Kristine E. Ensrud

Sleep-Disordered Breathing, Hypoxia, and Risk of Mild Cognitive Impairment and Dementia in Older Women

CONTEXTnSleep-disordered breathing (characterized by recurrent arousals from sleep and intermittent hypoxemia) is common among older adults. Cross-sectional studies have linked sleep-disordered breathing to poor cognition; however, it remains unclear whether sleep-disordered breathing precedes cognitive impairment in older adults.nnnOBJECTIVESnTo determine the prospective relationship between sleep-disordered breathing and cognitive impairment and to investigate potential mechanisms of this association.nnnDESIGN, SETTING, AND PARTICIPANTSnProspective sleep and cognition study of 298 women without dementia (mean [SD] age: 82.3 [3.2] years) who had overnight polysomnography measured between January 2002 and April 2004 in a substudy of the Study of Osteoporotic Fractures. Sleep-disordered breathing was defined as an apnea-hypopnea index of 15 or more events per hour of sleep. Multivariate logistic regression was used to determine the independent association of sleep-disordered breathing with risk of mild cognitive impairment or dementia, adjusting for age, race, body mass index, education level, smoking status, presence of diabetes, presence of hypertension, medication use (antidepressants, benzodiazepines, or nonbenzodiazepine anxiolytics), and baseline cognitive scores. Measures of hypoxia, sleep fragmentation, and sleep duration were investigated as underlying mechanisms for this relationship.nnnMAIN OUTCOME MEASURESnAdjudicated cognitive status (normal, dementia, or mild cognitive impairment) based on data collected between November 2006 and September 2008.nnnRESULTSnCompared with the 193 women without sleep-disordered breathing, the 105 women (35.2%) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (31.1% [n = 60] vs 44.8% [n = 47]; adjusted odds ratio [AOR], 1.85; 95% confidence interval [CI], 1.11-3.08). Elevated oxygen desaturation index (≥15 events/hour) and high percentage of sleep time (>7%) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR, 1.71 [95% CI, 1.04-2.83] and AOR, 2.04 [95% CI, 1.10-3.78], respectively). Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment.nnnCONCLUSIONnAmong older women, those with sleep-disordered breathing compared with those without sleep-disordered breathing had an increased risk of developing cognitive impairment.

Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes.

CONTEXTnType 2 diabetes mellitus (DM) is associated with higher bone mineral density (BMD) and paradoxically with increased fracture risk. It is not known if low BMD, central to fracture prediction in older adults, identifies fracture risk in patients with DM.nnnOBJECTIVEnTo determine if femoral neck BMD T score and the World Health Organization Fracture Risk Algorithm (FRAX) score are associated with hip and nonspine fracture risk in older adults with type 2 DM.nnnDESIGN, SETTING, AND PARTICIPANTSnData from 3 prospective observational studies with adjudicated fracture outcomes (Study of Osteoporotic Fractures [December 1998-July 2008]; Osteoporotic Fractures in Men Study [March 2000-March 2009]; and Health, Aging, and Body Composition study [April 1997-June 2007]) were analyzed in older community-dwelling adults (9449 women and 7436 men) in the United States.nnnMAIN OUTCOME MEASUREnSelf-reported incident fractures, which were verified by radiology reports.nnnRESULTSnOf 770 women with DM, 84 experienced a hip fracture and 262 a nonspine fracture during a mean (SD) follow-up of 12.6 (5.3) years. Of 1199 men with DM, 32 experienced a hip fracture and 133 a nonspine fracture during a mean (SD) follow-up of 7.5 (2.0) years. Age-adjusted hazard ratios (HRs) for 1-unit decrease in femoral neck BMD T score in women with DM were 1.88 (95% confidence interval [CI], 1.43-2.48) for hip fracture and 1.52 (95% CI, 1.31-1.75) for nonspine fracture, and in men with DM were 5.71 (95% CI, 3.42-9.53) for hip fracture and 2.17 (95% CI, 1.75-2.69) for nonspine fracture. The FRAX score was also associated with fracture risk in participants with DM (HRs for 1-unit increase in FRAX hip fracture score, 1.05; 95% CI, 1.03-1.07, for women with DM and 1.16; 95% CI, 1.07-1.27, for men with DM; HRs for 1-unit increase in FRAX osteoporotic fracture score, 1.04; 95% CI, 1.02-1.05, for women with DM and 1.09; 95% CI, 1.04-1.14, for men with DM). However, for a given T score and age or for a given FRAX score, participants with DM had a higher fracture risk than those without DM. For a similar fracture risk, participants with DM had a higher T score than participants without DM. For hip fracture, the estimated mean difference in T score for women was 0.59 (95% CI, 0.31-0.87) and for men was 0.38 (95% CI, 0.09-0.66).nnnCONCLUSIONSnAmong older adults with type 2 DM, femoral neck BMD T score and FRAX score were associated with hip and nonspine fracture risk; however, in these patients compared with participants without DM, the fracture risk was higher for a given T score and age or for a given FRAX score.

