Does hormone therapy affect attention and memory in sleep-deprived women?

OBJECTIVES: To evaluate whether hormone therapy (HT) modifies cognitive performance during sleep deprivation in postmenopausal women. Comparison was made with a group of young women. METHODS: Participants included 26 postmenopausal women (age 58-72 years, 16 HT users, 10 non-users), 11 young women (age 20-26 years). They spent four consecutive nights in the sleep laboratory. Cognitive tests of attention, working memory, and verbal episodic memory were carried out after the baseline night, 25-h sleep deprivation, and recovery night. RESULTS: Sleep deprivation impaired performance in all groups. It was manifested either as delayed practice effect or deteriorated performance (p < 0.05). In simple reaction time and 10-choice reaction time, non-users and young maintained their performance, whereas HT users suffered a minor impairment (p < 0.01). In other measurements, there was no interaction of group and condition. In 10-choice reaction time and vigilance, postmenopausal women made fewer errors and omissions than the young (p < 0.05). For most tasks, all groups showed improvement after one recovery night. CONCLUSIONS: HT had a minor adverse effect on cognitive performance during sleep deprivation. Attention and memory deteriorated similarly in postmenopausal and young women, despite the lower initial performance level of postmenopausal women. One night of sleep ensured recovery in most tasks.

Hippocampal volume, brain atrophy, and APOE genotype after traumatic brain injury.

OBJECTIVE: To examine the association between hippocampal volumes, general brain atrophy, and apolipoprotein E (APOE) polymorphism in patients with a remote traumatic brain injury (TBI). METHODS: MRI-based volumetric analyses of the hippocampus and lateral ventricles were performed in 58 patients with TBI of varying severity on average 31.3 years after the trauma. The APOE genotype was determined using standard methods and correlated with the MRI volumetric measurements. RESULTS: Hippocampal or lateral ventricle volumes did not differ significantly in those patients with the APOE-epsilon4 allele (APOE4) vs those without this allele. CONCLUSIONS: The APOE-epsilon4 allele was not associated with the development of hippocampal or ventricular atrophy after traumatic brain injury. If the APOE-epsilon4 allele is associated with an unfavorable outcome after traumatic brain injury as proposed, this association may involve mechanisms other than those responsible for the development of brain atrophy.

Longitudinal cognitive changes in traumatic brain injury: a 30-year follow-up study.

OBJECTIVE: To evaluate longitudinal cognitive changes in patients over three decades following traumatic brain injury (TBI). METHOD: Two hundred ten patients with substantial TBI of variable severity were initially assessed between 1966 and 1972 at Turku University Hospital (Finland). Of these, 61 patients could be studied using the same assessments in the follow-up examination, on average 30 years after the TBI. The results of the follow-up assessment were also compared with an age- and education-matched control group. During each examination, patients were assessed with five subtests of the Wechsler Adult Intelligence Scale, three tests for episodic memory, and the general cognitive decline was determined. RESULTS: The general pattern of slight cognitive decline during a 30-year follow-up contrasted with improvement in semantic memory. Women maintained their cognitive level, but men showed a decline during the follow-up, especially in visuospatial ability and visual memory. Younger patients were likely to maintain or even improve their cognitive functioning. CONCLUSIONS: Most of the patients had mild cognitive decline during the follow-up, but this decline was influenced by gender and age at injury. Unlike the long-term course in the other domains of cognition, semantic memory showed good recovery potential after traumatic brain injury (TBI). The profile of long-term cognitive decline after TBI seems to be qualitatively different from the early signs of dementia of the Alzheimer type.

Estradiol and cognition during androgen deprivation in men with prostate carcinoma.

BACKGROUND: The adverse effects of hormonal manipulation in prostate carcinoma need to be established in view of its increasing use as an adjuvant treatment. This prospective study investigated the association of androgen deprivation-induced estradiol decline with cognition in prostate carcinoma. METHODS: Cognitive testing of prostate carcinoma patients was carried out at baseline and at 6 and 12 months on androgen deprivation (AD). Cognitive performances were evaluated with standardized measures of information processing, including working memory and attention, visual and verbal skills, and memory performances in 31 tests. Testosterone and estradiol changes during AD were measured with the DELFIA (PerkinElmer, Inc., Wellesley, MA) system. Associations between changes in cognitive performances and estradiol decline were studied. RESULTS: Cognitive performances, which were significantly associated with decline in estradiol, included visual memory of figures (r = -0.52; P = 0.022) and recognition speed of numbers, which were impaired, (r = -0.57; P = 0.030) at 6 months, and improvement in verbal fluency (r = -0.52; P = 0.019) at 12 months. Other cognitive domains appeared unaffected by estradiol decline. The character of change (impairment or improvement) depended on the magnitude of estradiol decline. CONCLUSIONS: The cognitive domains of verbal fluency, visual recognition, and visual memory were associated with decline in estradiol during androgen deprivation. The results suggest selective associations among testosterone decline, estradiol, and cognitive performance. Documentation of these associations has implications for informed patient support in hormonally treated prostate carcinoma.

