Background

Sleep disturbances are associated with risk of cognitive decline but it is not clear if treating disturbed sleep mitigates decline. We examined differences in cognitive trajectories before and after sleep treatment initiation.

Method

Data came from the 2006-2014 Health and Retirement Study (HRS). At each of 5 waves, participants were administered cognitive assessments and scores were summed. Participants also reported if, in prior 2 weeks, they had taken medications or used other treatments to improve sleep. Our sample (N = 3 957) included individuals who at HRS 2006 were 50 years and older, had no cognitive impairment, reported no sleep treatment, and indicated experiencing sleep disturbance. We identified differences between those receiving versus not receiving treatment in subsequent waves and, among those treated (n = 1 247), compared cognitive trajectories before and after treatment.

Results

At baseline, those reporting sleep treatment at subsequent waves were more likely to be younger, female, Caucasian, to have more health conditions, to have higher body mass index, and more depressive symptoms (all ps ≤ .015). Decline in cognitive performance was mitigated in periods after sleep treatment versus periods before (B = -0.20, 95% CI = [-0.25, -0.15], p < .001 vs B = -0.26, 95% CI = [-0.32, -0.20], p < .001), and this same trend was seen for self-initiated and doctor-recommended treatments. Trends were driven by those with higher baseline cognitive performance-those with lower performance saw cognitive declines following sleep treatment.

Conclusions

In middle-aged and older adults with sleep disturbance, starting sleep treatment may slow cognitive decline. Future research should assess types, combinations, and timing of treatments most effective in improving cognitive health in later life.

Background

Dietary recommendations may underestimate the protein older adults need for optimal bone health. This study sought to determine associations of protein intake with bone mineral density (BMD) and fracture among community-dwelling White and Black older adults.

Method

Protein as a percentage of total energy intake (TEI) was assessed with a Food Frequency Questionnaire in 2160 older adults (73.5 ± 2.8 years; 51.5% women; 35.8% Black) in the Health, Aging, and Body Composition prospective cohort. Hip, femoral neck, and whole body BMD was assessed by dual-energy x-ray absorptiometry at baseline and 4 years, and lumbar trabecular, cortical, and integral BMD was assessed by computed tomography at baseline and 5 years. Fragility fractures over 5 years were adjudicated from self-report data collected every 6 months. Associations with tertiles of protein intake were assessed using analysis of covariance for BMD and multivariate Cox regression for fracture, adjusting for confounders.

Results

Participants in the upper protein tertile (≥15% TEI) had 1.8%-6.0% higher mean hip and lumbar spine BMD compared to the lower protein tertile (<13% TEI; p < .05). Protein intake did not affect change in BMD at any site over the follow-up period. Participants in the upper protein tertile had a reduced risk of clinical vertebral fracture over 5 years of follow-up (hazard ratio: 0.36 [95% confidence interval: 0.14, 0.97] vs lower protein tertile, p = .04).

Conclusions

Older adults with higher protein intake (≥15% TEI) had higher BMD at the hip, whole body, and lumbar spine, and a lower risk of vertebral fracture.

Background

Albuminuria is highly prevalent among older adults, especially those with diabetes. It is associated with several chronic diseases, but its overall impact on the health of older adults, as measured by hospitalization, has not been quantified.

Method

We followed up 3,110 adults, mean age 78 years, for a median 9.75 years, of whom 654 (21%) had albuminuria (≥30 mg albumin/gram creatinine) at baseline. Poisson regression models, adjusted for cardiovascular, renal, and demographic factors, were used to evaluate the association of albuminuria with all-cause and cause-specific hospitalizations, as defined by ICD, version 9, categories.

Results

The rates of hospitalization per 100 patient-years were 65.85 for participants with albuminuria and 37.55 for participants without albuminuria. After adjustment for covariates, participants with albuminuria were more likely to be hospitalized for any cause than participants without albuminuria (incident rate ratio, 1.39 [95% confidence intervals, 1.27. 1.53]) and to experience more days in hospital (incident rate ratio 1.56 [1.37, 1.76]). The association of albuminuria with hospitalization was similar among participants with and without diabetes (adjusted incident rate ratio for albuminuria versus no albuminuria: diabetes 1.37 [1.11, 1.70], no diabetes 1.40 [1.26, 1.55]; p interaction nonsignificant). Albuminuria was significantly associated with hospitalization for circulatory, endocrine, genitourinary, respiratory, and injury categories.

