Aims
To investigate the association between use of β‐blockers and β‐blocker characteristics – selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism – and ...fall risk.
Methods
Data from two prospective studies were used, including community‐dwelling individuals, n = 7662 (the Rotterdam Study) and 2407 (B‐PROOF), all aged ≥55 years. Fall incidents were recorded prospectively. Time‐varying β‐blocker use was determined using pharmacy dispensing records. Cox proportional hazard models adjusted for age and sex were applied to determine the association between β‐blocker use, their characteristics – selectivity, lipid solubility, ISA and CYP2D6 enzyme metabolism – and fall risk. The results of the studies were combined using meta‐analyses.
Results
In total 2917 participants encountered a fall during a total follow‐up time of 89 529 years. Meta‐analysis indicated no association between use of any β‐blocker, compared to nonuse, and fall risk, hazard ratio (HR) = 0.97 95% confidence interval (CI) 0.88–1.06. Use of a selective β‐blocker was also not associated with fall risk, HR = 0.92 (95%CI 0.83–1.01). Use of a nonselective β‐blocker was associated with an increased fall risk, HR = 1.22 (95%CI 1.01–1.48). Other β‐blocker characteristics including lipid solubility and CYP2D6 enzyme metabolism were not associated with fall risk.
Conclusion
Our study suggests that use of a nonselective β‐blocker, contrary to selective β‐blockers, is associated with an increased fall risk in an older population. In clinical practice, β‐blockers have been shown effective for a variety of cardiovascular indications. However, fall risk should be considered when prescribing a β‐blocker in this age group, and the pros and cons for β‐blocker classes should be taken into consideration.
Context: Serum 25-hydroxyvitamin D 25(OH)D may influence serum PTH and other parameters of bone health up to a threshold concentration, which may be between 25 and 80 nmol/liter.
Objective: The aim ...of the study was to assess the threshold serum 25(OH)D with regard to PTH, bone turnover markers, and bone mineral density (BMD).
Design and Setting: This was part of the Longitudinal Aging Study Amsterdam, an ongoing cohort study.
Participants: A total of 1319 subjects (643 men and 676 women) between the ages of 65 and 88 yr participated in the study.
Main Outcome Measures: Serum 25(OH)D, PTH, osteocalcin, urinary deoxypyridinoline/creatinine, quantitative ultrasound of the heel, BMD of lumbar spine and hip, total body bone mineral content, and physical performance. The relationship between the variables was explored by analysis of covariance and the locally weighted regression (LOESS) plots.
Results: Serum 25(OH)D was below 25 nmol/liter in 11.5%, below 50 nmol/liter in 48.4%, below 75 nmol/liter in 82.4%, and above 75 nmol/liter in 17.6% of the respondents. Mean serum PTH decreased gradually from 5.1 pmol/liter when serum 25(OH)D was below 25 nmol/liter to 3.1 pmol/liter when serum 25(OH)D was above 75 nmol/liter (P < 0.001) without reaching a plateau. All BMD values were higher in the higher serum 25(OH)D groups, although only significantly for total hip (P = 0.01), trochanter (P = 0.001), and total body bone mineral content (P = 0.005). A threshold of about 40 nmol/liter existed for osteocalcin and deoxypyridinoline/creatinine, 50 nmol/liter for BMD, and 60 nmol/liter for physical performance.
Conclusions: Low serum 25(OH)D concentrations are common in the elderly. Bone health and physical performance in older persons are likely to improve when serum 25(OH)D is raised above 50–60 nmol/liter.
Bone health and physical performance in older persons are likely to improve when serum 25(OH)D is raised over 50-60 nmol/l.
Evidence from randomized controlled trials (RCTs) for the causal role of vitamin D on noncommunicable disease outcomes is inconclusive.
The aim of this study was to investigate whether there are ...beneficial or harmful effects of cholecalciferol (vitamin D3) supplementation according to subgroups of remeasured serum 25-hydroxyvitamin D 25(OH)D on cardiovascular and glucometabolic surrogate markers with the use of individual participant data (IPD) meta-analysis of RCTs.
