BACKGROUND:The ICEBERG tool was initially validated in two small pilot studies to address the lack of a comprehensive geriatric screening tool in emergency settings. The present study builds on the second pilot study and extends it to a larger, multicenter sample. METHODS:We report results from a large ICEBERG tool validation study across three emergency rooms (ERs) including 1664 patients aged 70 years and older. The tool targets 9 domains and is administered by ER physicians or specialized nurses. To assess criterion validity-the extent to which ICEBERG scores are associated with relevant clinical outcomes-we compared patients who scored below versus above the median (<10; ≥10) ICEBERG score for six key clinical outcomes: length of stay in acute care, nursing care in minutes, one-on-one nursing care, in-hospital mortality, discharge to nursing home, and readmission within 30 days. Negative binomial regression was used for the outcomes length of stay and nursing care in minutes. Logistic regression was used for the other outcomes. All analyses were adjusted for age and sex. RESULTS:Patients with ICEBERG scores of 10 or higher had significantly longer stays in acute care (8.9 vs 6.6 days), required more nursing care (56.4 vs 32.8 h), had higher odds of one-on-one nursing care (Odds Ratio, OR = 2.85), in-hospital mortality (OR = 1.89), discharge to a nursing home (OR = 3.20), or being readmitted within 30 days (OR = 1.81). CONCLUSIONS:Based on our findings, the ICEBERG tool identifies older patients with a geriatric risk profile at ERs on all key clinical outcomes tested.

OBJECTIVE:Few studies have explored specific trajectories or patterns of falls over time in older adults, and the role of sex and self-reported risk factors for these trajectories were overlooked. This study aimed to identify sex-specific fall trajectories over 3 years and the self-reported risk factors associated with each trajectory in European older adults. DESIGN:Observational analysis of DO-HEALTH, a double-blind, randomized controlled trial. SETTING AND PARTICIPANTS:Multicenter trial conducted in 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without major health events in the 5 years prior to enrollment, with sufficient mobility and good cognitive status. METHODS:Falls were recorded prospectively via phone calls and in-person assessments every 3 months over 3 years of follow-up. Group-based trajectory modeling was used to identify sex-specific trajectories based on the number of falls experienced over the follow-up, and penalized logistic regression models identified the self-reported risk factors most associated with each trajectory. RESULTS:A total of 1958 participants were included in this analysis (mean age: 74.9 years, 61.7% women). We identified a "lower fall trajectory" and a "higher fall trajectory" among women and a "lower fall trajectory" and an "increasing fall trajectory" among men. In women, living alone was the only self-reported risk factor associated with the higher fall trajectory. In men, living alone (marginal), as well as reporting fatigue, pain or discomfort, mobility issues, and higher self-rated health, were significantly associated with experiencing the increasing fall trajectory. CONCLUSIONS AND IMPLICATIONS:This study provides a comprehensive assessment of falls over 3 years, highlighting differences in fall patterns and associated self-reported risk factors between men and women. These findings may offer valuable insights for developing sex-specific fall risk prediction models and targeted fall prevention strategies.

Vertebral fractures (VFs) are among the most common osteoporotic fractures. The effect of vitamin D3, omega-3s or a simple home exercise program (SHEP) on VFs is unclear. We examined whether vitamin D3, omega-3s, or SHEP, alone or in combination, over 3 years, reduce the incidence rate of VFs among European older adults. DO-HEALTH is a multi-center, 2 × 2 × 2 factorial design, randomized controlled trial, which included older adults (≥70 years) free from major health events in the 5 years prior to enrollment. The study interventions were vitamin D3 (2000IU/d), omega-3s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination. Quantitative and qualitative VF assessment was determined from lateral thoracolumbar DXA scans. The primary outcome for this analysis was the incidence rate (IR) of total VFs, defined as the number of any new and progressed VFs over the 3-year follow-up. Sensitivity analyses were conducted for only new VFs and only VF progressions. Negative binomial regression models were fit, adjusted for age, sex, prior fall, BMI, study site and participants' follow-up time. 1488 participants (mean age 74.9 years; 77% had low bone mass or osteoporosis; 43.8% had 25(OH)D levels <20 ng/mL) were included. There were 93 incident VFs, of which 58 were new VFs and 35 were progressions. None of the three treatments reduced the IR of total VFs overall, however, the IR was reduced with SHEP compared to the control exercise program in women (IR ratio 0.52, 95% CI 0.28, 0.98). In the sensitivity analysis for VF progressions, SHEP reduced the IR (IR ratio 0.34, 95% CI 0.16, 0.75). Among generally healthy older adults, vitamin D3 and omega-3s supplementation did not reduce the incidence rate of VFs. SHEP reduced the incidence rate of total VFs in women and of VF progressions overall. Exercise may play a role in the prevention of VFs.