Conclusions

Albuminuria in older adults is associated with an increased risk of hospitalization for a broad range of illnesses. Albuminuria in the presence or absence of diabetes appears to mark a generalized vulnerability to diseases of aging among older adults.

Background

Sleep characteristics related to duration, timing, continuity, and sleepiness are associated with mortality in older adults, but rarely considered in health recommendations. We applied machine learning to: (i) establish the predictive ability of a multidimensional self-reported sleep domain for all-cause and cardiovascular mortality in older adults relative to other established risk factors and (ii) to identify which sleep characteristics are most predictive.

Methods

The analytic sample includes N = 8,668 older adults (54% female) aged 65-99 years with self-reported sleep characterization and longitudinal follow-up (≤15.5 years), aggregated from three epidemiological cohorts. We used variable importance (VIMP) metrics from a random survival forest to rank the predictive abilities of 47 measures and domains to which they belong. VIMPs > 0 indicate predictive variables/domains.

Results

Multidimensional sleep was a significant predictor of all-cause (VIMP [99.9% confidence interval {CI}] = 0.94 [0.60, 1.29]) and cardiovascular (1.98 [1.31, 2.64]) mortality. For all-cause mortality, it ranked below that of the sociodemographic (3.94 [3.02, 4.87]), physical health (3.79 [3.01, 4.57]), and medication (1.33 [0.94, 1.73]) domains but above that of the health behaviors domain (0.22 [0.06, 0.38]). The domains were ranked similarly for cardiovascular mortality. The most predictive individual sleep characteristics across outcomes were time in bed, hours spent napping, and wake-up time.

Conclusion

Multidimensional sleep is an important predictor of mortality that should be considered among other more routinely used predictors. Future research should develop tools for measuring multidimensional sleep-especially those incorporating time in bed, napping, and timing-and test mechanistic pathways through which these characteristics relate to mortality.

Background

We examined the association of objective and subjective oral health markers with inflammatory, hemostatic, and cardiac biomarkers in older age.

Methods

Cross-sectional analyses were based on the British Regional Heart Study (BRHS) comprising British men aged 71-92 years (n = 2,147), and the Health, Aging and Body Composition (HABC) Study comprising American men and women aged 71-80 years (n = 3,075). Oral health markers included periodontal disease, tooth count, dry mouth. Inflammatory biomarkers included C-reactive protein (CRP), interleukin-6 (IL-6) in both studies, and tissue plasminogen activator (t-PA), von Willebrand Factor (vWF), fibrin D-dimer, high-sensitivity Troponin T (hsTnT), and N-terminal pro-brain natriuretic peptide (NTproBNP) only in the BRHS.

Results

In both studies, tooth loss, was associated with the top tertile of CRP-odds ratios (ORs) (95% confidence interval [CI]) are 1.31 (1.02-1.68) in BRHS; and 1.40 (1.13-1.75) in the HABC Study, after adjusting for confounders. In the HABC Study, cumulative (≥3) oral health problems were associated with higher levels of CRP (OR [95% CI] =1.42 [1.01-1.99]). In the BRHS, complete and partial tooth loss was associated with hemostatic factors, in particular with the top tertile of fibrin D-dimer (OR [95% CI] = 1.64 [1.16-2.30] and 1.37 [1.05-1.77], respectively). Tooth loss and periodontal disease were associated with increased levels of hsTnT.

Conclusions

Poor oral health in older age, particularly tooth loss, was consistently associated with some inflammatory, hemostatic, and cardiac biomarkers. Prospective studies and intervention trials could help understand better if poor oral health is causally linked to inflammatory, hemostatic, and cardiac biomarkers.

Background

We examined cross-sectional associations between dietary patterns, macronutrient intake, and measures of muscle mass and lean mass in older men.

Methods

Participants in the Osteoporotic Fractures in Men (MrOS) cohort (n = 903; mean ± SD age 84.2 ± 4 years) completed brief Block food frequency questionnaires (May 2014-May 2016); factor analysis was used to derive dietary patterns. The D3-creatine (D3Cr) dilution method was used to measure muscle mass; dual-energy x-ray absorptiometry (DXA) was used to measure appendicular lean mass (ALM). Generalized linear models were used to report adjusted means of outcomes by dietary pattern. Multiple linear regression models were used to determine associations between macronutrients and D3Cr muscle mass and DXA ALM. Multivariable models were adjusted for age, race, clinic site, education, depression, total energy intake, height, and percent body fat.

