The association between proton pump inhibitors and hyperparathyroidism: a potential mechanism for increased fracture-results of a large observational cohort study.

Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture; however, the mechanism is unclear. PPI users taking calcium supplements were more likely to have hyperparathyroidism compared to non-users (OR 1.56, CI 1.08-2.23, p = 0.018). This highlights the importance of monitoring PPI use, especially in older adults. PURPOSE: Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture. Hyperparathyroidism may be implicated, but few studies have considered this relationship. This study evaluated the relationship between PPI use and hyperparathyroidism in older adults. METHODS: Participants were from the TUDA study, a large cross-sectional cohort of older Irish adults. Participants with an estimated glomerular filtration rate (eGFR) < 30 ml/min and serum calcium > 2.5 mmol/l were excluded to avoid hyperparathyroidism due to chronic renal disease and primary hyperparathyroidism. Hyperparathyroidism was defined as a parathyroid hormone (PTH) > 65 pg/ml. Multivariate regression models were used to analyse the relationship between PPI use and hyperparathyroidism. RESULTS: A total of 4139 participants met the inclusion criteria, of whom 37.8% (n = 1563) were taking PPI medication. PPI use was identified in 41.4% of calcium supplement users and 35.4% of non-calcium supplement users. Overall, compared to non-users of PPIs, those taking PPIs were older (74.8 vs 72.9 years, p < 0.001) and had a higher prevalence of hyperparathyroidism (17.8 vs 11.0%, p < 0.001). In those taking calcium supplements (but not in non-users), PPI use was significantly associated with hyperparathyroidism (OR 1.56, CI 1.08-2.23, p = 0.018) after adjusting for age, sex, body mass index, serum vitamin D, eGFR, timed-up-and-go, dairy intake, medications, and comorbidities. DISCUSSION: The results are consistent with the hypothesis of PPIs reducing calcium absorption, leading to a rise in PTH which could mediate increased fracture risk. No relationship of PPI use with hyperparathyroidism was observed in non-users of calcium supplements, possibly owing to lower dietary calcium intake. These results highlight the importance of monitoring PPI use, especially in older adults at risk of fracture.

The 'Bermuda Triangle' of orthostatic hypotension, cognitive impairment and reduced mobility: prospective associations with falls and fractures in The Irish Longitudinal Study on Ageing.

BACKGROUND: Orthostatic hypotension (OH), cognitive impairment (Cog) and mobility impairment (MI) frequently co-occur in older adults who fall. This study examines clustering of these three geriatric syndromes and ascertains their relationship with future falls/fractures in a large cohort of community-dwelling people ≥ 65 years during 8-year follow-up. METHODS: OH was defined as an orthostatic drop ≥ 20 mmHg in systolic blood pressure (from seated to standing) and/or reporting orthostatic unsteadiness. CI was defined as Mini Mental State Examination ≤ 24 and/or self-reporting memory as fair/poor. MI was defined as Timed Up and Go ≥12 s. Logistic regression models, including three-way interactions, assessed the longitudinal association with future falls (explained and unexplained) and fractures. RESULTS: Almost 10% (88/2,108) of participants had all three Bermuda syndromes. One-fifth of participants had an unexplained fall during follow-up, whereas 1/10 had a fracture. There was a graded relationship with incident unexplained falls and fracture as the number of Bermuda syndromes accumulated. In fully adjusted models, the cluster of OH, CI and MI was most strongly associated with unexplained falls (odds ratios (OR) 4.33 (2.59-7.24); P < 0.001) and incident fracture (OR 2.51 (1.26-4.98); P = 0.045). Other clusters significantly associated with unexplained falls included OH; CI and MI; MI and OH; CI and OH. No other clusters were associated with fracture. DISCUSSION: The 'Bermuda Triangle' of OH, CI and MI was independently associated with future unexplained falls and fractures amongst community-dwelling older people. This simple risk identification scheme may represent an ideal target for multifaceted falls prevention strategies in community-dwelling older adults.

Reduced kidney function is associated with poorer domain-specific cognitive performance in community-dwelling older adults.

