Linda J. Clark

Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen

AbstractBackground. Tamoxifen is an anti-estrogen used in the treatment of breast cancer and to reduce the incidence of breast cancer in high risk women. Although the brain is an estrogen target organ and several studies have found a beneficial effect of estrogen on cognitive function, the effect of tamoxifen on cognition has not been reported. Therefore, we initiated a follow-up study of women who had participated in a study of breast cancer to assess the effect of tamoxifen treatment on cognitive function. Methods. We recruited previously interviewed patients who were cases in a population-based case-control study of 2,653 women with primary breast cancer diagnosed between 1987 and 1996 at ages 55–72 years in Los Angeles County, California, USA. In November 1997, each case was mailed a follow-up questionnaire. Cognitive function was assessed by (1) clock drawing, (2) copying a box drawing, and (3) narrative writing to describe a pictured scene. Women reporting treatment with tamoxifen were categorized as standard-term users (4–5 years), short-term users (<4 years) or long-term users (6 + years) and compared to never users. Tamoxifen users were also classified as past or current users. Differences in the mean cognitive test scores were tested after adjusting for age, age at diagnosis, stage of disease, radiation therapy, chemotherapy, race, education, marital status, previous use of oral contraceptives, type of menopause, age at last menstrual period, previous use of hormone replacement therapy, and depressive symptoms using analysis of covariance. All p-values for differences in the proportion of women who had errors on the tests are 2-sided and adjusted for age, stage of disease at diagnosis, and chemotherapy. Findings. Information from 1,163 women aged 57–75 years of age was analyzed; 710 had taken tamoxifen. There was little difference between women who had used tamoxifen for the standard five years and never users on the three cognitive tests. However, more women who had used tamoxifen for the standard term reported seeing their physician for memory problems than non-users (3.8% vs 1.5%, p = 0.04). This was especially true for current users of standard-term (8.0%, p = 0.003). Current users also had a significantly lower mean complexity score (p = 0.03) on the narrative writing task. No differences were seen between past users and non-users. Interpretation. Our study suggests that current use of tamoxifen may adversely effect cognition. Further study of tamoxifen and cognition is needed so that healthy women considering tamoxifen for the primary prevention of breast cancer have comprehensive information about the side effects of the treatment.

The effect of education and occupational complexity on rate of cognitive decline in Alzheimer's patients

We explored the effect of education and occupational complexity on the rate of cognitive decline (as measured by the Mini-Mental State Examination) in 171 patients with a confirmed Alzheimers disease (AD) diagnosis. Complexity was measured as substantive complexity of work and complexity of work with data, people, and things. Average lifetime occupational complexity was calculated based on years at each occupation. Participants were followed for an average of 2.5 years and 3.7 visits. In multivariate mixed-effects models, high education, high substantive complexity, and high complexity of work with data and people predicted faster rates of cognitive decline, controlling for age, gender, native language, dementia severity, and entry into the analyses at initial versus follow-up testing. These results provide support for the concept of cognitive reserve according to which greater reserve may postpone clinical onset of AD but also accelerate cognitive decline after the onset.

Longitudinal verbal fluency in normal aging, preclinical, and prevalent Alzheimer's disease.

Background: Few longitudinal studies evaluate differences in patterns of change of category compared to letter fluency across the spectrum of cognitive impairment. Methods: We compared change in category (animal and supermarket) and letter (F, A, S) fluency among 239 participants in 3 groups: remained cognitively normal throughout follow-up (n = 96), developed Alzheimer’s Disease (AD; preclinical AD, n = 21), and with AD at initial testing (prevalent AD, n = 122). Results: At baseline, prevalent and preclinical AD groups scored lower on animal than letter fluency. On all fluency measures, the prevalent AD declined faster than other groups (all P < .0001), and preclinical AD declined faster than unimpaired (all P ≤ .02). Overall, animal fluency declined faster than letter fluency; animal fluency declined significantly faster than letter fluency among cognitively normal and prevalent AD participants. Conclusion: Greater longitudinal declines in category compared to letter fluency are consistent with cross-sectional studies. Steeper declines on both fluency measures distinguish preclinical AD from cognitively unimpaired individuals.

