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Biomedical subjects

V W Henderson

Publications and source records attributed to V W Henderson.

At least 19 recordsLinked to original sources

Estrogen exposures and memory at midlife: a population-based study of women.

Estrogen loss after natural menopause is hypothesized to impair episodic memory. A total of 326 women aged 52 to 63 years participating in the Melbourne Women's Midlife Health Project completed a word list memory task. Estrogen exposures were inferred from menopausal status, time from final menstrual period, use of hormone therapy, serum estradiol concentration, and other indices. Memory did not vary significantly with most exposures. The authors conclude that episodic verbal memory assessed by word list learning is not substantially affected during the menopausal transition or in the years immediately after natural menopause.

Body Mass Index↗

Assessing working memory and language comprehension in Alzheimer's disease.

Studies of language impairments in patients with Alzheimer's disease have often assumed that impairments in linguistic working memory underlie comprehension deficits. Assessment of this hypothesis has been hindered both by vagueness of key terms such as "working memory" and by limitations of available working memory tasks, in that many such tasks either seem to have little relationship to language comprehension or are too confusing or difficult for Alzheimer's patients. Four experiments investigated the usefulness of digit ordering, a new task assessing linguistic working memory and/or language processing skill, in normal adults and patients with probable Alzheimer's disease. The digit ordering task was shown to be strongly correlated with the degree of dementia in Alzheimer's patients. The task correlated with measures of language processing on which patients and normal controls performed differently. The results are interpreted as indicating that linguistic representations, linguistic processing, and linguistic working memory are intertwined, such that a deficit of one (e.g., working memory) cannot be said to "cause" a deficit in the other. The implications of this approach are explored in terms of task demands in comprehension and memory measures, and interpretation of previous results in the literature.

Aged↗

Clock drawing: analysis in a retirement community.

OBJECTIVE: To test the hypothesis that performance on a clock-drawing test in a mailed survey to an older cohort is associated with known and potential risk and protective factors for Alzheimer's disease. DESIGN: The Leisure World Cohort Study is an ongoing study, begun in 1981, of nearly 14,000 older adults. In November 1992, the 8,406 living cohort members were mailed a follow-up questionnaire. SETTING: Leisure World Laguna Hills, a southern California retirement community. PARTICIPANTS: The study population is a predominantly white, well-educated, upper-middle-class community; approximately two-thirds are women. Data from 4,843 cohort members (mean age 80 years; range 52-101) were analyzed. MEASUREMENTS: The questionnaire included a clock-drawing task: a predrawn circle 3 1/4 inches (8.3 cm) in diameter was provided with instructions "In the circle below, draw in the numbers as on a clock face. Make no erasures." Clocks were scored on 7 items: all numbers 1-12 present without adding extra or omitting numbers, sequencing of numbers, position of numbers, orientation of numbers to circle, consistent number style (either Arabic or Roman), tilt of numbers, and superfluous marks. A total clock score was calculated by summing the number of correct individual items (0-7). We also classified individuals as cognitively impaired by a previously suggested method: individuals were affected if they did not have three numbers drawn in the upper left quadrant of the clock face. RESULTS: Ninety percent or more of the participants across all ages placed the numbers 1 to 12 on their clocks without omissions or additions; 35% completed the clock drawing without error. The mean total clock scores decreased with each successive 5-year age group in both men and women. Regression analysis indicated a significant effect for age (b = -0.15, P <.0001), education (b = 0.05, P =.0001), smoking (b = 0.13, P =.03), and female gender (b = -0.05, P =.05) and a marginally significant effect of nonrheumatoid arthritis (b = 0.05, P =.07) on total clock score. No other measured variable had a significant effect. Cognitively impaired individuals were more likely to be female and older. After adjusting for age and gender, they were also more likely to be hypertensive and to have taken blood pressure medication and less likely to be college graduates, have glaucoma or arthritis, and to have taken vitamin supplements. CONCLUSION: The clock-drawing task is an appealing measure of cognitive function for large epidemiological studies because it is a simple, self-administered test that is easily adapted to mail surveys and correlates with more-detailed and more-time-consuming cognitive screens. Although it is relatively free of influence by language, cultural, or ethnic factors, our study shows that even in a highly educated population, clock drawing is influenced by educational level and other known risk factors for Alzheimer's disease. Thus a clock-drawing task may help predict cognitive frailty and future disability in older people. Such determination can direct high-risk individuals to earlier diagnosis, potential therapies, and better management.

