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Francine Grodstein

Publications and source records attributed to Francine Grodstein.

At least 19 recordsLinked to original sources
PubMed2006

Midlife plasma insulin-like growth factor I and cognitive function in older men.

CONTEXT: Emerging biological and epidemiological evidence suggests possible benefits of higher IGF-I levels in cognitive aging. OBJECTIVE: The objective of the study was to examine the relation of midlife plasma IGF-I levels to late-life cognition. DESIGN, SETTING, AND PARTICIPANTS: We conducted a secondary analysis from the Physicians' Health Study II, a prospective cohort of U.S. male physicians. Participants provided blood samples from 1982 to 1984 (mean age 57 yr). Using stored samples, we measured free IGF-I in 376 men and total IGF-I and IGF binding protein-3 in 460 men. Starting in 2001, we administered telephone-based tests of general cognition [the Telephone Interview of Cognitive Status (TICS)], verbal memory, and category fluency. We estimated multivariable-adjusted mean differences in cognitive performance across levels of free IGF-I and IGF-I to IGF binding protein-3 molar ratio. MAIN OUTCOME MEASURES: Global score (averaging performance across all individual cognitive tests), the TICS, and a verbal memory score were measured. RESULTS: Each sd increment in free IGF-I was associated with a multivariable-adjusted increase of 0.08 U (P = 0.02) on the global score. This mean difference was equivalent to that observed between men 2 yr apart in age: i.e. each sd increase in free IGF-I appeared cognitively equivalent to staying 2 yr younger. No significant mean differences in TICS scores were observed across free IGF-I levels. For verbal memory, each sd increment in free IGF-I was associated with an adjusted mean difference of 0.08 U (P = 0.03). Results appeared consistent for the molar ratio but were not statistically significant. CONCLUSION: Higher midlife free IGF-I may be associated with better late-life cognition.

Adult↗
PubMed2006

Risk factors for urinary incontinence among middle-aged women.

OBJECTIVE: The purpose of this study was to identify risk factors for urinary incontinence in middle-aged women. STUDY DESIGN: We conducted a cross-sectional analysis of 83,355 Nurses' Health Study II participants. Since 1989, women have provided health information on mailed questionnaires; in 2001, at the ages 37 to 54 years, information on urinary incontinence was requested. We examined adjusted odds ratios of incontinence using logistic regression. RESULTS: Forty-three percent of the women reported incontinence. After adjustment, black (odds ratio, 0.49; 95% CI, 0.40-0.60) and Asian-American women (odds ratio, 0.57; 95% CI, 0.46-0.72) were at reduced odds of severe incontinence compared with white women. Increased age, body mass index, parity, current smoking, type 2 diabetes mellitus, and hysterectomy all were associated positively with incontinence. Women who were aged 50 to 54 years had 1.81 times the odds of severe incontinence compared with women who were <40 years old (95% CI, 1.66-1.97); women with a body mass index of > or =30 kg/m2 had 3.10 times the odds of severe incontinence compared with a body mass index of 22 to 24 kg/m2 (95% CI, 2.91-3.30). CONCLUSION: Urinary incontinence is highly prevalent among these middle-aged women. Potential risk factors include age, race/ethnicity, body mass index, parity, smoking, diabetes mellitus, and hysterectomy.

Adult↗
PubMed2006

High-sensitivity C-reactive protein and cognitive function in older women.

BACKGROUND: Inflammatory processes may be involved in the development of dementia, although findings from epidemiologic studies directly examining inflammatory markers and dementia or its precursor, impaired cognitive function, are inconsistent. METHODS: We measured plasma levels of the inflammatory marker, C-reactive protein, using a high-sensitivity assay (hs-CRP) in 4,231 older participants of the Women's Health Study, who provided blood samples between 1992 and 1996 when they were age 60 to 90 years. From 1998 to 2000, we administered a battery of 5 cognitive tests measuring general cognition, verbal memory, and category fluency. Using multiple linear regression, we compared mean cognitive test scores across quintiles of hs-CRP, adjusting for potential confounding factors. RESULTS: There was a wide distribution of hs-CRP levels among these women, and a large proportion had levels considered to reflect a high risk of cardiovascular disease. We observed no suggestion, however, that higher hs-CRP levels were associated with poorer cognitive performance. For example, on a global score combining results of all the cognitive tests, mean scores among women in the highest quintile of hs-CRP did not differ from those in the lowest quintile (multivariable-adjusted mean difference = 0.04; 95% confidence interval [CI]: -0.02 to 0.11, P for trend across quintiles = 0.38). CONCLUSION: Overall, in these women, we found no evidence of a link between hs-CRP, a marker of inflammation, and decrements in cognitive function.

