Sleep disturbances are common in older adults. Little is known about the sleep of cognitively intact older adults and its relationship to subsequent cognitive impairment. The objective of this study ...was to examine the association between objective sleep-wake measures and risk of incident cognitive impairment.
In this prospective cohort study encompassing four U.S. sites, 1,245 women (mean age: 82.6 years) without dementia participated in the Study of Osteoporotic Fractures and completed actigraphy at the baseline visit and comprehensive cognitive assessment at follow-up. The association between sleep-wake patterns measured by actigraphy and risk of incident mild cognitive impairment (MCI) and dementia was examined.
A total of 473 women (38%) developed cognitive impairment during an average (SD) follow-up of 4.9 (0.6) years; 290 (23.3%) developed MCI and 183 (14.7%) developed dementia. After controlling for multiple potential confounders, women in the lowest quartile of average sleep efficiency (<74%) had a 1.5-fold higher odds of developing MCI or dementia compared with women in the highest quartile of sleep efficiency (>86%) (odds ratio: Q1 versus Q4 1.53; 95% CI: 1.07, 2.19; Wald χ(2) 1, N = 1,223 = 5.34 for p for trend = 0.03). Longer average sleep latency, but not total sleep time, was also associated with higher odds of developing cognitive impairment. Greater variability in both sleep efficiency and total sleep time was associated with an increased odds of developing MCI or dementia.
Lower average sleep efficiency, longer average sleep latency, and greater variability in sleep efficiency and total sleep time are associated with increased odds of developing cognitive impairment. Further research is needed to explore the mechanisms underlying these associations.
IMPORTANCE: In one-third of older men with anemia, no recognized cause can be found. OBJECTIVE: To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone ...levels and unexplained anemia would increase their hemoglobin concentration. DESIGN, SETTING, AND PARTICIPANTS: A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin ≤12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014. INTERVENTIONS: Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES: The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors. RESULTS: The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95% CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95% CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95% CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline. CONCLUSIONS AND RELEVANCE: Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increases may be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799617
IMPORTANCE: As men age, they experience decreased serum testosterone concentrations, decreased bone mineral density (BMD), and increased risk of fracture. OBJECTIVE: To determine whether testosterone ...treatment of older men with low testosterone increases volumetric BMD (vBMD) and estimated bone strength. DESIGN, SETTING, AND PARTICIPANTS: Placebo-controlled, double-blind trial with treatment allocation by minimization at 9 US academic medical centers of men 65 years or older with 2 testosterone concentrations averaging less than 275 ng/L participating in the Testosterone Trials from December 2011 to June 2014. The analysis was a modified intent-to-treat comparison of treatment groups by multivariable linear regression adjusted for balancing factors as required by minimization. INTERVENTIONS: Testosterone gel, adjusted to maintain the testosterone level within the normal range for young men, or placebo gel for 1 year. MAIN OUTCOMES AND MEASURES: Spine and hip vBMD was determined by quantitative computed tomography at baseline and 12 months. Bone strength was estimated by finite element analysis of quantitative computed tomography data. Areal BMD was assessed by dual energy x-ray absorptiometry at baseline and 12 months. RESULTS: There were 211 participants (mean SD age, 72.3 5.9 years; 86% white; mean SD body mass index, 31.2 3.4). Testosterone treatment was associated with significantly greater increases than placebo in mean spine trabecular vBMD (7.5%; 95% CI, 4.8% to 10.3% vs 0.8%; 95% CI, −1.9% to 3.4%; treatment effect, 6.8%; 95% CI, 4.8%-8.7%; P < .001), spine peripheral vBMD, hip trabecular and peripheral vBMD, and mean estimated strength of spine trabecular bone (10.8%; 95% CI, 7.4% to 14.3% vs 2.4%; 95% CI, −1.0% to 5.7%; treatment effect, 8.5%; 95% CI, 6.0%-10.9%; P < .001), spine peripheral bone, and hip trabecular and peripheral bone. The estimated strength increases were greater in trabecular than peripheral bone and greater in the spine than hip. Testosterone treatment increased spine areal BMD but less than vBMD. CONCLUSIONS AND RELEVANCE: Testosterone treatment for 1 year of older men with low testosterone significantly increased vBMD and estimated bone strength, more in trabecular than peripheral bone and more in the spine than hip. A larger, longer trial could determine whether this treatment also reduces fracture risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799617
