Janet M. Johnston

Incidence of Alzheimer’s disease in a rural community in India: The Indo–US Study

Objective: To determine overall and age-specific incidence rates of AD in a rural, population-based cohort in Ballabgarh, India, and to compare them with those of a reference US population in the Monongahela Valley of Pennsylvania. Methods: A 2-year, prospective, epidemiologic study of subjects aged ≥55 years utilizing repeated cognitive and functional ability screening, followed by standardized clinical evaluation using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria for the diagnosis, and the Clinical Dementia Rating scale for the staging, of dementia and AD. Results: Incidence rates per 1000 person–years for AD with CDR ≥0.5 were 3.24 (95% CI: 1.48–6.14) for those aged ≥65 years and 1.74 (95% CI: 0.84–3.20) for those aged ≥55 years. Standardized against the age distribution of the 1990 US Census, the overall incidence rate in those aged ≥65 years was 4.7 per 1000 person–years, substantially lower than the corresponding rate of 17.5 per 1000 person–years in the Monongahela Valley. Conclusion: These are the first AD incidence rates to be reported from the Indian subcontinent, and they appear to be among the lowest ever reported. However, the relatively short duration of follow-up, cultural factors, and other potential confounders suggest caution in interpreting this finding.

Prevalence of Alzheimer's disease and other dementias in rural India: the Indo-US study.

Objective: To determine the prevalence of AD and other dementias in a rural elderly Hindi-speaking population in Ballabgarh in northern India. Design: The authors performed a community survey of a cohort of 5,126 individuals aged 55 years and older, 73.3% of whom were illiterate. Hindi cognitive and functional screening instruments, developed for and validated in this population, were used to screen the cohort. A total of 536 subjects (10.5%) who met operational criteria for cognitive and functional impairment and a random sample of 270 unimpaired control subjects (5.3%) underwent standardized clinical assessment for dementia using the Diagnostic and Statistical Manual of Mental Disorders-fourth edition diagnostic criteria, the Clinical Dementia Rating Scale (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimers Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable and possible AD. Results: We found an overall prevalence rate of 0.84% (95% CI, 0.61 to 1.13) for all dementias with a CDR score of at least 0.5 in the population aged 55 years and older, and an overall prevalence rate of 1.36% (95% CI, 0.96 to 1.88) in the population aged 65 years and older. The overall prevalence rate for AD was 0.62% (95% CI, 0.43 to 0.88) in the population aged 55+ and 1.07% (95% CI, 0.72 to 1.53) in the population aged 65+. Greater age was associated significantly with higher prevalence of both AD and all dementias, but neither gender nor literacy was associated with prevalence. Conclusions: In this population, the prevalence of AD and other dementias was low, increased with age, and was not associated with gender or literacy. Possible explanations include low overall life expectancy, short survival with the disease, and low age-specific incidence potentially due to differences in the underlying distribution of risk and protective factors compared with populations with higher prevalence.

Improved outcomes for women undergoing contemporary percutaneous coronary intervention: A report from the national heart, lung, and blood institute dynamic registry☆

OBJECTIVES The goal of this study was to determine whether women undergoing contemporary percutaneous coronary intervention (PCI) remain at increased risk in comparison with men and whether the outcomes in women have improved. BACKGROUND Previous studies have shown that women treated with coronary angioplasty have a higher incidence of procedural morbidity and mortality than men. METHODS Gender differences in wave 1 of the National Heart, Lung and Blood Institute (NHLBI) Dynamic registry were evaluated. Baseline characteristics and outcomes in women in the Dynamic registry were compared with those in women in the 1985-1986 and 1993-1994 NHLBI Percutaneous Transluminal Coronary Angioplasty (PTCA) registries. RESULTS Women were older with a higher prevalence of diabetes mellitus, hypertension, congestive heart failure, unstable angina and single vessel disease in comparison with men. Although procedural success and in-hospital death (2.2% vs. 1.3%), myocardial infarction (MI) (2.3% vs. 3.0%) and coronary artery bypass graft surgery (CABG) (1.3% vs. 1.4%) were similar in women and men, respectively, one-year mortality (6.5% vs. 4.3%, p = 0.02) and combined end point of death/MI/CABG (18.3% vs. 14.4%, p = 0.03) were higher in women than in men. After controlling for other factors, gender was not a significant predictor of death or death plus MI at one year. Despite a higher risk profile in women in the Dynamic registry in comparison with women in the 1985-1986 NHLBI PTCA registry, in-hospital death/MI/CABG was lower (6.0% vs. 11.6%, p < 0.001). CONCLUSIONS Despite persistent high-risk characteristics in women, gender differences in outcomes in patients undergoing contemporary PCI have decreased, and outcomes in women have improved.

