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PubMed2003

Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.

CONTEXT: Observational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. The Women's Health Initiative Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative (WHI) hormone therapy trials. On July 8, 2002, the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women. OBJECTIVE: To determine whether estrogen plus progestin therapy protects global cognitive function in older postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled clinical trial, WHIMS is an ancillary study of geographically diverse, community-dwelling women aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen plus progestin trial that started in June 1995. Of 4894 eligible postmenopausal women aged 65 years or older and free of probable dementia at baseline, 4532 (92.6%) were enrolled in the estrogen plus progestin component of WHIMS. A total of 4381 participants (96.7%) provided at least 1 valid cognitive function score between June 1995 and July 8, 2002. INTERVENTIONS: Participants received either 1 daily tablet containing 0.625 mg of conjugated equine estrogen with 2.5 mg of medroxyprogesterone acetate (n = 2145) or matching placebo (n = 2236). MAIN OUTCOME MEASURE: Global cognitive function measured annually with the Modified Mini-Mental State Examination. RESULTS: The Modified Mini-Mental State Examination mean total scores in both groups increased slightly over time (mean follow-up of 4.2 years). Women in the estrogen plus progestin group had smaller average increases in total scores compared with women receiving placebo (P =.03), but these differences were not clinically important. Removing women by censoring them after adjudicated dementia, mild cognitive impairment, or stroke, and nonadherence to study protocol, did not alter the findings. Prior hormone therapy use and duration of prior use did not affect the interpretation of the results, nor did timing of prior hormone therapy initiation with respect to the final menstrual period. More women in the estrogen plus progestin group had a substantial and clinically important decline (> or =2 SDs) in Modified Mini-Mental State Examination total score (6.7%) compared with the placebo group (4.8%) (P =.008). CONCLUSIONS: Among postmenopausal women aged 65 years or older, estrogen plus progestin did not improve cognitive function when compared with placebo. While most women receiving estrogen plus progestin did not experience clinically relevant adverse effects on cognition compared with placebo, a small increased risk of clinically meaningful cognitive decline occurred in the estrogen plus progestin group.

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PubMed2001

Cognitive function in postmenopausal women treated with raloxifene.

BACKGROUND: In postmenopausal women, estrogen may have a beneficial effect on cognition or reduce the risk of decline in cognitive function. Whether raloxifene, a selective estrogen-receptor modulator, might have similar actions is not known. METHODS: As part of the Multiple Outcomes of Raloxifene Evaluation trial, we studied 7478 postmenopausal women with osteoporosis (mean age, 66 years), who were enrolled at 178 sites in 25 countries. The women were randomly assigned to receive raloxifene (60 mg or 120 mg) or placebo daily for three years. We compared the mean scores of the groups on six tests of cognitive function, which were administered at base line and at six months and one, two, and three years. Women were classified as having a decline in cognitive function if the change in their scores at three years was in the worst 10 percent. RESULTS: The mean cognitive scores in the three groups of women were similar at base line. The scores improved slightly in all three groups during the three-year study period, with no significant differences among the groups. The risk of decline in the cognitive function, as measured by four of the six tests, did not differ significantly between the two raloxifene groups combined and the placebo group, but there was a trend toward less decline in the combined raloxifene group on the two tests of verbal memory (relative risk, 0.77) and attention, (relative risk, 0.87). Newly reported or worsening hot flashes did not negatively influence test scores or the effect of treatment on test performance. CONCLUSIONS: Raloxifene treatment for three years does not affect overall cognitive scores in postmenopausal women with osteoporosis.

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PubMed2001

The relationship of APOE genotype to cognitive functioning in older African-American and Caucasian community residents.

