Associations between quantitative sleep EEG and subsequent cognitive decline in older women.

The pathophysiological processes of Alzheimer's dementia predate its clinical manifestation. Sleep disturbances can accelerate the aging process and are common features of dementia. This study examined whether quantitative sleep electroencephalogram changes predate the clinical development of mild cognitive impairment and/or incident dementia. We collected data from a nested case-control sample of women (mean age 83 years) from the Sleep and Cognition Study, an ancillary study to the longitudinal Study of Osteoporotic Fractures, who were characterized as cognitively normal at the time of a baseline polysomnography study (Study of Osteoporotic Fractures visit 8) based on a Mini-Mental Status Exam (MMSE) score >24. Cases (n = 85) were women who developed new mild cognitive impairment or dementia by objective cognitive testing 5 years after polysomnography. Controls were women with no mild cognitive impairment/dementia (n = 85) at baseline or at follow-up. Differences in electroencephalogram absolute and relative power density were observed between the two groups. Specifically, higher electroencephalogram power values were found in the dementia/mild cognitive impairment group, for the alpha (p = .01) and theta bands (p = .04) in non-rapid eye movement sleep, as well as alpha (p = .04) and sigma (p = .04) bands in rapid eye movement sleep. In contrast, there were no group differences in traditional polysomnography measures of sleep architecture and sleep stage distribution, as well as sleep apnea and periodic limb movement indices. Our results provide evidence for quantitative electroencephalogram changes, which precede the clinical onset of cognitive decline and the diagnosis of dementia in elderly women, and support the application of quantitative sleep electroencephalogram analysis as a promising biomarker for imminent cognitive decline.

Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women.

CONTEXT: Sleep-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. OBJECTIVES: To determine the prospective relationship between sleep-disordered breathing and cognitive impairment and to investigate potential mechanisms of this association. DESIGN, SETTING, AND PARTICIPANTS: Prospective 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. MAIN OUTCOME MEASURES: Adjudicated cognitive status (normal, dementia, or mild cognitive impairment) based on data collected between November 2006 and September 2008. RESULTS: Compared 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. CONCLUSION: Among older women, those with sleep-disordered breathing compared with those without sleep-disordered breathing had an increased risk of developing cognitive impairment.

The association of testosterone levels with overall sleep quality, sleep architecture, and sleep-disordered breathing.

CONTEXT: Little is known about the association of low endogenous testosterone levels and abnormal sleep patterns in older men, although pharmacological doses of testosterone are associated with increased severity of sleep apnea and other sleep disturbances. OBJECTIVE: The objective of the study was to examine the association between serum testosterone levels with objectively measured sleep characteristics. DESIGN: This was a cohort study. SETTING: Community-dwelling men aged 65 yr or older from six clinical centers in the United States participated in the study. PARTICIPANTS AND MAIN OUTCOME MEASURES: A total of 1312 men had baseline total testosterone levels measured in 2000-2002, followed 3.4 yr later by 72-h (minimum) actigraphy and one-night in-home polysomnography to assess sleep duration, sleep fragmentation, and sleep apnea. Analyses were performed by quartile of total testosterone and categorically defined low vs. higher total testosterone (<250 ng/dl vs. > or =250 ng/dl). Lifestyle and body size were covariates. RESULTS: Total testosterone levels were unrelated to age or duration of sleep. Men with lower testosterone levels had lower sleep efficiency, with increased nocturnal awakenings and less time in slow-wave sleep as well as a higher apnea-hypopnea index and more sleep time with O(2) saturation levels below 90%. Low testosterone levels were associated with overweight, and all significant associations were attenuated or absent after adjusting for body mass index or waist circumference. In a post hoc analysis in men with higher body mass index (>27 kg/m2), testosterone was significantly associated with more periods awake after sleep onset and lower sleep efficiency. CONCLUSION: Low total testosterone levels are associated with less healthy sleep in older men. This association is largely explained by adiposity. Clinical trials are necessary to determine whether body weight acts directly or indirectly (via low testosterone) in the causal pathway for sleep-disordered breathing in older men.

Subclinical Thyroid Dysfunction and Frailty Among Older Men.

