Mortality, dementia, and apolipoprotein E genotype in elderly white women in the United States.

OBJECTIVES: To assess the risk of death in relation to apolipoprotein E (APOE) genotype and to evaluate how APOE genotype interacts with dementia and with other major medical conditions to affect survival. DESIGN: A 6-year prospective cohort study of dementia, APOE genotype and survival. SETTING: Health maintenance organization in southern California. PARTICIPANTS: One thousand eight hundred forty-two white women aged 75 and older. MEASUREMENTS: Dementia was determined using a multistage assessment procedure, medical record, and death certificate review. RESULTS: With women with the APOE 3/3 genotype as the referent, age-adjusted hazard ratios (HRs) for death according to genotype were 1.25 (95% confidence interval (CI)=1.00-1.56) for APOE 2/4, 3/4, or 4/4 and 0.83 (95% CI=0.62-1.13) for APOE 2/3 or 2/2. Survival was associated with APOE genotype (log rank test P=.02). Women with the APOE 2/4, 3/4, or 4/4 genotype died at an earlier age, and those with APOE 2/2 or 2/3 died later than those with the APOE 3/3 genotype. After adjustment for age, education, and hormone use, HRs for death were significantly higher in women with the APOE 2/4, 3/4, or 4/4 genotype who developed dementia (HR=3.74; 95% CI=2.81-4.99) and the APOE 2/3 genotype (HR=3.23; 95%=CI=1.97-5.28) than in women without dementia and the APOE 3/3 genotype. The HRs for death were greater with other medical conditions, but no interaction with any APOE genotype was found. CONCLUSION: In this population of elderly women, although having at least one epsilon4 allele increased the chances of an earlier death, having dementia increased the risk of death regardless of APOE genotype.

Social network, cognitive function, and dementia incidence among elderly women.

OBJECTIVES: We examined whether social networks had a protective association with incidence of dementia among elderly women. METHODS: We prospectively studied 2249 members of a health maintenance organization who were 78 years or older, were classified as free of dementia in 2001, and had completed at least 1 follow-up interview in 2002 through 2005. We used the Telephone Interview for Cognitive Status-modified, the Telephone Dementia Questionnaire, and medical record review to assess cognitive status. We used the Lubben Social Network Scale-6 to assess social network. We estimated hazard ratios for incident dementia with Cox proportional hazards models, adjusting for age at entry, education, hormone use, cognitive status scores, and health conditions. RESULTS: We identified 268 incident cases of dementia during follow-up. Compared with women with smaller social networks, the adjusted hazard ratio for incident dementia in women with larger social networks was 0.74 (95% confidence interval=0.57, 0.97). CONCLUSIONS: Our findings suggest that larger social networks have a protective influence on cognitive function among elderly women. Future studies should explore which aspects of social networks are associated with dementia risk and maintenance of cognitive health.

Incidence of dementia in long-term hormone users.

Results from epidemiologic studies of postmenopausal hormone use and dementia have been conflicting. Investigators from the Women's Health Initiative Memory Study reported that the incidence of dementia in women aged >/=65 years assigned to hormone use was increased. Here the authors report results from a prospective cohort study of 2,906 dementia-free women (1,519 hormone users and 1,387 hormone nonusers) aged > or =75 years who were recruited from a Southern California health plan in 1999 and followed through 2003. Cognitive status was assessed annually using the Telephone Interview of Cognitive Status-modified, supplemented by the Telephone Dementia Questionnaire and medical record review. The mean self-reported age at initiation of hormone use was 48.3 years for users of estrogen alone (n = 1,072) and 54.9 years for users of estrogen plus progestin (n = 447); self-reported mean durations of hormone use were 30.5 years and 23.2 years, respectively. There were 283 incident dementia cases identified during follow-up. After adjustment for age, education, and medical history, hazard ratios for incident dementia were 1.34 (95% confidence interval: 0.95, 1.89) in estrogen/progestin users and 1.23 (95% confidence interval: 0.94, 1.59) in estrogen users. These findings do not provide support for an effect of estrogen or estrogen/progestin use in preventing dementia.

Validation of the Cognitive Assessment of Later Life Status (CALLS) instrument: a computerized telephonic measure.