APOE-epsilon4 predicts dementia but not other psychiatric disorders after traumatic brain injury.

The authors studied the association between APOE-epsilon4 genotype and axis I and II psychiatric disorders an average of 30 years after traumatic brain injury. Sixty patients were dichotomized into subjects with and without APOE-epsilon4 allele. Dementia and subclinical dementia were significantly more common with the presence of APOE-epsilon4. The occurrence of other psychiatric disorders did not differ between patients with and without APOE-epsilon4 allele.

Androgen deprivation and cognition in prostate cancer.

Androgen deprivation (AD) is commonly used in neoadjuvant and adjuvant setting with prostate cancer (PC) radiotherapy. This prospective study assessed whether cognitive functioning is impaired during 12 months of AD therapy. Longitudinal testing of 25 patients treated with AD and curative radiotherapy was undertaken at baseline, and at 6 and 12 months. CogniSpeed software was used for measuring attentional performances. Other cognitive performances were evaluated using verbal, visuomotor and memory tests. The Beck depression inventory was employed to evaluate depressive mood and EORTC QLQ-C30 for quality of life (QoL). During longitudinal testing of the AD group, no impairment in cognitive performances was found. Instead, improvement was observed in object recall (immediate, P=0.035; delayed, P<0.001), and in semantic memory (P=0.037). In QoL, impairment in physical function was observed. Androgen deprivation of 12 months appears to be associated with preserved cognitive functioning, although physical impairment occurs. These results have implications for counseling and psychosocial support of patients in the context of treatment options in PC.

Visual object recognition in early Alzheimer's disease: deficits in semantic processing.

OBJECTIVES: The purpose of the present study was to divide visual object recognition into different stages and to reveal which of these stages are impaired in early Alzheimer's disease (AD). METHODS: Performance in object detection, familiarity detection, semantic name and word categorization, and identification with naming were studied by using two-choice reaction-time tasks. Ten patients with newly diagnosed AD and 14 healthy subjects were studied. RESULTS: Patients with early AD had impairments in several stages of the object recognition process. After controlling for the basic visuomotor slowness, they were as fast and as accurate as the controls in object detection, but had difficulties in all stages that required semantic processing. CONCLUSIONS: Semantic memory impairments contribute to the deficits in visual object recognition in early AD. Thus, the semantic memory deficit may be manifested in several ways in the difficulties that AD patients experience in everyday life.

Cognitive functioning in severe somatization--a pilot study.

OBJECTIVE: Somatizing patients often report cognitive complaints but neuropsychological research on somatization is scarce. We investigated somatizing patients for functioning in different cognitive domains. METHOD: Ten female patients with somatization disorder or undifferentiated somatoform disorder and 10 non-somatizing controls participated in neuropsychological examinations. RESULTS: The patients performed at a lower level than the controls in tests involving semantic memory, verbal episodic memory and visuo-spatial tasks, and were slower in attentional tasks. CONCLUSION: Somatization patients may suffer from substantial problems in cognitive performance.

Cognitive impairment and the 10-year survival probability of a normal 62-year-old population.

The predictive value of cognitive impairment together with demographic and health factors on long-term survival was evaluated. The population sample comprised 389 subjects, all 62 years old. Cognitive performances were measured using verbal, visuomotor and memory tests. Cognitive impairment was determined by comparing performances with norms derived from healthy controls. Ten years after testing, the probability of survival was 89% for the cognitively preserved subjects, 80% for those with mild impairment, and 71% for those with moderate impairment (p = 0.009). Relative risk (RR) for shortened survival was 1.7 (95% CI 0.9-3.2) for the mildly, and 2.6 (95% CI 1.4-4.8) for the moderately impaired. Perceived health problems were, as expected, related to reduced survival (p < 0.001, RR 3.6, 95% CI 2.1-6.0), and there was an association between cognitive impairment and impaired perceived health (p = 0.040). Multivariate analyses with Cox's regression models showed that cognitive impairment, in particular, impaired episodic memory had an association with survival, in addition to the expected effects. Thus, memory impairment may reflect very early signs of underlying disease, and so the findings provide predictive validity for the cognitive methods used.