OBJECTIVES: To determine whether cognitive decline associated with the apolipoprotein E (APOE) epsilon4 allele is different in older African Americans than it is in Caucasians. DESIGN: Performance on a brief screen of cognitive functioning was examined at baseline (N = 1,891) and 4 years later (N = 1,389) to determine the extent to which the presence of APOE epsilon4 affected level of and change in performance, and whether this differed as a function of race, age, initial score, and change in score. SETTING: Five adjacent counties in the Piedmont area of North Carolina. PARTICIPANTS: In 1986, a stratified random household sample of community residents age 65 and older (n = 4,162; 54% African-American, 45% Caucasian, 1% other race) formed the Duke Established Populations for Epidemiologic Studies of the Elderly. Of those available at the sixth annual wave, 76% were genotyped, with 1,891 providing baseline data on this wave, and the available survivors (n = 1,389) providing longitudinal data 4 years later. MEASUREMENTS: The Short Portable Mental Status Questionnaire (SPMSQ), a brief screen of cognitive functioning, was administered to all subjects on both occasions. We examined score at baseline and cognitive decline (i.e., increase of 2+ errors) at follow-up. Control measures included demographic characteristics, health behaviors, health and functional status, and medication use. APOE status was coded as epsilon4 present versus absent. RESULTS: APOE epsilon4 was significantly and uniquely related to lower score at baseline and significantly increased the odds of cognitive decline by 59%. There was no statistically significant interaction between APOE epsilon4 and age, race, initial SPMSQ score, or SPMSQ score at follow-up. CONCLUSION: APOE epsilon4 is modestly, if significantly, related to poorer cognitive functioning and to decline in cognitive functioning. No differences were found by age or race in this community representative sample.

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PubMedDate not supplied

Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study.

OBJECTIVE: This study examines the effects of a dietary supplement of isoflavones on cognitive function in postmenopausal women. DESIGN: Participants for this 6-month, double-blind, randomized, placebo-controlled clinical trial were women who were in good health, were postmenopausal at least 2 years, and were not using estrogen replacement therapy. Between July 24, 2000, and October 31, 2000, 56 women aged 55 to 74 years were randomized; 2 in the placebo group and 1 in the active treatment group did not complete the 6-month evaluation, and none withdrew because of adverse effects. Women randomized to active treatment (n = 27) took two pills per day, each containing 55 mg of soy-extracted isoflavones (110 mg total isoflavones per day; Healthy Woman: Soy Menopause Supplement, Personal Products Company, McNeil-PPC Inc., Skillman, NJ, USA). Women assigned to placebo (n = 26) took two identical-appearing pills per day containing inert ingredients. Cognitive function tests administered at baseline and follow-up included the following: Trails A and B, category fluency, and logical memory and recall (a paragraph recall test assessing immediate and delayed verbal memory). RESULTS: At baseline, all women were cognitively intact; there were no significant differences by treatment assignment in age, education, depressed mood, or cognitive function (all P values > 0.10). Compliance was 98% and 97%, respectively, in the placebo and treatment groups; all women took at least 85% of their pills. The women in the treatment group did consistently better, both as compared with their own baseline scores and as compared with the placebo group responses at 6 months. Comparisons of percentage change in cognitive function between baseline and follow-up showed greater improvement in category fluency for women on active treatment as compared with the case of those on placebo (P = 0.02) and showed (nonsignificantly) greater improvement on the two other tests of verbal memory and Trails B. CONCLUSION: These results suggest that isoflavone supplementation has a favorable effect on cognitive function, particularly verbal memory, in postmenopausal women.

Age Factors↗

PubMed2002

Motor and cognitive functions of the ventral premotor cortex.

Recent data show that the ventral premotor cortex in both humans and monkeys has motor and cognitive functions. The cognitive functions include space perception, action understanding and imitation. The data also show a clear functional homology between monkey area F5 and human area 44. Preliminary evidence suggests that the ventral part of the lateral premotor cortex in humans may correspond to monkey area F4. A tentative map of the human lateral premotor areas founded on the reviewed evidence is presented.

Anatomy, Comparative↗

PubMed1990

[Effects of kidney transplantation on cognitive functioning of children].

The purpose of the study was the assessment of cognitive functioning in 20 children (age 4-14 years) with end stage renal disease (ESRD) before and after kidney transplantations by means of an intelligence-test (WISC-R or WPPSI). Research questions were: I. do the test scores of children with ESRD deviate significantly from those of the norm-group before transplantation; 2. do the test scores of children with ESRD increase significantly from pre- to post-transplantation; 3. do the test scores of children with ESRD after transplantation deviate significantly from those of the norm-group. The results show that children with ESRD before transplantation perform significantly more poorly on the verbal part of the WISC-R. After transplantation they show a significant increase on cognitive functioning, mainly in the verbal part of the test. However, kidney transplantation does not cause a complete recovery of cognitive functioning; after transplantation children with ESRD still showed lower scores on several tasks (e.g. tasks concerning concentration).

