Objectives: To determine the association between vision and hearing impairment and subsequent cognitive and functional decline in community‐residing older women.
Design: Prospective cohort study.
...Setting: Four metropolitan areas of the United States.
Participants: A total of 6,112 women aged 69 and older participating in the Study of Osteoporotic Fractures (SOF) between 1992 and 1994.
Measurements: Five thousand three hundred forty‐five participants had hearing measured, 1,668 had visual acuity measured, and 1,636 had both measured. Visual impairment was defined as corrected vision worse than 20/40. Hearing impairment was defined as the inability to hear a tone of 40 dB or greater at 2,000 hertz. Participants completed the modified Mini‐Mental State Examination and/or a functional status assessment at baseline and follow‐up. Cognitive and functional decline were defined as the amount of decline from baseline to follow‐up that exceeded the observed average change in scores by at least 1 standard deviation.
Results: About one‐sixth (15.7%) of the sample had cognitive decline; 10.1% had functional decline. In multivariate models adjusted for sociodemographic characteristics and chronic conditions, vision impairment at baseline was associated with cognitive (odds ratio (OR)=1.78, 95% confidence interval (CI)=1.21–2.61) and functional (OR=1.79, 95% CI=1.15–2.79) decline. Hearing impairment was not associated with cognitive or functional decline. Combined impairment was associated with the greatest odds for cognitive (OR=2.19, 95% CI=1.26–3.81) and functional (OR=1.87, 95% CI=1.01–3.47) decline.
Conclusion: Sensory impairment is associated with cognitive and functional decline in older women. Studies are needed to determine whether treatment of vision and hearing impairment can decrease the risk for cognitive and functional decline.
In a large cohort of U.S. women aged 65 and older, we report the relationships of BMD measured at several sites, and subsequent fracture risk at multiple sites over >8 years of follow‐up. Although we ...found almost all fracture types to be related to low BMD, the overall proportion of fractures attributable to low BMD is modest.
Introduction: Although several studies have reported the relationship between bone mineral density (BMD) and subsequent fracture risk, most have been limited by short follow‐up time, BMD measures at only one or two sites, or availability of data for only select fracture types.
Materials and Methods: In the multicenter Study of Osteoporotic Fractures (SOF), we studied the relationship of several different BMD measures to fracture risk of multiple types in 9704 non‐black women aged 65 and older. We previously reported on the relationship of peripheral BMD measures to risk of several types of fracture during an average 2.2‐year follow‐up period. In this expanded analysis, we present results of the relationship of both peripheral and central BMD measures and fractures of multiple types during 10.4 and 8.5 years of follow‐up, respectively. We also report population attributable risk (PAR) estimates for osteoporosis and risk of several types of fracture.
Results: Our results show that almost all types of fractures have an increased incidence in women with low BMD. However, hip BMD is somewhat more strongly related to most of the fracture types studied than spine or peripheral BMD measures. Nonetheless, the proportion of fractures attributable to osteoporosis (based on a standard definition of osteoporosis) is modest, ranging from <10% to 44% based on the most commonly used definition of osteoporosis (BMD T‐score < −2.5).
Conclusion: Finding effective prevention strategies for fractures in older women will require additional interventions beside preventions for bone loss, such as prevention of falls and other fracture risk factors.
Background. The association between objectively measured sleep and cognition among community-dwelling elderly persons remains understudied. This observational, cross-sectional analysis examined this ...association. Methods. Results are from 2932 women (mean age 83.5 years) in the Study of Osteoporotic Fractures between 2002 and 2004. Cognitive function was measured by Mini-Mental State Examination (MMSE) and Trail Making B Test (Trails B). Cognitive impairment was defined as MMSE < 26 or Trails B > 278 seconds. Sleep parameters measured objectively using actigraphy included total sleep time, sleep efficiency, sleep latency, wake after sleep onset (WASO), and total nap time. Results. There were 305 women (10.6%) with MMSE < 26 and 257 women (9.3%) with Trails B > 278 seconds. Compared with women with sleep efficiency ≥70%, those with <70% had a higher risk of cognitive impairment (MMSE < 26 multivariate odds ratio MOR = 1.61; 95% confidence interval CI, 1.20–2.16; Trails B > 278 MOR = 1.96; 95% CI, 1.43–2.67). Higher sleep latency was associated with higher risk of cognitive impairment (per half hour: MMSE < 26 MOR = 1.23; 95% CI, 1.13–1.33; Trails B > 278 MOR = 1.13; 95% CI, 1.04–1.24), as was higher WASO (per half hour: MMSE < 26 MOR = 1.15; 95% CI, 1.06–1.23; Trails B > 278 MOR = 1.24; 95% CI, 1.15–1.34). Women who napped ≥2 hours per day had a higher risk (MMSE < 26 MOR = 1.42; 95% CI, 1.05–1.93; Trails B > 278 MOR = 1.74; 95% CI, 1.26–2.40). There was no significant relationship for total sleep time. Conclusion. Objectively measured disturbed sleep was consistently related to poorer cognition, whereas total sleep time was not. This finding may suggest that it is disturbance of sleep rather than quantity that affects cognition.