Proton-pump inhibitors (PPI) are widely used among older adults and PPI intake has been associated with increased fracture risk. However, their association with bone microarchitecture and strength remains unclear as prior clinical PPI studies were restricted to lower-resolution bone imaging techniques such as DXA. Using high-resolution peripheral computed tomography (HR-pQCT), we prospectively investigated whether long-term PPI use was associated with changes in volumetric bone mineral densities, bone microarchitecture, and strength in older patients. 189 patients aged ≥ 60 years (n = 24 persistent PPI users [p-PPI user], and n = 165 non-PPI users), enrolled as part of a 2-year vitamin D RCT, underwent HR-pQCT scanning of the tibia and radius at 0 and 2 years. Bone volumetric density (vBMD), microarchitectural and strength parameters were computed and adjusted linear regression models without and with adjustments, including age, sex, BMI, and treatment groups, were employed to compare changes between p-PPI users and non-PPI users. At baseline, both groups were comparable with respect to age, vBMDs, bone microarchitecture, and sex. During follow-up, p-PPI users lost significantly more distal tibial total volumetric BMD (ΔTt.BMD: − 8.58 vs. − 2.45 mg/cm3, p = 0.012) and cortical volumetric BMD (ΔCt.BMD, − 28.96 vs. -14.07 mg/cm3, p = 0.005), and showed a significantly greater loss in tibial bone strength (Δstiffness − 4848.1 vs. 20.7 N/mm, p = 0.029; Δfailure load − 204.5 vs. 16.7 N, p = 0.026) than non-PPI users. At the radius, p-PPI users showed over the 2 years significantly greater increases in cortical porosity and intracortical pore diameter than non-PPI users (ΔCt.Po, p = 0.005; ΔCt.PoDm, p = 0.009). Long-term PPI intake was associated with a significant decline in cortical microarchitecture at the radius and with a significant deterioration of volumetric bone mineral density and strength at the tibia in older patients.

OBJECTIVE:To examine the association between polypharmacy and mild cognitive impairment (MCI) at baseline and over 3 years in community-dwelling older adults. DESIGN:Observational analysis of the DO-HEALTH trial. SETTING AND PARTICIPANTS:Community-dwelling adults aged ≥70 years with good cognitive function and without major diseases at baseline. METHODS:Main exposure was polypharmacy at baseline (≥5 medications). The outcome was MCI (Montreal Cognitive Assessment [MoCA] score <26), assessed at baseline and years 1, 2, and 3. Logistic regression and generalized estimating equations (GEEs) for repeated binary outcomes were used for the cross-sectional and longitudinal analysis, respectively. Minimally adjusted models included age, sex, prior fall, study site, body mass index, and education. Fully adjusted models additionally adjusted for mental health and multimorbidity. GEE models also accounted for time and DO-HEALTH treatment effects. Sensitivity analysis used a stricter MCI definition (MoCA < 24). RESULTS:A total of 2153 participants completed MoCA at baseline. Baseline MCI prevalence was higher in participants with polypharmacy compared with those with no polypharmacy (MCI < 26: 53.5% vs 46.5%; MCI < 24: 34.9% vs 17.2%). Polypharmacy was associated with greater MCI odds at baseline in the minimally adjusted models (MoCA < 26: odds ratio [OR], 1.32; 95% CI, 1.05-1.66; MoCA < 24: OR, 1.37; 95% CI, 1.06-1.79). Over 3 years, polypharmacy was associated with increased MCI odds in the minimally adjusted models (MoCA < 26: OR, 1.28; 95% CI, 1.08-1.52; MoCA < 24: OR, 1.33; 95% CI, 1.07-1.65). Notably, these associations were somewhat attenuated and nonsignificant after controlling for mental health and multimorbidity. CONCLUSION AND IMPLICATIONS:Our findings suggest that MCI is more prevalent in older adults with polypharmacy compared with those without polypharmacy. Although polypharmacy was associated with MCI at baseline and over 3 years, these associations were attenuated by mental health and multimorbidity, suggesting that mental health and multimorbidity contribute to both polypharmacy and MCI.

Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are validated and frequently used screening tools for cognitive function. To present MMSE and MoCA scores by sex, age and education among community-dwelling older adults. This is a post-hoc observational analysis using data from the DO-HEALTH trial, which included generally healthy adults (≥ 70 years) from Switzerland, Germany, Austria, France, and Portugal who scored at least 24 points on the MMSE at baseline. We present MMSE and MoCA scores overall and by country, sex, age (70–74 years, ≥ 75 years), education (≤ and > median education years). 2151 DO-HEALTH participants (mean age 74.9 years, 57

BACKGROUND:Although numerous cross-sectional studies have examined the relationship between anemia and cognitive impairment or dementia in older adults, data from larger longitudinal studies, especially in generally healthy older adults, are limited. OBJECTIVES:To investigate the associations between baseline hemoglobin levels, anemia, and mild cognitive impairment (MCI) over 3 y in generally healthy older adults. METHODS:This is an observational analysis of the 3-y DO-HEALTH trial, a double-blind, randomized controlled trial including 2157 European community-dwelling adults age 70+. Cognition was assessed at baseline, 12, 24, and 36 mo using the Montreal Cognitive Assessment (MoCA). MCI was defined as a MoCA score <26 at 2 consecutive time points. The exposures were the quintiles of hemoglobin levels and anemia at baseline. Logistic regression models based on generalized estimating equations controlled for age, sex, prior falls, study site, treatment allocation, body mass index, number of comorbidities, smoking status, use of iron supplements, alcohol consumption, renal function, and vitamin B12 levels. RESULTS:A total of 2150 participants were included in the analyses (mean age of 74.9 y; 61.7% females). Compared with the lowest quintile, participants in all higher quintiles had a significantly lower odds of MCI: 2nd = 34% lower odds of MCI [odds ratio (OR) = 0.66; 95% confidence interval (CI): 0.47, 0.93; P = 0.02], 3rd = 39% (OR = 0.61; 95% CI: 0.43, 0.86; P = 0.005), 4th = 44% (OR = 0.56; 95% CI: 0.39, 0.82; P = 0.003), and 5th = 36% (OR = 0.64; 95% CI: 0.43, 0.97; P = 0.03). For anemia, there was no association with the odds of MCI over time. CONCLUSIONS:Baseline hemoglobin levels >130 g/L were associated with reduced odds of MCI over 3 y. Although this study does not establish causality, it suggests further investigations in monitoring and managing hemoglobin levels, even in generally healthy older adults. This trial was registered at clinicaltrials.gov as NCT01745263.