Eye problems in breast cancer patients treated with tamoxifen

AbstractBackground:Tamoxifen is an oral anti-estrogen used in the treatment of breast cancer and recently approved to reduce the incidence of breast cancer in high risk women. As a large clinical trial of tamoxifen has reported an increased risk of cataract, we conducted a study of women with breast cancer to evaluate the association of tamoxifen with cataracts and other eye problems. Methods:We attempted to recruit previously interviewed patients who were cases in a population-based case-control study of 2653 women with primary breast cancer diagnosed between 1987 and 1996 at ages 55–72 years in Los Angeles County, California, USA. In November 1997, each case was mailed a questionnaire to ascertain self-reported incidence of eye diseases and Amsler grid test scores. Information from 1297 women aged 57–75 years of age was analyzed. Women reporting treatment with tamoxifen were categorized as standard-term users (4–5 years), short-term users (<4 years), or long-term users (6+ years) and compared to non-users. All p-values, relative risks, and confidence intervals for differences in eye problems and grid test results are adjusted for age and stage of disease at diagnosis. Findings:Standard-term and long-term users of tamoxifen more frequently reported developing cataracts than non-users (18.2%, 21.4% vs. 14.8%). The relative risk was 1.40 (95% confidence interval 0.94–2.10) for standard-term users and 1.70 (1.11–2.59) for long-term users. Tamoxifen use was unrelated to frequency of glaucoma or macular degeneration or to Amsler grid test results. Interpretation:Our study suggests that five or more years of tamoxifen use increases risk of cataracts. Healthy women considering tamoxifen use to reduce risk of breast cancer should be advised of the possibility of cataract development. Women choosing such therapy should be diligent about receiving regular ocular exams.

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 Alzheimers disease.

Preliminary Assessment of Cognitive Function in Older Adults by Clock Drawing, Box Copying and Narrative Writing

Objective: To examine 3 cognitive screening tasks in older adults and determine which demographic, medical and lifestyle variables obtained 13–17 years previously predicted cognitive performance. Design: Population-based longitudinal cohort study begun in 1981. Setting: Leisure World Laguna Hills, a California retirement community. Participants: The cohort is predominantly white, well educated, upper-middle class; two thirds are women. Data from 1,744 participants (mean age 83 years, range 57–103) were analyzed. Measurements: The baseline postal survey (1981–1985) asked demographic information, medical history, selected drug use and personal habits. The 1998 follow-up included 3 tasks to assess cognitive function: (1) clock drawing, (2) copying a box drawing and (3) narrative writing to describe a pictured scene. Results: Within age groups, women tended to have lower scores than men on box copying, similar scores on clock drawing, but higher informational and complexity scores on narrative writing. Performance decreased with increasing age and was poorest in individuals ≧90 years old. In addition to age, sex and education, significant predictors of performance were: exercise, body mass index and cataract surgery (clock); vitamin E supplements, daily aspirin use and gallbladder surgery (box); vitamin A supplements (narrative writing). Mean scores on all tasks were lower in those later identified as demented compared with nondemented but significantly different only for clock and box drawings. Conclusion: Performance on 3 cognitive tests showed significant effects of age, sex and education and was related to later dementia. Better performance by users of antioxidant supplements and aspirin suggests that these drugs may maintain cognitive function in later life.

Longitudinal Assessment of Cognitive Function by Clock Drawing in Older Adults

Aims: To test the hypotheses that performance on a clock-drawing task (CDT) diminishes over time and that poor performance is associated with development of dementia and reduced survival. Methods: Participants in the population-based Leisure World Cohort Study were asked to complete a CDT in follow-up questionnaires mailed in 1992 and 1998. Dementia status was determined using in-person evaluations, follow-up questionnaires, hospital data, and death certificates. Results: Of the 4,842 cohort members (mean age 80 years) who completed the CDT in 1992, 1,521 also completed it in 1998. Although performance in the CDT diminished over time in only a proportion of the cohort, the mean total score and the percentage of subjects with correctly drawn clocks decreased with each successive 5-year age group (p = 0.0001) and over time. Mean scores were lower in non-demented subjects later identified as demented compared with those who remained free of dementia. A low CDT score in 1992 was associated with a 28% increased risk of dementia and 13% reduced survival. Conclusion: A CDT may help predict cognitive decline and future disability in the elderly. Identification of high-risk individuals using a CDT may lead to earlier diagnosis and treatment and improved patient management.

Latex condom deterioration accelerated by environmental factors: I. Ozone

Commercial non-lubricated latex condoms were unpackaged and exposed in an environmental chamber to ozone levels (0.3 ppm) commonly present in urban smog conditions. Deterioration was observed by scanning electron microscopy after 18 hours exposure. Loss of mechanical strength was quantitated by measurement of the air pressures necessary to burst the condom and volumes at burst. After 24 hours exposure to ozone the latex surface was covered with craters and after 48 hours the pressure required to burst the condom was 44% that of control samples. Data suggest the need for study of the effectiveness of lubrication and packaging in protecting condoms from environmental factors which may accelerate deterioration.