Publications by authors named "Natasja van Schoor"

172 Publications

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Nat Commun 2021 06 7;12(1):3417. Epub 2021 Jun 7.

Servei de Neurologia, Hospital Universitari i Politècnic La Fe, Valencia, Spain.

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.
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http://dx.doi.org/10.1038/s41467-021-22491-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184987PMC
June 2021

Older adults report cancellation or avoidance of medical care during the COVID-19 pandemic: results from the Longitudinal Aging Study Amsterdam.

Eur Geriatr Med 2021 May 28. Epub 2021 May 28.

Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Location VU University Medical Center, P.O. Box 7057, 1007MB, Amsterdam, The Netherlands.

Purpose: Delay of routine medical care during the COVID-19 pandemic may have serious consequences for the health and functioning of older adults. The aim of this study was to investigate whether older adults reported cancellation or avoidance of medical care during the first months of the COVID-19 pandemic, and to explore associations with health and socio-demographic characteristics.

Methods: Cross-sectional data of 880 older adults aged ≥ 62 years (mean age 73.4 years, 50.3% female) were used from the COVID-19 questionnaire of the Longitudinal Aging Study Amsterdam, a cohort study among community-dwelling older adults in the Netherlands. Cancellation and avoidance of care were assessed by self-report, and covered questions on cancellation of primary care (general practitioner), cancellation of hospital outpatient care, and postponed help-seeking. Respondent characteristics included age, sex, educational level, loneliness, depression, anxiety, frailty, multimorbidity and information on quarantine.

Results: 35% of the sample reported cancellations due to the COVID-19 situation, either initiated by the respondent (12%) or by healthcare professionals (29%). Postponed help-seeking was reported by 8% of the sample. Multimorbidity was associated with healthcare-initiated cancellations (primary care OR = 1.92, 95% CI = 1.09-3.50; hospital OR = 1.86, 95% CI = 1.28-2.74) and respondent-initiated hospital outpatient cancellations (OR = 2.02, 95% CI = 1.04-4.12). Depressive symptoms were associated with postponed help-seeking (OR = 1.15, 95% CI = 1.06-1.24).

Conclusion: About one third of the study sample reported cancellation or avoidance of medical care during the first months of the pandemic, and this was more common among those with multiple chronic conditions. How this impacts outcomes in the long term should be investigated in future research.
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http://dx.doi.org/10.1007/s41999-021-00514-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159721PMC
May 2021

Genetic variants modify the associations of concentrations of methylmalonic acid, vitamin B-12, vitamin B-6, and folate with bone mineral density.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.

Background: Elevated plasma homocysteine has been found to be associated with an increased risk of osteoporosis, especially hip and vertebral fractures. The plasma concentration of homocysteine is dependent on the activities of several B vitamin-dependent enzymes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and cystathionine β-synthase (CBS).

Objectives: We investigated whether genetic variants in some of the genes involved in 1 carbon metabolism modify the association of B vitamin-related measures with bone mineral density (BMD) and strength.

Methods: We measured several B vitamins and biomarkers in participants of the Framingham Offspring Study, and performed analyses of methylmalonic acid (MMA) continuously and <210 nmol/L; pyridoxal-5'-phosphate; vitamin B-12 continuously and ≥258 pmol/L; and folate. The outcomes of interest included areal and volumetric BMD, measured by DXA and quantitative computed tomography (QCT), respectively. We evaluated associations between the bone measures and interactions of single nucleotide polymorphism with a B vitamin or biomarker in Framingham participants (n = 4310 for DXA and n = 3127 for QCT). For analysis of DXA, we validated the association results in the B-PROOF cohort (n = 1072). Bonferroni-corrected locus-wide significant thresholds were defined to account for multiple testing.

Results: The interactions between rs2274976 and vitamin B-12 and rs34671784 and MMA <210 nmol/L were associated with lumbar spine BMD, and the interaction between rs6586281 and vitamin B-12 ≥258 pmol/L was associated with femoral neck BMD. For QCT-derived traits, 62 interactions between genetic variants and B vitamins and biomarkers were identified.