OBJECTIVES: Whilst chronic kidney disease has been associated with cognitive impairment, the association between reduced estimated Glomerular Filtration Rate (eGFR) and domain-specific cognitive performance is less clear and may represent an important target for the promotion of optimal brain health in older adults. METHODS: Participants aged >60 years from the Trinity-Ulster-Department of Agriculture study underwent detailed cognitive assessment using the Mini-Mental State Examination (Mini-Mental State Examination (MMSE)), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Poisson and linear regression models assessed the relationship between eGFR strata and cognitive performance. RESULTS: In 4887 older adults (73.9 ± 8.3 years; 67.7% female), declining eGFR strata was associated with greater likelihood of error on the MMSE/FAB and poorer overall performance on the RBANS. Following robust covariate adjustment, findings were greatest for GFR <45 ml/ml/1.73 m2 (Incidence Rate Ratio: 1.17; 95% CI 1.08, 1.27; p < 0.001 for MMSE; IRR: 1.13; 95% CI 1.04, 1.13; p < 0.001 for FAB; ß: -3.66; 95% CI -5.64, -1.86; p < 0.001 for RBANS). Additionally, eGFR <45 ml/ml/1.73 m2 was associated with poorer performance on all five RBANS domains, with greatest effect sizes for immediate memory, delayed memory and attention. Associations were strongest in those aged 60-70, with no associations observed in those >80 years. CONCLUSIONS: Reduced kidney function was associated with poorer global and domain-specific neuropsychological performance. Associations were strongest with eGFR <45 ml/min/1.73 m2 and in those aged 60-70 years, suggesting that this population may potentially benefit from potential multi-domain interventions aimed at promoting optimal brain health in older adults.

Glycated haemoglobin (HbA1c ), diabetes and neuropsychological performance in community-dwelling older adults.

AIMS: Given that diabetes is associated with cognitive impairment and dementia in later life, we aimed to investigate the relationship between glycated haemoglobin (HbA1c ), diabetes and domain-specific neuropsychological performance in older adults. METHODS: Cross-sectional cohort study using data from the Trinity-Ulster-Department of Agriculture (TUDA) study. Participants underwent detailed cognitive and neuropsychological assessment using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Assessment for Neuropsychological Status (RBANS). Linear regression was used to assess associations between HbA1c , diabetes status and neuropsychological performance, with adjustment for important clinical covariates. RESULTS: Of 4938 older adults (74.1 ± 8.3 years; 66.9% female), 16.3% (n = 803) had diabetes (HbA1c  ≥ 6.5%; 48 mmol/mol), with prediabetes (HbA1c  ≥ 5.7%-6.4%; 39-47 mmol/mol) present in 28.3% (n = 1395). Increasing HbA1c concentration was associated with poorer overall performance on the FAB [ß: -0.01 (-0.02, -0.00); p = 0.04 per % increase] and RBANS [ß = -0.66 (-1.19, -0.13); p = 0.02 per % increase]. Increasing HbA1c was also associated with poorer performance on immediate memory, visuo-spatial, language and attention RBANS domains. Diabetes was associated poorer performance on neuropsychological tests of immediate memory, language, visual-spatial and attention. CONCLUSIONS: Both increasing HbA1c and the presence of diabetes were associated with poorer cognitive and domain-specific performance in older adults. HbA1c , and not just diabetes status per se, may represent an important target in the promotion of optimal brain health in older adults.

Long-term anticholinergic, benzodiazepine and Z-drug use in community-dwelling older adults: What is the impact on cognitive and neuropsychological performance?

