Activating effects of cross-sex hormones on cognitive functioning: a study of short-term and long-term hormone effects in transsexuals.

In an earlier study we demonstrated that 3 months of cross-sex hormone treatment clearly influenced cognitive functioning in transsexuals. The aims of the present study were to examine: (a) whether we could replicate these findings in a new group of transsexuals; (b) whether a similar pattern of change could be found for novel tasks, i.e. tasks, not used in the previous study, that measured closely related cognitive abilities; (c) whether the cognitive changes following cross-sex hormone treatment had stabilized after 3 months or continued to develop over a period of 1 year; and finally, (d) whether the effects were quickly reversible when the hormone treatment was temporarily stopped. Again a pronounced effect of androgen treatment was found on spatial ability in female-to-male transsexuals (FMs) over a period of one and a half years. As expected, untreated male-to-female transsexuals (MFs) had higher scores on visuo-spatial tasks than untreated FMs; after 3 months of cross-sex hormone treatment, the group difference had disappeared, while after about 10 months of hormone treatment, the sex difference was reversed. These effects did not disappear after termination of cross-sex hormone therapy for a period of 5 weeks, but continued to change slightly in the same direction. Earlier findings of an opposite effect of cross-sex hormones on verbal fluency (i.e. MFs improved and FMs deteriorated after 3 months of cross-sex hormone treatment) were not replicated in this study, nor did we find an hormonal influence on other cognitive functions. This study shows that testosterone had an enhancing, and not quickly reversible effect, on spatial ability performance, but no deteriorating effect on verbal fluency in adult women (FMs). In contrast, anti-androgen treatment in combination with estrogen therapy had no declining effect on spatial ability, nor an enhancing effect on verbal fluency in adult men (MFs).     

Accelerated forgetting in subjects with memory complaints

A study was carried out to investigate accelerated forgetting of new verbal and visual material in participants complaining of memory loss, individuals with Mild Cognitive Impairment(MCI) and controls. All groups were evaluated with a standard neuropsychological battery and two tests of delayed recall 6 weeks apart for the experimental tasks.Individuals with memory complaints,but not MCI, performed normally compared to controls on immediate and 30 minute recall,but showed a striking impairment in verbal and visual memory after 6 weeks. Accelerated forgetting may go undetected on standard neuropsychological evaluation in some patients complaining of memory problems.     

Enhancement by an Ampakine of Memory Encoding in Humans

A centrally active drug that enhances AMPA receptor-mediated currents was tested for its effects on memory in humans. Evidence for a positive influence on encoding was obtained in four tests: (i) visual associations, (ii) recognition of odors, (iii) acquisition of a visuospatial maze, and (iv) location and identity of playing cards. The drug did not improve scores in a task requiring cued recall of verbal information. The selectivity of drug effects on memory was confirmed using tests of visual recognition, motor performance, and general intellectual functioning. These results suggest that positive modulators of AMPA receptors selectively improve at least some aspects of memory.     

Specific AD impairment in concurrent performance of two memory tasks

The current study examined the hypothesis that patients with Alzheimer's disease (AD) have a selective deficit in the coordination mechanism of the central executive, which is reflected in their inability to coordinate the performance of two tasks concurrently. One criticism of the previous studies in the literature is that they employ tasks that do not necessarily draw upon the separate peripheral mechanisms within working memory but combine a memory load with a perceptuomotor load. Therefore, the aim of the study was to examine the effects of AD and healthy adult ageing on a verbal memory plus visuospatial memory dual task paradigm. We investigated the performance of 15 AD patients and 20 healthy younger and 20 healthy older individuals on three different dual task combinations (i) digit recall and visual pattern recall; ii) digit recall and tracking; and iii) digit recall and articulatory suppression. The results demonstrate a significant dual task impairment in AD patients when two memory tasks are performed simultaneously compared to healthy younger and older adults. In contrast, there was not a significant age-related disruption in performance in healthy individuals compared to single task conditions. As the demands of each task were adjusted for individual ability levels, this provides further support for there being a specific AD dual task decrement in the mechanism responsible for coordinating dual task performance, which is separate from the resources needed to perform the tasks independently.     

