Terri Blackwell

Diabetes, impaired fasting glucose, and development of cognitive impairment in older women

Objective: To investigate the association between diabetes and impaired fasting glucose (IFG) and cognition and risk of developing both dementia and mild cognitive impairment (MCI) in older women. Methods: The authors analyzed data from a 4-year randomized trial of raloxifene among 7,027 osteoporotic postmenopausal women (mean age, 66.3 years) at 178 sites. Diabetes was defined by history, fasting blood glucose ≥7.0 mmol/L (≥126 mg/dL), or use of hypoglycemic agents; IFG was defined as fasting glucose <7.0 mmol/L but >6.11 mmol/L (110 mg/dL); all others were considered to have normal glucose (NG). The main outcome was baseline and 4-year change on five standardized cognitive tests (z scores with lower scores indicating worse performance) and risk of developing clinically significant impairment (dementia, mild cognitive impairment, or very low cognitive score). Results: A total of 267 (3.8%) women had diabetes and 297 (4.2%) had IFG. Women with IFG had worse baseline cognitive scores compared to women with NG but better scores than diabetics (age-adjusted composite z score based on five tests: NG 0.40, 95% CI 0.30 to 0.49; IFG 0.14, 95% CI −0.36 to 0.64; diabetics −0.78, 95% CI −1.23 to −0.33; p < 0.001). There was greater 4-year decline among diabetics (age and treatment-adjusted composite z score: NG −0.05, 95% CI −0.16 to 0.05; IFG 0.11, 95% CI −0.53 to 0.75; diabetics −1.00, 95% CI −1.50 to −0.50; p = 0.001). Further adjustment for education, race, and depression led to similar results. Risk of developing cognitive impairment among women with IFG or diabetes was increased by almost twofold (age and treatment-adjusted OR = 1.64; 95% CI 1.03 to 2.61 for IFG; OR = 1.79; 95% CI 1.14 to 2.81 for diabetics). Conclusions: Diabetic as well as pre-diabetic women have impaired cognitive performance and greater risk of developing cognitive impairment.

Central Nervous System–Active Medications and Risk for Falls in Older Women

OBJECTIVES: To determine whether current use of central nervous system (CNS)‐active medications, including benzodiazepines, antidepressants, anticonvulsants, and narcotics, increases the risk for subsequent falls.

Central nervous system active medications and risk for fractures in older women.

BACKGROUND Use of central nervous system (CNS) active medications may increase the risk for fractures. Prior studies are limited by incomplete control of confounders. METHODS To determine whether use of CNS active medications, including benzodiazepines, antidepressants, anticonvulsants, and narcotics, increases fracture risk in elderly, community-dwelling women, we examined use of these 4 categories of medications in a cohort of 8127 older women and followed the participants prospectively for incident nonspine fractures, including hip fractures. Current use of CNS active medications was assessed by interview with verification of use from containers between 1992 and 1994 and between 1995 and 1996. Use was coded as a time-dependent variable. Incident nonspine fractures occurring after the initial medication assessment until May 31, 1999, were confirmed by radiographic reports. RESULTS During an average follow-up of 4.8 years, 1256 women (15%) experienced at least one nonspine fracture, including 288 (4%) with first hip fractures. Compared with nonusers, women taking narcotics (multivariate hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.83) and those taking antidepressants (multivariate HR, 1.25; 95% CI, 0.99-1.58) had increases in the risks for any nonspine fractures. Women taking tricyclic antidepressants and those using selective serotonin reuptake inhibitors (SSRIs) had similar fracture rates. There were no independent associations between benzodiazepine use or anticonvulsant use and risk for nonspine fracture. Women taking antidepressants compared with nonusers had a 1.7-fold increase in the risk for hip fracture (multivariate HR, 1.65; 95% CI, 1.05-2.57). We did not observe independent associations between use of any of the other 3 classes of CNS active medications and risk of hip fracture. CONCLUSIONS Community-dwelling older women taking narcotics have an increased risk for any nonspine fracture, and those taking antidepressants have a greater risk for nonspine fractures, including hip fracture. Rates of fracture were similar in women taking tricyclic antidepressants and those using SSRIs. Benzodiazepine use and anticonvulsant use were not independently associated with an increased risk of nonspine fractures, including hip fracture.

Rate of bone loss is associated with mortality in older women: a prospective study.