Effects of the menopause transition and hormone use on cognitive performance in midlife women

Background: There is almost no longitudinal information about measured cognitive performance during the menopause transition (MT). Methods: We studied 2,362 participants from the Study of Womens Health Across the Nation for 4 years. Major exposures were time spent in MT stages, hormone use prior to the final menstrual period, and postmenopausal current hormone use. Outcomes were longitudinal performance in three domains: processing speed (Symbol Digit Modalities Test [SDMT]), verbal memory (East Boston Memory Test [EBMT]), and working memory (Digit Span Backward). Results: Premenopausal, early perimenopausal, and postmenopausal women scored higher with repeated SDMT administration (p ≤ 0.0008), but scores of late perimenopausal women did not improve over time (p = 0.2). EBMT delayed recall scores climbed during premenopause and postmenopause (p ≤ 0.01), but did not increase during early or late perimenopause (p ≥ 0.14). Initial SDMT, EBMT-immediate, and EBMT-delayed tests were 4%–6% higher among prior hormone users (p ≤ 0.001). On the SDMT and EBMT, compared to the premenopausal referent, postmenopausal current hormone users demonstrated poorer cognitive performance (p ≤ 0.05) but performance of postmenopausal nonhormone users was indistinguishable from that of premenopausal women. Conclusions: Consistent with transitioning womens perceived memory difficulties, perimenopause was associated with a decrement in cognitive performance, characterized by women not being able to learn as well as they had during premenopause. Improvement rebounded to premenopausal levels in postmenopause, suggesting that menopause transition–related cognitive difficulties may be time-limited. Hormone initiation prior to the final menstrual period had a beneficial effect whereas initiation after the final menstrual period had a detrimental effect on cognitive performance.

Impact of age on procedural and 1-year outcome in percutaneous transluminal coronary angioplasty: A report from the NHLBI Dynamic Registry

BACKGROUND Older age has been associated with adverse outcomes in patients undergoing percutaneous coronary intervention (PCI). As PCI technology evolves and the US population becomes proportionally older, assessment of PCI in older age groups is essential. METHODS From the National Heart, Lung, and Blood Institute Dynamic Registry, 4620 PCI-treated patients (1997 to 1999) were studied. Differences in clinical presentation, treatment strategy, and inhospital and 1-year outcomes were compared between patient age groups: younger (<65 years, n = 2537); older (65 to 79 years, n = 1776); and elderly (> or =80 years, n = 307). RESULTS Older and elderly patients had more cardiac and comorbid noncardiac conditions and more extensive and complex arteriosclerosis, including stenoses in bypass grafts. Stent use was similar as age increased (72% vs 73% vs 73%), as was the use of IIb/IIIa receptor antagonists (29% vs 26% vs 28%). Rates of successful treatment of all attempted lesions were 93%, 92%, and 89%, respectively. Adjusted relative risks of inhospital death (1.0 vs 2.91 vs 3.64) and myocardial infarction (1.0 vs 1.35 vs 2.57) increased by age group, as did 1-year mortality rates (1.0 vs 1.87 vs 3.02). However, the relative magnitude of excess mortality rates at 1 year was comparable to that observed by age in the US general population. Age was not associated with 1-year risk of myocardial infarction or coronary artery bypass grafting. CONCLUSIONS Although new technologies may allow for treatment of complex disease in older and elderly patients with comorbid disease, the increased procedural risk remains substantial in these patients. After PCI, the long-term relative risk of death is similar to that expected among persons of similar ages in the general population.