Recovery of cognitive function soon after stroke: a study of visual neglect, attention span and verbal recall.

Sixty two consecutive patients admitted to hospital and surviving 6 months were tested regularly over the first 3 months after their stroke to plot recovery in three aspects of cognition: visual neglect, assessed using a cancellation task, attention span assessed using digit span, and verbal recall, tested by counting number of words remembered from a list of 10 words. Normative data were collected for the cancellation test. Fifteen patients showed recovery from visual neglect, 10 improvement in attention span and nine improvement in verbal recall. The difficulties of measuring recovery of cognitive function after stroke are discussed.     

Use of functional MRI in epilepsy]

For the purpose of examining pathophysiological mechanisms of a memory function in epileptic patients or an utility of fMRI for a presurgical assessment in neurosurgical treatment of epilepsy, activated areas in fMRI during verbal or visual memory task were investigated in patient group of temporal lobe epilepsy and normal subject group. Patient group of temporal lobe epilepsy consisted of 7 cases, of which 3 and 3 cases had left and right temporal foci, respectively, except 1 case having undetermined laterality of temporal foci. Normal subjects were 16 cases. All the epileptic and normal subjects were right-handed except for 1 lefty normal subject. Verbal memory tasks were composed of covert and overt recall tasks of 10 words given auditorily, while visual ones were recall tasks of 6 figures given visually. Eventually, in normal subjects, the left side-dominant medial frontal lobes including the superior frontal and anterior cingulate gyri were mainly activated in fMRI during the covert recall tasks of verbal memory, while the left side-dominant inferior frontal and precentral gyri as the motor language areas were chiefly activated in addition to the medial frontal lobe during the overt recall tasks. Further, the bilateral occipital lobes were activated in fMRI during the recall tasks of visual memory. Also in patient groups of temporal lobe epilepsy, the activated areas in fMRI during these tasks were the same as in normal subject group, regardless of the laterality of epileptic temporal foci. These results suggest that fMRI is useful for the determination of the lateralization of the cerebral hemisphere contributing to verbal memory function and therefore for the presurgical assessment of memory function in neurosurgical treatment of epilepsy.     

Individual Memory Change After Anterior Temporal Lobectomy: A Base Rate Analysis Using Regression-Based Outcome Methodology

Summary: Purpose: To characterize patterns of base rate change on measures of verbal and visual memory after anterior temporal lobectomy (ATL) using a newly developed regression-based outcome methodology that accounts for effects of practice and regression towards the mean, and to comment on the predictive utility of baseline memory measures on postoperative memory outcome. Methods: Memory change was operationalized using regression-based change norms in a group of left (n = 53) and right (n = 48) ATL patients. All patients were administered tests of episodic verbal (prose recall, list learning) and visual (figure reproduction) memory, and semantic memory before and after ATL. Results: ATL patients displayed a wide range of memory outcome across verbal and visual memory domains. Significant performance declines were noted for 25–50% of left ATL patients on verbal semantic and episodic memory tasks, while one-third of right ATL patients displayed significant declines in immediate and delayed episodic prose recall. Significant performance improvement was noted in an additional one-third of right ATL patients on delayed prose recall. Base rate change was similar between the two ATL groups across immediate and delayed visual memory. Approximately one-fourth of all patients displayed clinically meaningful losses on the visual memory task following surgery. Robust relationships between preoperative memory measures and nonstandardized change scores were attenuated or reversed using standardized memory outcome techniques. Conclusions: Our results demonstrated substantial group variability in memory outcome for ATL patients. These results extend previous research by incorporating known effects of practice and regression to the mean when addressing meaningful neuropscyhological change following epilepsy surgery. Our findings also suggest that future neuropsychological outcome studies should take steps towards controlling for regression-to-the-mean before drawing predictive conclusions.     