Brief rationale: Limited evidence exists on calcifediol’s effect on lower extremity function in postmenopausal women with osteoporosis or osteopenia. Main result: Calcifediol (20 µg/day) showed no greater benefit than vitamin D3 (3200 IU/day) or placebo. Significance of the paper: Findings do not support high-dose vitamin D3 or calcifediol for improving lower extremity function. To test the effect of 20 µg/day of calcifediol compared with 3200 IU/day of vitamin D3 and placebo on lower extremity function in postmenopausal women with osteopenia or osteoporosis. This is a 3-arm double-blind RCT among postmenopausal women aged 50–70 years with serum 25(OH)D < 30 ng/mL, and a DXA-based diagnosis of osteopenia or osteoporosis. Participants were randomized to receive either daily 20 µg calcifediol, daily 3200 IU vitamin D3, or placebo. The primary endpoint was a composite measure of lower extremity function, assessed at baseline, 3, and 6 months, including four tests: gait speed, knee flexor and extensor strength, and repeated sit-to-stand test. The primary endpoint was the probability of success (improvement or maintenance from baseline) in any of the eight tests, four tests at 3 months and four tests at 6 months. The trial enrolled 152 women (mean age, 61.0 years; mean serum 25(OH)D level, 23.4 ng/mL), and all but one woman completed all follow-up visits. Baseline characteristics, including the four tests of lower extremity function, were balanced across the three groups. The adjusted probability of success in any of the eight tests was 53.6 https://clinicaltrials.gov/ct2/show/NCT02527668

While observational studies and small pilot trials suggest that vitamin D, omega-3 and exercise may slow biological aging, larger clinical trials testing these treatments individually or in combination are lacking. Here, we report the results of a post hoc analysis among 777 participants of the DO-HEALTH trial on the effect of vitamin D (2,000 IU per day) and/or omega-3 (1 g per day) and/or a home exercise program on four next-generation DNA methylation (DNAm) measures of biological aging (PhenoAge, GrimAge, GrimAge2 and DunedinPACE) over 3 years. Omega-3 alone slowed the DNAm clocks PhenoAge, GrimAge2 and DunedinPACE, and all three treatments had additive benefits on PhenoAge. Overall, from baseline to year 3, standardized effects ranged from 0.16 to 0.32 units (2.9–3.8 months). In summary, our trial indicates a small protective effect of omega-3 treatment on slowing biological aging over 3 years across several clocks, with an additive protective effect of omega-3, vitamin D and exercise based on PhenoAge. Applying epigenetic clocks to samples from the DO-HEALTH trial, Bischoff-Ferrari et al. report a small protective effect of omega-3 supplementation over 3 years on several clocks and an additive protective effect of omega-3, vitamin D and exercise using PhenoAge.

OBJECTIVES:Physical function and physical activity (PA) are key drivers of health and autonomy at older age. We examined the effects of supplemental vitamin D3, supplemental marine omega-3 fatty acids (omega-3s), and a simple home exercise program (SHEP), alone or in combination, on change in physical function and PA among generally healthy older adults. DESIGN:Multi-center, 2 × 2 × 2 factorial design, randomized controlled trial, follow-up of three years METHODS: Self-reported PA and physical function were pre-defined outcomes of the DO-HEALTH trial, which included older adults (≥70 years) free of major comorbidities. The interventions were vitamin D3 (2000 IU/d), marine omega-3s (1 g/d), and a SHEP (3 × 30 min/wk), applied alone or in combination in eight treatment arms. The outcomes were change in PA (self-reported total PA, metabolic equivalent [MET] h/wk) and physical function (five times sit-to-stand test, hand grip strength, gait speed) from baseline to 12, 24 and 36 months. Mixed effect models were used and adjusted for age, sex, BMI, prior fall, time and baseline level of the outcome. RESULTS:All 2157 DO-HEALTH participants (mean age 75 years; 83% physically active; 59% vitamin D3 replete) were included. Baseline PA was 75 MET h/wk. Participants receiving omega-3s versus no omega-3s and randomized to SHEP versus control exercise did not differ in PA change over 3 years. However, participants receiving vitamin D3 compared to those receiving no vitamin D3 (Δadjusted means: -7.1 [95% CI -12.7, -1.5] MET h/wk, P = 0.01) showed a decline in PA. Results did not differ in subgroups by sex and age (70-74 yrs, ≥75 yrs). Vitamin D3, omega-3s or SHEP did not improve physical function. CONCLUSION:Among generally healthy, active, and largely vitamin D3 replete adults aged 70 years and older, vitamin D3, omega-3s and SHEP, individually and in combination had no benefits on self-reported PA and objectively measured physical function. The detrimental effect of vitamin D supplementation on PA change needs further examination.