Age Distribution↗

Associations between circulating sex steroid hormones and cognition in normal elderly women.

OBJECTIVE: To provide exploratory analyses of associations between levels of several sex hormones and cognitive performance in elderly women. BACKGROUND: Sex steroid hormones are implicated in the cognitive processes of the adult brain. Comparing cognitive performance across or between conditions associated with different hormone levels, such as phases of the menstrual cycle, surgical menopause, and estrogen replacement therapy suggests conditions with higher levels of estrogen are associated with better verbal memory and possibly worse visuospatial ability. METHOD: The authors measured circulating sex hormone levels in 39 highly educated, nondemented, predominantly white elderly women. Levels were correlated with neuropsychological performance, controlling for age, education, frequency of prior testing, use of estrogen replacement, and depression. RESULTS: High estradiol levels were associated with better delayed verbal memory and retrieval efficiency, whereas low levels were associated with better immediate and delayed visual memory. Levels of testosterone were related positively to verbal fluency. Levels of progesterone and androstenedione were unrelated to cognitive performance. CONCLUSIONS: Both estrogen and testosterone showed associations with cognitive performance. Estrogen may enhance, and depress, specific cognitive skills.

Aged↗

Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial.

BACKGROUND: AD, the most prevalent cause of dementia, affects twice as many women as men. Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder. METHODS: Forty-two women with mild-to-moderate dementia due to AD were enrolled into a randomized, double-blind, placebo-controlled, parallel-group trial of unopposed conjugated equine estrogens (1.25 mg/day) for 16 weeks. RESULTS: Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks. At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer's Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status. Exploratory analyses of mood and specific aspects of cognitive performance also failed to demonstrate substantial group differences. CONCLUSION: Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.

Affect↗

In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging.

BACKGROUND: The basal ganglia contain the highest levels of iron in the brain, and postmortem studies indicate a disruption of iron metabolism in the basal ganglia of patients with Alzheimer disease (AD). Iron can catalyze free radical reactions and may contribute to oxidative damage observed in AD brains. Treatments aimed at reducing oxidative damage have offered novel ways to delay the rate of progression and could possibly defer the onset of AD. Brain iron levels were quantified in vivo using a new magnetic resonance imaging method. METHODS: Thirty-one patients with AD and 68 control subjects participated in this study. A magnetic resonance imaging method was employed that quantifies the iron content of ferritin molecules (ferritin iron) with specificity through the combined use of high and low field-strength magnetic resonance imaging instruments. Three basal ganglia structures (caudate, putamen, and globus pallidus) and one comparison region (frontal lobe white matter) were evaluated. RESULTS: Basal ganglia ferritin iron levels were significantly increased in the caudate (P = .007; effect size, 0.69) and putamen (P = .008; effect size, 0.67) of AD subjects, with a trend toward an increase in the globus pallidus (P = .13). The increased basal ganglia ferritin iron levels were not a generalized phenomenon; white matter ferritin iron levels were unchanged in patients with AD (P = .50). CONCLUSIONS: The data replicate and extend prior results and suggest that basal ganglia ferritin iron levels are increased in AD. Prospective studies are needed to evaluate whether premorbid iron levels are increased in individuals who develop AD.

Age Factors↗

Oestrogens and dementia.

The decline in circulating oestrogen concentrations that occurs after the menopause has the potential to impact Alzheimer's disease and other forms of dementia. Relevant actions include neurotrophic and neuroprotective effects; effects on acetylcholine and other neurotransmitters; and effects on proteins implicated in Alzheimer's disease pathogenesis. Since 1990, 14 case-control and cohort studies have considered the relation between postmenopausal oestrogen therapy and Alzheimer's disease. Most, but not all, report that oestrogen therapy is associated with a reduced Alzheimer risk of approximately one-half. Almost no epidemiological data address the potential link between oestrogen and other forms of dementia. Several small interventional trials have considered whether oestrogen might improve cognitive function of women with Alzheimer's disease. Data, however, are limited, and there is no compelling evidence that the short-term use of oestrogen monotherapy has a substantial impact on dementia symptoms. In summary, the use of oestrogen to reduce Alzheimer risk is biologically credible, and the preponderance of epidemiological evidence suggests that oestrogen therapy is indeed protective. This potentially important role of oestrogens for the primary prevention of Alzheimer's disease remains to be verified through well-designed randomized controlled trials.