Conclusions: Some genetic variants in the 1-carbon methylation pathway modify the association of B vitamin and biomarker concentrations with bone density and strength.  These interactions require further replication and functional validation for a mechanistic understanding of the role of the 1-carbon metabolism pathway on BMD and risks of fracture.
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http://dx.doi.org/10.1093/ajcn/nqab093DOI Listing
May 2021

Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.

Nat Commun 2021 01 28;12(1):654. Epub 2021 Jan 28.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10), arthritis (GDF5 p = 4 × 10), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.
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http://dx.doi.org/10.1038/s41467-021-20918-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844411PMC
January 2021

Neighborhood environment, social participation, and physical activity in older adults with lower limb osteoarthritis: A mediation analysis.

Health Place 2021 Mar 25;68:102513. Epub 2021 Jan 25.

Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands; Faculty of Social Work & Applied Psychology, University of Applied Sciences Leiden, the Netherlands.

Older adults with lower limb osteoarthritis (LLOA) are highly dependent on their physical and social environment for being physically active. Longitudinal data from 2286 older adults (M = 73.8 years; 50.3% female) in six European countries were analyzed using cross-lagged Structural Equation Modeling (SEM) and multi-group SEM. In cross-sectional analyses, neighborhood resources were associated with physical activity (r = 0.26;p < .001) and social participation (r = 0.13;p = .003). Physical activity at follow-up was associated with neighborhood resources, with this relationship mediated by social participation in people with LLOA (β = 0.018;p = .013). To promote future physical activity, opportunities to socially engage in neighborhoods need to be targeted primarily to people with LLOA.
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http://dx.doi.org/10.1016/j.healthplace.2021.102513DOI Listing
March 2021

Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum.

J Gerontol A Biol Sci Med Sci 2021 Apr;76(5):750-759

Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, The Netherlands.

Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. Using a cohort of centenarians with maintained cognitive health (N = 343), a population-matched cohort of older adults from 5 cohorts (N = 2905), and summary statistics data from genome-wide association studies on parental longevity, we constructed a PRS including 330 variants that significantly discriminated between centenarians and older adults. This PRS was also associated with longer survival in an independent sample of younger individuals (p = .02), leading up to a 4-year difference in survival based on common genetic factors only. We show that this PRS was, in part, able to compensate for the deleterious effect of the APOE-ε4 allele. Using an integrative framework, we annotated the 330 variants included in this PRS by the genes they associate with. We find that they are enriched with genes associated with cellular differentiation, developmental processes, and cellular response to stress. Together, our results indicate that an extended human life span is, in part, the result of a constellation of variants each exerting small advantageous effects on aging-related biological mechanisms that maintain overall health and decrease the risk of age-related diseases.
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http://dx.doi.org/10.1093/gerona/glaa289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087277PMC
April 2021

Genetic basis of falling risk susceptibility in the UK Biobank Study.

Commun Biol 2020 09 30;3(1):543. Epub 2020 Sep 30.

Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Both extrinsic and intrinsic factors predispose older people to fall. We performed a genome-wide association analysis to investigate how much of an individual's fall susceptibility can be attributed to genetics in 89,076 cases and 362,103 controls from the UK Biobank Study. The analysis revealed a small, but significant SNP-based heritability (2.7%) and identified three novel fall-associated loci (P ≤ 5 × 10). Polygenic risk scores in two independent settings showed patterns of polygenic inheritance. Risk of falling had positive genetic correlations with fractures, identifying for the first time a pathway independent of bone mineral density. There were also positive genetic correlations with insomnia, neuroticism, depressive symptoms, and different medications. Negative genetic correlations were identified with muscle strength, intelligence and subjective well-being. Brain, and in particular cerebellum tissue, showed the highest gene expression enrichment for fall-associated variants. Overall, despite the highly heterogenic nature underlying fall risk, a proportion of the susceptibility can be attributed to genetics.
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http://dx.doi.org/10.1038/s42003-020-01256-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527955PMC
September 2020

Immune response and endocytosis pathways are associated with the resilience against Alzheimer's disease.

Transl Psychiatry 2020 09 29;10(1):332. Epub 2020 Sep 29.

Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.