An attempt to improve auditory short-term memory in Down''s syndrome individuals through reducing distractions

Down's syndrome (DS) individuals, relative to nonretarded individuals, have greater difficulty remembering brief sequences of verbal information presented auditorily. Previous research suggests at least two possible attentional explanations of their difficulty: They are especially susceptible to both auditory distraction and off-task glancing during laboratory tasks. DS, non-DS mentally retarded and nonretarded persons listened to, looked at, and attempted to remember sequences of digits. Although the three groups did not differ in their recall of visually-presented stimuli, DS subjects showed significantly poorer recall of auditorially-presented stimuli than the other two groups (which did not differ). Furthermore, the poor auditory memory of DS subjects did not improve under testing conditions designed to minimize auditory and visual distractions. It was suggested that poor auditory short-term memory for verbal information is tied more closely to Down's syndrome than to low intelligence and does not seem to be caused by a special susceptibility of Down's syndrome individuals to attentional distractors.     

Compromised memory function in schizophrenia and temporal lobe epilepsy

The purpose of this study was to investigate compromised memory function of schizophrenia patients in comparison with temporal lobe epilepsy patients, whose memory impairments result from a clear lesion. The authors hypothesized that schizophrenia patients would show poorer immediate and delayed recall performances in verbal and visual memory tasks. The study sample consisted of a healthy comparison group of 30 subjects and three patient groups comprising 76 schizophrenia patients, 93 left temporal lobe epilepsy patients, and 72 right temporal lobe epilepsy patients. The authors assessed immediate recall, delayed recall, and delayed retention. Tasks were subdivided into two categories (easy and difficult), and then patient memory dysfunction was compared among the memory tests. The authors observed material-specific memory impairment, where the left temporal lobe epilepsy group showed severe verbal memory impairment and the right temporal lobe epilepsy group showed severe visual memory impairment. A moderate impairment was found in immediate and delayed verbal memory in schizophrenia patients, and the impairment of visual memory was amplified with delayed recall. Such a result can be interpreted not only as a generalized cognitive deficit, but also as an integrative dysfunction involving the mesial temporal and frontal lobes in the left and right hemispheres, whereby the lesion site cannot be determined selectively. Our results show that the selection of a memory task that cannot be influenced by verbal mediation is very important for analyzing memory dysfunction in schizophrenia patients.     

Differential associations between types of verbal memory and prefrontal brain structure in healthy aging and late life depression

Verbal memory deficits attributed to late life depression (LLD) may result from executive dysfunction that is more detrimental to list-learning than story-based recall when compared to healthy aging. Despite these behavioral dissociations, little work has been done investigating related neuroanatomical dissociations across types of verbal memory performance in LLD. We compared list-learning to story-based memory performance in 24 non-demented individuals with LLD (age ~ 66.1 ± 7.8) and 41 non-demented/non-depressed healthy controls (HC; age ~ 67.6 ± 5.3). We correlated significant results of between-group analyses across memory performance variables with brain volumes of frontal, temporal and parietal regions known to be involved with verbal learning and memory. When compared to the HC group, the LLD group showed significantly lower verbal memory performance for spontaneous recall after repeated exposure and after a long-delay but only for the list-learning task; groups did not differ on story-based memory performance. Despite equivalent brain volumes across regions, only the LLD group showed brain associations with verbal memory performance and only for the list-learning task. Specifically, frontal volumes important for subjective organization and response monitoring correlated with list-learning performance in the LLD group. This study is the first to demonstrate neuroanatomical dissociations across types of verbal memory performance in individuals with LLD. Results provide structural evidence for the behavioral dissociations between list-learning and story-based recall in LLD when compared to healthy aging. More specifically, it points toward a network of predominantly anterior brain regions that may underlie the executive contribution to list-learning in older adults with depression.     

Working memory in Down syndrome: is there a dual task deficit?