Adolescent↗

PubMed2003

How "soft" are soft neurological signs? The relationship of subjective neuropsychiatric complaints to cognitive function in systemic lupus erythematosus.

OBJECTIVE: As part of a longitudinal study of cognitive function in systemic lupus erythematosus (SLE), we documented the range and frequency of subjective neurologic and/or psychiatric (NP) complaints in Never-NP-SLE patients, and related these to cognitive function, using the latter as a primary indicator of nervous system involvement. METHODS: Thirty patients with SLE who did not have major neurologic and psychiatric involvement underwent baseline and followup neuropsychological testing roughly 5 years apart. Within 0-13 months prior to retesting, each patient completed a 42 item questionnaire recording NP symptoms. RESULTS: The group as a whole endorsed 26% of symptoms. Fourteen patients labelled high endorsers (> 35% of items) endorsed, on average, 42% of symptoms. There was a significant association between higher item endorsement and lower cognitive function (r = -0.46, p < 0.02) and significantly poorer cognitive performance in the high compared to low endorser groups (t = -3.07, p < 0.005). In addition, a subset of 8 items was endorsed at least twice as often by SLE patients as by patients with rheumatoid arthritis (n = 12) or healthy controls (n = 10). CONCLUSION: These results suggest that "minor" NP symptoms and, in particular, a small subset of subjective complaints may be sufficient to raise suspicion of subclinical nervous system involvement in the absence of clinically evident NP-SLE.

Adult↗

PubMedDate not supplied

[Randomized study of the therapeutic effect of electroconvulsive therapy, uni- or bilateral, on certain cognitive functions in depression, with electroencephalography monitoring. Preliminary results].

Cognitive functions are known to be impaired by ECT. The aim of this study is to differentiate the effects of electroconvulsive therapy on some cognitive functions according to the mode of application of the electrodes. The brief-pulse Thymatron DG apparatus allows to control four electrical parameters and to assess electroencephalographic data. The preliminary sample comprises nine patients suffering of major depressive disorder; they are randomly assigned to the mode of application of the electrodes, bilateral or unilateral to the non dominant hemisphere. Clinical evolution is surveyed by the Montgomery and Asbert Depression Rating Scale. Non mnesic functions are assessed: arousal by CFF (Critical Fusion Frequency), and attentional, motor and decisional abilities by CRT (Choice Reaction Test). Different mnesic function are studied by selective reminding test, cued recall test, block tapping test and picture fragmentation test. After treatment by ECT, verbal mnesic functions assessed by selective reminding test are impaired with the bilateral application. Whereas they are not modified with the unilateral application. The variance of CFF regains a physiological value in the bilateral group, but remains altered in the unilateral.

Adult↗

PubMed1996

Comparison of cognitive function in human and non-human primates.

Fundamental to any comparative study of cognitive function in monkey and man is the demonstration of behavioral homology, viz. that the same cognitive function is being studied in both species. This paper considers a variety of psychological issues that need to be taken into account when attempting to demonstrate behavioural homology. Examples are taken from studies of attentional set-shifting, discrimination reversal learning, spatial working memory and episodic memory. Whilst highlighting the pitfalls to be avoided in the future, these examples also demonstrate the enormous contribution that such studies have had to our understanding of the functions of the temporal lobes and frontal lobes. Moreover, they also illustrate the enormous potential in defining the cognitive functions and dysfunctions of the prefronto-striatal circuitry which underlie so many neurodegenerative and neuropsychiatric disorders.

Animals↗

PubMed2001

Type 2 diabetes and cognitive function in community-dwelling elderly women.