IMPORTANCE: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. OBJECTIVE: To test the hypothesis that testosterone treatment of older ...men with low testosterone slows progression of noncalcified coronary artery plaque volume. DESIGN, SETTING, AND PARTICIPANTS: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. INTERVENTION: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). RESULTS: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, −27 Agatston units; 95% CI, −80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. CONCLUSIONS AND RELEVANCE: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799617
IMPORTANCE: Most cognitive functions decline with age. Prior studies suggest that testosterone treatment may improve these functions. OBJECTIVE: To determine if testosterone treatment compared with ...placebo is associated with improved verbal memory and other cognitive functions in older men with low testosterone and age-associated memory impairment (AAMI). DESIGN, SETTING, AND PARTICIPANTS: The Testosterone Trials (TTrials) were 7 trials to assess the efficacy of testosterone treatment in older men with low testosterone levels. The Cognitive Function Trial evaluated cognitive function in all TTrials participants. In 12 US academic medical centers, 788 men who were 65 years or older with a serum testosterone level less than 275 ng/mL and impaired sexual function, physical function, or vitality were allocated to testosterone treatment (n = 394) or placebo (n = 394). A subgroup of 493 men met criteria for AAMI based on baseline subjective memory complaints and objective memory performance. Enrollment in the TTrials began June 24, 2010; the final participant completed treatment and assessment in June 2014. INTERVENTIONS: Testosterone gel (adjusted to maintain the testosterone level within the normal range for young men) or placebo gel for 1 year. MAIN OUTCOMES AND MEASURES: The primary outcome was the mean change from baseline to 6 months and 12 months for delayed paragraph recall (score range, 0 to 50) among men with AAMI. Secondary outcomes were mean changes in visual memory (Benton Visual Retention Test; score range, 0 to −26), executive function (Trail-Making Test B minus A; range, −290 to 290), and spatial ability (Card Rotation Test; score range, −80 to 80) among men with AAMI. Tests were administered at baseline, 6 months, and 12 months. RESULTS: Among the 493 men with AAMI (mean age, 72.3 years SD, 5.8; mean baseline testosterone, 234 ng/dL SD, 65.1), 247 were assigned to receive testosterone and 246 to receive placebo. Of these groups, 247 men in the testosterone group and 245 men in the placebo completed the memory study. There was no significant mean change from baseline to 6 and 12 months in delayed paragraph recall score among men with AAMI in the testosterone and placebo groups (adjusted estimated difference, −0.07 95% CI, −0.92 to 0.79; P = .88). Mean scores for delayed paragraph recall were 14.0 at baseline, 16.0 at 6 months, and 16.2 at 12 months in the testosterone group and 14.4 at baseline, 16.0 at 6 months, and 16.5 at 12 months in the placebo group. Testosterone was also not associated with significant differences in visual memory (−0.28 95% CI, −0.76 to 0.19; P = .24), executive function (−5.51 95% CI, −12.91 to 1.88; P = .14), or spatial ability (−0.12 95% CI, −1.89 to 1.65; P = .89). CONCLUSIONS AND RELEVANCE: Among older men with low testosterone and age-associated memory impairment, treatment with testosterone for 1 year compared with placebo was not associated with improved memory or other cognitive functions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799617
Antidepressant use is very common in the elderly, but the effects of antidepressants on cognition in the elderly are controversial with some studies suggesting harm and others protection. We aimed to ...investigate the association between different antidepressant use and change in cognition and risk of mild cognitive impairment (MCI) or dementia in very old women.