Developing Alzheimer's disease (AD) is influenced by multiple genetic variants that are involved in five major AD-pathways. Per individual, these pathways may differentially contribute to the modification of the AD-risk. The pathways involved in the resilience against AD have thus far been poorly addressed. Here, we investigated to what extent each molecular mechanism associates with (i) the increased risk of AD and (ii) the resilience against AD until extreme old age, by comparing pathway-specific polygenic risk scores (pathway-PRS). We used 29 genetic variants associated with AD to develop pathway-PRS for five major pathways involved in AD. We developed an integrative framework that allows multiple genes to associate with a variant, and multiple pathways to associate with a gene. We studied pathway-PRS in the Amsterdam Dementia Cohort of well-phenotyped AD patients (N = 1895), Dutch population controls from the Longitudinal Aging Study Amsterdam (N = 1654) and our unique 100-plus Study cohort of cognitively healthy centenarians who avoided AD (N = 293). Last, we estimated the contribution of each pathway to the genetic risk of AD in the general population. All pathway-PRS significantly associated with increased AD-risk and (in the opposite direction) with resilience against AD (except for angiogenesis, p < 0.05). The pathway that contributed most to the overall modulation of AD-risk was β-amyloid metabolism (29.6%), which was driven mainly by APOE-variants. After excluding APOE variants, all pathway-PRS associated with increased AD-risk (except for angiogenesis, p < 0.05), while specifically immune response (p = 0.003) and endocytosis (p = 0.0003) associated with resilience against AD. Indeed, the variants in these latter two pathways became the main contributors to the overall modulation of genetic risk of AD (45.5% and 19.2%, respectively). The genetic variants associated with the resilience against AD indicate which pathways are involved with maintained cognitive functioning until extreme ages. Our work suggests that a favorable immune response and a maintained endocytosis pathway might be involved in general neuro-protection, which highlight the need to investigate these pathways, next to β-amyloid metabolism.
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http://dx.doi.org/10.1038/s41398-020-01018-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524800PMC
September 2020

Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease: Extended follow-up of the B-PROOF trial.

Clin Nutr 2021 Mar 5;40(3):1199-1206. Epub 2020 Aug 5.

Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands; Amsterdam UMC, (University) of Amsterdam, Section of Geriatric Medicine, Department of Internal Medicine, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.

Background & Aims: In the initial B-proof, we found inconsistent results of B vitamin supplementation. However, the debate regarding the effects of B vitamins on age-related diseases continues. Therefore, our aim was to investigate the long-term effects (5-7 years follow-up) of an intervention with folic acid and vitamin-B12 supplementation on fracture and cardiovascular disease risk.

Methods: Extended follow-up of the B-PROOF trial, a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2-3 years daily supplementation with folic acid (400 μg) and vitamin-B12 (500 μg) versus placebo (n = 2,919). Primary outcome was verified self-reported fracture incidence and secondary outcomes were self-reported cardiovascular endpoints, which were collected through a follow-up questionnaires Proportional hazard analyses was used for the effect of the intervention on risk of fracture(s) and logistic regression for the effect of the intervention on risk of cardiovascular disease.

Results: A total of 1,298 individuals (44.5%) participated in the second follow-up round with median of 54 months [51-58], (n = 662 and n = 636, treatment versus placebo group). Median age at baseline was 71.0 years [68.0-76.0] for both groups. No effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62-1.59 and HR: 0.77; 95% CI: 0.50-1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80-1.44 and OR: 0.85; 95%CI: 0.50-1.45, respectively). Potential interaction by baseline homocysteine concentration was observed for osteoporotic- and any fracture (p = 0.10 and 0.06 respectively), which indicated a significantly lower risk of any fracture in the treatment group with higher total homocysteine concentrations (>15.1 μmol/l). No age-dependent effects were present.

Conclusions: This study supports and extends previous null-findings of the B-PROOF trial and shows that supplementation of folic acid and vitamin-B12 has no effect on fracture risk, nor on cardiovascular disease in older individuals over a longer follow-up period. However, B-vitamin supplementation may be beneficial in reducing fractures in individuals with high total homocysteine concentrations, a finding which needs to be replicated.
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http://dx.doi.org/10.1016/j.clnu.2020.07.033DOI Listing
March 2021

Factors associated with functional decline in hand and hip/knee osteoarthritis after a year's time: Data from the eposa study.