Older women with low bone density have an increased risk of fracture, cardiovascular disease, and mortality. However, it is not known whether this association is caused by ongoing bone loss or by lower bone mass earlier in life. To determine whether rate of bone loss is associated with total and cause‐specific mortality, we prospectively studied 6046 women aged 65 years or older who had serial bone mineral density (BMD) measurements as a part of the Study of Osteoporotic Fractures. Rates (mean ± SD) of loss of BMD at the heel (for a mean of 5.7 years) and hip (for a mean of 3.5 years) were estimated. Cause‐specific mortality was ascertained from death certificates and hospital records. BMD loss at the heel was 5.9 ± 6.0 mg/cm2 per year (1.5 ± 1.5%) and BMD loss at the hip was 4.1 ± 10.2 mg/cm2 per year (0.6 ± 1.4%). During an average follow‐up of 3.2 years after the second measurement of BMD, 371 deaths occurred. Each SD increase in BMD loss at the hip was associated with a 1.3‐fold (95% CI, 1.1‐1.4) increase in total mortality, adjusted for age, baseline BMD, diabetes, hypertension, incident fractures, smoking, physical activity, health status, weight loss, and calcium use. In particular, hip BMD loss was associated with increased mortality from coronary heart disease (relative hazard [RH] = 1.3 per SD; 95% CI, 1.0‐1.8) and pulmonary diseases (RH = 1.6 per SD; 95% CI, 1.1‐2.5). The findings were similar for bone loss at the heel, except there was no significant association with pulmonary mortality. These results raise the possibility that bone loss may share common etiologies with coronary and pulmonary diseases.

Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women.

Previous cross‐sectional studies have observed alterations in activity rhythms in dementia patients but the direction of causation is unclear. We determined whether circadian activity rhythms measured in community‐dwelling older women are prospectively associated with incident dementia or mild cognitive impairment (MCI).

The Association between Sleep Duration and Obesity in Older Adults

Background:Reduced sleep has been reported to predict obesity in children and young adults. However, studies based on self-report have been unable to identify an association in older populations. In this study, the cross-sectional associations between sleep duration measured objectively and measures of weight and body composition were assessed in two cohorts of older adults.Methods:Wrist actigraphy was performed for a mean (s.d.) of 5.2 (0.9) nights in 3055 men (age: 67–96 years) participating in the Osteoporotic Fractures in Men Study (MrOS) and 4.1 (0.8) nights in 3052 women (age: 70–99 years) participating in the Study of Osteoporotic Fractures (SOF). A subgroup of 2862 men and 455 women also underwent polysomnography to measure sleep apnea severity.Results:Compared to those sleeping an average of 7–8 h per night, and after adjusting for multiple risk factors and medical conditions, a sleep duration of less than 5 h was associated with a body mass index (BMI) that was on average 2.5 kg/m2 (95% confidence interval (CI): 2.0–2.9) greater in men and 1.8 kg/m2 (95% CI: 1.1–2.4) greater in women. The odds of obesity (BMI ⩾30 kg/m2) was 3.7-fold greater (95% CI: 2.7–5.0) in men and 2.3-fold greater in women (95% CI: 1.6–3.1) who slept less than 5 h. Short sleep was also associated with central body fat distribution and increased percent body fat. These associations persisted after adjusting for sleep apnea, insomnia and daytime sleepiness.Conclusions:In older men and women, actigraphy-ascertained reduced sleep durations are strongly associated with greater adiposity.

The Metabolic Syndrome and Development of Cognitive Impairment Among Older Women

BACKGROUND Several studies support a role for cardiovascular risk factors in cognitive aging. The metabolic syndrome, a constellation of cardiovascular risk factors, is common in elderly people. A growing but conflicting body of literature suggests that the metabolic syndrome may be associated with cognitive impairment. OBJECTIVE To investigate the association between the metabolic syndrome and its components and incident cognitive impairment in older women. DESIGN We prospectively determined if the metabolic syndrome and its components were associated with a 4-year risk of developing cognitive impairment (dementia, mild cognitive impairment, or low global cognitive test score). SETTING The study was conducted at 180 clinical centers in 25 countries. PARTICIPANTS A total of 4895 older women (mean age, 66.2 years) with osteoporosis who were part of an ancillary study to determine clinically relevant cognitive impairment were included in this study. These women were free of baseline cognitive impairment and had metabolic syndrome component measures. MAIN OUTCOME MEASURES Clinically significant cognitive impairment was defined to include women with clinically adjudicated dementia or MCI and women who had a Short Blessed test score greater than 6 (consistent with impairment), but whose cases were not clinically adjudicated. Logistic regression analysis was used to examine the association between presence of the metabolic syndrome and development of clinically significant cognitive impairment. RESULTS A total of 497 women (10.2%) had the metabolic syndrome and, of these, 36 (7.2%) developed cognitive impairment compared with 181 (of 4398 or 4.1%) without the syndrome (age-adjusted odds ratio, 1.66; 95% confidence interval, 1.14-2.41). The mean (SD) number of metabolic syndrome components for all women was 1.0 (1.1); 518 women (10.6%) were obese, 895 (18.3%) had hypertriglyceridemia, 1200 (24.5%) had low high-density lipoprotein cholesterol levels, 1944 (39.7%) had high blood pressure, and 381 (7.8%) had high fasting blood glucose levels. There was a 23.0% age-adjusted increase in the risk of developing cognitive impairment (odds ratio, 1.23; 95% confidence interval, 1.09-1.39) per unit increase in the number of components. Further multivariable adjustment somewhat reduced the effect. CONCLUSION We found an association between the metabolic syndrome and the number of components and risk of developing cognitive impairment in older women. Additional studies are needed to determine if screening and close management of these at-risk elderly women would diminish the incidence of cognitive impairment.