Results

Greater adherence to a Western dietary pattern (high factor loadings for red meat, fried foods, and high-fat dairy) was associated with higher D3Cr muscle mass (p-trend = .026). Adherence to the Healthy dietary pattern (high factor loadings for fruit, vegetables, whole grains, and lean meats) was not associated with D3Cr muscle mass or DXA ALM. Total protein (β = 0.09, 95% CI = 0.03, 0.14) and nondairy animal protein (β = 0.16, 95% CI = 0.10, 0.21) were positively associated with D3Cr muscle mass. Nondairy animal protein (β = 0.06, 95% CI = 0.002, 0.11) was positively associated with DXA ALM. Associations with other macronutrients were inconsistent.

Conclusions

Nondairy animal protein intake (within a Western dietary pattern and alone) was positively associated with D3Cr muscle mass in older men.

Background

Whether low muscle mass is a risk factor for disability and mortality is unclear. Associations between approximations of muscle mass (including lean mass from dual-energy x-ray absorptiometry [DXA]), and these outcomes are inconsistent.

Methods

Muscle mass measured by deuterated creatine (D3Cr) dilution and appendicular lean mass (ALM, by DXA) were assessed at the Year 14 Visit (2014-2016) of the prospective Osteoporotic Fractures in Men study (N = 1,425, age 77-101 years). Disability in activities of daily living (ADLs), instrumental ADLs, and mobility tasks was self-reported at the Year 14 visit and 2.2 years later; deaths were centrally adjudicated over 3.3 years. Relative risks and 95% confidence intervals (CI) were estimated per standard deviation decrement with negative binomial, logistic regression, or proportional hazards models.

Results

In age- and clinical center-adjusted models, the relative risks per decrement in D3Cr muscle mass/wgt was 1.9 (95% CI: 1.2, 3.1) for incident self-reported ADL disability; 1.5 (95% CI: 1.3, 1.9) for instrumental ADL disability; and 1.8 (95% CI: 1.5, 2.2) for mobility disability. In age-, clinical center-, and weight-adjusted models, the relative risks per decrement in D3Cr muscle mass was 1.8 (95% CI: 1.5, 2.2) for all-cause mortality. In contrast, lower DXA ALM was not associated with any outcome. Associations of D3Cr muscle mass with these outcomes were slightly attenuated after adjustment for confounding factors and the potentially mediating effects of strength and physical performance.

Conclusions

Low muscle mass as measured by D3Cr dilution is a novel risk factor for clinically meaningful outcomes in older men.

Initial results from sequencing studies suggest that there are relatively few low-frequency (<5%) variants associated with large effects on common phenotypes. We performed low-pass whole-genome sequencing in 680 individuals from the InCHIANTI study to test two primary hypotheses: (i) that sequencing would detect single low-frequency-large effect variants that explained similar amounts of phenotypic variance as single common variants, and (ii) that some common variant associations could be explained by low-frequency variants. We tested two sets of disease-related common phenotypes for which we had statistical power to detect large numbers of common variant-common phenotype associations-11 132 cis-gene expression traits in 450 individuals and 93 circulating biomarkers in all 680 individuals. From a total of 11 657 229 high-quality variants of which 6 129 221 and 5 528 008 were common and low frequency (<5%), respectively, low frequency-large effect associations comprised 7% of detectable cis-gene expression traits [89 of 1314 cis-eQTLs at P < 1 × 10(-06) (false discovery rate ∼5%)] and one of eight biomarker associations at P < 8 × 10(-10). Very few (30 of 1232; 2%) common variant associations were fully explained by low-frequency variants. Our data show that whole-genome sequencing can identify low-frequency variants undetected by genotyping based approaches when sample sizes are sufficiently large to detect substantial numbers of common variant associations, and that common variant associations are rarely explained by single low-frequency variants of large effect.

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%-9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension.

Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10(-41) and rs6258, p = 2.3×10(-22)). Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10(-16)). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.