The Magnitude of Acute Serum Creatinine Increase After Cardiac Surgery and the Risk of Chronic Kidney Disease, Progression of Kidney Disease, and Death

BACKGROUNDnLong-term outcomes after acute kidney injury remain poorly defined. We determined the association between the magnitude of creatinine increase after cardiac surgery and the risk of incident chronic kidney disease (CKD), CKD progression, and death.nnnMETHODSnWe identified 29,388 individuals who underwent cardiac surgery at Veterans Affairs hospitals between November 1999 and September 2005. The magnitude of creatinine increase was defined by the percent change from baseline to peak creatinine levels after cardiac surgery and categorized as none (≤0%) or as class I, (1%-24%), II (25%-49%), III (50%-99%), or IV (≥100%). Cox proportional hazard models were used to examine the association between the magnitude of creatinine increase and outcomes.nnnRESULTSnThe relative hazards for outcomes increased monotonically with greater increases in creatinine levels compared with no change in creatinine levels. The relative hazards for adverse outcomes were significantly higher immediately after the creatinine increase and attenuated over time. Three months after surgery, creatinine increase classes I, II, III, and IV were associated with a greater risk of incident CKD (hazard ratios [HRs] 2.1, 4.0, 5.8, and 6.6, respectively; all P<.01), progression of CKD stage (HRs 2.5, 3.8, 4.4, and 8.0; all P<.01), and long-term mortality (HRs 1.4, 1.9, 2.8, and 5.0; all P<.01). At 5 years, the associations were lower in magnitude: incident CKD (HRs 1.4, 1.9, 2.3, and 2.3; all P<.01), CKD progression (HRs 1.5, 1.7, 1.7, and 2.4; all P<.01), and mortality (HRs 1.0, 1.2, 1.4, and 1.8; all P<.01, except class I).nnnCONCLUSIONnThe magnitude of creatinine increase after cardiac surgery is associated in a graded manner with an increased risk of incident CKD, CKD progression, and mortality.

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).

BMI and fracture risk in older men: The osteoporotic fractures in men study (MrOS)

Low body mass index (BMI) is a risk factor for fracture, but little is known about the association between high BMI and fracture risk. We evaluated the association between BMI and fracture in the Osteoporotic Fractures in Men Study (MrOS), a cohort of 5995 US men 65 years of age and older. Standardized measures included weight, height, and hip bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA); medical history; lifestyle; and physical performance. Only 6 men (0.1%) were underweight (<18.5u2009kg/m2); therefore, men in this category were excluded. Also, 27% of men had normal BMI (18.5 to 24.9u2009kg/m2), 52% were overweight (25 to 29.9u2009kg/m2), 18% were obese I (30 to 34.9u2009kg/m2), and 3% were obese II (35 to 39.9u2009kg/m2). Overall, nonspine fracture incidence was 16.1 per 1000 person‐years, and hip fracture incidence was 3.1 per 1000 person‐years. In age‐, race‐, and BMD‐adjusted models, compared with normal weight, the hazard ratio (HR) for nonspine fracture was 1.04 [95% confidence interval (CI) 0.87–1.25] for overweight, 1.29 (95% CI 1.00–1.67) for obese I, and 1.94 (95% CI 1.25–3.02) for obese II. Associations were weaker and not statistically significant after adjustment for mobility limitations and walking pace (HRu2009=u20091.02, 95% CI 0.84–1.23, for overweight; HRu2009=u20091.12, 95% CI 0.86–1.46, for obese I, and HRu2009=u20091.44, 95% CI 0.90–2.28, for obese II). Obesity is common among older men, and when BMD is held constant, it is associated with an increased risk of fracture. This association is at least partially explained by worse physical function in obese men.