Twelve RCTs (16 wk to 1 y of follow-up) were included. For standardization, 25(OH)D concentrations for all participants (n = 2994) at baseline and postintervention were re-measured in bio-banked serum samples with the use of a certified liquid chromatography–tandem mass spectrometry method traceable to a reference measurement procedure. IPD meta-analyses were performed according to subgroups of remeasured 25(OH)D. Main outcomes were blood pressure and glycated hemoglobin (HbA1c). Secondary outcomes were LDL, HDL, and total cholesterol and triglycerides; parathyroid hormone (PTH); fasting glucose, insulin, and C-peptide; and 2-h glucose. In secondary analyses, other potential effect modifiers were studied.
Remeasurement of 25(OH)D resulted in a lower mean 25(OH)D concentration in 10 of 12 RCTs. Vitamin D supplementation had no effect on the main outcomes of blood pressure and HbA1c. Supplementation resulted in 10–20% lower PTH concentrations, irrespective of the 25(OH)D subgroups. The subgroup analyses according to achieved 25(OH)D concentrations showed a significant decrease in LDL-cholesterol concentrations after vitamin D supplementation in 25(OH)D subgroups with <75, <100, and <125 nmol of −0.10 mmol/L (95% CI: −0.20, −0.00 mmol/L), −0.10 mmol/L (95% CI: −0.18, −0.02 mmol/L), and −0.07 mmol/L (95% CI: −0.14, −0.00 mmol/L), respectively. Patient features that modified the treatment effect could not be identified.
For the main outcomes of blood pressure and HbA1c, the data support no benefit for vitamin D supplementation. For the secondary outcomes, in addition to its effect on PTH, we observed indications for a beneficial effect of vitamin D supplementation only on LDL cholesterol, which warrants further investigation. This trial was registered at www.clinicaltrials.gov as NCT02551835.
OBJECTIVE
To determine whether there is an association between osteoarthritis (OA) and incident social isolation using data from the European Project on OSteoArthritis (EPOSA) study.
DESIGN
...Prospective, observational study with 12 to 18 months of follow‐up.
SETTING
Community dwelling.
PARTICIPANTS
Older people living in six European countries.
MEASUREMENTS
Social isolation was assessed using the Lubben Social Network Scale and the Maastricht Social Participation Profile. Clinical OA of the hip, knee, and hand was assessed according to American College of Rheumatology criteria. Demographic characteristics, including age, sex, multijoint pain, and medical comorbidities, were assessed.
RESULTS
Of the 1967 individuals with complete baseline and follow‐up data, 382 (19%) were socially isolated and 1585 were nonsocially isolated at baseline; of these individuals, 222 (13.9%) experienced social isolation during follow‐up. Using logistic regression analyses, after adjustment for age, sex, and country, four factors were significantly associated with incident social isolation: clinical OA, cognitive impairment, depression, and worse walking time. Compared to those without OA at any site or with only hand OA, clinical OA of the hip and/or knee, combined or not with hand OA, led to a 1.47 times increased risk of social isolation (95% confidence interval = 1.03‐2.09).
CONCLUSION
Clinical OA, present in one or two sites of the hip and knee, or in two or three sites of the hip, knee, and hand, increased the risk of social isolation, adjusting for cognitive impairment and depression and worse walking times. Clinicians should be aware that individuals with OA may be at greater risk of social isolation. J Am Geriatr Soc 68:87–95, 2019
BACKGROUND
Alzheimer's disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages > 100 years without cognitive decline. We studied the genetic factors associated ...with such resilience against AD.
METHODS
Genome‐wide association studies identified 86 single nucleotide polymorphisms (SNPs) associated with AD risk. We estimated SNP frequency in 2281 AD cases, 3165 age‐matched controls, and 346 cognitively healthy centenarians. We calculated a polygenic risk score (PRS) for each individual and investigated the functional properties of SNPs enriched/depleted in centenarians.
RESULTS
Cognitively healthy centenarians were enriched with the protective alleles of the SNPs associated with AD risk. The protective effect concentrated on the alleles in/near ANKH, GRN, TMEM106B, SORT1, PLCG2, RIN3, and APOE genes. This translated to >5‐fold lower PRS in centenarians compared to AD cases (P = 7.69 × 10−71), and 2‐fold lower compared to age‐matched controls (P = 5.83 × 10−17).