We examined vertebral fracture (VF) prevalence, incidence, and treatment among 1488 older adults. VF prevalence and incidence were higher in women, older participants, and those with low bone density. In addition to VFs being underdiagnosed (only 20.7

ObjectiveTo test whether transdermal testosterone at a dose of 75 mg per day and/or monthly 24’000 IU Vitamin D reduces the fall risk in pre-frail hypogonadal men aged 65 and older.Design2 × 2 factorial design randomized controlled trial, follow up of 12 months.MethodsHypogonadism was defined as total testosterone <11.3 nmol/L and pre-frailty as ≥1 Fried- frailty criteria and/or being at risk for falling at the time of screening. The primary outcomes were number of fallers and the rate of falls, assessed prospectively. Secondary outcomes were appendicular lean mass (ALM), sit-to-stand, gait speed, and the short physical performance test battery. Analyses were adjusted for age, BMI, fall history and the respective baseline measurement.ResultsWe aimed to recruit 168 men and stopped at 91 due to unexpected low recruitment rate (1266 men were pre-screened). Mean age was 72.2 years, serum total testosterone was 10.8 ± 3.0 nmol/l, and 20.9% had 25(OH)D levels below 20 ng/mL. Over 12 months, 37 participants had 72 falls. Neither the odds of falling nor the rate of falls were reduced by testosterone or by vitamin D. Testosterone improved ALM compared to no testosterone (0.21 kg/m2 [0.06, 0.37]), and improved gait speed (0.11 m/s, [0.03, 0.20]) compared to placebo.ConclusionTransdermal testosterone did not reduce fall risk but improved ALM and gait speed in pre-frail older men. Monthly vitamin D supplementation had no benefit.

The association between fall risk-increasing drugs (FRIDs, medications known to be associated with falls) and the number of falls among generally healthy and active community-dwelling older adults is understudied. Prior studies have focused on individual medication classes or have predominantly relied on retrospective assessments of falls. The aim of this study was to investigate the association between FRID use at baseline and the prospective incidence rates of total, injurious and recurrent falls in community-dwelling older adults. This is a 3-year observational analysis of DO-HEALTH, a randomized controlled trial, among community-dwelling adults aged ≥ 70 years without major diseases at baseline. The main exposures were use of at least one FRID and multiple FRIDs (≥ 2 FRIDs) at baseline. The number of total falls (including high- and low-trauma falls, as well as injurious falls) over 3 years of follow-up was defined as the primary outcome, and the number of injurious and the number of recurrent total falls (≥ 2 falls), as the two separate secondary outcomes. To examine these associations, separate negative binomial regression models controlled for the fixed effects of treatment allocation in the DO-HEALTH trial, study site, fall in the last year, age, sex, BMI, and walking aid were used. Additionally, an offset of the logarithm of each participant’s time in the study was included in the models. A total of 2157 participants were included, with a baseline median age of 74.0 years, 61.7

ObjectiveAlthough aging has a strong impact on visual acuity (VA) and falls, their interaction is understudied in generally healthy older adults. This study aimed to examine if and to what extent baseline VA is associated with an increased risk of all and injurious falls over 3 years in generally healthy community-dwelling older adults.DesignObservational analysis of DO-HEALTH, a double-blind, randomized controlled trial.Setting and ParticipantsMulticenter trial with 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without any major health events in the 5 years prior to enrollment, sufficient mobility, and good cognitive status.MethodsThe numbers of all and injurious falls were recorded prospectively by diary and in-person assessment every 3 months. Decreased VA at baseline was defined as better-eye VA lower than 1.0. We applied negative binomial regression models for all and injurious falls, adjusted for age, sex, prior falls, treatment allocation, study site, baseline body mass index, and use of walking aids.ResultsAmong the 2131 participants included in this analysis (mean age: 74.9 years, 61.7% were women, 82.6% at least moderately physically active), 1464 (68.7%) had decreased VA. Overall, 3290 falls including 2116 injurious falls were recorded over 3 years. Decreased VA at baseline was associated with a 22% increased incidence rate of all falls [adjusted incidence rate ratio (aIRR) = 1.22, 95% CI 1.07, 1.38, P = .003] and 20% increased incidence rate of injurious falls (aIRR = 1.20, 95% CI 1.05, 1.37, P = .007).Conclusions and ImplicationsOur findings suggest that decreased VA is an independent predictor of an about 20% increased risk of all and injurious falls, highlighting the importance of regular eye examinations and VA measurements for fall prevention, even in generally healthy and active older adults.