BACKGROUND: Brief screening tests have been developed to measure cognitive performance and dementia, yet they measure limited cognitive domains and often lack construct validity. Neuropsychological assessments, while comprehensive, are too costly and time-consuming for epidemiological studies. This study's aim was to develop a psychometrically valid telephone administered test of cognitive function in aging. METHODS: Using a sequential hierarchical strategy, each stage of test development did not proceed until specified criteria were met. The 30 minute Cognitive Assessment of Later Life Status (CALLS) measure and a 2.5 hour in-person neuropsychological assessment were conducted with a randomly selected sample of 211 participants 65 years and older that included equivalent distributions of men and women from ethnically diverse populations. RESULTS: Overall Cronbach's coefficient alpha for the CALLS test was 0.81. A principal component analysis of the CALLS tests yielded five components. The CALLS total score was significantly correlated with four neuropsychological assessment components. Older age and having a high school education or less was significantly correlated with lower CALLS total scores. Females scored better overall than males. There were no score differences based on race. CONCLUSION: The CALLS test is a valid measure that provides a unique opportunity to reliably and efficiently study cognitive function in large populations.

Cognitive domains associated with performance on the telephone interview for cognitive status-modified.

Global cognitive screening tests are increasingly used in clinical and research settings. However, many have not been developed following systematic psychometric principles; thus, construct validity is not clearly defined. It is the aim of this study to identify the cognitive domains that are associated with the total score from the Telephone Interview for Cognitive Status-modified (TICS-m). Data came from 104 women (75 years of age and older) who were participants in a longitudinal study of dementia and had been given the TICS-m and a battery of standardized neuropsychological tests. Factor analysis of all these neuropsychological tests yielded six interpretable factors. episodic memory for words, episodic memory for contextual information, working memory, episodic memory for nonverbal information, attention, and visuospatial processing efficiency. The TICS-m score showed modest associations with several distinct cognitive domains, including episodic memory for words and nonverbal information and attention.

Cognitive performance of older women who have survived cancer.

Based on anecdotal reports and a few empirical studies, there is concern about the cognitive effects of cancer and its treatment effects among adults. A cross-sectional comparison of the cognitive performance of 541 elderly women who reported at least one hospitalization for cancer and 3,123 who had no reported hospitalizations for cancer was conducted. The difference between cancer survivors and those with no history of cancer on a screening test of global cognitive functioning was not significant, nor were there differences on a subtest of the global test that assesses verbal memory. Older women who report being hospitalized for cancer as adults may perform similar to women with no history of cancer on rudimentary cognitive tasks.

Validation of multi-stage telephone-based identification of cognitive impairment and dementia.

BACKGROUND: Many types of research on dementia and cognitive impairment require large sample sizes. Detailed in-person assessment using batteries of neuropyschologic testing is expensive. This study evaluates whether a brief telephone cognitive assessment strategy can reliably classify cognitive status when compared to an in-person "gold-standard" clinical assessment. METHODS: The gold standard assessment of cognitive status was conducted at the University of Southern California Alzheimer Disease Research Center (USC ADRC). It involved an examination of patients with a memory complaint by a neurologist or psychiatrist specializing in cognitive disorders and administration of a battery of neuropsychologic tests. The method being evaluated was a multi-staged assessment using the Telephone Interview of Cognitive Status-modified (TICSm) with patients and the Telephone Dementia Questionnaire (TDQ) with a proxy. Elderly male and female patients who had received the gold standard in-person assessment were asked to also undergo the telephone assessment. The unweighted kappa statistic was calculated to compare the gold standard and the multistage telephone assessment methods. Sensitivity for classification with dementia and specificity for classification as normal were also calculated. RESULTS: Of 50 patients who underwent the gold standard assessment and were referred for telephone assessment, 38 (76%) completed the TICS. The mean age was 78.1 years and 26 (68%) were female. When comparing the gold standard assessment and the telephone method for classifying subjects as having dementia or no dementia, the sensitivity of the telephone method was 0.83 (95% confidence interval 0.36, 1.00), the specificity was 1.00 (95% confidence interval 0.89,1.00). Kappa was 0.89 (95% confidence interval 0.69, 1.000). Considering a gold-standard assessment of age-associated memory impairment as cognitive impairment, the sensitivity of the telephone approach is 0.38 (95% confidence interval 0.09, 0.76) specificity 0.96 (CI 0.45, 0.89) and kappa 0.61 (CI 0.37, 0.85). CONCLUSION: Use of a telephone interview to identify people with dementia or cognitive impairment is a promising and relatively inexpensive strategy for identifying potential participants in intervention and clinical research studies and for classifying subjects in epidemiologic studies.