OBJECTIVE: To examine the relationship of type 2 diabetes to cognitive function in community-dwelling women. RESEARCH DESIGN AND METHODS: From 1995 to 1999, we administered four tests of cognitive function (Telephone Interview of Cognitive Status [TICS], immediate and delayed recall of the East Boston Memory Test, and verbal fluency) by telephone to 2,374 participants (70-78 years of age) of the Nurses' Health Study. Information on diabetes was collected biennially beginning in 1976; 82 women reported type 2 diabetes before their cognitive testing. We used linear and logistic regression models to calculate multivariate-adjusted mean differences in scores and relative risks of a low score (bottom 10% of the distribution) for diabetic women compared with nondiabetic women. RESULTS: After multivariate adjustment, women with type 2 diabetes scored lower on all our cognitive tests than women without diabetes. On the general test of cognition (TICS), the mean difference in score between women with and without diabetes was -0.60 (95% CI -1.18 to -0.03, P = 0.04) and the relative risk of a low TICS score was 1.98 (95% CI 1.06 to 3.69). On a global score combining results of the four tests, the mean for diabetic women was lower than that among women without diabetes (adjusted difference in score -0.73, 95% CI -1.42 to -0.04, P = 0.04), and the relative risk of a low global score was 2.16 (95% CI 1.10 to 4.21). Relative to women without diabetes, longer duration of diabetes was associated with lower scores. Few diabetic women were pharmacologically treated (n = 31), but those taking medication had scores similar to those of women without diabetes. CONCLUSIONS: In these women, diabetes was related to lower scores on several aspects of cognitive function. Longer duration of diabetes may be associated with poorer scores, but hypoglycemic therapy may ameliorate scores.

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PubMed1991

Cognitive function after spinal or general anesthesia for transurethral prostatectomy in elderly men.

Cognitive functions in 53 elderly men who underwent a transurethral prostatectomy were assessed pre-operatively and 4 days and 3 months post-operatively. Thirteen patients had a preference for one particular type of anesthesia, and the remaining 40 were randomly allocated to receive either spinal or general anesthesia. Cognitive function was not different between the groups receiving different types of anesthesia at either time point and did not decrease post-operatively. No pre- or perioperative variable could distinguish the subgroup of patients who had a post-operative decrease of 2 points or more on the Mini-Mental State Examination. No difference in post-operative performance was found in the patient groups with pre-operative Mini-Mental State Examination scores above or under their age-specific norm. It is concluded that neither hospitalization nor the two forms of anesthesia investigated cause a decrease in cognitive function in elderly men.

Aged↗

PubMed1995

Cognitive function, thyroid status and postpartum depression.

Impairment of cognitive function can occur with thyroid disorder and also with depression. Since depression occurs in conjunction with postpartum autoimmune thyroiditis, the question arises as to whether any impairment of cognitive function in postpartum women is related to change in thyroid status or to depressed mood. A total of 242 women (110 thyroid antibody-positive and 132 antibody-negative) were assessed at 8, 12, 20 and 28 weeks postpartum in the outpatients of a district general hospital. Thyroid antibody levels (antimicrosomal and antithyroglobulin) were monitored at monthly intervals, together with plasma T3, T4 and thyroid-stimulating hormone. The main outcome measures were Research Diagnostic Criteria for depression, the 17-item Hamilton Depression Rating Scale and the Edinburgh Postnatal Depression Scale, together with reaction time and digit span. Subjects with postnatal depression showed detectable cognitive impairment independent of thyroid antibody status and actual thyroid dysfunction.

Antibodies↗

PubMed1993

Cognitive function during moderate hypoxaemia.

The effect of hypoxaemia (mean SpO2 78%) on cognitive function was measured in two groups of twelve normal subjects. A series of psychometric tests was administered to each subject in the same sequence and consisted of the Reitan trail-making test, a digit symbol substitution test, a visuospatial orientation test and the simple unprepared reaction-time test. Psychomotor performance was assessed in a double-blind manner while the subjects were breathing first air and then either air or a hypoxic mixture. While there was improvement in time for the trail-making test during a repeat study breathing air, there was significant deterioration of time to completion of the test in conditions of hypoxia. A significant learning effect in the orientation test was seen in the control group but this did not occur in hypoxic subjects. Hypoxaemia was shown to cause a significant impairment of simple unprepared reaction time compared with controls. All the changes in cognitive function were small and there were no subjective differences in the air or hypoxic groups. The usefulness of the Reitan trail-making and the simple unprepared reaction-time test in the assessment of psychomotor performance deficit under conditions of hypoxaemia has been demonstrated by this study in normal subjects. It was concluded that a mean oxygen saturation of 78% caused only minor changes in cognitive function in normal subjects.