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PubMed2006

Prospective study of plasma folate, vitamin B12, and cognitive function and decline.

BACKGROUND: The relation between B vitamins and cognitive decline is controversial. In this study, we explored the association of plasma folate and vitamin B12 with cognitive function measured approximately 10 years later. METHODS: We determined plasma folate and vitamin B12 levels from blood samples collected in 1989 to 1990 and initially evaluated cognition in 1995 to 2001 among 635 women, age 70+ years, from the Nurses' Health Study. In a subset of 391, 3 repeated cognitive tests were completed for evaluation of cognitive decline over 4 years; repeated testing is ongoing for the remaining women. Our primary outcome was a global composite score of 6 neuropsychologic tests administered by telephone. We used linear regression models to estimate multivariable-adjusted mean cognitive performance across quartiles of the vitamins and longitudinal models for cognitive decline. RESULTS: Higher vitamin levels were not associated with either initial cognitive performance or subsequent cognitive decline. Mean difference in initial global score for top versus bottom quartiles was 0.06 standard units for folate (95% confidence interval [CI] = -0.10 to 0.22) and 0.15 units for vitamin B12 (0.00 to 0.31). There were no dose-response trends for either nutrient. Women with high levels of both nutrients initially performed better than women low in both nutrients (global score, mean difference = 0.34; 95% CI = 0.05 to 0.62); this association did not hold for subsequent cognitive decline. CONCLUSIONS: Combined B vitamin deficiency may be associated with impaired cognition, but in these healthy, well-nourished women, plasma folate and vitamin B12 were not related to cognitive function.

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PubMed2006

Plasma C-peptide and cognitive performance in older men without diabetes.

BACKGROUND: Emerging evidence suggests that type 2 diabetes may be related to diminished cognition, but little data are available directly regarding the role of insulin levels. OBJECTIVE: The objective of this prospective cohort study was to examine the relation of insulin secretion to cognitive function among men without diabetes. SETTING: The study setting was the Physicians' Health Study-U.S. male physicians. PARTICIPANTS: Three hundred sixty-seven men who provided blood samples in 1982, when they had no lifetime history of diabetes and ranged in age from 47-65 years (mean age: 57 years). MEASUREMENTS: The authors assayed plasma C-peptide, reflecting insulin secretion, in the stored blood samples. Beginning in 2001, an average 18 years after blood collection, the authors administered telephone interviews, including tests of general cognition (Telephone Interview of Cognitive Status [TICS]), verbal memory, and category fluency. The authors used regression models to estimate mean differences in cognitive performance across levels of C-peptide controlling for a wide variety of potential confounding factors. RESULTS: On the TICS, men in the top tertile of C-peptide performed significantly worse than those in the bottom (multivariable-adjusted mean difference: -1.01 points, 95% confidence interval: -1.78 to -0.24); this apparent impact of C-peptide on cognition was equivalent to the cognitive differences the authors observed between men 6 years apart in age. Performance on the global score (combining results from all the individual tests) and verbal memory score (combining results from four tests of verbal memory) appeared lower among men in the highest C-peptide tertile, but results were not statistically significant. CONCLUSION: Higher midlife insulin secretion may be related to decreased later-life cognitive function, even among men without diabetes.

C-Peptide↗
PubMed2005

The relation of education and income to cognitive function among professional women.

