and ranged from 0.5 ppm to 26.7 ppm with a median of 5.9 ppm. When the children were 6 1/2 months of age, an examiner blinded to the maternal mercury value performed a neurological examination, the Fagan test of visual recognition memory, and the Denver Developmental Screening Test-Revised (DDST-R). On the DDST-R 2% scored other than normal while 3.4% had an overall neurological score other than normal. The Fagan test of visual recognition memory showed a median score of 60.5%, and the Rose attention measure from that test showed a median score of 37.9. The association between fetal mercury exposure and neurodevelopmental endpoints was examined by multiple regression analyses. After adjusting for covariates, no association between the maternal hair mercury level during pregnancy and an adverse neurodevelopmental outcome of the child was identified at 6 1/2 months of age.

Adult↗
PubMed2005

Effects of long-term estrogen replacement on social investigation and social memory in ovariectomized C57BL/6 mice.

Estrogen has been shown to play a role in modulating social recognition memory. However, the literature regarding the influence of estrogen on social memory is sparse and only covers two experimental manipulations: acute injections and receptor knockout. Long-term effects of estrogen replacement on social investigation and social recognition are unknown. Furthermore, existing social recognition protocols focus on memory of very short durations (<2 h). In the present study, we examined long-term effects of estrogen replacement on both short- (<30 min) and long-term (24 h) social recognition in ovariectomized female C57BL/6 mice by implanting 60-day time-release pellets containing physiological doses of estradiol (0, 0.18, or 0.72 mg of 17beta-estradiol). After 55 days of treatment, evidence of social recognition memory, measured by 24-h habituation, was found only in mice receiving the 0.72-mg pellet. This result is remarkable as previous reports indicate that individually-housed untreated rats and mice do not show habituation beyond 2 h. Our study further revealed that estrogen also increased frequencies of baseline social investigation without affecting general activity levels and decreased delayed post-swim-stress serum corticosterone concentration. Thus, these results suggest that long-term estrogen replacement increased the interest in social interaction as well as decreased stress responses. It is likely that the 24-h habituation observed in the estrogen replacement group is mediated jointly by the non-mnemonic effects of estrogen on the behavior displayed during the stage of memory encoding as well as mnemonic effects during the stage of memory consolidation.

Animals↗
PubMed2000

Cognitive function in aged ovariectomized female rhesus monkeys.

To determine whether ovariectomy exacerbates age-related cognitive decline, the performance of 6 aged monkeys that had been ovariectomized early in life (OVX-Aged) was compared to that of 8 age-matched controls with intact ovaries (INT-Aged) and that of 5 young controls with intact ovaries (INT-Young) in tasks of visual recognition memory, object and spatial memory, and executive function. The OVX-Aged monkeys were marginally more impaired than the INT-Aged monkeys on the delayed nonmatching-to-sample with a 600-s delay. In contrast, they performed significantly better than the INT-Aged controls on the spatial condition of the delayed recognition span test. The hypothesis that prolonged estrogenic deprivation may exaggerate the age-related decline in visual recognition memory will require additional support. However, the findings suggest that long-term ovariectomy may protect against the development with aging of spatial memory deficits.

Aging↗
PubMed1998

Haptic memory and handedness in 2-month-old infants.

This study examined the robustness of infant haptic memory, asymmetry between hands, and sex differences in haptic memory in infancy. A total of 96 2-month-old infants (half males, half females) were habituated haptically to an object with their right and their left hand, out of the field of view. Haptic memory was then tested under three conditions: after haptic interference, after a 30-second delay, or after no delay. The results show that haptic habituation occurred for both hands. The girls needed more time to habituate with their left hand than with their right hand, and they habituated more slowly than the boys did. Discrimination was also found in both hands and in both sexes. Haptic delayed recognition memory was only found in young boys mainly after a short delay and under certain conditions after interference. In young girls, recognition memory was found after interference only with the left hand. This result seemed to depend on the information processing speed. Thus, for memory performance, a sex difference was clearly observed. Moreover, the infants' left hand retained better information on object shape than did the right hand for both the sexes. Asymmetries in infancy are discussed in connection with the difference in brain maturation rate.

Journal Article↗
PubMed2004

Neuropsychological outcome of subjects participating in the PKU adult collaborative study: a preliminary review.

Adult subjects with classical phenylketonuria (PKU) who were diagnosed and treated neonatally participated in this long-term follow-up study. Twenty-four subjects received neuropsychological (NP) assessment and a subset received magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to identify: (1) pattern of cognitive dysfunction; (2) effect of high blood phenylalanine (Phe) level at time of cognitive testing; and (3) treatment variables that may be associated with cognitive difficulties in adulthood. All subjects had average IQ except one subject in the borderline range. Diet was initiated by the 15th day of life. All subjects except one were on diet until age 6 years (mean years of treatment = 15). Blood Phe levels at cognitive testing ranged from 157 to 1713 micromol/L (mean = 1038); 11 subjects had levels < 1000 micromol/L and 13 subjects had levels >1000 micromol/L. Results suggest that adults with early-treated PKU demonstrate specific cognitive deficits, a number of which are associated with the frontal and temporal area of the brain. Deficits were noted in several domains including executive functioning, attention, verbal memory, expressive naming and verbal fluency. Self-report measures of depression and anxiety were generally in the normal/mild range. The group with a Phe level > 1000 micromol/L scored lower than the group with Phe level < 1000 micromol/L on measures of focused attention, verbal fluency, reaction time, verbal recognition memory, visual memory and naming. Tests of cognitive functioning were often correlated with measures of treatment during childhood rather than with Phe level at the time of cognitive testing. Subjects with abnormal MRI scored significantly lower on two cognitive tests (Trails A and CVLT Recognition Memory). We found no significant correlation between current brain Phe level obtained through MRS (n = 10) and neuropsychological functioning. Future longitudinal investigation with a larger sample size will assist in clarifying the aetiology of neuropsychological deficits and association with treatment history.