BACKGROUND: Long-term use of anticholinergics, benzodiazepines and related drugs (or "Z-drugs") have been associated with cognitive impairment and dementia. However, the relationship of these medications with cognitive function and domain-specific neuropsychological performance in older adults without dementia, is unclear. METHODS: 5135 older adults (74.0 ± 8.3 years; 67.4% female) without a diagnosis of dementia were recruited in Ireland to the Trinity-Ulster-Department of Agriculture (TUDA) study. Detailed cognitive and neuropsychological assessment was conducted using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). RESULTS: A total of 44% (2259 of 5153) used either a potential or definite anticholinergic medication. Overall, 9.7% (n = 500) used a definite anticholinergic medication. Regular benzodiazepine use was reported by 7% (n = 363), whilst 7.5% (n = 387) used a "Z-drug". Use of definite, but not potential anticholinergic medication was associated with poorer performance on all three assessments (ß: -0.09; 95% CI: -0.14, -0.03, p = 0.002 for MMSE; ß: -0.04; 95% CI: -0.06, -0.02; p < 0.001 for FAB; ß: -4.15; 95% CI: -5.64, -2.66; p < 0.001 for RBANS) in addition to all domains of the RBANS. Regular benzodiazepine use was also associated with poorer neuropsychological test performance, especially in Immediate Memory (ß: -4.98; 95% CI: -6.81, -3.15; p < 0.001) and Attention (ß: -6.81; 95% CI: -8.60, -5.03; p < 0.001) RBANS domains. CONCLUSIONS: Regular use of definite anticholinergic medications and benzodiazepines, but not potential anticholinergics or "Z-drugs", was associated with poorer overall and domain-specific neuropsychological performance in older adults.

Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project.

BACKGROUND: Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. METHODS: Observational data on 6076 adults of 18-102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008-2012 using standardised methods. RESULTS: The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34-6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P < 0.027). CONCLUSIONS: The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.

The FUT2 secretor variant p.Trp154Ter influences serum vitamin B12 concentration via holo-haptocorrin, but not holo-transcobalamin, and is associated with haptocorrin glycosylation.

Vitamin B12 deficiency is common in older individuals. Circulating vitamin B12 concentration can be used to diagnose deficiency, but this test has substantial false positive and false negative rates. We conducted genome-wide association studies (GWAS) in which we resolved total serum vitamin B12 into the fractions bound to transcobalamin and haptocorrin: two carrier proteins with very different biological properties. We replicated reported associations between total circulating vitamin B12 concentrations and a common null variant in FUT2. This allele determines the secretor phenotype in which blood group antigens are found in non-blood body fluids. Vitamin B12 bound to haptocorrin (holoHC) remained highly associated with FUT2 rs601338 (p.Trp154Ter). Transcobalamin bound vitamin B12 (holoTC) was not influenced by this variant. HoloTC is the bioactive the form of the vitamin and is taken up by all tissues. In contrast, holoHC is only taken up by the liver. Using holoHC from individuals with known FUT2 genotypes, we demonstrated that FUT2 rs601338 genotype influences the glycosylation of haptocorrin. We then developed an experimental model demonstrating that holoHC is transported into cultured hepatic cells (HepG2) via the asialoglycoprotein receptor (ASGR). Our data challenge current published hypotheses on the influence of genetic variation on this clinically important measure and are consistent with a model in which FUT2 rs601338 influences holoHC by altering haptocorrin glycosylation, whereas B12 bound to non-glycosylated transcobalamin (i.e. holoTC) is not affected. Our findings explain some of the observed disparity between use of total B12 or holoTC as first-line clinical tests of vitamin B12 status.

A Common Polymorphism in HIBCH Influences Methylmalonic Acid Concentrations in Blood Independently of Cobalamin.

Methylmalonic acid (MMA) is a by-product of propionic acid metabolism through the vitamin B12 (cobalamin)-dependent enzyme methylmalonyl CoA mutase. Elevated MMA concentrations are a hallmark of several inborn errors of metabolism and indicators of cobalamin deficiency in older persons. In a genome-wide analysis of 2,210 healthy young Irish adults (median age 22 years) we identified a strong association of plasma MMA with SNPs in 3-hydroxyisobutyryl-CoA hydrolase (HIBCH, p = 8.42 × 10(-89)) and acyl-CoA synthetase family member 3 (ACSF3, p = 3.48 × 10(-19)). These loci accounted for 12% of the variance in MMA concentration. The most strongly associated SNP (HIBCH rs291466; c:2T>C) causes a missense change of the initiator methionine codon (minor-allele frequency = 0.43) to threonine. Surprisingly, the resulting variant, p.Met1?, is associated with increased expression of HIBCH mRNA and encoded protein. These homozygotes had, on average, 46% higher MMA concentrations than methionine-encoding homozygotes in young adults with generally low MMA concentrations (0.17 [0.14-0.21] µmol/L; median [25(th)-75(th) quartile]). The association between MMA levels and HIBCH rs291466 was highly significant in a replication cohort of 1,481 older individuals (median age 79 years) with elevated plasma MMA concentrations (0.34 [0.24-0.51] µmol/L; p = 4.0 × 10(-26)). In a longitudinal study of 185 pregnant women and their newborns, the association of this SNP remained significant across the gestational trimesters and in newborns. HIBCH is unique to valine catabolism. Studies evaluating flux through the valine catabolic pathway in humans should account for these variants. Furthermore, this SNP could help resolve equivocal clinical tests where plasma MMA values have been used to diagnose cobalamin deficiency.