Associations of Endogenous Sex Hormones with the Vasculature in Menopausal Women: The Study of Women's Health Across the Nation (SWAN)

Objective: As associations between endogenous sex hormones and the vasculature are not well characterized, the objective was to examine the cross-sectional associations of menopausal status and endogenous sex hormones with vascular characteristics. Design: Common carotid artery adventitial diameter and intima-media thickness were determined using B-mode ultrasonography among 483 middle-aged women enrolled in the Pittsburgh and Chicago sites of the Study of Womens Health Across the Nation. Results: Sixty-two percent of women were pre- or early perimenopausal (<3 mo amenorrhea), 12% were late perimenopausal (3-12 mo amenhorrhea), and 27% were postmenopausal (≥12 mo amenorrhea). After adjustment for age, compared with pre-/early perimenopause, late perimenopause was associated with a 0.28-mm larger adventitial diameter (P = 0.001), whereas postmenopause was associated with a 0.15-mm larger adventitial diameter (P = 0.040). Adjustment for traditional cardiovascular risk factors slightly attenuated these associations, but the association with late perimenopause remained statistically significant (P = 0.001). Each SD lower log estradiol value was associated with a 0.07-mm larger adventitial diameter after adjustment for traditional cardiovascular risk factors (P = 0.023), whereas other endogenous hormones showed no associations. Intima-media thickness values were not significantly associated with menopausal status or endogenous sex hormones after adjustment for age. Conclusions: The menopausal transition and declining estrogen levels are associated with alterations of the peripheral vasculature, which may help to explain the increased risk of cardiovascular disease with postmenopause.

Depressive symptoms, cognitive impairment and functional impairment in a rural elderly population in India: a Hindi version of the geriatric depression scale (GDS-H)

Objective To measure depressive symptomatology in a largely illiterate elderly population in India, using a new Hindi version of the Geriatric Depression Scale (GDS-H), and to examine its distribution and associations with age, gender, literacy, cognitive impairment and functional impairment. Design A Hindi version of the Geriatric Depression Scale was developed and administered to participants along with measures of demographic characteristics, cognitive functioning and functional ability. Setting The rural community of Ballabgarh in northern India. Participants A community sample of 1554 mostly illiterate Hindi-speaking residents of Ballabgarh aged 55+. Measures The Hindi version of the Geriatric Depression Scale (GDS-H); the Hindi Mental State Exam (HMSE); the Everyday Abilities Scale for India (EASI); age, gender and literacy. Results The GDS-H had high internal consistency and a factor structure comparable to the original English language version. The overall distribution of scores was higher than reported from other populations. Greater numbers of depressive symptoms, as measured by higher scores on the GDS-H, were associated with older age and illiteracy. Among the illiterate, there was no gender difference while among the literate, higher GDS-H scores were found among women. Cognitive impairment and functional disability were independently associated with higher scores on the GDS-H after adjustment for age, gender and literacy. Conclusion A reliable and valid Hindi version of the GDS has been developed. Depressive symptoms as measured by the GDS-H were prominent in this elderly illiterate northern Indian population and strongly associated with both cognitive and functional impairment. Copyright

Modeling and Risk Prediction in the Current Era of Interventional Cardiology A Report From the National Heart, Lung, and Blood Institute Dynamic Registry