We examined 1,234 community-dwelling women (mean age 83.2 years) from the Study of Osteoporotic Fractures. Baseline antidepressant use was reported and verified by medication containers, and medications were coded with computerized dictionary. Cognitive status (normal, MCI, or dementia) was adjudicated by an expert clinical panel 5 years later. Change in a short-form Mini-Mental State Examination and Trails B were evaluated over 5 years.
Eleven per cent of the women were taking antidepressants. Users of selective serotonin reuptake inhibitors (SSRIs) had the greatest cognitive decline over 5 years, after adjustment for demographics, medical comorbidities, benzodiazepine use, and baseline cognition. Multivariable logistic regression shows that the users of SSRIs were more than twice (OR = 2.69, 95% CI = 1.64-4.41) and trazodone users more than three times (3.48, 1.12-10.81) as likely to develop MCI or dementia compared with the nonusers. Further adjustment for baseline cognition or depressive symptoms did not appreciably alter the results, and the association remained after excluding women with high depressive symptoms. The use of tricyclic antidepressants or other antidepressants was not significantly associated with cognitive outcomes.
The use of antidepressants, especially SSRIs and trazodone, was associated with an increased risk of cognitive impairment 5 years later among the oldest old women.
IMPORTANCE: Warfarin is prescribed to patients with atrial fibrillation (AF) for the prevention of cardioembolic complications. Whether warfarin adversely affects bone health is controversial. The ...availability of alternate direct oral anticoagulant (DOAC) options now make it possible to evaluate the comparative safety of warfarin in association with fracture risk. OBJECTIVE: To test the hypothesis that, among patients with nonvalvular AF, use of DOACs vs warfarin is associated with lower risk of incident fracture. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness cohort study used the MarketScan administrative claims databases to identify patients with nonvalvular AF and who were prescribed oral anticoagulants from January 1, 2010, through September 30, 2015. To reduce confounding, patients were matched on age, sex, CHA2DS2-VASc (congestive heart failure, hypertension, age >65 years = 1 point; >75 years = 2 points, diabetes, and previous stroke/transient ischemic attack 2 points, vascular disease) score, and high-dimensional propensity scores. The final analysis included 167 275 patients with AF. Data were analyzed from February 27, 2019 to September 18, 2019. EXPOSURES: Warfarin and DOACs (dabigatran etexilate, rivaroxaban, and apixaban). MAIN OUTCOMES AND MEASURES: Incident hip fracture, fracture requiring hospitalization, and all clinical fractures (identified using inpatient or outpatient claims) defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTS: In the study population of 167 275 patients with AF (38.0% women and 62.0% men; mean SD age, 68.9 12.5 years), a total of 817 hip fractures, 2013 hospitalized fractures, and 7294 total fractures occurred during a mean (SD) follow-up of 16.9 (13.7) months. In multivariable-adjusted, propensity score–matched Cox proportional hazards regression models, relative to new users of warfarin, new users of DOACs tended to be at lower risk of fractures requiring hospitalization (hazard ratio HR, 0.87; 95% CI, 0.79-0.96) and all clinical fractures (HR, 0.93; 95% CI, 0.88-0.98), whereas the association with hip fractures (HR, 0.91; 95% CI, 0.78-1.07) was not statistically significant. When comparing individual DOACs with warfarin, the strongest findings were for apixaban (HR for hip fracture, 0.67 95% CI, 0.45-0.98; HR for fractures requiring hospitalization, 0.60 95% CI, 0.47-0.78; and HR for all clinical fractures, 0.86 95% CI, 0.75-0.98). In subgroup analyses, DOACs appeared more beneficial among patients with AF who also had a diagnosis of osteoporosis than among those without a diagnosis of osteoporosis. CONCLUSIONS AND RELEVANCE: In this real-world population of 167 275 patients with AF, use of DOACs—particularly apixaban—compared with warfarin use was associated with lower fracture risk. These associations were more pronounced among patients with a diagnosis of osteoporosis. Given the potential adverse effects of warfarin on bone health, these findings suggest that caution should be used when prescribing warfarin to patients with AF at high risk of fracture.