Evidence on the effects of Vitamin D, omega-3s, and exercise on areal bone mineral density (aBMD) in healthy older adults is limited. We examined whether vitamin D3, omega-3s, or a simple home-based exercise program (SHEP), alone or in combination, over 3 years, improve lumbar spine (LS), femoral neck (FN), or total hip (TH) aBMD assessed by DXA. Areal BMD was a secondary outcome in DO-HEALTH, a 3-year, multicenter, double-blind, randomized 2 × 2 × 2 factorial design trial in generally healthy older adults age ≥ 70 years. The study interventions were vitamin D3 (2000IU/d), omega-3s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination in eight treatment arms. Mixed effects models were used, adjusting for age, sex, BMI, prior fall, study site, and baseline level of the outcome. Main effects were assessed in the absence of an interaction between the interventions. Subgroup analyses by age, sex, physical activity level, dietary calcium intake, serum 25(OH)D levels, and fracture history were conducted. DXA scans were available for 1493 participants (mean age 75 years; 80.4% were physically active, 44% had 25(OH)D levels <20 ng/mL). At the LS and FN sites, none of the treatments showed a benefit. At the TH, vitamin D versus no vitamin D treatment showed a significant benefit across 3 years (difference in adjusted means [AM]: 0.0035 [95% CI, 0.0011, 0.0059] g/cm). Furthermore, there was a benefit for vitamin D versus no vitamin D treatment on LS aBMD in the male subgroup (interaction P = .003; ∆AM: 0.0070 [95% CI, 0.0007, 0.0132] g/cm). Omega-3s and SHEP had no benefit on aBMD in healthy, active, and largely vitamin D replete older adults. Our study suggests a small benefit of 2000 IU vitamin D daily on TH aBMD overall and LS aBMD among men; however, effect sizes were very modest and the clinical impact of these findings is unclear.

Context: Sclerostin inhibits canonical Wnt signaling, a pathway promoting bone formation. The effects of vitamin D-3, omega-3 fatty acids (omega-3s), and exercise on serum sclerostin levels and bone metabolism are unclear. Objective: To investigate the effects of 2000 IU/day vitamin D-3, 1 g/day omega-3s, and a simple home-based strength exercise program (SHEP), alone or in combination, on serum sclerostin and bone turnover marker levels. Methods: Sclerostin, procollagen type 1 N propeptide (P1NP) and C-terminal telopeptide (beta-CTx) levels were predefined secondary outcomes of DO-HEALTH, a double blind, randomized controlled trial in healthy physically active older adults in 5 European countries. Outcome measures were changes in yearly serum sclerostin, P1NP, and beta-CTx levels over 3 years, adjusted for age, sex, prior falls, study site, baseline body mass index, and baseline level of the respective outcome. Results: A total of 1848 participants were included (mean age 74.8 +/- 4.4 years, 58.9% women, 41.4% 25(OH)D < 20 ng/mL, 83.9% at least moderately physically active at baseline). Vitamin D-3 and omega-3s supplementation alone did not change sclerostin levels significantly, while SHEP compared with control exercise (joint mobility) led to greater decrease in sclerostin levels (-1.56 pmol/L [-2.54, -0.58], P = .002). Omega-3s plus SHEP led to a greater decrease in sclerostin levels than no omega-3s/control exercise (-1.93 pmol/L [-3.31, -0.54], P = .007). For P1NP and beta-CTx there were no significant effects for any of the individual treatments and treatment combinations. Conclusion: In this 3-year prevention trial among largely vitamin D replete adults age 70 and older, SHEP alone or in combination with omega-3s reduced serum sclerostin levels, while vitamin D-3 and omega-3s alone did not affect serum sclerostin levels.