The relationship between adiposity and cognitive function in a large community-dwelling population: data from the Trinity Ulster Department of Agriculture (TUDA) ageing cohort study.

Previous reports investigating adiposity and cognitive function in the population allude to a negative association, although the relationship in older adults is unclear. The aim of this study was to investigate the association of adiposity (BMI and waist:hip ratio (WHR)) with cognitive function in community-dwelling older adults (≥60 years). Participants included 5186 adults from the Trinity Ulster Department of Agriculture ageing cohort study. Neuropsychological assessment measures included the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multi-variable linear regression models were used to assess the association between adiposity and cognitive function adjusting for insulin resistance, inflammation and cerebrovascular disease. The mean ages were 80·3 (sd 6·7), 71·0 (sd 7·3) and 70·2 (sd 6·3) years on the cognitive, bone and hypertensive cohorts, respectively. In the cognitive cohort, BMI was positively associated with immediate and delay memory, visuospatial/constructional ability, language and MMSE, and negatively with FAB (log-transformed), whereas WHR was negatively associated with attention. In the bone cohort, BMI was not associated with any cognitive domain, whereas WHR was negatively associated with visuospatial/constructional ability, attention and MMSE. In the hypertensive cohort, BMI was not associated with any cognitive domain, whereas WHR was negatively associated with immediate and delayed memory, visuospatial/constructional ability, language and MMSE and positively with FAB (log-transformed). In the cognitive and bone cohorts, the association of WHR and attention disappeared by further controlling for C-reactive protein and HbA1C. In this study of older adults, central adiposity was a stronger predictor of poor cognitive performance than BMI. Older adults could benefit from targeted public health strategies aimed at reducing obesity and obeseogenic risk factors to avoid/prevent/slow cognitive dysfunction.

Ambient UVB Dose and Sun Enjoyment Are Important Predictors of Vitamin D Status in an Older Population.

Background: UVB-induced skin synthesis is considered the key source of vitamin D, yet exposure to UVB is poorly accounted for in epidemiological studies.Objectives: The aim of this study was to examine the association of serum 25-hydroxyvitamin D [25(OH)D] concentration with accurately measured ambient UVB dose, sun enjoyment, supplements, and other factors.Methods: An all-Irish cohort of community-dwelling participants aged >60 y [median age: 73; 67% female; median 25(OH)D: 54.5 nmol/L] was used. Participants from this large, cross-sectional study completed a questionnaire to provide information on demographic factors and lifestyle (including supplement use and sun enjoyment). The Tropospheric Emission Monitoring Internet Service database was used to extract the daily ambient UVB dose at wavelengths that could induce vitamin D synthesis (D-UVB) over Ireland (latitude: 51°N-55°N). Blood sampling occurred throughout the year. Ambient exposure at the place of residence was calculated for each participant individually. Associations between determinants and serum 25(OH)D concentration were examined in a multivariate model. Random forest analysis was used to establish prediction models of vitamin D deficiency, and area under the curve (AUC) is shown.Results: In total, 5138 individuals were included. Median D-UVB was 63 mJ/cm2, which varied between seasons and latitudes, despite the small latitude differential. Vitamin D supplementation (ß = 27.7; P < 10 × 10-10), D-UVB (ß = 1.58 per 1000 mJ/cm2; P < 10 × 10-10), and sun enjoyment (ß = 6.6; P < 0.001) were strongly positively associated with serum 25(OH)D. Those who avoided sunshine were largely at risk of deficiency (<40 nmol/L), whereas those who enjoyed sunshine tended to be vitamin D sufficient (≥50 nmol/L). D-UVB and sun enjoyment improved prediction of deficiency in non-supplement-taking individuals; the overall AUC improved by 3.5%.Conclusion: D-UVB and sun enjoyment are important predictors of vitamin D status, even in this elderly population at northern latitudes. Accurate estimation of ambient UVB can help to further clarify the role of other determinants of vitamin D status and inform sunshine recommendation guidelines.