Nocturnal Arrhythmias Across a Spectrum of Obstructive and Central Sleep-Disordered Breathing in Older Men: Outcomes of Sleep Disorders in Older Men (MrOS Sleep) Study

BACKGROUND Rates of cardiac arrhythmias increase with age and may be associated with clinically significant morbidity. We studied the association between sleep-disordered breathing (SDB) with nocturnal atrial fibrillation or flutter (AF) and complex ventricular ectopy (CVE) in older men. METHODS A total of 2911 participants in the Outcomes of Sleep Disorders in Older Men Study underwent unattended polysomnography. Nocturnal AF and CVE were ascertained by electrocardiogram-specific analysis of the polysomnographic data. Exposures were (1) SDB defined by respiratory disturbance index (RDI) quartile (a major index including all apneas and hypopneas), and ancillary definitions incorporating (2) obstructive events, obstructive sleep apnea (OSA; Obstructive Apnea Hypopnea Index quartile), or (3) central events, central sleep apnea (CSA; Central Apnea Index category), and (4) hypoxia (percentage of sleep time with <90% arterial oxygen percent saturation). Multivariable logistic regression analyses were performed. RESULTS An increasing RDI quartile was associated with increased odds of AF and CVE (P values for trend, .01 and <.001, respectively). The highest RDI quartile was associated with increased odds of AF (odds ratio [OR], 2.15; 95% confidence interval [CI], 1.19-3.89) and CVE (OR, 1.43; 95% CI, 1.12-1.82) compared with the lowest quartile. An increasing OSA quartile was significantly associated with increasing CVE (P value for trend, .01) but not AF. Central sleep apnea was more strongly associated with AF (OR, 2.69; 95% CI, 1.61-4.47) than CVE (OR, 1.27; 95% CI, 0.97-1.66). Hypoxia level was associated with CVE (P value for trend, <.001); those in the highest hypoxia category had an increased odds of CVE (OR, 1.62; 95% CI, 1.23-2.14) compared with the lowest quartile. CONCLUSIONS In this large cohort of older men, increasing severity of SDB was associated with a progressive increase in odds of AF and CVE. When SDB was characterized according to central or obstructive subtypes, CVE was associated most strongly with OSA and hypoxia, whereas AF was most strongly associated with CSA, suggesting that different sleep-related stresses may contribute to atrial and ventricular arrhythmogenesis in older men.

Metabolic Syndrome and Cognitive Decline in Elderly Latinos: Findings from the Sacramento Area Latino Study of Aging Study

OBJECTIVES: To investigate the effect of metabolic syndrome on cognitive function in an elderly Latino population and to determine whether inflammation modifies this association.

Antiepileptic drug use increases rates of bone loss in older women: A prospective study

Objective: To test the hypothesis that older women with antiepileptic drug (AED) use have increased rates of bone loss. Methods: AED use was ascertained and calcaneal and hip bone mineral density (BMD) measured in a cohort of 9,704 elderly community-dwelling women enrolled in the Study of Osteoporotic Fractures, and they were followed prospectively for changes in BMD. Current use of AED was assessed by interview, with verification of use from medication containers at baseline and follow-up examinations. Women were classified as continuous users, partial (intermittent) users, or nonusers. Rates of change in BMD were measured at the total hip and two subregions (average 4.4 years between examinations) and at the calcaneus (average 5.7 years between examinations). Results: After adjustment for confounders, the average rate of decline in total hip BMD steadily increased from −0.70%/year in nonusers to −0.87%/year in partial AED users to −1.16%/year in continuous AED users (p value for trend = 0.015). Higher rates of bone loss were also observed among continuous AED users at subregions of the hip and at the calcaneus. In particular, continuous phenytoin users had an adjusted 1.8-fold greater mean rate of loss at the calcaneus compared with nonusers of AED (−2.68 vs −1.46%/year; p < 0.001) and an adjusted 1.7-fold greater mean rate of loss at the total hip compared with nonusers of AED (−1.16 vs −0.70%/year; p = 0.069). Conclusions: Continuous AED use in elderly women is associated with increased rates of bone loss at the calcaneus and hip. If unabated, the rate of hip bone loss among continuous AED users is sufficient to increase the risk of hip fracture by 29% over 5 years among women age 65 years and older.