Adult↗
PubMed1993

The effects of fornix and medial prefrontal lesions on delayed non-matching-to-sample by rats.

The present study compared the effects of fornix lesions and medial prefrontal lesions on a test of object recognition memory, delayed non-matching-to-sample. Neither lesion impaired the acquisition of this non-spatial test of working memory, indeed there was clear evidence that fornix damage resulted in improved non-matching performance during initial acquisition. This improvement in performance could be related to the loss of a spatial bias during the early stages of training. A series of experiments then systematically increased the familiarity of the stimuli (i.e. testing recency rather than recognition judgements). Neither the fornix nor the prefrontal lesions disrupted performance under these conditions, even though this manipulation affected nonmatching in a predictable manner. The same animals were also tested on a spatial forced-alternation task in a T-maze (spatial delayed non-matching-to-sample). The animals with fornix lesions performed at chance while the prefrontal animals were mildly, but significantly, impaired. The present findings are considered in the light of a number of seemingly contradictory findings regarding the effects of hippocampal system damage on nonspatial tests of recognition memory.

Animals↗
PubMed1999

Risperidone versus haloperidol on secondary memory: can newer medications aid learning?

The introduction of the new generation of antipsychotic medications for the treatment of schizophrenia has been accompanied by a growing interest in the neurocognitive effects of these drugs. The present study compared the effects of risperidone and haloperidol on secondary memory in a group of treatment-resistant schizophrenia patients. The study design included a baseline phase and two double-blind phases in which patients were randomly assigned to medication under two different dose conditions (fixed dose and flexible dose). Secondary memory was assessed at baseline, fixed-dose, and flexible-dose phases, using the California Verbal Learning Test (CVLT). Six measures were selected, which formed three factors (general verbal learning ability, retention, and learning strategy). Risperidone-treated patients showed greater improvement than haloperidol-treated patients in general verbal learning ability, a finding characterized by significant treatment effects on CVLT measures of learning acquisition, recall consistency, and recognition memory. After controlling for benztropine status, differences on the measures of learning acquisition and recall consistency remained significant, and differences in recognition memory weakened slightly (p = 0.07). No significant treatment effects were noted on retention or learning strategy. These findings suggest that risperidone may exert a facilitating effect on the acquisition of new verbal information, an effect that does not appear to be due to the activation of semantic encoding strategies.

Adult↗
PubMed1998

Does ketamine-mediated N-methyl-D-aspartate receptor antagonism cause schizophrenia-like oculomotor abnormalities?

Evidence from histological and pharmacological challenge studies indicates that N-methyl-D-aspartate (NMDA) receptor hypofunction may play an important role in the pathophysiology of schizophrenia. Our goal was to characterize effects of NMDA hypofunction further, as related to schizophrenia-associated neuropsychological impairment. We administered progressively higher doses of ketamine (target plasma concentrations of 50, 100, 150, and 200 ng/ml) to 10 psychiatrically healthy young men in a randomized, single-blind, placebo-controlled design and assessed oculomotor, cognitive, and symptomatic changes. Mean ketamine plasma concentrations approximated target plasma concentrations at each infusion step. Verbal recall, recognition memory, verbal fluency, pursuit tracking, visually guided saccades, and fixation all deteriorated significantly during ketamine infusion; lateral gaze nystagmus explained some, but not all, of the smooth pursuit abnormalities. We concluded that ketamine induces changes in recall and recognition memory and verbal fluency reminiscent of schizophreniform psychosis. During smooth pursuit eye tracking, ketamine induces nystagmus as well as abnormalities characteristic of schizophrenia. These findings help delineate the similarities and differences between schizophreniform and NMDA-blockade-induced cognitive and oculomotor abnormalities.

Adult↗
PubMed2002

A dose-finding study on the effects of branch chain amino acids on surrogate markers of brain dopamine function.

RATIONALE: We have previously shown in healthy volunteers that an amino acid mixture lacking tyrosine and phenylalanine reduces tyrosine availability to the brain and produces cognitive and neuroendocrine effects consistent with reduced dopamine function. This could provide a potential nutritional approach to disorders such as mania and schizophrenia, which are characterised by overactivity of dopamine pathways. The amino acid mixture we tested previously is unpalatable, whereas mixtures containing only branch chain amino acids can be made more palatable. However, the effects of such mixtures on dopamine function in humans have not been studied. OBJECTIVE: To assess the tolerability of different doses of branch chain amino acids and to measure their effects on neuroendocrine and cognitive measures sensitive to changes in dopamine function. METHODS: We used a randomised, double-blind, cross-over design in 12 healthy volunteers to assess the effect of single oral doses of 10 g, 30 g and 60 g branch chain amino acids on plasma prolactin and a test of spatial recognition memory RESULTS: The branch chain amino acids were well tolerated. The availability of tyrosine for brain catecholamine synthesis decreased in a dose-related manner. As hypothesised, the drink increased both the plasma prolactin and the latency to respond on the spatial recognition memory task. CONCLUSIONS: A drink containing branch chain amino acids is well tolerated in healthy volunteers and produces effects consistent with lowered dopamine function.

Adult↗