Rationale
Environmental stimuli, or cues, associated with the use of drugs such as cocaine are one of the primary drivers of relapse. Thus, identifying mechanisms to reduce the motivational ...properties of drug cues is an important research goal.
Objectives
The purpose of this study was to identify cellular signaling events in the nucleus accumbens (NAc) that are induced when a cocaine cue memory is either extinguished through repeated cue presentation in the absence of drug, or when the memory is reactivated and reconsolidated by a brief cue re-exposure. Signaling events specific to extinction or reconsolidation represent potential targets for pharmacotherapeutics that may enhance extinction or disrupt reconsolidation to reduce the likelihood of relapse.
Methods
Male Sprague-Dawley rats were trained to self-administer cocaine paired with an audiovisual cue. Following a period of self-administration, the memory for the cocaine-associated cue was either extinguished, reactivated, or not manipulated (control) 15 min before sacrifice. Tissue from the NAc was subsequently analyzed using mass spectrometry based phosphoproteomics to identify cellular signaling events induced by each condition.
Results
Extinction and reconsolidation of the cocaine cue memory produced both common and distinct changes in protein phosphorylation. Notably, there were no significant changes in protein phosphorylation that were modulated in the opposite direction by the two behavioral conditions. Comparison of NAc phosphoproteomic changes to previously identified changes in the basolateral amygdala (BLA) revealed that cue extinction increases phosphorylation at serine (S) 883 of the GABA
B
receptor subunit 2 and on S14 of syntaxin 1a in both regions, while no common regional signaling events were identified in the reconsolidation group.
Conclusions
Phosphoproteomics is a useful tool for identifying signaling cascades involved in different memory processes and revealed novel potential targets for selectively targeting extinction versus reconsolidation of a cocaine cue memory. Furthermore, cross region analysis suggests that cue extinction may produce unique signaling events associated with increased inhibitory signaling.
Abstract
Introduction:
As the US population ages, aging related health is becoming increasingly relevant. In particular, 1/3 of US older adults over the age of 65 experience a fall each year. ...Evidence demonstrates the psychological and physical implications of falling, including morbidity and early nursing home placement, as well as increased risk of future falls. Previous studies have confirmed that disturbed sleep, in both men and women, is associated with increased falls risk. Less is known about the relationship between sleep disturbances and fear of falling, a strong predictor of falls risk.
Methods:
Residents over the age of 65 (N=307, mean age 84), were recruited from 11 retirement communities in San Diego to participate in a multilevel physical activity intervention (MIPARC) or an attention control. Evaluation of the RCT included collection of participant surveys. Fear of falls was assessed using the 16-item FES-I scale where participants rated their concern for falling (1=Not at all concerned; 5=Very concerned) when performing various tasks. FES-I sum scores greater than 23 indicates a higher concern of falling. Sleep disturbances were assessed using the PROMIS 6-item sleep disturbance scale. The within person relationship between change in self-reported sleep disturbance scale and change in fear of falling was examined from baseline to 12 months with adjusted hierarchical linear models.
Results:
Study participants reported a mean fear of falls score of 25.95 at baseline, and a mean score of 27.18 at 12 months. Change in participants’ sleep disturbance score was significantly related to an increase in participants’ fear of falling (0.11, p=0.045) over the course of the 12-month intervention, when adjusting for participant age, gender, and study condition.