Adult↗

PubMed2002

Cognitive function in patients with cerebral arteriovenous malformations after radiosurgery: prospective long-term follow-up.

PURPOSE: To evaluate the long-term cognitive function of patients with cerebral arteriovenous malformations (AVMs) after radiosurgery. METHODS AND MATERIALS: The data of 95 AVM patients were prospectively assessed up to 3 years after radiosurgery. Of these patients, 39 had a follow-up of at least 2 years. Radiosurgery was performed using a modified linear accelerator (minimal doses to the target volume 15-22 Gy, median dose 20). The neuropsychological evaluation included testing of intelligence, attention, and memory. The effect of a preexisting intracranial hemorrhage, as well as AVM occlusion, on cognitive functions was analyzed after 1 and 2 years. RESULTS: No cognitive declines were observed during follow-up. Instead significant improvements occurred in intelligence (1 year, +6.1 IQ points; 2 years, +5.1 IQ points), memory (1 year, +18.3 percentile score; 2 years, +12.2 percentile score), and attention (1 year, +19 percentile score; 2 years, +18 percentile score). Patients without previous intracranial hemorrhage improved more than patients with intracranial hemorrhage, although this difference was not statistically significant. The role of AVM occlusion on cognitive function is not clear at present. CONCLUSION: Radiosurgery does not induce measurable deterioration of cognitive function in patients with cerebral AVMs.

Adult↗

PubMed1983

Association between nutritional status and cognitive functioning in a healthy elderly population.

We evaluated the association between nutritional status and cognitive functioning in 260 noninstitutionalized men and women older than 60 years who had no known physical illnesses and were receiving no medications. Nutritional status was evaluated by three-day food records and also by biochemical determination of blood levels of specific nutrients. Cognitive status was evaluated by the Halstead-Reitan Categories Test (a nonverbal test of abstract thinking ability) and by the Wechsler Memory Test. Subjects with low blood levels of vitamins C or B12 scored worse on both tests. Subjects with low levels of riboflavin or folic acid scored worse on the categories test. These differences remained significant after controlling for age, gender, level of income, and amount of education. "Subclinical" malnutrition may play a small role in the depression of cognitive function detectable in some elderly individuals, or depressed cognitive function may result in reduced nutrient intake.

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PubMed1997

Functional outcome following thalamic haemorrhage: relationship between motor and cognitive functions and ADL.

Twenty-two patients with thalamic haemorrhage were examined to investigate the relationship between motor and cognitive function, and activities of daily living (ADL). Patients with unilateral spatial neglect had lower ADL scores on admission than patients without unilateral spatial neglect (Mean: 17.0 and 24.6, respectively; F = 4.38, df = 1, p < 0.05). Unilateral spatial neglect related to feeding, bowel control and transfer in Barthel index on admission. Patients with aphasia on admission had lower ADL at discharge than patients without aphasia on admission (Mean: 57.0 and 84.7, respectively; F = 7.70, df = 1, p < 0.05). Aphasia related to the bathing, toilet, stair climbing, dressing, and ambulation in Barthel index on discharge. There was a significant difference between the severity of paresis in upper and lower limb on admission and ADL at discharge. The two-way repeated measures ANOVA showed a significant difference between severity of paresis in lower limb and ADL improvement. It can be suggested that the most important predictor of outcome was paresis in lower limb, and not aphasia or unilateral spatial neglect.

Activities of Daily Living↗

PubMed1997

[Isolated systolic hypertension and cognitive function in the aged. Experience of the Syst-Eur study].