We investigated the relation of educational attainment and annual household income to cognitive function and cognitive decline in community-dwelling women aged 66 years or older. Subjects were 6,314 health professionals participating in the Women's Health Study, among whom information on education and income was self-reported. From 1998 to 2000, we administered five cognitive tests, measuring general cognition, episodic memory and verbal fluency, using a validated telephone interview. Second cognitive assessments were conducted approximately 2 years later; information was complete for 5,573 women at the time of analysis, with 94% follow-up. We used linear and logistic regression to calculate multivariate-adjusted mean differences as well as odds of cognitive impairment (defined as worst 10% of test distribution) and of substantial decline in performance (worst 10% of distribution), across various levels of education and income. After adjusting for numerous potential confounding factors, we found strong trends of increasing mean cognitive performance with increasing level of education (p trend<0.0005 on all cognitive measures). Odds of cognitive impairment also consistently decreased with increasing education. For income, we found significant trends of increasing mean cognitive performance with increasing income on the summary score and on episodic memory (p trends<0.0001). Results were generally similar for cognitive decline over 2 years, although slightly weaker. Thus, in these well-educated, professional women, educational attainment and income both predicted cognitive function and decline.

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PubMed2005

Plasma IGF-I levels and cognitive performance in older women.

BACKGROUND: Emerging biologic and epidemiologic evidence suggests benefits of insulin-like growth factor-I (IGF-I) in cognitive aging. OBJECTIVE: To examine the relation of circulating IGF-I to cognition. METHODS: We measured plasma IGF-I and IGF-binding protein-3 (IGFBP-3) in 590 women aged 60-68 years. An average 10 years later, we administered telephone-based tests of general cognition (Telephone Interview of Cognitive Status [TICS]), verbal memory, category fluency, and attention. We estimated multivariable-adjusted mean differences in performance across levels of IGF-I/IGFBP-3 molar ratio. RESULTS: On the TICS, each standard deviation (S.D.) increase in molar ratio was significantly associated with better performance: multivariable-adjusted mean difference=0.2 units, 95% confidence interval (0.0,0.4), p=0.05. This effect estimate for each S.D. increase in molar ratio was cognitively equivalent to the mean difference we observed on the TICS between women 1 year apart in age. On a global score combining all tests, there was also a trend of better performance with each S.D. increase in molar ratio (p=0.07). IGF-I levels were not associated with performance in verbal memory. CONCLUSIONS: Higher IGF-I levels may be associated with better general cognition.

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PubMed2005

Plasma C peptide level and cognitive function among older women without diabetes mellitus.

BACKGROUND: Growing evidence suggests that type 2 diabetes mellitus and hyperinsulinemia may be related to diminished cognition. To help differentiate between the effects of diabetes and insulin, we examined the relation of insulin to cognitive function among nondiabetic participants of the Nurses' Health Study. METHODS: We measured the C peptide level, representing insulin secretion, in blood samples provided by 718 women from June 14, 1989, to October 4, 1990, when they were aged 61 to 69 years. We administered telephone interviews an average of 10 years after blood collection, testing general cognition, verbal memory, category fluency, and attention; second cognitive assessments were conducted 2 years later. The primary outcomes were global cognitive function across all tests and verbal memory. We used regression models to estimate multivariable-adjusted mean differences in cognitive function and cognitive decline, and odds of cognitive impairment, across C peptide levels. RESULTS: Cognitive function was worse among women in the fourth C peptide quartile compared with those in the first quartile (eg, on the global score combining all cognitive tests, the multivariable-adjusted mean difference was -1.7 standard units [95% confidence interval, -2.9 to -0.6 standard units]; P = .002); the odds of cognitive impairment (defined as the worst 10% of the distribution) were 3-fold higher among women in the fourth vs first quartile (95% confidence interval, 1.3-7.8). On verbal memory, women in the fourth quartile scored significantly worse than those in the first quartile; the odds of impairment were 2.8-fold higher (95% confidence interval, 1.1-7.0). Consistent findings were observed for cognitive decline. CONCLUSION: Higher insulin secretion may be related to worse cognition, even among those without diabetes.

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PubMed2005

Effects of moderate alcohol consumption on cognitive function in women.