Conclusion:
It may be worthwhile for future sleep research to include the assessment of fear of falling as an intermediate target for sleep studies in older adults that are not long enough to assess falls incidence.
Support (If Any):
NHLBI #R01HL098425
CONTEXT Black women have a lower rate of fracture than white women, but whether
bone mineral density (BMD) predicts fracture risk as well in black women as
it does in white women is not established. ...OBJECTIVE To examine the association between BMD and incident nonspinal fractures
in older black and white women. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of baseline data collected from 1986 through
1990 (7334 white women aged 67-99 years) and from 1996 through 1998 (636 black
women aged 65-94 years) at 4 US clinical centers in the Study of Osteoporotic
Fractures; mean (SD) follow-up of 6.1 (1.5) years until October 1, 2004. MAIN OUTCOME MEASURES Incident nonspinal fractures were confirmed by radiograpic report. Total
hip and femoral neck BMD and bone mineral content were measured by dual energy
x-ray absorptiometry. RESULTS A total of 58 black women had a combined total of 61 fractures and 1606
white women had a combined total of 1712 fractures. In age-adjusted proportional
hazard models, a 1-SD decrease in femoral neck BMD was associated with a 37%
increased risk of fracture in black women (relative risk RR, 1.37; 95% confidence
interval CI, 1.08-1.74) and a 49% increase in fracture in white women (RR,
1.49; 95% CI, 1.40-1.58). Adjustment for body weight and other risk factors
for fracture weakened the association between BMD and fracture, especially
among black women (multivariable adjusted RR per 1-SD decrease in femoral
neck BMD for black vs white women: RR, 1.20 95% CI, 0.93-1.55 vs RR, 1.42
95% CI, 1.32-1.52). The absolute incidence of fracture across the pooled
BMD distribution was 30% to 40% lower among black women at every BMD tertile.
The lower risk of fracture among black compared with white women was independent
of BMD and other risk factors (RR, 0.48; 95% CI, 0.36-0.64). CONCLUSIONS Decreased total hip and femoral neck BMD is associated with an increased
risk of fracture in both older black and white women, but this relationship
was largely explained by other risk factors in black women. Black women have
a lower fracture risk than white women at every level of BMD. Race-specific
normative databases may be appropriate for the densitometric definition of
osteoporosis.
Biochemical evidence of hyperthyroidism may be associated with low bone mass, particularly in older postmenopausal women, but no prospective studies of thyroid function and subsequent fracture risk ...have been done.
To examine the association between low levels of thyroid-stimulating hormone (TSH) and fracture in older women.
Prospective cohort study with case-cohort sampling.
Four clinical centers in the United States.
686 women older than 65 years of age from a cohort of 9704 women recruited from population-based listings between 1986 and 1988.
Baseline assessment of calcaneal bone mass, spine radiography, and history of thyroid disease. Spine radiography was repeated after a mean follow-up of 3.7 years; nonspine fractures were centrally adjudicated. Thyroid-stimulating hormone was measured in sera obtained at baseline from 148 women with new hip fractures, 149 women with new vertebral fractures, and a subsample of 398 women randomly selected from the cohort.
After adjustment for age, history of previous hyperthyroidism, self-rated health, and use of estrogen and thyroid hormone, women with a low TSH level (0.1 mU/L) had a threefold increased risk for hip fracture (relative hazard, 3.6 95% CI, 1.0 to 12.9) and a fourfold increased risk for vertebral fracture (odds ratio, 4.5 CI, 1.3 to 15.6) compared with women who had normal TSH levels (0.5 to 5.5 mU/L). After adjustment for TSH level, a history of hyperthyroidism was associated with a twofold increase in hip fracture (relative hazard, 2.2 CI, 1.0 to 4.4), but use of thyroid hormone itself was not associated with increased risk for hip fracture (relative hazard, 0.5 CI, 0.2 to 1.3).
Women older than 65 years of age who have low serum TSH levels, indicating physiologic hyperthyroidism, are at increased risk for new hip and vertebral fractures. Use of thyroid hormone itself does not increase risk for fracture if TSH levels are normal.