Background Recent studies have shown that individuals with Down syndrome (DS) are poorer than controls in performing verbal and visuospatial dual tasks. The present study aims at better investigating the dual task deficit in working memory in individuals with DS. Method Forty‐five individuals with DS and 45 typically developing children matched for verbal mental age completed a series of verbal and visuospatial working memory tasks, involving conditions that either required the combination of two tasks in the same modality (verbal or visual) or of cross‐modality pairs of tasks. Results and conclusions Two distinct deficits were found in individuals with DS: impairment in verbal tasks and further impairment in all dual task conditions. The results confirm the hypothesis of a central executive impairment in individuals with DS.     

Long-term memory for verbal and visual information in Down syndrome and Williams syndrome: performance on the Doors and People test

Previous studies have suggested that Williams syndrome and Down syndrome may be associated with specific short-term memory deficits. Individuals with Williams syndrome perform relatively poorly on tests of visuo-spatial short-term memory and individuals with Down syndrome show a relative deficit on verbal short-term memory tasks. However, these patterns of impairments may reflect the impact of generally impaired visuo-spatial processing skills in Williams syndrome, and verbal abilities in Down syndrome. The current study explored this possibility by assessing long-term memory among 15 individuals with Williams syndrome and 20 individuals with Down syndrome using the Doors and People test, a battery which assesses recall and recognition of verbal and visual information. Individuals' performance was standardised for age and level of intellectual ability with reference to that shown by a sample of 110 typically developing children. The results showed that individuals with Down syndrome have no differential deficits in long-term memory for verbal information, implying that verbal short-term memory deficits in this population are relatively selective. Instead both individuals with Down syndrome and with Williams syndrome showed some evidence of relatively poor performance on tests of long-term memory for visual information. It is therefore possible that visuo-spatial short-term memory deficits that have previously been demonstrated in Williams syndrome may be secondary to more general problems in visuo-spatial processing in this population.     

Testosterone supplementation improves spatial and verbal memory in healthy older men.

OBJECTIVE: To determine the relationship between exogenous testosterone administration and cognitive abilities in a population of healthy older men. BACKGROUND: Serum levels of total and bioavailable testosterone gradually decrease with age in men and are associated with reductions in muscle mass, osteoporosis, decreased sexual activity, and changes in cognition. METHODS: Twenty-five healthy, community-dwelling volunteers, aged 50 to 80 years, completed a randomized, double-blind, placebo-controlled study. Participants received weekly intramuscular injections of either 100 mg testosterone enanthate or placebo (saline) for 6 weeks. Cognitive evaluations were conducted at baseline, week 3, and week 6 of treatment by use of a battery of neuropsychologic tests. RESULTS: Circulating total testosterone was raised an average of 130% from baseline at week 3 and 116% at week 6 in the treatment group. Because of aromatization of testosterone, estradiol increased an average of 77% at week 3 and 73% at week 6 in the treatment group. Significant improvements in cognition were observed for spatial memory (recall of a walking route), spatial ability (block construction), and verbal memory (recall of a short story) in older men treated with testosterone compared with baseline and the placebo group, although improvements were not evident for all measures. CONCLUSIONS: The results suggest that short-term testosterone administration enhances cognitive function in healthy older men. However, it remains unclear whether these improvements in cognition are attributable to increased testosterone or estradiol levels, or both. The potential role of testosterone vs its metabolites on cognition requires further research.     

Episodic memory impairment in bipolar disorder and obsessive-compulsive disorder: the role of memory strategies