The Frontal Assessment Battery: Normative Performance in a Large Sample of Older Community-Dwelling Hospital Outpatient or General Practitioner Attenders.

BACKGROUND: The Frontal Assessment Battery (FAB) is a short battery designed to assess frontal executive functioning, but data for interpretation of performance are limited. OBJECTIVES: The Trinity, Ulster, Department of Agriculture (TUDA) study provided the opportunity to derive performance data from a large sample of community-dwelling hospital outpatient or general practitioner (GP) attenders. METHODS: Normative analysis based on 2508 TUDA participants meeting these criteria: Mini-Mental State Examination (MMSE) >26/30, not depressed (Center for Epidemiologic Studies Depression <16) or anxious (Hospital Anxiety and Depression Scale <8), no history of stroke, or transient ischemic attack. Correlation and regression analyses were used to evaluate the effects of age, education, gender, and general cognition (MMSE). Norms for FAB were created stratified by age and education, using overlapping midpoint ranges of 10 years with a 3-year interval from age 60 to 97. RESULTS: Age and education accounted for 9.6% of variance in FAB score ( r2 = .096) with no significant effect of gender. The FAB and MMSE were modestly correlated ( r = .29, P < .01) with MMSE increasing the model's total explained variance in FAB score from 9.6% to 14%. CONCLUSION: This is the largest study to date to create normative data for the FAB. Age and education had the most significant impact on FAB performance, which was largely independent of global cognition (MMSE). These data may be of benefit in interpreting FAB performance in individuals with similar demographic/health status characteristics in hospital outpatient or GP settings.

The clinical utility of naturalistic action test in differentiating mild cognitive impairment from early dementia in memory clinic.

OBJECTIVE: This study aimed to examine the validity of the Naturalistic Action Test in differentiating Mild Cognitive Impairment from early dementia compared to clinical diagnosis and ascertain Naturalistic Action Test cut-off points. METHODS: This was a cross-sectional study of 70 consecutive patients diagnosed with Mild Cognitive Impairment attending the memory clinic in St James's Hospital, Dublin, Ireland. Patients with a diagnosis of Mild Cognitive Impairment who attended for routine annual assessment were asked to participate in the study. The Naturalistic Action Test was carried out after the patient had completed their routine assessment in the clinic. RESULTS: The Area under the Curve, AUC ± SE was 0.808 ± 0.058, p < 0.001 with 95% CI (0.695-0.922). There was concordance in 40 and discrepancy in 30 patients between the NAT and the gold standard consensus diagnosis (PPV 38%, NPV 96%, sensitivity 94%, specificity 46% and accuracy 59%) using cut-off point of ≥14 for normal function on Naturalistic Action Test. The difference was not related to age, sex, level of education or informant. Using the Youden index, we determined a Naturalistic Action Test cut-off score of ≥11 for Mild Cognitive Impairment in our study (PPV 50%, NPV 91%, sensitivity 78%, specificity 73% and accuracy of 74%). There was discrepancy in 18 patients using the new cut-off point (≥11 for Mild Cognitive Impairment vs ≤10 for dementia). CONCLUSION: The Naturalistic Action Test is a useful tool that can increase diagnostic accuracy in differentiating Mild Cognitive Impairment from early dementia.

Determinants of 25-hydroxyvitamin D in older Irish adults.