Efficacy of Escitalopram for Hot Flashes in Healthy Menopausal Women: A Randomized Controlled Trial

CONTEXTnConcerns regarding the risks associated with estrogen and progesterone to manage menopausal symptoms have resulted in its declining use and increased interest in nonhormonal treatments with demonstrated efficacy for hot flashes.nnnOBJECTIVEnTo determine the efficacy and tolerability of 10 to 20 mg/d escitalopram, a selective serotonin reuptake inhibitor, in alleviating the frequency, severity, and bother of menopausal hot flashes.nnnDESIGN, SETTING, AND PATIENTSnA multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel group trial that enrolled 205 women (95 African American; 102 white; 8 other) between July 2009 and June 2010.nnnINTERVENTIONnWomen received 10 to 20 mg/d of escitalopram or a matching placebo for 8 weeks.nnnMAIN OUTCOME MEASURESnPrimary outcomes were the frequency and severity of hot flashes assessed by prospective daily diaries at weeks 4 and 8. Secondary outcomes were hot flash bother, recorded on daily diaries, and clinical improvement (defined as hot flash frequency ≥50% decrease from baseline).nnnRESULTSnMean (SD) daily hot flash frequency was 9.78 (5.60) at baseline. In a modified intent-to-treat analysis that included all randomized participants who provided hot flash diary data, the mean difference in hot flash frequency reduction was 1.41 (95% CI, 0.13-2.69) fewer hot flashes per day at week 8 among women taking escitalopram (P < .001), with mean reductions of 4.60 (95% CI, 3.74-5.47) and 3.20 (95% CI, 2.24-4.15) hot flashes per day in the escitalopram and placebo groups, respectively. Fifty-five percent of women in the escitalopram group vs 36% in the placebo group reported a decrease of at least 50% in hot flash frequency (P = .009) at the 8-week follow-up. Reductions in hot flash severity scores were significantly greater in the escitalopram group (-0.52; 95% CI, -0.64 to -0.40 vs -0.30; 95% CI, -0.42 to -0.17 for placebo; P < .001). Race did not significantly modify the treatment effect (P = .62). Overall discontinuation due to adverse events was 4% (7 in the active group, 2 in the placebo group). Three weeks after treatment ended, women in the escitalopram group reported a mean 1.59 (95% CI, 0.55-2.63; P = .02) more hot flashes per day than women in the placebo group.nnnCONCLUSIONnAmong healthy women, the use of escitalopram (10-20 mg/d) compared with placebo resulted in fewer and less severe menopausal hot flashes at 8 weeks of follow-up.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00894543.

Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: The women's health initiative (WHI)

Low 25‐hydroxyvitamin D [25(OH)D] levels have been linked to hip fracture in white women. To study the association of 25(OH)D with risk of fracture in multiethnic women, we performed a nested case‐control study within the prospective Womens Health Initiative (WHI) Observational Study. Incident fractures were identified in 381 black, 192 Hispanic, 113 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 white women who fractured was chosen. One control individual was selected per case and matched on age, race/ethnicity, and blood draw date. 25(OH)D, parathyroid hormone, and vitamin D–binding protein (DBP) were measured in fasting baseline serum. Conditional logistic regression models were used to calculate the odds ratio (OR) and 95% CI. In multivariable models, higher 25(OH)D levels compared with levels less than 20u2009ng/mL were associated with a lower risk of fracture in white women (20 to <30u2009ng/mL: ORu2009=u20090.82, 95% CI 0.58–1.16; ≤30.0u2009ng/mL: ORu2009=u20090.56, 95% CI 0.35–0.90; p trendu2009=u20090.02). In contrast, higher 25(OH)D (≥20u2009ng/mL) compared with levels less than 20u2009ng/mL were associated with a higher risk of fracture in black women (ORu2009=u20091.45, 95% CI 1.06–1.98; p trendu2009=u20090.043). Higher 25(OH)D (≥30.0u2009ng/mL) was associated with higher fracture risk in Asian women after adjusting for DBP (ORu2009=u20092.78, 95% CI 0.99–7.80; p trendu2009=u20090.04). There was no association between 25(OH)D and fracture in Hispanic or Native American women. Our results suggest divergent associations between 25(OH)D and fracture by race/ethnicity. The optimal level of 25(OH)D for skeletal health may differ in white and black women.