BACKGROUND: There is evidence that individuals with bipolar disorder exhibit neuropsychological impairments not only during mood episodes but also when they are euthymic. One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is an impairment in verbal episodic memory. Verbal learning and memory depend on individuals' ability to organize verbal information appropriately during learning. The purpose of the present study was (i) to determine whether episodic memory impairment in euthymic individuals with bipolar disorder is mediated by impairments in organization of verbal information during learning and (ii) to compare the characteristics of memory impairment in bipolar disorder with that previously found in obsessive-compulsive disorder (OCD). METHODS: Study participants were 30 individuals with DSM-IV bipolar I disorder (BP-I), 30 individuals with DSM-IV OCD and 30 normal control participants matched for age, gender and education. Participants completed the California Verbal Learning Test (CVLT), a well-established measure of verbal learning and memory that enables assessment of verbal organization strategies during learning. RESULTS: Compared with control subjects, both BP-I and OCD participants showed impaired performance in long-delayed free recall and verbal organization strategies during learning. BP-I participants showed greater long-delay free recall difficulties but not greater verbal organization difficulties during learning than OCD participants. For OCD participants, the long-delay recall impairment was mediated by difficulties using verbal organizational strategies during learning. In contrast, the group difference in long-delayed free recall between BP-I and control participants remained significant even when semantic clustering was introduced as a mediator. This indicated that BP-I participants' long-delayed free recall difficulties were mediated to a lesser extent by difficulties using verbal organizational strategies than for OCD participants. CONCLUSIONS: Verbal episodic memory problems in individuals with bipolar I disorder and OCD are mediated to different degrees by difficulties using semantic clustering encoding strategies compared with control participants.     

Nonvisual spatial navigation fMRI lateralizes mesial temporal lobe epilepsy in a patient with congenital blindness

Nonvisual spatial navigation functional magnetic resonance imaging (fMRI) may help clinicians determine memory lateralization in blind individuals with refractory mesial temporal lobe epilepsy (MTLE). We report on an exceptional case of a congenitally blind woman with late-onset left MTLE undergoing presurgical memory fMRI. To activate mesial temporal structures despite the lack of visual memory, the patient was requested to recall familiar routes using nonvisual multisensory and verbal cues. Our findings demonstrate the diagnostic value of a nonvisual fMRI task to lateralize MTLE despite congenital blindness and may therefore contribute to the risk assessment for postsurgical amnesia in rare cases with refractory MTLE and accompanying congenital blindness.     

Testosterone and cognition in elderly men: a single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial or verbal memory.

BACKGROUND: The relevance of the age-associated decline in testosterone for cognition in elderly men is still poorly understood. One hypothesis is that testosterone enhances spatial abilities, while it might impair verbal skills. METHODS: Thirty elderly men received a single testosterone (250 mg testosterone enanthate) or placebo injection. Cognitive performance was tested before and 5 days after treatment using spatial as well as verbal tests. RESULTS: Five days after injection, testosterone and estradiol levels were still in the supraphysiologic range. In the verbal fluency task, the placebo group, but not the testosterone group, showed a practice effect. Therefore, the testosterone group performed significantly worse than the placebo group after treatment. No effects of testosterone were observed in the other verbal and spatial tasks. CONCLUSIONS: The present finding, that testosterone blocks the practice effect in verbal fluency, partly supports the general idea that sex steroids modulate performance in tests with known gender differences. Moreover it demonstrates that these effects can occur rapidly. However, beneficial effects on spatial cognition or memory might need more time to develop and/or might only occur when a less pronounced testosterone increase is induced.     

Cognition and functional outcome among deaf and hearing people with schizophrenia

Recent research has highlighted the relationships between impairments in cognitive functioning and poorer functional outcomes among people with schizophrenia (PWS). The purpose of this study was to replicate and extend this work by testing the relationships between cognition and functional outcome among deaf adults with schizophrenia. Empirical findings from deafness-oriented research reveals enhanced abilities in certain aspects of visual-spatial processing compared to hearing people. Sixty-five PWS (34 deaf, 31 hearing) were assessed using measures of verbal and visual memory, attention, and visual processing. The first hypothesis tested whether cognition predicted functional outcome in a similar fashion for both deaf and hearing subjects (n=63). For all subjects, higher levels of cognitive ability were associated with higher levels of functional outcome, and the strongest predictors of outcome were verbal memory and visual-spatial memory (recall condition) (VSM recall). However, the deaf and hearing groups did show different patterns of relationships between cognition and functioning when all cognitive variables were examined. The second hypothesis was that deaf subjects would display superior performance in early visual processing, visual-spatial memory (copy condition) (VSM copy), and VSM recall. Deaf subjects displayed superior performance on each task; however, no significant differences emerged. Deaf subjects outperformed hearing subjects in an unexpected domain (word memory/recognition). This study extends prior work in the area of cognition and schizophrenia and indicates that deaf and hearing subjects may benefit from interventions that address different domains of cognition.     