Blood pressure levels before dementia.

BACKGROUND: The association between blood pressure (BP) and dementia is not easily interpreted, but some prospective studies suggest that dementia may lower BP. OBJECTIVE: To examine the relationship between BP during a 10-year period and the prevalence of dementia. DESIGN: Comparison of longitudinal BP between participants who had dementia, participants who were cognitively impaired, and unimpaired participants selected from an ongoing cohort study. SETTING: A prepaid health plan in southern California. PARTICIPANTS: Three hundred participants had dementia, 285 were cognitively impaired, and 585 were unimpaired. MAIN OUTCOME MEASURES: Retrospective medical record review of up to 3 randomly selected BP measurements per year for the 10 years before cognitive classification of each participant. RESULTS: Systolic BP increased with time in the unimpaired participants, and increased less in women who developed cognitive impairment and in women who developed dementia. Diastolic BP declined significantly (P<.001) with time in all 3 groups. Compared with unimpaired women, the adjusted rate of decline in diastolic BP was significantly (P = .04) greater for the women who developed dementia. CONCLUSIONS: These findings are consistent with previous findings that the relationship between BP and dementia is affected by age at data collection. Valid inferences about the effect of BP on the development of dementia require prospective data collection in which subjects are free of dementia or cognitive impairment at enrollment.

Physician recognition of cognitive impairment: evaluating the need for improvement.

OBJECTIVES: To assess physician recognition of dementia and cognitive impairment, compare recognition with documentation, and identify physician and patient factors associated with recognition. DESIGN: Survey of physicians and review of medical records. SETTING: Health maintenance organization in southern California. PARTICIPANTS: Seven hundred twenty-nine physicians who provided care for women participating in a cohort study of memory (Women's Memory Study). MEASUREMENTS: Percentage of patients with dementia or cognitive impairment (using the Telephone Interview of Cognitive Status supplemented by the Telephone Dementia Questionnaire) recognized by physicians. Relationship between physician recognition and patient characteristics and physician demographics, practice characteristics, training, knowledge, and attitudes about dementia. RESULTS: Physicians (n=365) correctly identified 81% of patients with dementia and 44% of patients with cognitive impairment without definite dementia. Medical records documented cognitive impairment in 83% of patients with dementia and 26% of patients with cognitive impairment without definite dementia. In a multivariable model, physicians with geriatric credentials (defined as geriatric fellowship experience and/or the certificate of added qualifications) recognized cognitive impairment more often than did those without (risk ratio (RR)=1.56, 95% confidence interval (CI)=1.04-1.66). Physicians were more likely to recognize cognitive impairment in patients with a history of depression treatment (RR=1.3, 95% CI=1.03-1.45) or stroke (RR=1.37, 95% CI=1.04-1.45) and less likely to recognize impairment in patients with cognitive impairment without definite dementia than in those with dementia (RR=0.46, 95% CI=0.23-0.72) and in patients with a prior hospitalization for myocardial infarction (RR=0.37, 95% CI=0.09-0.88) or cancer (RR=0.49, 95% CI=0.18-0.90). CONCLUSION: Medical record documentation reflects physician recognition of dementia, yet physicians are aware of, but have not documented, many patients with milder cognitive impairment. Physicians are unaware of cognitive impairment in more than 40% of their cognitively impaired patients. Additional geriatrics training may promote recognition, but systems solutions are needed to improve recognition critical to provision of emerging therapies for early dementia.

Hormone use and cognitive performance in women of advanced age.