BACKGROUND: vitamin D deficiency is prevalent in older adults living in Northern Europe and is influenced by several factors which may vary significantly with age. OBJECTIVE: we aimed to investigate the determinants of 25-hydroxyvitamin D [25(OH)D] in older Irish adults and in particular to examine the effect of supplement use and surrogate markers of sun exposure. METHODS: subjects were non-institutionalised community dwelling Irish adults aged over 60 years who were participants of a large cross-sectional study comprising three disease defined cohorts. Serum 25(OH)D was measured by liquid chromatography mass spectroscopy. Associations between 25(OH)D and potential confounders were explored in forward regression models in each cohort. RESULTS: the three cohorts comprised 1895, 1233 and 1316 participants (respective mean ages 70.1, 71.0 and 80.4 years). Statistical models explained between a fifth to a third of the variation in 25(OH)D. Supplement use and global solar radiation were positive predictors of 25(OH)D in all cohorts whereas the only universal negative predictor was body mass index. Supplement use was associated with a mean increase in 25(OH)D of between 21.4 and 35.4 nmol/l. The other main predictors varied by cohort but included sun holiday travel, enjoyment of sunshine when outside, use of vitamin D fortified milk, smoking, oily fish and egg consumption and physical frailty. CONCLUSION: supplement use was the most important determinant of vitamin D status. Vitamin D fortified milk and spending time in the sun, even in the oldest old may also be useful strategies to improve 25(OH)D.

The relationship between syncope, depression and anti-depressant use in older adults.

BACKGROUND: syncope is a common problem which increases in older age groups. In syncope clinics, patients who are depressed have higher rates of unexplained syncope and higher rates of recurrent syncope. OBJECTIVES: : we aim to examine the rates of depression in older patients reporting syncope and the effect of anti-depressants (ADs) on the rates of syncope. DESIGN: : epidemiological, point-prevalence study. SETTING AND PARTICIPANTS: : data came from the Irish Longitudinal Study on Ageing, which includes 8,175 adults aged 50 and older, living in the community in Ireland. MEASUREMENTS: : the Centre for Epidemiological Studies Depression scale was used to assess levels of depression. Multinomial regression was used to analyse the data with a P-value of <0.05 determining significance. RESULTS: : 7,993 participants aged 50 and older were included, and of these 349 reported at least one syncopal episode in the last year. Prevalence of syncope was 4.4%. After controlling for participant characteristics and general health, those with severe depression had a greater risk of single and multiple syncopal events (relative risk ratios [RRR]: 2.78 and 2.84, respectively, P < 0.050) and participants treated with tricyclic anti-depressants (TCAs) were also at greater risk for single and multiple syncopal episode in the last year (RRR: 2.31, P = 0.062; RRR: 2.95, P < 0.05). CONCLUSIONS: : this study demonstrates an increased risk of syncope in patients with depression, with higher rates of syncope reported with increasing severity of depression. Treatment with TCAs increases both the risk and frequency of syncope in the community. Depression is a potentially modifiable risk factor for syncope but treatment options need to be tailored in the older patient population.

Low-Grade systemic inflammation is associated with domain-specific cognitive performance and cognitive decline in older adults: Data from the TUDA study.

Studies examining the relationships between chronic inflammation, cognitive function and cognitive decline in older adults have yielded conflicting results. In a large cohort of older adults free from established dementia (n = 3270; 73.1 ± 7.9 years; 68.4% female), we evaluated the cross-sectional and longitudinal relationships between serum cytokines (IL-6, IL-10, TNF-α) and both global and domain-specific cognitive performance (Repeatable Battery for Assessment of Neuropsychological Status [RBANS]). Higher IL-6 (OR: 1.33; 1.06, 1.66, p = 0.01), TNF-α (OR: 1.35; 1.09, 1.67, p = 0.01) and IL-6:IL-10 Ratio (OR: 1.43; 1.17, 1.74, p = 0.001) were cross-sectionally associated with impaired global RBANS performance. For specific cognitive domains, greatest effect sizes were observed between higher TNF-α levels and poorer visual-spatial and attention performance. In a subset of participants (n = 725; 69.8 ± 5.5 years; 67.0% female) with repeat assessment performed at a median of 5.4 years, only higher baseline IL-6:IL-10 ratio was associated with impaired incident overall, immediate memory and visual-spatial performance. Associations were stronger in females, but not modified by age or APOE genotype.

Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults. METHOD: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years. Exclusion criteria included an estimated glomerular filtration rate (eGFR) <30 ml/min and serum calcium >2.5 mmol/l to remove hyperparathyroidism due to advanced chronic kidney disease (CKD) and primary hyperparathyroidism respectively. The relationship between SHPT and bone turnover markers and BMD (measured by densitometry) was examined in a subsample (n = 1488). Vitamin D deficiency was defined as 25-hydroxyvitamin D [25 (OH)D] <30 nmol/l. RESULTS: Participants had a mean age of 73.6 ± 7.9 years, 65.1 % were female and 19.4 % were found to be vitamin D deficient. The prevalence of SHPT decreased as vitamin D increased, from 30.6 % in those deficient to 9.8 % in those with 25(OH)D ≥ 50 nmol/l and increased with declining kidney function. In non­calcium supplement users, principal determinants of SHPT were vitamin D deficiency (OR 4.18, CI 3.05-5.73, p < 0.001), eGFR 30-44 ml/min (OR 3.69, CI 2.44-5.57, p < 0.001), loop diuretic use (OR 3.52, CI 2.59-4.79, p < 0.001) and to a lesser extent body mass index (p = 0.001), eGFR 45-59 ml/min (p < 0.001) and 25(OH)D level 30-49 nmol/l (p = 0.002). Similar findings were observed in calcium supplement users, though proton pump inhibitors were also associated with SHPT (OR 1.55, CI 1.08-2.22, p = 0.018) while vitamin D 30-49 nmol/l was not. In participants with SHPT versus those without, bone turnover markers were higher: bone alkaline phosphatase (p = 0.017) and tartrate-resistant acid phosphatase (p = 0.033), whilst there was lower BMD at the neck of femur (0.880 vs. 0.903 g/cm2, p = 0.033) and total hip (0.968 vs. 0.995 g/cm2, P = 0.017). DISCUSSION: The results show that up to one in six older Irish adults had SHPT and this was associated with lower BMD and higher concentrations of bone turnover markers. Both vitamin D deficiency and 25(OH)D level 30-49 nmol/l were important predictors of SHPT. Loop diuretics and PPIs may also increase the risk of SHPT, and their use may need to be carefully considered in this population. Further studies examining the potential impact of these factors on bone health in similar populations to our study sample are warranted.

Identification of nutrition factors in the metabolic syndrome and its progression over time in older adults: analysis of the TUDA cohort.

BACKGROUND: Nutrition is recognized as playing an important role in the metabolic syndrome (MetS), but the dietary components involved are unclear. We aimed to investigate nutrition factors in relation to MetS and its progression in older adults over a follow-up period of 5.4 years. METHODS: Community-dwelling adults (≥ 60y) from the Trinity-Ulster-Department-of-Agriculture study, sampled at baseline (2008-12) and follow-up (2014-18; n 953), were classified as 'with MetS' by having three or more of: waist circumference (≥ 102 cm, males; ≥ 88 cm, females); HDL-cholesterol (< 1.0 mmol/L, males; < 1.3 mmol/L, females); triglycerides (≥ 1.7 mmol/L); blood pressure (systolic ≥ 130 and/or diastolic ≥ 85 mmHg); and hemoglobin A1c (≥ 39 mmol/mol). RESULTS: MetS was identified in 67% of participants, increasing to 74% at follow-up. Predictors at baseline for the development of metabolic syndrome (MetS) at follow-up were higher waist circumference (odds ratio [95%CI]; 1.06 [1.01-1.11]), but not BMI, and increased triglyceride concentrations (2.01 [1.29-3.16]). In dietary analysis (at follow-up), higher protein (g/kg bodyweight/day) and monounsaturated fatty acid (g/day) intakes were each associated with lower risk of MetS (0.06 [0.02-0.20] and 0.88 [0.78-1.00], respectively), whilst higher protein was also associated with lower abdominal obesity (0.10 [0.02-0.51]) and hypertension (0.22 [0.00-0.80]). Furthermore, participants with, compared to without, MetS consumed less high-quality protein foods (P = 0.006) and more low-quality protein foods (P < 0.001), as defined by the protein digestibility-corrected amino acid score. CONCLUSIONS: Dietary interventions targeting protein quantity and quality may have specific benefits in preventing or delaying the progression of MetS in at-risk older people, but this requires investigation in the form of randomized trials.

An electronic medical record reminder is independently associated with improved opportunistic influenza vaccination rates for older inpatients.