DISCUSSION
Maintaining cognitive health until extreme ages requires complex genetic protection against AD, which concentrates on the genes associated with the endolysosomal and immune systems.
Highlights
Cognitively healthy cent enarians are enriched with the protective alleles of genetic variants associated with Alzheimer's disease (AD).
The protective effect is concentrated on variants involved in the immune and endolysosomal systems.
Combining variants into a polygenic risk score (PRS) translated to > 5‐fold lower PRS in centenarians compared to AD cases, and ≈ 2‐fold lower compared to middle‐aged healthy controls.
Background: Falls frequently occur in the elderly and are a major cause of morbidity and mortality.
Objective: The objective of the study was to prospectively investigate the association between ...serum 25-hydroxyvitamin D 25(OH)D levels and risk of recurrent falling in older men and women.
Design: This was a prospective cohort study.
Setting: An age- and sex-stratified random sample of the Dutch older population was determined.
Subjects: Subjects included 1231 men and women (aged 65 yr and older) participating in the Longitudinal Aging Study Amsterdam.
Measurements: Baseline serum 25(OH)D was determined by a competitive protein binding assay. During 1 yr, falls were prospectively recorded by means of a fall calendar.
Results: Low 25(OH)D (<10 ng/ml) was associated with an increased risk of falling. After adjustment for age, sex, education level, region, season, physical activity, smoking, and alcohol intake, the odds ratios (95% confidence interval) were 1.78 (1.06–2.99) for subjects who experienced two falls or more as compared with those who did not fall or fell once and 2.23 (1.17–4.25) for subjects who fell three or more times as compared with those who fell two times or less. There was a statistically significant effect modification by age, and stratified analyses (<75 and ≥ 75 yr) showed that the associations were particularly strong in the younger age group; the odds ratios (95% confidence interval) were 5.21 (2.03–13.40) for two falls or more and 4.96 (1.52–16.23) for three falls or more.
Conclusions: Poor vitamin D status is independently associated with an increased risk of falling in the elderly, particularly in those aged 65–75 yr.
Objective
To investigate factors that together with hand or hip/knee osteoarthritis (OA) could contribute to functional decline over a year’s time in elderly individuals.
Methods
The data of 1,886 ...individuals between ages 65 and 85 years in a prospective, observational population‐based study with 12–18 months of follow‐up in the context of the European Project on Osteoarthritis were analyzed. The outcome measures were self‐reported hand and hip/knee functional decline, evaluated using a minimum clinically important difference of 4 on the Australian/Canadian Hand OA Index and of 2 on the Western Ontario and McMaster Universities Osteoarthritis Index hip/knee physical function subscales, both normalized to 0–100. Using regression models adjusted for sex, age, country, and education level, the baseline factors considered were clinical hand or hip/knee OA, pain, analgesic/antiinflammatory medications, comorbidities, social isolation, income, walking time, grip strength, physical activity time, and medical/social care.
Results
After a year, 453 participants were identified as having worse hand functionality and 1,389 as not worse. Hand OA, anxiety, walking time, and grip strength were risk factors for hand functional decline; pain was a confounder of the effect of hand OA.
Analgesic/antiinflammatory medications mediated the combined effect of hip/knee OA plus pain on functional decline in the 554 individuals classified as having worse hip/knee functionality and the 1,291 persons who were not worse. Peripheral artery disease, obesity, and cognitive impairment were other baseline risk factors.
Conclusion
Study findings showed that together with emotional status and chronic physical and cognitive conditions, OA affects hand and hip/knee functional decline.
poor physical performance (PP) is known to be associated with disability, lower quality of life and higher mortality rates. Knee and hip osteoarthritis (OA) might be expected to contribute to poor ...PP, through joint pain and restricted range of movement. Both clinical and self-reported OA are often used for large-scale community and epidemiological studies.
to examine the relationships between hip and knee OA and PP in a large data set comprising cohorts from six European countries.
a total of 2,942 men and women aged 65-85 years from the Germany, Italy, Netherlands, Spain, Sweden and the UK were recruited. Assessment included an interview and clinical assessment for OA. PP was determined from walking speed, chair rises and balance (range 0-12); low PP was defined as a score of ≤9.
the mean (SD) age was 74.2 (5.1) years. Rates of self-reported OA were much higher than clinical OA. Advanced age, female gender, lower educational attainment, abstinence from alcohol and higher body mass index were independently associated with low PP. Clinical knee OA, hip OA or both were associated with a higher risk of low PP; OR (95% CI) 2.93 (2.36, 3.64), 3.79 (2.49, 5.76) and 7.22 (3.63, 14.38), respectively, with relationships robust to adjustment for the confounders above as well as pain.
lower limb OA at the hip and knee is associated with low PP, and for clinical diagnosis relationships are robust to adjustment for pain. Those at highest risk have clinical OA at both sites.