OBJECTIVES: To explore the association between hormone replacement therapy (HRT) and cognitive performance in a group of elderly women (>/=75) using a battery of well-standardized neuropsychological instruments. DESIGN: Equivalent samples from existing cohort. SETTING: Healthcare provider organization. PARTICIPANTS: All women enrolled were participants in an ongoing study of the association between HRT and the prevalence and incidence of dementia. Prescription records were used to establish HRT status. Fifty-eight users and 47 nonusers of HRT participated in this substudy. MEASUREMENTS: Given previous reports that HRT has a positive effect on verbal memory, the California Verbal Learning Test and the Logical Memory Test were used as primary outcomes. A range of validated tests that assess other cognitive domains was also included. RESULTS: There were no significant differences between users and nonusers of HRT on any cognitive measures. CONCLUSION: Given equivalent groups of users and nonusers of HRT no support was found for the hypothesis that use of HRT improves cognitive performance in older women.

Diabetes mellitus and cognitive performance in older women.

PURPOSE: This cross-sectional study sought to identify diabetes accurately in a study population of 3681 women age 75 and older and to determine the association of diabetes with cognitive performance. METHODS: A previously validated test, the Telephone Interview of Cognitive Screening-Modified (TICSm) was given to assess cognitive status. A diabetes case identification database, medical record review and self-report were used to determine diabetes cases. 489 (13.3%) of the women in the study were classified with diabetes and 3192 without diabetes. RESULTS: t-tests and linear regression analyses determined that diabetic women had a mean TICSm score 1.4 points lower (i.e. more impaired) than non-diabetic women. Using linear regression to adjust for age, education, and vascular disease, diabetic women showed a 1.1 lower score on the TICSm. Similar adjustments were made for potential confounding variables such as depression, hormone replacement therapy (HRT), high body weight, smoking, alcohol use and exercise and diabetics again showed a 1.0 lower score. CONCLUSION: This study, which utilizes highly rigorous case identification methodology, provides further evidence that diabetes is associated with significantly worse cognitive performance in the elderly.

Prevalence of dementia in users of hormone replacement therapy as defined by prescription data.

BACKGROUND: Studies of hormone replacement therapy (HRT) and dementia and cognitive impairment show mixed results. This study assessed the prevalence of dementia and cognitive impairment in users and nonusers of HRT defined using computer-stored prescription information. METHODS: The study involved 3924 women 75 years of age and older who were members of the Southern California Kaiser Permanente Medical Care Program in 1998. HRT use was determined based on prescription data for 1992-1998. Cognitive function and dementia were assessed using the Telephone Interview of Cognitive Status supplemented by the Telephone Dementia Questionnaire and medical record review. RESULTS: Odds ratios (ORs) for cognitive impairment/dementia showed expected associations with age, education, ethnicity, and a history of stroke or Parkinson's disease. After adjustment, the OR for cognitive impairment or dementia in HRT users compared with HRT nonusers was 0.91 (95% confidence interval 0.75-1.10). The adjusted ORs for all dementia and dementia without cause in HRT users compared with nonusers were 0.77 (95% confidence interval 0.59- 1.00) and 0.78 (0.58-1.05), respectively. Twenty percent of women with cognitive impairment or dementia who had been classified as HRT users by prescription (one prescription each year from 1992-1998) denied hormone use compared with 8.8% of women without impairment. Medical record review validated prescription information for the impaired women. CONCLUSIONS: The study identified an important methodologic problem in studies of HRT and cognitive impairment and dementia that depend on recalled information about drug exposure. A protective effect of HRT for cognitive impairment and dementia was neither established nor ruled out based on the prescription data.

A preliminary psychometric analysis of a computer-assisted administration of the Telephone Interview of Cognitive Status-modified.

Most screening tests of cognitive functioning require face to face administration by trained examiners. This limits their utility in epidemiology and in primary care settings. Further, existing screening tests have not been developed using established psychometric principles. We adapted the Telephone Interview of Cognitive Status-modified (TICSm) for administration as a computer-assisted telephone interview (CATI). We screened 3,681 elderly women with the CATI version of the TICSm, using lay staff as part of a longitudinal study. A preliminary analysis of the psychometric properties of the TICSm indicated good internal consistency. Test-retest reliability is needed to confirm reliability. Further work remains to adequately judge the validity of the TICSm including comparisons with well-standardized tests and assessment of its predictive properties in identifying dementia. However, the CATI version of the TICSm appears to have potential as a cost-effective means of testing cognitive performance.