BackgroundThe Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet may slow cognitive decline in older adults. A potential mechanism could be possible anti-inflammatory properties of the MIND-diet.ObjectiveTo examine whether adherence to the MIND diet at baseline is associated with the odds of mild cognitive impairment (MCI) and changes in biomarkers of inflammation (High-sensitivity C-reactive Protein(hsCRP), interleukin-6(IL-6)) over three years in adults ≥70 years.MethodsAdherence to the MIND diet was assessed by food frequency questionnaire (FFQ) at baseline and after three years. Presence of MCI based on the Montreal Cognitive Assessment (MoCA) was defined as <26 (MCI26), or <24 (MCI24). We performed a minimally adjusted model controlling for sex, prior fall, linear spline at age 85, time, treatment and study site. The fully adjusted model also adjusted for education, BMI, physical activity, depression score, daily energy intake, and comorbidity score. To assess the change in inflammatory markers from baseline, we used linear-mixed-effect models adjusted for the same variables plus the respective baseline concentrations. Sensitivity analyses accounting for practice effects of repeated cognitive tests using the reliable change index for both MoCA cut-offs were done.ResultsWe included 2028 of 2157 DO-HEALTH participants (60.5% women; mean age 74.88 years) with complete data. Adherence to the MIND diet at baseline was not associated with cognitive decline over three years, neither at MoCA < 26 (OR (95%CI) = 0.99 (0.94–1.04)) nor at MoCA < 24 (OR (95%CI) = 1.03 (0.96–1.1)). Applying the reliable change index to the two cut-offs confirmed the findings. Further, the MIND diet adherence was not associated with the change in MoCA score from baseline in DO-HEALTH. For inflammatory biomarkers MIND-diet baseline adherence was not associated with changes in hsCRP or IL-6.ConclusionAdherence to the MIND-diet was neither associated with the odds of MCI, nor with hsCRP or IL-6 at baseline. Moreover, change in MIND-diet over three years was not associated with changes in hsCRP or IL-6.

BACKGROUND:We aimed to investigate the effect of daily supplemental vitamin D, omega-3s, and a thrice-weekly home exercise program, alone or in combination, on change of appendicular lean muscle mass index (ALMI) and incident sarcopenia in older adults. METHODS:This is a secondary endpoint analysis of a 3-year randomized, double-blind, placebo-controlled trial with a 2 × 2 × 2 factorial design among 2157 community-dwelling, healthy adults aged 70 + years, from 2012 to 2018 (DO-HEALTH). Participants were randomized to 2000 IU/d vitamin D and/or 1 g/d marine omega-3s and/or exercise. Change in ALMI over 3 years was calculated in all participants who underwent dual energy X-ray absorptiometry (DXA) (n = 1495) using mixed effect models. Incident sarcopenia was analyzed based on the Sarcopenia Definitions and Outcomes Consortium in all non-sarcopenic participants (n = 1940). RESULTS:Among 1495 participants (mean age 74.9 (sd 4.4); 63.3% were women; 80.5% were at least moderately physically active at baseline) mean gait speed at baseline was 1.2 m/s (sd 0.3), mean ALMI at baseline was 6.65 (SD 0.95) in women, and 8.01 (SD 0.88) kg/m2 in men. At year 3, average change of ALMI was -0.09 (sd 0.34) kg/m2 (-1.35%) in women and - 0.17 (sd 0.33) kg/m2 (-2.0%) in men. None of the treatments individually or in combination had a benefit on ALMI change compared to control over 3 years, with omega-3s showing a small protective effect on ALMI at year 1 only (-0.021 vs. no-omega-3s -0.066 kg/m2, p = 0.001). Of 1940 non-sarcopenic participants at baseline, 88 (4.5%) developed incident sarcopenia over 3 years. None of the treatments individually or in combination reduced the odds of incident sarcopenia compared with placebo. CONCLUSION:Among healthy, physically active older adults, ALMI and incidence of sarcopenia were not improved by treatment of daily 2000 IU vitamin D, daily 1 g omega-3s, or a simple home exercise program compared with control over 3 years.