Aging↗

Anosognosia and Alzheimer's disease: the role of depressive symptoms in mediating impaired insight.

The relation between anosognosia and dementia severity in Alzheimer's disease (AD) has been unclear. We constructed a measure that quantified the difference between the perceptions of deficits of patients with AD (n = 23) and ratings from a knowledgeable informant as a measure of anosognosia. There was no correlation between dementia severity and anosognosia. However, dementia severity was positively correlated with the degree of anosognosia after controlling for depressive symptomatology (p =.03). Post-hoc analyses, also controlling for depressive symptoms, indicated that higher levels of anosognosia were associated with lower performance on specific cognitive tasks. These results suggest depressive symptoms may confound the relationship between anosognosia and dementia severity.

Aged↗

Estrogen, cognition, and a woman's risk of Alzheimer's disease.

Alzheimer's disease affects women more often than men, and women with this form of dementia show greater naming (semantic memory) deficits during the course of their illness. Gonadal steroids exert organizational and activational effects on central nervous system neurons and influence brain function in other important ways. Several estrogenic actions are potentially relevant to Alzheimer's disease, and it is hypothesized that one consequence of estrogen deprivation after the menopause is a higher risk of this dementing disorder. In healthy women without dementia, estrogen may enhance cognitive performance, especially in the domain of verbal memory, although the magnitude of such effects is small. Several small treatment trials of estrogen replacement in women with Alzheimer's disease, however, suggest that estrogen's effects on cognition could be larger in this population and may be most apparent on tasks of semantic memory. Analyses in voluntary cohorts associate postmenopausal estrogen replacement therapy with a lower risk of subsequent Alzheimer's disease. In 3 recent epidemiologic studies, information on postmenopausal estrogen use was collected prospectively; while inconclusive, findings raise the possibility that postmenopausal estrogen replacement reduces a woman's risk of subsequent dementia. New information from basic research and from large randomized treatment studies, cohort studies, and case-control studies is needed to resolve important unanswered clinical issues.

Affect↗

The epidemiology of estrogen replacement therapy and Alzheimer's disease.

The burden of Alzheimer's disease (AD) falls more heavily on women than men. It is hypothesized that plummeting levels of circulating estrogens after the menopause increase a woman's risk for this disorder and, conversely, that estrogen replacement therapy may lower the risk for dementia due to AD. A number of estrogenic properties support the biological credibility of this hypothesis. Estrogen interacts with neurotrophins and neurotransmitter systems relevant to AD and in some model systems estrogen modulates synaptic plasticity. Effects on beta-amyloid and apolipoprotein E may be especially germane to putative effects. Estrogen also may blunt neurotoxic consequences of the stress response mediated by the hypothalamic-pituitary-adrenal axis, augment cerebral glucose utilization, and enhance cerebral blood flow. Clinical studies of postmenopausal women suggest beneficial estrogen effects on specific cognitive skills, and small preliminary trials of estrogen replacement in women with AD support claims of clinical meaningful efficacy. Consistent with the estrogen hypothesis, cross-sectional studies imply that postmenopausal estrogen use could be associated with a lower risk for AD. Several recent epidemiologic studies in which information on estrogen replacement therapy was collected prospectively further support this contention, with a dose-response relation evident in some reports. Because estrogen users tend to differ from nonusers in a number of lifestyle characteristics, convincing demonstration of putative protective effects could best some from randomized, placebo-controlled, primary intervention trials. For the present, however, the issue of estrogen efficacy in lowering a woman's risk for AD remains unsettled.

Alzheimer Disease↗

The relationship between extrapyramidal signs and cognitive performance in patients with Alzheimer's disease enrolled in the CERAD Study. Consortium to Establish a Registry for Alzheimer's Disease.