BACKGROUND: Influenza vaccination will have added importance this winter given the possibility of further waves of the COVID-19 pandemic. This study examines the impact of an electronic medical record (EMR) reminder on influenza vaccine uptake among eligible hospital inpatients. METHODS: We included a convenience sample of 750 adults (median age 77 years) who are eligible for influenza vaccination (⩾65 years and/or length of stay >30 days). A live electronic dashboard identified patients eligible for vaccination, prompting reminders sent to the clinical teams via the EMR. RESULTS: The EMR reminder was associated with almost a 50% higher likelihood of vaccination after adjusting for other covariates (odds ratio 1.48 (95% confidence interval 1.00-2.20); p = 0.048). DISCUSSION: Reminders sent to the clinical team via the EMR appear to be an effective means of increasing vaccine uptake and should be considered as part of this year's drive to vaccinate eligible patients in hospital.

Association of dietary flavan-3-ol intakes with plasma phenyl-γ-valerolactones: analysis from the TUDA cohort of healthy older adults.

BACKGROUND: Dietary polyphenols, including flavan-3-ols (F3O), are associated with better health outcomes. The relationship of plasma phenyl-γ-valerolactones (PVLs), the products of colonic bacterial metabolism of F3O, with dietary intakes is unclear. OBJECTIVES: To investigate whether plasma PVLs are associated with self-reported intakes of total F3O and procyanidins+(epi)catechins. DESIGN: We measured 9 PVLs by uHPLC-MS-MS in plasma from adults (>60y) in the Trinity-Ulster-Department of Agriculture (TUDA study (2008 to 2012; n=5186) and a follow-up subset (2014 to 2018) with corresponding dietary data (n=557). Dietary (poly)phenols collected by FFQ were analyzed using Phenol-Explorer. RESULTS: Mean (95% confidence interval [CI]) intakes were estimated as 2283 (2213, 2352) mg/d for total (poly)phenols, 674 (648, 701) for total F3O, and 152 (146, 158) for procyanidins+(epi)catechins. Two PVL metabolites were detected in plasma from the majority of participants, 5-(hydroxyphenyl)-γ-VL-sulfate (PVL1) and 5-(4'-hydroxyphenyl)-γ-VL-3'-glucuronide (PVL2). The 7 other PVLs were detectable only in 1-32% of samples. Self-reported intakes (mg/d) of F3O (r = 0.113, P = 0.017) and procyanidin+(epi)catechin (r = 0.122, P = 0.010) showed statistically significant correlations with the sum of PVL1 and PVL 2 (PVL1+2). With increasing intake quartiles (Q1-Q4), mean (95% CI) PVL1+2 increased; from 28.3 (20.8, 35.9) nmol/L in Q1 to 45.2 (37.2, 53.2) nmol/L in Q4; P = 0.025, for dietary F3O, and from 27.4 (19.1, 35.8) nmol/L in Q1 to 46.5 (38.2, 54.9) nmol/L in Q4; P = 0.020, for procyanidins+(epi)catechins. CONCLUSIONS: Of 9 PVL metabolites investigated, 2 were detected in most samples and were weakly associated with intakes of total F3O and procyanidins+(epi)catechins. Future controlled feeding studies are required to validate plasma PVLs as biomarkers of these dietary polyphenols.

Vitamin D and orthostatic hypotension.

INTRODUCTION: we aimed to investigate on the potential relationship between vitamin D and orthostatic hypotension (OH) in a case-control model in older adults. METHODS: all participants were community-dwelling adults who were not taking vitamin D supplements. Cases were subjects aged 64 or older who were diagnosed with OH at a Falls and Blackout Unit. Controls were age- (within 5 years) and gender-matched subjects who had no history of blackouts, falls or orthostatic dizziness in the preceding year. OH was defined according to standard criteria and was diagnosed with an active stand test. Serum vitamin D [25(OH)D] was measured by radioimmunoassay. RESULTS: seventy-six subjects were included in the analysis (38 controls and 38 cases). Twenty-four in each group were female and mean age was between 78 and 79 years. Subjects with OH had lower serum 25(OH)D compared to controls (mean difference = 20.6 nmol/l, P = 0.0002). Lower vitamin D status was associated with an increased risk of OH after adjustment for season, body mass index, presence of stroke, diabetes and angina (P = 0.035) but not with impaired orthostatic haemodynamics. DISCUSSION: findings suggest that vitamin D may play a role in the aetiology of OH. Further studies will be required to explore on this relationship.