CONTEXT: Both subclinical thyroid dysfunction and frailty are common among older individuals, but data on the relationship between these 2 conditions are conflicting. OBJECTIVE: The purpose of this study was to assess the cross-sectional and prospective associations between subclinical thyroid dysfunction and frailty and the 5 frailty subdomains (sarcopenia, weakness, slowness, exhaustion, and low activity). SETTING AND DESIGN: The Osteoporotic Fractures in Men Study is a prospective cohort study. PARTICIPANTS: Men older than 65 years (n = 1455) were classified into 3 groups of thyroid status: subclinical hyperthyroidism (n = 26, 1.8%), subclinical hypothyroidism (n = 102, 7.0%), and euthyroidism (n = 1327, 91.2%). MAIN OUTCOME MEASURES: Frailty was defined using a slightly modified Cardiovascular Health Study Index: men with 3 or more criteria were considered frail, men with 1 to 2 criteria were considered intermediately frail, and men with no criteria were considered robust. We assessed the cross-sectional relationship between baseline thyroid function and the 3 categories of frailty status (robust/intermediate/frail) as well as the prospective association between baseline thyroid function and subsequent frailty status and mortality after a 5-year follow-up. RESULTS: At baseline, compared with euthyroid participants, men with subclinical hyperthyroidism had an increased likelihood of greater frailty status (adjusted odds ratio, 2.48; 95% confidence interval, 1.15-5.34), particularly among men aged <74 years at baseline (odds ratio for frailty, 3.63; 95% confidence interval, 1.21-10.88). After 5 years of follow-up, baseline subclinical hypothyroidism and hyperthyroidism were not consistently associated with overall frailty status or frailty components. CONCLUSION: Among community-dwelling older men, subclinical hyperthyroidism, but not subclinical hypothyroidism, is associated with increased odds of prevalent but not incident frailty.

Hyponatremia and Fractures: Findings From the MrOS Study.

Hyponatremia may be a risk factor for fracture. To determine the relationship between hyponatremia and fracture we conducted cross-sectional and longitudinal analyses using data from the Osteoporotic Fractures in Men (MrOS) study. The MrOS study enrolled 5122 community dwelling men aged ≥65 years from six centers across the United States. We excluded men taking bisphosphonates, those with unknown medication history, those without serum sodium measures, or those with out of range assays for serum sodium. Serum sodium was measured at study entry. Subjects were followed for fractures (nonspine [including hip], hip, incident morphometric, and prevalent morphometric) for up to 9 years. We used Cox proportional hazards models to analyze the association between serum sodium levels (<135 mmol/L versus ≥135 mmol/L) and risk of nonspine and hip fractures, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs). We examined the association between morphometric vertebral fractures and serum sodium using logistic regression models, presented as odds ratios (ORs) and 95% CI. Hyponatremia was observed in 64 men (1.2% of the cohort). After adjusting for age, BMI, study center, and other covariates, we found that, compared to men with serum sodium ≥135 mmol/L, those with serum sodium <135 mmol/L, had an increased risk of hip fracture (HR = 3.04; 95% CI, 1.37 to 6.75), prevalent morphometric spine fracture (OR = 2.46; 95% CI, 1.22 to 4.95), and incident morphometric spine fracture (OR = 3.53; 95% CI, 1.35 to 9.19), but not nonspine fracture (OR = 1.44; 95% CI, 0.85 to 2.44). Adjusting for bone mineral density (BMD) did not change our findings. Our data show that hyponatremia is associated with up to a doubling in the risk of hip and morphometric spine fractures, independent of BMD. Further studies, to determine how hyponatremia causes fractures and if correction of hyponatremia decreases fractures, are needed.

Femoral volumetric bone density, geometry, and strength in relation to 25-hydroxy vitamin D in older men.

Low serum 25-hydroxy vitamin D (25(OH)D) concentrations are associated with increased hip fracture risk and decreased femoral areal bone mineral density (BMD) among elderly men. Structural dimensions of the proximal femur and volumetric BMD in cortical and trabecular compartments are also associated with hip fracture risk. However, associations of volumetric BMD or structural dimensions with serum 25(OH)D concentrations among older men remain unclear. In a random sample of 1608 men aged ≥65 years from the Osteoporotic Fractures in Men Study (MrOS), baseline serum 25(OH)D concentrations were measured by liquid chromatography/mass spectrometry assays. Femoral neck geometry and volumetric BMD derived from quantitative computed tomography included integral, cortical, and trabecular volumetric BMD; cross-sectional area; integral and cortical volume; and cortical volume as a percent of integral volume. We studied 888 men with vitamin D, parathyroid hormone (PTH), femoral neck geometry, and BMD measures. Whole-bone femoral strength and load-strength ratio from finite element (FE) analysis were also available for 356 men from this sample. Multivariable linear regression was used to estimate least square means of each femoral measure within quartiles of 25(OH)D adjusted for age, race, body mass index, height, latitude, and season of blood draw. Tests of linear trend in the means were performed across increasing quartile of serum 25(OH)D levels. Mean cortical volume (p trend = 0.006) and cortical volume as a percent of integral volume (p trend < 0.001) increased across increasing quartile of 25(OH)D level. However, overall femoral neck size (area and integral volume) did not vary by 25(OH)D level. Femoral neck volumetric BMD measures increased in a graded manner with higher 25(OH)D levels (p trend < 0.001). Femoral strength, but not load-strength ratio, increased with increasing 25(OH)D. Adjustment for PTH did not materially change these associations. We conclude that in older men, higher levels of endogenous 25(OH)D may increase whole-bone strength by increasing femoral volumetric BMD and cortical volume.