BACKGROUND: The adverse effects of excess alcohol intake on cognitive function are well established, but the effect of moderate consumption is uncertain. METHODS: Between 1995 and 2001, we evaluated cognitive function in 12,480 participants in the Nurses' Health Study who were 70 to 81 years old, with follow-up assessments in 11,102 two years later. The level of alcohol consumption was ascertained regularly beginning in 1980. We calculated multivariate-adjusted mean cognitive scores and multivariate-adjusted risks of cognitive impairment (defined as the lowest 10 percent of the scores) and a substantial decline in cognitive function over time (defined as a change that was in the worst 10 percent of the distribution of the decline). We also stratified analyses according to the apolipoprotein E genotype in a subgroup of women. RESULTS: After multivariate adjustment, moderate drinkers (those who consumed less than 15.0 g of alcohol per day [about one drink]) had better mean cognitive scores than nondrinkers. Among moderate drinkers, as compared with nondrinkers, the relative risk of impairment was 0.77 on our test of general cognition (95 percent confidence interval, 0.67 to 0.88) and 0.81 on the basis of a global cognitive score combining the results of all tests (95 percent confidence interval, 0.70 to 0.93). The results for cognitive decline were similar; for example, on our test of general cognition, the relative risk of a substantial decline in performance over a two-year period was 0.85 (95 percent confidence interval, 0.74 to 0.98) among moderate drinkers, as compared with nondrinkers. There were no significant associations between higher levels of drinking (15.0 to 30.0 g per day) and the risk of cognitive impairment or decline. There were no significant differences in risks according to the beverage (e.g., wine or beer) and no interaction with the apolipoprotein E genotype. CONCLUSIONS: Our data suggest that in women, up to one drink per day does not impair cognitive function and may actually decrease the risk of cognitive decline.

Aged↗
PubMed2005

Fruit and vegetable consumption and cognitive decline in aging women.

We prospectively examined fruit and vegetable intake in relation to cognitive function and decline among aging women. Participants were followed from in 1976 with biennial questionnaires, and food frequency questionnaires were administered in 1984, 1986, and every 4 years thereafter. From 1995 to 2001, we administered, by telephone, six cognitive tests measuring general cognition, verbal memory, category fluency, and working memory. We repeated assessments two years later for 13,388 women (>90% follow-up). We averaged dietary intakes from 1984 through the first cognitive assessment, and used linear regression to obtain multivariable-adjusted mean differences in performance and decline in performance across intake levels. Fruits were not associated with cognition or cognitive decline. However, total vegetable intake was significantly associated with less decline. Specifically, on a global score combining all tests, women in the highest quintile of cruciferous vegetables declined slower (by 0.04 unit; 95% confidence interval, 0.003, 0.07; p trend = 0.1) compared with the lowest quintile. Women consuming the most green leafy vegetables also experienced slower decline than women consuming the least amount (by 0.05 unit; 95% confidence interval, 0.02, 0.09; p trend < 0.001). These mean differences were equivalent to those observed for women about 1 to 2 years apart in age.

Adult↗
PubMed2005

Apolipoprotein E, cardiovascular disease and cognitive function in aging women.

The apolipoprotein E (APOE) e4 allele increases risk of Alzheimer disease and cardiovascular diseases. We examined APOE genotypes alone or combined with cardiovascular conditions in relation to cognitive function in 4227 Nurses' Health Study participants, 70-80 years old. From 1995 to 2001, and again 2 years later, participants received telephone cognitive assessments of general cognition, category fluency, verbal memory and working memory. In biennial questionnaires since 1976, participants have provided extensive health information including cardiovascular conditions. Compared with women with the e3/3 genotype, e4 carriers performed worse at baseline across all tests (mean global composite score was lower by 0.10 points (95% confidence interval=-0.15, -0.05)) and declined more (mean change in global score was -0.07 points (95% CI=-0.12, -0.03)), with a strong allele dose-response trend (P-trend=0.0003). Among participants 75+ years, e2 carriers performed best. Women with an e4 allele and cardiovascular conditions such as transient ischemic attack or untreated hypertension had the worst cognition. Thus, APOE genotypes strongly influenced cognitive function and decline; prevention of cardiovascular disease may limit these effects.

Aged↗
PubMed2005

Type 2 diabetes mellitus and risk of developing urinary incontinence.