Objectives Falling and living alone have been identified as public health challenges in an ageing society. Our study investigates whether living alone influences fall risk in community-dwelling older adults in Switzerland.Design and methods Secondary analysis of three randomised controlled trials investigating how different doses of vitamin D and an exercise programme may influence the risk of further falls in people 60+ at risk of falling. We used logistic regression to examine the association between living alone and the odds of becoming a faller, and negative binomial regression to examine the association between living alone and the rate of falls. We assessed both any falls and falls with injury. All analyses were adjusted for sex, body mass index, age, grip strength, comorbidities, use of walking aids, mental health, trial and treatment group. Predefined subgroups were by sex and age.Results Among 494 participants (63% women; mean age was 74.7±7.5 years) 643 falls were recorded over 936.5 person-years, including 402 injurious falls. Living alone was associated with a 1.76-fold higher odds of becoming a faller (OR (95% CI)=1.76 (1.11 to 2.79)). While the odds did not differ by sex, older age above the median age of 74.6 years increased the odds to 2.19-fold (OR (95% CI)=2.19 (1.11 to 4.32)). The rate of total or injurious falls did not differ by living status.Conclusions Community-dwelling older adults living alone have a higher odds of becoming a faller. The increased odds is similar for men and women but accentuated with higher age.Trial registration numbers ZDPT: NCT01017354, NFP53: NCT00133640, OA: NCT00599807.

BACKGROUND:The effects of non-pharmaceutical interventions in the prevention of cardiovascular diseases (CVD) in older adults remains unclear. Therefore, the aim was to investigate the effect of 2000 IU/day of vitamin D3, omega-3 fatty acids (1 g/day), and a simple home strength exercise program (SHEP) (3×/week) on lipid and CVD biomarkers plasma changes over 3 years, incident hypertension and major cardiovascular events (MACE). METHODS:The risk of MACE (coronary heart event or intervention, heart failure, stroke) was an exploratory endpoint of DO-HEALTH, incident hypertension and change in biomarkers were secondary endpoints. DO-HEALTH is a completed multicentre, randomised, placebo-controlled, 2 × 2 × 2 factorial design trial enrolling 2157 Europeans aged ≥70 years. RESULTS:Participants' median age was 74 [72, 77] years, 61.7% were women, 82.5% were at least moderately physically active, and 40.7% had 25(OH)D < 20 ng/mL at baseline. Compared to their controls, omega-3 increased HDL-cholesterol (difference in change over 3 years: 0.08 mmol/L, 95% CI 0.05-0.10), decreased triglycerides (-0.08 mmol/L, (95%CI -0.12 to -0.03), but increased total- (0.15 mmol/L, 95%CI 0.09; 0.2), LDL- (0.11 mmol/L, 0.06; 0.16), and non-HDL-cholesterol (0.07 mmol/L, 95%CI 0.02; 0.12). However, neither omega-3 (adjustedHR 1.00, 95%CI 0.64-1.56), nor vitamin D3 (aHR 1.37, 95%CI 0.88-2.14), nor SHEP (aHR 1.18, 95%CI 0.76-1.84) reduced risk of MACE or incident hypertension compared to control. CONCLUSION:Among generally healthy, active, and largely vitamin D replete, older adults, treatment with omega-3, vitamin D3, and/or SHEP had no benefit on MACE prevention. Only omega-3 supplementation changed lipid biomarkers, but with mixed effects. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER:NCT01745263.