Positron emission tomography shows that impaired frontal lobe functioning in Parkinson's disease is related to dopaminergic hypofunction in the caudate nucleus.

We examined the relation between the dopaminergic function and the cognitive performance of patients with Parkinson's disease (PD). The subject sample consisted of ten patients in the early course of PD and with no previous antiparkinsonian medication. The dopaminergic function of the caudate nucleus and the putamen was studied with [(18)F]fluorodopa positron emission tomography, and the cognitive performance with a comprehensive battery of neuropsychological tests including tests sensitive to frontal lobe function. The decreased [(18)F]fluorodopa uptake in the right caudate nucleus was found to be related to slow processing time, measured as the difference between the incongruent and the congruent subtests of the Stroop Test (r=-0.85, P=0.002), a similar trend was seen in the left caudate (r=-0.60, P=0.07). Similar correlation was not detected in the putamen. The present findings provide evidence that the decreased dopaminergic function in the right caudate nucleus is related to the impaired performance in tests sensitive to frontal lobe function in patients at an early stage of PD and with no antiparkinsonian medication.

Short-term effects of radiotherapy on attention and memory performances in patients with brain tumors.

BACKGROUND: The objective of the current study was to evaluate the short-term effects of radiotherapy on attention and memory performance in patients with brain tumors. METHODS: Thirteen patients underwent a neuropsychologic examination on three occasions: at baseline before radiotherapy, which lasted for 6 weeks; within 2 weeks after the completion of radiotherapy; and 3 months after the completion of radiotherapy. Thirty healthy individuals were studied at baseline as a control group. Verbal, visuomotor, and memory tests were administered. Attentional performances were examined using CogniSpeed reaction time software. RESULTS: At baseline, the patients scored significantly lower than the controls in tests of semantic memory (Similarities; P = 0.002), visuoconstructive skill (Block Design; P = 0.028), and visual and verbal memory (recall of 20 objects: immediate, P = 0.017; delayed, P = 0.002; recall of 30 paired word associates: immediate, P = 0.002; delayed, P = 0.005). The patients performed significantly more poorly than the control group on the Two-Choice Reaction Time test (P = 0.047), the Subtraction test (P = 0.042), and the Vigilance test (P = 0.023). After radiotherapy, the performance of the patients did not worsen on any measure, whereas their conscious cognitive processing was improved (P = 0.002). CONCLUSIONS: Treatment with radiotherapy did not cause negative short-term effects on attentional and memory functions in patients with brain tumors who received a radiation dose of 54.5 grays. The cognitive deficits found in these patients were evident at baseline before radiotherapy. Thus, it seems likely that the deficits were associated with the tumor itself and/or the surgical procedures.

Impairment of semantic knowledge in Parkinson disease.

BACKGROUND: Parkinson disease (PD) is commonly characterized by cognitive deterioration, but it is still unclear whether PD is associated with semantic impairments. OBJECTIVE: To evaluate semantic knowledge of concepts in patients with idiopathic PD, addressing concrete and abstract concepts, conceptual attributes, and conceptual relations. METHODS: Twelve patients with preserved cognitive status, 12 patients with mildly deteriorated cognitive status, and 12 control subjects were studied. The cognitive status of patients and controls was determined using detailed cognitive testing. Patients were participants in a university-based movement disorder program, and their PD diagnoses were clinically confirmed during long-term follow-up. The 2 patient groups were similar in age, level of education, disease duration, and parkinsonian disability. Patients were required to produce verbal descriptions of concrete and abstract concepts, to give ratings of the importance of concept attributes, and to assess and construct conceptual hierarchies. The description tasks included guiding questions, which were used if the spontaneous productions of the patients lacked any essentials expected in the answers. RESULTS: Patients with mild cognitive deterioration performed less well than the other groups in defining concrete and abstract concepts (P<.001 for both). External guidance did not help them markedly improve their performance. They also had difficulties in tasks calling for knowledge of the importance of given attributes to the concepts and in tasks demanding evaluation of hierarchical semantic relations between concepts (P<.001 for both). CONCLUSION: Semantic disruption is implied in idiopathic PD in association with incipient cognitive impairment.

Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18F]fluorodopa positron emission tomographic study.