Arthritis Care Res (Hoboken) 2020 Aug 8. Epub 2020 Aug 8.

National Research Council, Neuroscience Institute - Aging Branch, Padova, Italy.

Objective: The study investigated 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 the ages of 65-85 in a prospective, observational population-based study with 12-18 month 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 Minimal Clinically Important Difference of 4 on the AUStralian/CANadian hand OA Index and of 2 on the Western Ontario and McMaster Universities hip/knee OA 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/anti-inflammatory 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/anti-inflammatory medications mediated the combined effect of hip/knee OA+pain on functional decline in the 554 individuals classified as having "worse" hip/knee functionality and the 1,291 "not worse" persons. Peripheral artery disease, obesity, and cognitive impairment were other baseline risk factors.

Conclusion: Study findings showed that together with emotional status, chronic physical and cognitive conditions, OA affects hand and hip/knee functional decline.
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http://dx.doi.org/10.1002/acr.24404DOI Listing
August 2020

Neighborhood Resources Associated With Active Travel in Older Adults-A Cohort Study in Six European Countries.

J Aging Phys Act 2020 Jun 23:1-14. Epub 2020 Jun 23.

Objectives: To study associations between perceived neighborhood resources and time spent by older adults in active travel.

Methods: Respondents in six European countries, aged 65-85 years, reported on the perceived presence of neighborhood resources (parks, places to sit, public transportation, and facilities) with response options "a lot," "some," and "not at all." Daily active travel time (total minutes of transport-related walking and cycling) was self-reported at the baseline (n = 2,695) and 12-18 months later (n = 2,189).

Results: Reporting a lot of any of the separate resources (range B's = 0.19-0.29) and some or a lot for all four resources (B = 0.22, 95% confidence interval [0.09, 0.35]) was associated with longer active travel time than reporting none or fewer resources. Associations remained over the follow-up, but the changes in travel time were similar, regardless of the neighborhood resources.

Discussion: Perceiving multiple neighborhood resources may support older adults' active travel. Potential interventions, for example, the provision of new resources or increasing awareness of existing resources, require further study.
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http://dx.doi.org/10.1123/japa.2019-0267DOI Listing
June 2020

The Association Between High-Molecular-Weight Adiponectin, Ghrelin and Leptin and Age-Related Cognitive Decline: Results From Longitudinal Aging Study Amsterdam.

J Gerontol A Biol Sci Med Sci 2021 Jan;76(1):131-140

Department of Internal Medicine, Endocrine Section, VU University Medical Center, Amsterdam, the Netherlands.

Background: Age-related cognitive decline has large-scale functional and economic consequences and understanding its' pathophysiological mechanisms is therefore essential. Previous research has suggested associations between hormones adiponectin, ghrelin and leptin and neurodegenerative disease. However, their association with age-related cognitive decline has not been fully described. We examine the association between serum high-molecular-weight (HMW) adiponectin, ghrelin and leptin and age-related cognitive decline in older adults.

Methods: The associations between HMW adiponectin, ghrelin and leptin and the Mini-Mental-State-Examination, Coding task (Coding), 15 Words Test (15WT) and composite Z-score (general cognitive function) were analyzed by means of a sex-stratified multivariable linear regression analysis in a population-based cohort of 898 older adults at baseline and after 3 years of follow-up.

Results: In women, we found a positive association between HMW adiponectin and general cognitive function at baseline (fully adjusted model composite Z-score standardized regression co-efficient beta [β] = .089, p = .025). After 3 years of follow-up, HMW adiponectin was associated with more decline in general cognitive function and information processing speed (fully adjusted model composite Z-score β = -.123, p = .018; Coding β = -.116, p = .027). Ghrelin and leptin were significantly associated with memory in a baseline subgroup analysis of older women. For men, we found no significant associations at baseline or follow-up.

Conclusion: Our results show variable associations between hormones HMW adiponectin, ghrelin and leptin and age-related cognitive decline in women but not in men. As there was no clear trend, all our results should be interpreted with caution.
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http://dx.doi.org/10.1093/gerona/glaa126DOI Listing
January 2021

Genetic Liability for Depression, Social Factors and Their Interaction Effect in Depressive Symptoms and Depression Over Time in Older Adults.