Decline in verbal memory in non-demented older adults

Decline in memory function was detected in 30% of healthy community-dwelling elderly over 6 years using a task assessing delayed word list recall. Individuals with memory decline over time also demonstrated relative deficits on additional tasks of memory and learning, a task of working memory and executive function, and on a verbal (category) fluency task at their most recent assessment. These relative deficits in the performance of individuals with memory decline cannot be explained by age-related changes, education, intelligence, mood, health-related factors, or the individuals' APOE epsilon 4 status. Decline in memory performance did not result in greater complaints of cognitive difficulties when compared with normal elderly, nor did it limit overall participation in life activities. Although the significance of memory decline in the current study was not determined quantitatively, memory decline is consistent with the early deterioration characteristic of mild cognitive impairment and preclinical Alzheimer's disease and confirms the need to monitor individuals with objective memory decline, even when these individuals fall within normal limits for a given neuropsychological task.     

Grouping,semantic relation and imagery effects in individuals with Down syndrome

Down syndrome (DS) is associated with a specific verbal short-term memory (STM) deficit. This study explored the effects of grouping, semantic relations and visual presentation upon verbal STM recall performance in a group of 15 individuals with DS and 15 vocabulary-matched typically developing (TD) children. Participants were presented with memoranda in either a temporally grouped schedule, such that items were grouped as pairs, or in an equally spaced presentation schedule. The two items constituting each pair were either semantically related or unrelated. Performance across these conditions was compared in verbal or verbal plus visual presentation modes. Significant memory recall benefits were observed across populations as a result of temporal grouping, semantic relations and verbal and visual combined presentation. However, a reduced benefit of semantic relation in the DS group compared to the TD group indicated that those with DS were less influenced by LTM relational knowledge. In addition, those with DS only experienced a grouping benefit during verbal and visual combined presentation, in contrast to the TD group who experienced grouping benefits throughout. This indicates that individuals with DS are poorer at encoding temporal context for purely verbal memoranda. These findings were replicated in a follow-up experiment, aimed at aligning baseline performance in the two populations. This study provides encouraging evidence that, despite their difficulties in some areas, individuals with DS can benefit from the use of grouping and LTM knowledge to assist their verbal STM performance under certain circumstances.     

Long-term accelerated forgetting of verbal and non-verbal information in temporal lobe epilepsy

IntroductionWe investigated whether pre-surgical patients with temporal lobe epilepsy (TLE) forget verbal and non-verbal material faster than healthy controls over retention intervals of an hour and 6 weeks, and whether any observed memory loss was associated with structural changes to the hippocampus and/or seizure frequency.MethodsA mixed factorial design compared the performance of 27 patients with TLE and 22 healthy control participants, matched for IQ, age and gender, on tests of story recall and complex figure recall at three delays: immediate, 1 h and 6 weeks. Performance of the patient and control groups was matched at the immediate delay, which enabled comparisons of forgetting rate over the longer delays.ResultsWe found that TLE can affect the acquisition and retention of new memories over a relatively short delay of 1 h. This deficit was associated with structural hippocampal abnormality, with a material-specific effect that was particularly evident for the verbal task. We also found evidence of accelerated long-term forgetting in both patient groups, for the verbal and non-verbal tasks. It was demonstrated most strongly on the verbal task by the patients with right lateralized hippocampal sclerosis whose verbal recall was normal at the 1-h delay. Accelerated long-term forgetting was not associated with hippocampal pathology, but was associated with the frequency of epileptic seizures.DiscussionThe findings from the verbal task in particular provide evidence consistent with an extended period of memory consolidation that can be disrupted by both left and right TLE. The material-specific effects at the 1-h delay only, suggest that the initial consolidation of verbal and non-verbal, information depends on the integrity of the left and right hippocampus, respectively.