GSM and Quality of Life Measures Diem, Susan J; Danan, Elisheva R
Clinical obstetrics and gynecology,
03/2024, Letnik:
67, Številka:
1
Journal Article
Recenzirano
The impact of bothersome vulvovaginal symptoms related to hypoestrogenism on quality of life (QOL) has been evaluated in large international surveys and qualitative studies of vulvovaginal atrophy, ...most of which were completed before the introduction of the term genitourinary syndrome of menopause (GSM) and focus primarily on vulvovaginal atrophy. The QOL domain most affected in these studies is sexual function, although women also report impacts on self-confidence, self-esteem, sleep, and general enjoyment of life. Health-related QOL measures are available that evaluate the impact of some symptoms associated with GSM on QOL; new measures are in development that assess the full range of symptoms associated with GSM.
Context:
The Testosterone Trials are a coordinated set of seven trials to determine the efficacy of T in symptomatic men ≥65 years old with unequivocally low T levels. Initial results of the Sexual ...Function Trial showed that T improved sexual activity, sexual desire, and erectile function.
Objective:
To assess the responsiveness of specific sexual activities to T treatment; to relate hormone changes to changes in sexual function; and to determine predictive baseline characteristics and T threshold for sexual outcomes.
Design:
A placebo-controlled trial.
Setting:
Twelve academic medical centers in the United States.
Participants:
A total of 470 men ≥65 years of age with low libido, average T <275 ng/dL, and a partner willing to have sexual intercourse at least twice a month.
Methods:
Men were assigned to take T gel or placebo for 1 year. Sexual function was assessed by three questionnaires every 3 months: the Psychosexual Daily Questionnaire, the Derogatis Interview for Sexual Function, and the International Index of Erectile Function.
Results:
Compared with placebo, T administration significantly improved 10 of 12 measures of sexual activity. Incremental increases in total and free T and estradiol levels were associated with improvements in sexual activity and desire, but not erectile function. No threshold T level was observed for any outcome, and none of the 27 baseline characteristics predicted responsiveness to T.
Conclusions:
In older men with low libido and low T levels, improvements in sexual desire and activity in response to T treatment were related to the magnitude of increases in T and estradiol levels, but there was no clear evidence of a threshold effect.
Testosterone Treatment and Sexual Function in Older Men with Low Testosterone Levels. Improvements in sexual desire and activity were related to the magnitude of increases in testosterone.
Real-time clinical care, policy, and research decisions need real-time evidence synthesis. However, as we found during the COVID-19 pandemic, it is challenging to rapidly address key clinical and ...policy questions through rigorous, relevant, and usable evidence. Our objective is to present three exemplar cases of rapid evidence synthesis products from the Veterans Healthcare Administration Evidence Synthesis Program (ESP) and, in the context of these examples, outline ESP products, challenges, and lessons learned. We faced challenges in (1) balancing scientific rigor with the speed in which evidence synthesis was needed, (2) sorting through rapidly evolving large bodies of evidence, and (3) assessing the impact of evidence synthesis products on clinical care, policy, and research. We found solutions in (1) engaging stakeholders early, (2) utilizing artificial intelligence capabilities, (3) building infrastructure to establish living reviews, and (4) planning for dissemination to maximize impact.Real-time clinical care, policy, and research decisions need real-time evidence synthesis. However, as we found during the COVID-19 pandemic, it is challenging to rapidly address key clinical and policy questions through rigorous, relevant, and usable evidence. Our objective is to present three exemplar cases of rapid evidence synthesis products from the Veterans Healthcare Administration Evidence Synthesis Program (ESP) and, in the context of these examples, outline ESP products, challenges, and lessons learned. We faced challenges in (1) balancing scientific rigor with the speed in which evidence synthesis was needed, (2) sorting through rapidly evolving large bodies of evidence, and (3) assessing the impact of evidence synthesis products on clinical care, policy, and research. We found solutions in (1) engaging stakeholders early, (2) utilizing artificial intelligence capabilities, (3) building infrastructure to establish living reviews, and (4) planning for dissemination to maximize impact.
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