Reliability and Validity of the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale in Older Men

BACKGROUNDnThe Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) are commonly used to quantify sleep and excessive daytime sleepiness in older adults. These measures, however, have not been comprehensively evaluated for their psychometrics in older men. We determined the internal consistency reliability and construct validity of the PSQI and ESS in a sample of older men.nnnMETHODSnParticipants were 3,059 men (mean age = 76.4 years) in the Osteoporotic Fractures in Men Study (MrOS) who completed the two questionnaires, wrist actigraphy, and a range of additional psychosocial and health measures.nnnRESULTSnInternal consistency was adequate for the PSQI (Cronbachs α =.69) and the ESS (α = .70) total scores. PSQI daytime dysfunction and sleep medications components were weakly associated with the total score, but their removal did not notably improve internal consistency. PSQI and ESS totals were associated with each other and with theoretically related variables (ie, actigraphic variables, depressive symptoms, mobility/instrumental activities of daily living, health-related quality of life) in expected directions. The PSQI differentiated participants reporting no sleep disorder from those reporting particular disorders more reliably than the ESS.nnnCONCLUSIONSnIn general, we found evidence of the internal consistency reliability and construct validity of the PSQI and ESS in older men. Despite low correlation with the PSQI global score, the PSQI daytime dysfunction and sleep medications components do not appreciably reduce the PSQI total scores reliability or validity in older men.

Prediction of New Clinical Vertebral Fractures in Elderly Men using Finite Element Analysis of CT Scans

Vertebral strength, as estimated by finite element analysis of computed tomography (CT) scans, has not yet been compared against areal bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA) for prospectively assessing the risk of new clinical vertebral fractures. To do so, we conducted a case‐cohort analysis of 306 men aged 65 years and older, which included 63 men who developed new clinically‐identified vertebral fractures and 243 men who did not, all observed over an average of 6.5 years. Nonlinear finite element analysis was performed on the baseline CT scans, blinded to fracture status, to estimate L1 vertebral compressive strength and a load‐to‐strength ratio. Volumetric BMD by quantitative CT and areal BMD by DXA were also evaluated. We found that, for the risk of new clinical vertebral fracture, the age‐adjusted hazard ratio per standard deviation change for areal BMD (3.2; 95% confidence interval [CI], 2.0–5.2) was significantly lower (pu2009<u20090.005) than for strength (7.2; 95% CI, 3.6–14.1), numerically lower than for volumetric BMD (5.7; 95% CI, 3.1–10.3), and similar for the load‐to‐strength ratio (3.0; 95% CI, 2.1–4.3). After also adjusting for race, body mass index (BMI), clinical center, and areal BMD, all these hazard ratios remained highly statistically significant, particularly those for strength (8.5; 95% CI, 3.6–20.1) and volumetric BMD (9.4; 95% CI, 4.1–21.6). The area‐under‐the‐curve for areal BMD (AUCu2009=u20090.76) was significantly lower than for strength (AUCu2009=u20090.83, pu2009=u20090.02), volumetric BMD (AUCu2009=u20090.82, pu2009=u20090.05), and the load‐to‐strength ratio (AUCu2009=u20090.82, pu2009=u20090.05). We conclude that, compared to areal BMD by DXA, vertebral compressive strength and volumetric BMD consistently improved vertebral fracture risk assessment in this cohort of elderly men.

Association of sleep characteristics and cognition in older community-dwelling men: The MrOS sleep study

STUDY OBJECTIVESnTo examine the association of objectively and subjectively measured sleep characteristics with cognition in older men.nnnDESIGNnA population-based cross-sectional study.nnnSETTINGn6 centers in the United States.nnnPARTICIPANTSn3,132 community-dwelling older men (mean age 76.4 ± 5.6 years).nnnINTERVENTIONSnNone.nnnMEASUREMENTS AND RESULTSnObjectively measured sleep predictors from wrist actigraphy were total sleep time (TST), sleep efficiency (SE), and wake after sleep onset (WASO). Subjective sleep predictors were self-reported poor sleep (Pittsburgh Sleep Quality Index [PSQI] > 5), excessive daytime sleepiness (EDS, Epworth Sleepiness Scale Score > 10), and TST. Cognitive outcomes were measured with the Modified Mini-Mental State examination (3MS), the Trails B test, and the Digit Vigilance Test (DVT). After adjustment for multiple potential confounders, WASO was modestly related to poorer cognition. Compared to those with WASO < 90 min, men with WASO ≥ 90 min took 6.1 sec longer to complete the Trails B test and had a 0.9-point worse 3MS score, on average (P<0.05). Actigraphically measured long sleepers had a slightly worse 3MS score compared to those with 7-8 h of sleep, but had similar Trails B and DVT completion times. Compared to those who self-reported sleeping 7-8 h, long sleepers (>8 h) on average took 8.6 sec more to complete the Trails B test, had a 0.6-point worse 3MS score, and took 46 sec longer to complete the DVT (P<0.05). PSQI and EDS were not independently related to cognitive outcomes.nnnCONCLUSIONSnThere were modest cross-sectional associations of WASO and self-reported long sleep with cognition among older community-dwelling men. EDS and PSQI were not related to cognition.