The objective of this study was to determine the relationship between the presence of extrapyramidal signs and the severity of cognitive and functional impairment in patients with Alzheimer's disease (AD). Eleven university medical centers in the United States and France participated in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) study of extrapyramidal signs in AD. Forty-seven patients with probable AD who had extrapyramidal signs were matched by sex, race, education, and age with 132 probable AD patients without extrapyramidal signs. The main outcome measures were the Clinical Dementia Rating, Blessed Dementia Scale, and the CERAD Neuropsychology Battery (verbal fluency, naming, Mini-Mental State Examination, word list learning, word list recall, savings ratio, word list recognition, and constructional praxis). AD patients with extrapyramidal signs performed more poorly than AD patients without parkinsonism on various neuropsychological tests, even after controlling for the Clinical Dementia Rating and reported duration of cognitive impairment. The severity of the extrapyramidal manifestations was related to the degree of cognitive and functional impairment. Muscular rigidity and bradykinesia were the most frequent extrapyramidal signs associated with AD. Patients with AD associated with extrapyramidal signs have greater cognitive and functional impairment than AD patients without clinical evidence of parkinsonism.

Aged↗

Estrogen replacement therapy and risk of Alzheimer disease.

BACKGROUND: With Alzheimer disease emerging as a major public health problem, the identification of factors that might prevent this disease are important. Estrogen loss associated with menopause may contribute to the development of Alzheimer disease. OBJECTIVE: To evaluate the effects of different estrogen preparations, varying dosages of estrogen, and duration of estrogen replacement therapy on the risk of Alzheimer disease in postmenopausal women. STUDY DESIGN AND METHODS: A case-control study nested within a prospective cohort study of residents of Leisure World Laguna Hills, a retirement community in Southern California. The cohort comprised 8877 women who were first mailed a health survey in 1981. Of the 3760 female cohort members who died between 1981 and 1995, 248 women with Alzheimer disease or other dementia diagnoses likely to represent Alzheimer disease (senile dementia, dementia, or senility) mentioned on the death certificate were identified. Five controls were individually matched to each case according to year of death and year of birth (+/- 1 year). RESULTS: The risk of Alzheimer disease and related dementia was significantly reduced in estrogen users compared with nonusers (odds ratio, 0.65; 95% confidence interval, 0.49-0.88). The risk was reduced for both oral and nonoral (i.e., injections and/or creams) routes of administration. The risk decreased significantly with both increasing dosages (P = .01) and increasing duration (P = .01) of oral therapy with conjugated equine estrogen, the most commonly used estrogen preparation. Within each dose category, the risk decreased with increasing duration of therapy, with the lowest observed risk in long-term users who received high doses (odds ratio, 0.48; 95% confidence interval, 0.19-1.17). CONCLUSION: This study suggests that estrogen replacement therapy may be useful for preventing or delaying the onset of Alzheimer disease in postmenopausal women.

Aged↗

Gender comparisons of cognitive performances among vascular dementia, Alzheimer disease, and older adults without dementia.

BACKGROUND: We hypothesized that women with Alzheimer disease (AD) would perform worse on a test of semantic memory but not on tests of other cognitive domains. We did not expect that women without dementia would perform more poorly than men without dementia on the same task. OBJECTIVE: To explore the specificity of a semantic memory deficit among women with AD by exploring gender differences among a group of subjects with vascular dementia (VD). DESIGN: A case-control study in which differences between men and women were explored using regression models to control for the potentially confounding effects of age, education, duration of dementia, and severity of dementia. SETTING: Alzheimer's Disease Research Center Consortium of Los Angeles and Orange Counties, California. SUBJECTS: Volunteers, recruited from the community or clinic referrals, who met clinical criteria for AD (n = 159) or VD (n = 117) or met criteria for control status without dementia (n = 134). MAIN OUTCOME MEASURES: Five neuropsychological measures, commonly used in the diagnosis and assessment of dementia. RESULTS: Women with VD scored lower than men with VD on 3 tests. However, when controlling for potential confounds, the gender difference was maintained only for the semantic memory task. Women with AD showed a strong trend to perform worse than men with AD on the test of semantic memory only. No gender differences were found among subjects without dementia. CONCLUSIONS: Findings support the existence of a semantic memory deficit for women with AD and suggest that a similar deficit may exist among women with VD.

Aged↗

Introduction. The investigation of lexical semantic representation in Alzheimer's disease.