OBJECTIVE: To determinate cognitive status and its correlates in older patients with isolated systolic hypertension. METHODS: Syst-Eur is a double-blind placebo-controlled outcome trial conducted in European patients over 60 years of age with isolated systolic hypertension. Moreover, a side-project--the Vascular Dementia Project--is designed to assess cognitive functions and to follow-up their evolution to determine the influence of antihypertensive therapy on vascular dementia incidence. Cognitive functions were evaluated at entry with the MiniMental State Examination (MMSE) in 2250 patients included in Syst-Eur. Cognitive impairment was defined with a MMSE score < or = 23 and led to further evaluation. Baseline blood pressure (BP) was based on the average of six sitting blood pressure readings at three run-in visits 1 month apart. Statistical analysis used Spearman correlation. RESULTS: The MMSE was analysed in 1374 women and 751 men whose mean age was 70 years (range: 60-100). The median level of education expressed as the age at which they stopped their education at school, was 15 years. Baseline blood pressure averaged 173 +/- 10/86 +/- 6 mmHg. Before randomisation in the trial, 899 (40%) patients had received antihypertensive therapy and 602 (27%) had experienced cardiovascular complications. The MMSE-scores ranged from 15 to 30 (median = 29). The maximal score of 30 was reached by 609 (30%) subjects. Among the 59 (3%) patients with a MMSE-score of 23 or less, 5 were considered to be demented according to the DSM IIIR criteria. The MMSE-scores decreased with advancing age in men (r = -0.16; p < 0.001) and women alike (r = -0.24; p < 0.001). In both men and women, they were positively correlated with the level of education (r = 0.30 and 0.32, respectively; p < 0.001). They were negatively correlated with systolic blood pressure (r = 0.10; p < 0.001) and slightly positively correlated with diastolic blood pressure (r = 0.05; p = 0.03). Previously treated patients or patients reporting cardiovascular complications at baseline had lower MMSE-scores than their non-treated counterparts or subjects without cardiovascular complications (median = 28 and 29, respectively, p < 0.003). CONCLUSION: In a European cohort of 2225 patients over 60 years of age with isolated systolic hypertension, the level of cognitive functions evaluated with the MMSE decreases with advancing age or lesser educational level. It also decreases with higher systolic blood pressure or lower diastolic blood pressure. The influence of antihypertensive therapy on cognitive status will be prospectively evaluated in Syst-Eur Vascular Dementia Project.

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PubMed2002

Hysterectomy, oophorectomy, and cognitive function in older women.

OBJECTIVES: It has been proposed that estrogen deficiency is a cause of memory loss in postmenopausal women. Bilateral oophorectomy leads to an abrupt decrease in gonadal hormone levels including testosterone. Hysterectomy with ovarian conservation may also lead to a decline in ovarian hormones. This study examines the effects of hysterectomy and oophorectomy on cognitive function in a large sample of older, postmenopausal women with and without current estrogen replacement therapy. DESIGN: Cross-sectional. SETTING: Community-based sample in Southern California. PARTICIPANTS: Subjects were 885 postmenopausal women aged 60 to 89 who were initially enrolled in the Rancho Bernardo Study between 1972 and 1974 and had a follow-up clinic visit in 1988-91. All were Caucasian, middle to upper-middle class, relatively well educated, and ambulatory. MEASUREMENTS: Participants completed 12 standardized tests of cognitive function in 1988-91. Hysterectomy and oophorectomy status were assessed and use of estrogen therapy was also ascertained and validated. RESULTS: Of the 885 women, whose mean age +/- standard deviation was 74.3 +/- 7.5, 225 reported having had a hysterectomy with conservation of one or both ovaries and 190 reported having a hysterectomy with bilateral oophorectomy. Current estrogen use was reported by 35.4%. Among women not using estrogen, there were no significant differences on mean cognitive function scores by hysterectomy and oophorectomy status. Among current estrogen users, after adjustment for age, education, age at menopause, and past estrogen use, those with a hysterectomy and bilateral oophorectomy performed significantly less well on serial sevens and Trails B. These differences, although statistically significant, were small and unlikely to be of clinical significance. No differences in cognitive function were observed between women who had a hysterectomy with ovarian conservation and intact women. CONCLUSIONS: The present study suggests that, overall, there are no long-term effects of hysterectomy and bilateral oophorectomy on cognitive function and does not support the thesis that estrogen deficiency is associated with poor cognitive function in postmenopausal women.

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