OBJECTIVE: To investigate the role of the brain dopaminergic system in cognitive impairment in patients with Parkinson disease (PD). DESIGN: We studied 28 patients with PD and 16 age-matched healthy control subjects using [18F] fluorodopa (fluorodopa F 18) positron emission tomography. Patients with PD showed a variable degree of cognitive impairment, which was assessed using the Mini-Mental State Examination and detailed neuropsychologic assessment, including tests sensitive for frontal lobe function. RESULTS: [18F] Fluorodopa uptake was reduced in the putamen (to 36% of the control mean; P<.001), the caudate nucleus (to 61% of the control mean; P<.001), and the frontal cortex (to 45% of the control mean; P<.001) in patients with PD compared with controls. There was no significant association between the degree of overall cognitive impairment of patients and [18F] fluorodopa uptake values. The influx constant (Ki(occ)) in the caudate nucleus had a negative association with performance in the attention-demanding Stroop interference task, especially with the interference time. The Ki(occ) in the frontal cortex had a positive correlation with performance in the digit span (backwards), verbal fluency, and verbal immediate recall tests. Thus, the better the patient performed in tasks demanding immediate and working memory and executive strategies, the better the [18F] fluorodopa uptake in the frontal cortex. In the putamen, no significant correlation was seen between the Ki(occ) value and any of the cognitive tests. The severity of the motor symptoms of PD and [18F]fluorodopa uptake showed a negative correlation in the putamen (r = -0.38; P = .04), and in the caudate nucleus a similar trend was seen (r = -0.36; P = .06). CONCLUSIONS: Reduced [18F]fluorodopa uptake in PD in the caudate nucleus (and frontal cortex) is related to impairment in neuropsychologic tests measuring verbal fluency, working memory, and attentional functioning reflecting frontal lobe function. This indicates that dysfunction of the dopamine system has an impact on the cognitive impairment of patients with PD. However, our results do not exclude the possibility of more generalized cognitive impairment in PD, the pathophysiology of which is probably different and more generalized.

Does P3 reflect attentional or memory performances, or cognition more generally?

The study evaluated the off-line relationship of attention, memory and other cognitive performances with the auditory event-related potentials P3 (P300) and N2. The sample comprised 200 middle-aged construction workers. Verbal, visuomotor and memory tests were administered. Attentional domains were examined using CogniSpeed software. Slowed reaction times in the test of sustained attention (vigilance) were associated with delayed P3 latency (p < 0.001) and decreased P3 amplitude (p = 0.005), as well as with delayed N2 latency (p < 0.001). Visuomotor slowing in Digit Symbol was also related to delayed P3 latency (p = 0.030) and decreased P3 amplitude (p = 0.014). In contrast, mild cognitive impairment, short- and long-term memory, and concentrating or sharing attention with high working memory demands were not related to P3. The results suggest that P3 is linked to attentional performance with low working memory demands rather than to effortful working memory updating, retrieval from memory stores, or mild cognitive impairment.

Sematic memory deficit in multiple sclerosis; impaired understanding of conceptual meanings.

The aim of the present study was to determine whether a cognitive decline, related to multiple sclerosis (MS), also involves deficits in semantic memory. Semantic memory function was evaluated by studying the conscious understanding of conceptual meanings. A group of MS patients with cognitive decline was presented with four tasks concerning concepts, their attributes and relationships to other concepts. The tasks were designed to measure spontaneous, cued and recognition performance separately. The patients had difficulties in understanding conceptual meanings. Easing the retrieval demands of the tasks did not help them to improve their performance which was poorer than the control group's on every task used. The results indicate a retrieval deficit combined with an underlying storage deficit in the semantic memory of MS patients with cognitive decline.

Serum estrogen level, attention, memory and other cognitive functions in middle-aged women.

OBJECTIVE: To evaluate the relationship between serum estradiol level and cognitive processing efficiency and memory. METHODS: Sixty-three healthy women aged 45-65 years were recruited through a newspaper announcement. The subjects were divided into two subgroups (low-estrogen group, n = 37 and high-estrogen group, n = 26) according to their serum follicle stimulating hormone (FSH) and estradiol levels. In the high-estrogen group, estrogen was either endogenous or supplied by estrogen replacement therapy. Automatic and controlled cognitive processing and attentional resources were measured using CogniSpeed software, together with conventional tests of cognitive performance: similarities, digit span, digit symbol, block design, object naming and recall, paired word associates (PWA) recall, Benton visual retention and paced auditory serial addition test (PASAT). The Beck depression inventory was also assessed. RESULTS: Cognitive reaction speeds were similar in both groups. Women with low estrogen levels made more errors in the vigilance test (sustained attention, p = 0.040). There were no differences in short-term or long-term memory, or verbal, visual or working memory between the study groups. Older women were slower in the ten-choice reaction time (10-CRT) test (r = 0.25, p = 0.047) and made more errors in the test of suppressing attention (Stroop incongruence test; r = 0.34, p = 0.007) and in the sustaining attention test (vigilance test; r = 0.47, p < 0.001). Depression scores did not correlate with cognitive variables. CONCLUSIONS: Cognitive performance was well preserved in healthy middle-aged women. Cognitive speed, accuracy, attentional resources and memory did not show impairment with decline of serum estrogen level in this age group.