Objectives: To test the hypothesis that unintentional weight loss increases the rate of bone loss and risk of hip fracture more than intentional weight loss.
Design: Prospective cohort study.
...Setting: Four communities within the United States.
Participants: Six thousand seven hundred eighty‐five elderly white women with measurement of weight change and assessment of intention to lose weight.
Measurements: Weight change between baseline and fourth examinations (average 5.7 years between examinations) and assessment of intention to lose weight. Weight loss was defined as a decrease of 5% or more from baseline weight, stable weight was defined as less than a 5% change from baseline weight, and weight gain was defined as an increase of 5% or more from baseline weight. Rate of change in bone mineral density at the hip between fourth and sixth examinations (average 4.4 years between examinations) was measured using dual‐energy x‐ray absorptiometry. Incident hip fractures occurring after the fourth examination until June 1, 2001 (average follow‐up 6.6 years) was confirmed using radiographic reports.
Results: The adjusted average rate of decline in total hipbone density steadily increased from −0.52% per year in women with weight gain to −0.68% per year in women with stable weight to −0.92% per year in women with weight loss (P‐value for trend <.001). Higher rates of hip‐bone loss were observed in women with weight loss irrespective of body mass index (BMI) or intention to lose weight. During follow‐up of an average 6.6 years after the fourth examination, 400 (6%) of the cohort suffered a first hip fracture. Women with weight loss had 1.8 times the risk (95% confidence interval (CI)=1.43–2.24) of subsequent hip fracture as those with stable or increasing weight. The association between weight loss and increased risk of hip fracture was consistent across categories of BMI and intention to lose weight. Even voluntary weight loss in overweight women with a BMI of 25.9 kg/m2 (median) or greater increased the risk of hip fracture (multivariate hazard ratio=2.48, 95% CI=1.33–4.62).
Conclusion: Older women who experience weight loss in later years have increased rates of hip‐bone loss and a two‐fold greater risk of subsequent hip fracture, irrespective of current weight or intention to lose weight. These findings indicate that even voluntary weight loss in overweight elderly women increases hip fracture risk.
Bone mass is a major determinant of fracture, but there have been few comprehensive studies of the correlates of bone mineral density (BMD) in older men. The objective of the current cross-sectional ...analysis was to determine the factors associated with BMD of the lumbar spine and proximal femur in a large population-based sample of older men enrolled in The Osteoporotic Fractures in Men Study, "Mr.OS." We enrolled 5,995 men 65 years of age or older, 89% Caucasian, in Mr.OS at six US clinical centers. Demographic, medical and family history and lifestyle information was obtained by interview and physical function and anthropometric data by examination. Spine and hip BMD was measured using dual-energy X-ray absorptimetry. The multivariable linear regression models predicted 19 and 10% of the overall variance in BMD of the femoral neck and spine, respectively. African-American men had 6 to 11% higher BMD than Caucasian men independent of multiple factors. Hip BMD declined with advancing age, while spine BMD increased. Body weight (per 10 kg) and self report of diabetes were each associated with 2 to 4% higher BMD, while history of a non-trauma fracture and current use of selective serotonin reuptake inhibitors, but not other antidepressants, were associated with at least 4% lower BMD. Both maternal and paternal histories of fracture were associated with 1.4-1.7% lower BMD. Osteoarthritis, physical activity, grip strength, alcohol intake, and dietary calcium were positively related to BMD, while a history of chronic lung disease, prostate cancer, and kidney stones was associated with lower BMD. Smoking, caffeine intake, and thiazide diuretics were not related to BMD in older men. A number of lifestyle and behavioral characteristics and medical conditions were associated with BMD in older men. Identification of these correlates could improve methods to identify men at risk for fracture and improve our understanding of fracture etiology.
We report the structural characterization of a thiolate-ligated ferryl radical. Using x-ray absorption spectroscopy, we examined chloroperoxidase (CPO) compound I (CPO-I). Our results indicate that ...CPO-I is an authentic ferryl species with an Fe-O bond of 1.65 Å. Axial-ligand interactions result in a remarkably long 2.48-Å Fe-S bond. Analogous forms of cytochrome P450 and CPO have been shown to possess virtually identical coordination environments. Thus, it seems likely that our findings provide a good structural description of the elusive P450-I.
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