The study of lexical semantic representation is central to an understanding of brain and language. In Alzheimer's disease, neuropathological alterations consistently involve neocortical areas in which lexical semantic information is represented, and patients with this common dementing disorder evince priminent lexical semantic disturbances. General issues concern the establishment of new semantic memories, the manner in which meaning is represented within the lexicon, the retrieval of semantic information from the lexicon, and the relation between lexical semantics and nonlinguistic cognitive processes. Studies of lexical semantic representation in patients with Alzheimer's disease are especially informative in considering all but the first of these key issues.

Aged↗

Cognitive skills associated with estrogen replacement in women with Alzheimer's disease.

To delineate putative cognitive effects of estrogen in women with Alzheimer's disease, we compared neuropsychological performances in three groups of patients with clinically diagnosed Alzheimer's disease: women receiving estrogen replacement therapy (n = 9), women not receiving replacement therapy (n = 27), and men (n = 26). Untreated women and men were matched by age, education, and duration of dementia symptoms to women receiving estrogen replacement. We hypothesized that treated women would have better scores on neuropsychological tasks. Results showed that women receiving hormonal therapy performed significantly better than other women on some, but not all, tasks; on no task did women receiving estrogen score significantly worse. The largest group difference was on the Boston Naming Test, a semantic memory task previously shown to be more impaired in women with Alzheimer's disease than in men with this diagnosis. Of tests considered in a discriminant analysis, the naming task was the only neuropsychological variable to distinguish between the two women's groups. Mean differences between estrogen-treated women and men were small and were not statistically significant. Findings support the hypothesis that estrogen therapy for women with Alzheimer's disease is associated with better cognitive skills and that previously noted gender-associated differences in Alzheimer's disease may reflect a state of acquired estrogen deficiency among women with this disorder.

Aged↗

Concurrent validity of Spanish-language versions of the Mini-Mental State Examination, Mental Status Questionnaire, Information-Memory-Concentration test, and Orientation-Memory-Concentration test: Alzheimer's disease patients and nondemented elderly comparison subjects.

One-hundred fifty-eight elderly Spanish-speaking U.S. residents (81 patients diagnosed with Alzheimer's disease and 77 subjects without dementia) were tested with Spanish-language versions of four brief cognitive assessment instruments: the Mini-Mental State Examination (S-MMSE), the Mental Status Questionnaire (S-MSQ), the Information-Memory-Concentration test (S-IMC), and the Orientation-Memory-Concentration test (S-OMC). Within-group performances were highly correlated for all four instruments. All tests distinguished between the demented and nondemented groups, but best discrimination was achieved with the S-IMC, which correctly classified 98% of subjects. This version was also the best predictor of functional disability, as measured by impairments in instrumental activities of daily living. Within the normal comparison group, neither gender nor a subject's monolingual/bilingual status affected test performance. These four Spanish-language cognitive screening tasks may aid in the evaluation of dementia among Spanish-speaking patients.

Adult↗

The effects of hormone replacement therapy, lipoprotein cholesterol levels, and other factors on a clock drawing task in older women.

OBJECTIVES: To assess the associations of a clock drawing task with hormone replacement therapy and other factors in older women. DESIGN: Group comparisons. SETTING: Leisure World Laguna Hills, retirement community in southern California. PARTICIPANTS: Two hundred ninety-two postmenopausal women who were analyzed for lipoprotein levels in 1987-88 were contacted by postal survey, which included a clock drawing task, in 1992; 168 women who drew normal clocks were compared with 46 who drew abnormal or blank clocks. MEASUREMENTS: Clock drawings; lipoprotein cholesterol levels; serum progesterone, estrone, estradiol, and steroid hormone binding globin levels; self-reported data on smoking, alcohol intake, prior medical diagnoses, and use of certain medications including hormone replacement therapy and analgesics. RESULTS: Women with normal clocks had significantly lower total cholesterol (P = .01), LDL cholesterol (P = .03), and serum progesterone levels (P = .03). They weighed, on average, 5 more pounds at the time of last menstrual period (P = .05), were more likely to use combined hormonal replacement therapy (P = .06), and were less likely to use acetaminophen daily (P = .02) than women with abnormal clocks. Serum estrone and estradiol levels did not differ significantly between women with normal and abnormal clocks. CONCLUSION: The associations found here suggest that high serum cholesterol and progesterone levels might have a negative effect on clock drawing performance. Acetaminophen may also be related to worse performance on this task.

Acetaminophen↗