Background—Validation of in-hospital mortality models after percutaneous coronary interventions using multicenter data remains limited. Methods and Results—This study evaluated whether multivariable mortality models developed during the pre-stent era by New York State, American College of Cardiology (ACC)–National Cardiovascular Data Registry, Northern New England Cooperative Group, Cleveland Clinic Foundation, and the University of Michigan are relevant in patients undergoing percutaneous coronary intervention in the 1997 to 1999 National Heart, Lung, and Blood Institute Dynamic Registry. Of 4448 Dynamic Registry patients, 73% received ≥1 stent and 28% received a IIB/IIIA receptor inhibitor. In-hospital mortality occurred in 64 patients (1.4%). The New York state model predicted mortality in 69 patients (1.5%; 95% confidence bounds [CI], 0.89% to 1.70%); Northern New England predicted mortality in 60 patients (1.3%; 95% CI, 1.0% to 1.7%); and Cleveland Clinic predicted mortality in 76 patients (1.7%; 95% CI, 1.3% to 2.1%). Among high-risk subgroups, with these 3 models, observed and predicted in-hospital mortality rates in general were not different. The other 2 models yielded different results. The University of Michigan predicted fewer deaths (n=47; 1.1%; 95% CI, 0.7% to 1.3%), and the ACC Registry model predicted 603 deaths (13.5%; 95% CI, 12.6% to 14.4%). Using the ACC Registry model, predicted mortality was higher than observed in each subgroup. Conclusions—Application of 5 mortality risk models developed from different data sets to patients undergoing percutaneous coronary intervention in the Dynamic Registry predicted, in 3 models, mortality rates that were not significantly different than those observed. In both high and low risk subgroups, the University of Michigan slightly underpredicted mortality, and the ACC Registry predicted significantly higher mortality than that observed.

Comparison of in-hospital and one-year outcomes in patients with left ventricular ejection fractions ≤40%, 41% to 49%, and ≤50% having percutaneous coronary revascularization

Outcome studies of percutaneous coronary intervention (PCI) with conventional balloon angioplasty have established increased in-hospital and 1-year mortality in patients with left ventricular (LV) dysfunction compared with others. It is unclear whether recent PCI practice innovations, including stents and adjunctive pharmacotherapy, have made PCI safer and more effective in patients with LV dysfunction. We evaluated the influence of LV ejection fraction (EF) indexes on in-hospital and 1-year outcomes in 1,458 patients within the National Heart, Lung, and Blood Institute-sponsored Dynamic Registry. Patients (n = 300) with acute myocardial infarction were excluded. The remaining 1,158 patients were subdivided into 3 categories: group 1, EF <or=40% (n = 166); group 2, EF 41% to 49% (n = 126); and group 3, EF >or=50% (n = 866). We determined the frequency of individual and composite adverse events (death/myocardial infarction [MI]/coronary artery bypass grafting) at discharge and 1 year. In the Dynamic Registry patients, mean EF in the 3 groups was 32%, 45%, and 62% and in-hospital mortality was 3.0%, 1.6%, and 0.1%, respectively (p <0.001). The composite end point of death/MI was also significant, but other in-hospital adverse events did not differ between groups. The respective mortality rates were 11.0%, 4.5%, and 1.9% (p <0.001) after 1 year. The composite end points of death/MI and death/MI/coronary artery bypass grafting also occurred more frequently in group 1 patients. Thus, significant LV dysfunction was still associated with increased in-hospital and 1-year mortality in patients having contemporary PCI.

One-year clinical outcomes of protected and unprotected left main coronary artery stenting

Aims To evaluate outcomes for left main coronary artery (LMCA) stenting and compare results between protected (left coronary grafted) and unprotected LMCA stenting in the current bare-metal stent era. Methods We reviewed outcomes among 142 consecutive patients who underwent protected or unprotected LMCA stenting since 1997. All-cause mortality, myocardial infarction (MI), target-lesion revascularization (TLR), and the combined majoradverse clinical event (MACE) rates at one year were computed. Results Ninety-nine patients (70%) underwent protected and 43 patients (30%) underwent unprotected LMCA stenting. In the unprotected group, 86% were considered poor surgical candidates. Survival at one year was 88% for all patients, TLR 20%, and MACE 32%. At one year, survival was reduced in the unprotected group (72% vs. 95%, P <0.001) and MACE was increased in the unprotected patients (49% vs. 25%, P =0.005). Conclusions In the current era, stenting for both protected and unprotected LMCA disease is still associated with high long-term mortality and MACE rates. Stenting for unprotected LMCA disease in a high-risk population should only be considered in the absence of other revascularization options. Further studies are needed to evaluate the role of stenting for unprotected LMCA disease.