OBJECTIVES: To evaluate the association between type 2 diabetes mellitus (DM) and development of urinary incontinence in women. DESIGN: Prospective, observational study. SETTING: The Nurses' Health Study cohort. PARTICIPANTS: Eighty-one thousand eight hundred forty-five women who reported information on urinary function in 1996. MEASUREMENTS: Self-reported, physician-diagnosed DM was ascertained using questionnaire from 1976 to 1996 and confirmed using standard criteria. Self-reported urinary incontinence, defined as leakage at least weekly, was ascertained in 1996 and 2000. Logistic regression models were used to calculate multivariate-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the relationship between DM (as of 1996) and prevalent and incident incontinence. RESULTS: The risk of prevalent incontinence (multivariate RR=1.28, 95% CI=1.18-1.39) and incident incontinence (multivariate RR=1.21, 95% CI=1.02-1.43) was significantly greater in women with DM than women without. Using a validated severity index, risk of developing severe incontinence was even more substantial in women with DM than in those without (multivariate RR=1.40, 95% CI=1.15-1.71 for leakage enough to wet the underwear; RR=1.97, 95% CI=1.24-3.12 for leakage enough to wet the outer clothing). In addition, risk of incontinence increased with duration of DM (P-trend=.03 for prevalent incontinence; P=.001 for incident incontinence). CONCLUSION: DM independently increases risk of urinary incontinence in women. Because risk of incontinence appeared associated with longer duration of DM, even delaying the onset of DM could have important public health implications.

Adult↗
PubMed2005

Prevalence and effects of lobar microhemorrhages in early-stage dementia.

BACKGROUND: 80-100% of patients with Alzheimer's disease have vascular pathology related to cerebral amyloid angiopathy (CAA), and 5-7% have CAA-related lobar microhemorrhages (LMH) at autopsy. The prevalence and effects of LMH detectable by gradient echo MRI (GE-MRI) in early-stage dementia are unknown. OBJECTIVE: To obtain, using GE-MRI, a prevalence estimate for LMH in patients with early-stage dementia and to assess the effects of LMH on dementia severity. METHODS: Eighty-four subjects aged >or=55 years (range 58-89; mean 76) underwent cognitive and GE-MRI evaluation. The 84 subjects consisted of 61 consecutive subjects evaluated as part of an initial clinical evaluation for dementia and 23 consecutively evaluated healthy older subjects (controls). Data were analyzed for presence and number of LMH on GE-MRI and the effect of number of LMH on dementia severity. RESULTS: Nine (15%) of the 61 dementia patients versus 1 (4%) of the 23 control subjects demonstrated LMH on GE-MRI. Multiple (>or=2) LMH were found in 7 of the 9 (88%) dementia subjects with LMH (range of LMH counts 1-330) and no (0%) control subjects. Multivariable causal modeling indicated that number of LMH (p < 0.02), age (p < 0.01) and duration of symptoms (p < 0.001) significantly increased dementia severity while higher educational level (p < 0.001) was protective. CONCLUSIONS: LMH were detected by GE-MRI in 15% of patients with early-stage dementia and may contribute to dementia severity.

Aged↗
PubMed2004

Physical activity, including walking, and cognitive function in older women.

CONTEXT: Physical activity may help maintain cognitive function in older adults. OBJECTIVE: To examine the relation of long-term regular physical activity, including walking, to cognitive function. DESIGN: Women reported participation in leisure-time physical activities on biennial mailed questionnaires beginning in 1986. We assessed long-term activity by averaging energy expenditures from questionnaires in 1986 through participants' baseline cognitive assessments (1995 to 2001). We used linear regression to estimate adjusted mean differences in baseline cognitive performance and cognitive decline over 2 years, across levels of physical activity and walking. SETTING AND PARTICIPANTS: Nurses' Health Study, including 18 766 US women aged 70 to 81 years. MAIN OUTCOME MEASURE: Validated telephone assessments of cognition administered twice approximately 2 years apart (1995 to 2001 and 1997 to 2003), including tests of general cognition, verbal memory, category fluency, and attention. RESULTS: Higher levels of activity were associated with better cognitive performance. On a global score combining results of all 6 tests, women in the second through fifth quintiles of energy expenditure scored an average of 0.06, 0.06, 0.09, and 0.10 standard units higher than women in the lowest quintile (P for trend <.001). Compared with women in the lowest physical activity quintile, we found a 20% lower risk of cognitive impairment for women in the highest quintile of activity. Among women performing the equivalent of walking at an easy pace for at least 1.5 h/wk, mean global scores were 0.06 to 0.07 units higher compared with walking less than 40 min/wk (P< or =.003). We also observed less cognitive decline among women who were more active, especially those in the 2 highest quintiles of energy expenditure. Women in the fourth and fifth quintiles had mean changes in global scores that were 0.04 (95% confidence interval, 0.02-0.10) and 0.06 (95% confidence interval, 0.02-0.11) standard units better than those in the lowest quintile. CONCLUSION: Long-term regular physical activity, including walking, is associated with significantly better cognitive function and less cognitive decline in older women.