Semantic processing of spoken words in Alzheimer's disease: an electrophysiological study.

Patients suffering from Alzheimer's disease (AD) have severe difficulties in tasks requiring the use of semantic knowledge. The semantic deficits associated with AD have been extensively studied by using behavioral methods. Many of these studies indicate that AD patients have a general deficit in voluntary access to semantic representations but that the structure of the representations themselves might be preserved. However, several studies also provide evidence that to some extent semantic representations in AD may in fact be degraded. Recently, a few studies have utilized event-related brain potentials (ERPs) that are sensitive to semantic factors in order to investigate the electrophysiological correlates of the semantic impairment in AD. Interest has focused on the N400 component, which is known to reflect the on-line semantic processing of linguistic and pictorial stimuli. The results from studies of N400 changes in AD remain somewhat controversial: Some studies report normal or enlarged N400 components in AD, whereas others report diminished ones. One issue not reported in previous studies is whether word-elicited ERPs other than N400 remain normal in AD. In the present study our aim was to find out whether the ERP waveforms N1, P2, N400, and Late Positive Component (LPC) to semantically congruous and incongruous spoken words are abnormal in AD and whether such abnormalities specifically reflect deficiencies in semantic activation in AD. Auditory ERPs from 20 scalp sites to semantically congruous and incongruous final words in spoken sentences were recorded from 17 healthy elderly adults and 9 AD patients. The early ERP waveforms N1 and P2 were relatively normal for the AD patients, but the N400 and LPC effects (amplitude difference between congruous and incongruous conditions) were significantly reduced. We interpret the present results as showing that semantic-conceptual activation and other high-level integration processes are defective in AD. However, a word congruity effect earlier than N400 (phonological mismatch negativity), reflecting lexical selection processes, is at least to some extent preserved in AD.

Automatic influences of memory in Alzheimer's disease.

Automatic and controlled influences of memory were examined in 12 patients with early Alzheimer's disease (AD) and 12 control subjects. The subjects studied a list of words and then received three-letter word stems in three different retrieval tasks. In an indirect memory task (word-stem completion priming), they were asked to produce the first word that came to mind in response to each stem. In an inclusion task, they were required to produce a studied word in response to each stem, and in an exclusion task they were asked to produce a new, unstudied word for each stem. The performance of the subjects with AD was equal in the inclusion and exclusion conditions, showing no evidence of controlled recollection for the studied words, while their automatic memory as well as priming were preserved. The results provide neuropsychological support for the distinction between controlled and automatic memory processes.

The effect of short-term estrogen replacement therapy on cognition: a randomized, double-blind, cross-over trial in postmenopausal women.

OBJECTIVE: To evaluate the effect of estrogen replacement therapy on cognitive functioning. METHODS: The study consisted of two 3-month treatment periods, one with estrogen and one with the placebo, in random order, separated by a 1-month wash-out period. The study group comprised 70 healthy postmenopausal women, aged 47-65 years, with previous hysterectomy. Sixty-two women completed the study. Cognitive speed and accuracy, attention, and memory were evaluated. Serum estradiol (E2) and FSH levels were controlled at the end of the estrogen, placebo, and wash-out periods. RESULTS: Most of the cognitive tests correlated with age: older women were slower and made more errors than younger women. Estrogen replacement therapy was not superior to the placebo in any test of cognitive performance. In two out of ten visual detection tasks, recognition thresholds were longer with estrogen than with the placebo (P < .001 and P = .004). On the most demanding test of working memory, the reaction times (P = .045) and error rates (P = .043) differed between treatments, yet this finding proved to be an effect of learning rather than treatment. There was no correlation between cognitive performance and serum E2 levels. CONCLUSION: Cognitive performance decreased with age. Short-term estrogen replacement therapy did not provide any advantage over the placebo in terms of improving the performance.

Tone duration discrimination in Parkinson's disease.

Patients with Parkinson's disease (PD) and healthy controls took a computerized test of tone duration discrimination (TDD) using pairs of tones of 0.4-1.6 sec duration, presented at intervals of 0.5-4 sec. In PD patients as well as controls, TDD was impaired by even slight degrees of cognitive deterioration. PD yielded impaired TDD in females, but not in males. This suggests that the dopamine-powered biological clock, which is vulnerable to PD, is more important for the processing of durations in the 1-sec range in women than in men.