Context: Vitamin D deficiency is common among older people and can cause mineralization defects, bone loss, and muscle weakness.
Objective: The aim of this study was to investigate the association of ...serum 25-hydroxyvitamin D (25-OHD) concentration with current physical performance and its decline over 3 yr among elderly.
Design: The study consisted of a cross-sectional and longitudinal design (3-yr follow-up) within the Longitudinal Aging Study Amsterdam.
Setting: An age- and sex-stratified random sample of the Dutch older population was used.
Other Participants: Subjects included 1234 men and women (aged 65 yr and older) for cross-sectional analysis and 979 (79%) persons for longitudinal analysis.
Main Outcome Measure(s): Physical performance (sum score of the walking test, chair stands, and tandem stand) and decline in physical performance were measured.
Results: Serum 25-OHD was associated with physical performance after adjustment for age, gender, chronic diseases, degree of urbanization, body mass index, and alcohol consumption. Compared with individuals with serum 25-OHD levels above 30 ng/ml, physical performance was poorer in participants with serum 25-OHD less than 10 ng/ml regression coefficient (B) = −1.69; 95% confidence interval (CI) = −2.28; −1.10, and with serum 25-OHD of 10–20 ng/ml (B = −0.46; 95% CI = −0.90; −0.03). After adjustment for confounding variables, participants with 25-OHD less than 10 ng/ml and 25-OHD between 10 and 20 ng/ml had significantly higher odds ratios (OR) for 3-yr decline in physical performance (OR = 2.21; 95% CI = 1.00–4.87; and OR = 2.01; 95% CI = 1.06–3.81), compared with participants with 25-OHD of at least 30 ng/ml. The results were consistent for each individual performance test.
Conclusions: Serum 25-OHD concentrations below 20 ng/ml are associated with poorer physical performance and a greater decline in physical performance in older men and women. Because almost 50% of the population had serum 25-OHD below 20 ng/ml, public health strategies should be aimed at this group.
Purpose
Higher folate and vitamin-B12 have been linked to lower risk of overweight. However, whether this is a causal effect of these B-vitamins on obesity risk remains unclear and evidence in older ...individuals is scarce. This study aimed to assess the role of B-vitamin supplementation and levels on body composition in older individuals.
Methods
A double-blind, randomized controlled trial in 2919 participants aged ≥ 65 years with elevated homocysteine levels. The intervention comprised a 2-year supplementation with a combination of folic acid (400 µg) and vitamin B12 (500 µg), or with placebo. Serum folate, vitamin-B12, active vitamin-B12 (HoloTC), methylmalonic acid (MMA), and anthropometrics were measured at baseline and after 2 years of follow-up. Dietary intake of folate and vitamin-B12 was measured at baseline in a subsample (
n
= 603) using a validated food-frequency questionnaire. Fat mass index (FMI) and fat-free mass index (FFMI) were assessed with Dual Energy X-ray absorptiometry (DXA).
Results
Cross-sectional analyses showed that a 1 nmol/L higher serum folate was associated with a 0.021 kg/m
2
lower BMI (95% CI − 0.039; − 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m
2
higher FMI (95% CI 0.262; 1.647), and higher MMA (per μgmol/L) was associated with a 1.108 kg/m
2
lower FMI (95% CI − 1.899; − 0.316). However, random allocation of B-vitamins did not have a significant effect on changes in BMI, FMI or FFMI during 2 years of intervention.
Conclusions
Although observational data suggested that folate and vitamin B12 status are associated with body composition, random allocation of a supplement with both B-vitamins combined versus placebo did not confirm an effect on BMI or body composition.
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