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PubMed2004

Postmenopausal hormone therapy and risk of cognitive decline in community-dwelling aging women.

BACKGROUND: A randomized trial of postmenopausal women over age 65 reported increased risks of cognitive decline with 4 years of combined estrogen and progestin treatment. However, questions remain, including the effect of longer duration or of hormone therapy initiated at younger ages. METHODS: The Nurses' Health Study is a prospective cohort begun in 1976, comprising 121,700 female nurses who report health information via biennial mailed questionnaires. This substudy includes 13,807 participants age 70 to 81 who completed two telephone cognitive assessments, 2 years apart, between 1995 and 2003. General cognition, verbal memory, category fluency, and attention were tested. Multiple linear regression was used to estimate adjusted mean declines and logistic regression to estimate adjusted risks of substantial decline in cognition (> or =2 SD of baseline performance) across hormone groups. APOE genotype was available in a subset of 3,667 participants. RESULTS: Overall, little difference was found in mean cognitive decline between current hormone users and never users. However, for long-term users of estrogen alone or combined with progestin, increased risk of substantial decline was observed on most cognitive tests (relative risk [RR] = 1.25 to 1.72). Decline was particularly high among women initiating hormones at older ages compared with never users: for example, on our test of general cognition, RR of substantial decline was 1.74 (95% CI 1.08, 2.81) and mean difference in decline was -0.43 (95% CI -0.73, -0.12). No significant interactions between hormone use and APOE epsilon4 allele were observed. CONCLUSION: Postmenopausal hormone therapy provides no appreciable cognitive benefits in older women.

Age Factors↗
PubMed2004

Effects of marital transitions on changes in dietary and other health behaviours in US women.

BACKGROUND: Previous studies have indicated that married people have lower mortality and are generally healthier. Most previous studies have been cross-sectional and few studies investigated the effect of marital transition on health. With a prospective design and repeated measures of variables, we sought to analyse the temporal relation between marital transition and change in health behaviours. METHODS: We followed up 80 944 women aged 46-71 for 4 years (1992-1996). All information was self-reported. We used multivariate-adjusted linear and logistic regression models to examine the impact of changes in marital status on concomitant changes in health behaviours, controlling for potential confounders and baseline health behaviours. RESULTS: Compared with women who remained married, women who divorced/widowed had body mass index (BMI) decreases of 0.65 kg/m(2) (P < 0.001) and 0.44 kg/m(2) (P < 0.001), respectively. Compared with women who remained unmarried, women who remarried had an increase in mean BMI of 0.41 kg/m(2) (P < 0.001). Women who divorced increased physical activity by 1.23 metabolic equivalent hours (MET)/week (P = 0.07) compared with women who stayed married. Among non-smokers and past smokers, women who divorced/widowed had more than a twofold increased risk of relapsing/starting smoking (OR = 2.47, 95% CI: 1.56, 3.89; OR = 2.08, 95% CI: 1.56, 2.76, respectively) than women who stayed married. Divorced and widowed women had decreased vegetable intake relative to women who stayed married (-2.93 servings/week [P < 0.001] and -1.67 servings/week [P < 0.001], respectively). CONCLUSIONS: These patterns suggest both health-damaging and health-promoting changes accompanying divorce and widowhood, and generally health-promoting changes following remarriage.

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