Am J Geriatr Psychiatry 2020 08 8;28(8):844-855. Epub 2020 Mar 8.

Amsterdam UMC- Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, (NS, NMS, MH) Amsterdam, the Netherlands; Department of Sociology, Vrije Universiteit, (BS, MH) Amsterdam, the Netherlands.

Objectives: The objectives of this study were to investigate the effect of genetic and social factors on depressive symptoms and depression over time and to test whether social factors moderate the relationship between depressive symptoms and its underlying genetics in later life.

Methods: The study included 2,279 participants with a mean follow-up of 15 years from the Longitudinal Aging Study Amsterdam with genotyping data. The personal genetic loading for depression was estimated for each participant by calculating a polygenic risk scores (PRS-D), based on 23,032 single nucleotide polymorphisms associated with major depression in a large genome-wide association study. Partner status, network size, received and given emotional support were assessed via questionnaires and depressive symptoms were assessed using the CES-D Scale. A CES-D Scale of 16 and higher was considered as clinically relevant depression.

Results: Higher PRS-D was associated with more depressive symptoms whereas having a partner and having a larger network size were independently associated with less depressive symptoms. After extra adjustment for education, cognitive function and functional limitations, giving more emotional support was also associated with less depressive symptoms. No evidence for gene-environment interaction between PRS-D and social factors was found. Similar results were found for clinically relevant depression.

Conclusion: Genetic and social factors are independently associated with depressive symptoms over time in older adults. Strategies that boost social functioning should be encouraged in the general population of older adults regardless of the genetic liability for depression.
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http://dx.doi.org/10.1016/j.jagp.2020.02.011DOI Listing
August 2020

PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment.

Acta Neuropathol 2020 06 12;139(6):1025-1044. Epub 2020 Mar 12.

Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC-Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer's disease (AD) was identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2) that is highly expressed in microglia. To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies. Furthermore, association with CSF levels of pTau, total tau, and Aβ was assessed in 1261 MCI patients. We found that MCI patients who carried the p.P522R variant showed a slower rate of cognitive decline compared to non-carriers and that this effect was mediated by lower pTau levels in CSF. The effect size of the association of p.P522R with the cognitive decline and pTau was similar to that of APOE-ε4, the strongest genetic risk factor for AD. Interestingly, the protective effect of p.P522R was more pronounced in MCI patients with low Aβ levels suggesting a role of PLCG2 in the response to amyloid pathology. In line with this hypothesis, we observed no protective effect of the PLCG2 variant on the cognitive decline in population-based studies probably due to the lower prevalence of amyloid positivity in these samples compared to MCI patients. Concerning the potential biological underpinnings, we identified a network of co-expressed proteins connecting PLCG2 to APOE and TREM2 using unsupervised co-regulatory network analysis. The network was highly enriched for the complement cascade and genes differentially expressed in disease-associated microglia. Our data show that p.P522R in PLCG2 reduces AD disease progression by mitigating tau pathology in the presence of amyloid pathology and, as a consequence, maintains cognitive function. Targeting the enzyme PLCG2 might provide a new therapeutic approach for treating AD.
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http://dx.doi.org/10.1007/s00401-020-02138-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244617PMC
June 2020

Physical Activity as Moderator of the Association Between APOE and Cognitive Decline in Older Adults: Results from Three Longitudinal Cohort Studies.

J Gerontol A Biol Sci Med Sci 2020 09;75(10):1880-1886

Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC-Vrije Universiteit, the Netherlands.

Background: Previous studies have suggested that the association between APOE ɛ 4 and dementia is moderated by physical activity (PA), but the results remain inconclusive and longitudinal data on cognitive decline are missing. In this study, we examine whether there is a gene-environment interaction between APOE and PA on cognitive decline in older adults using 9-year follow-up data of three cohort studies.

Methods: We followed 7,176 participants from three longitudinal cohort studies: Longitudinal Aging Study Amsterdam (LASA), InCHIANTI, and Rotterdam Study for 9 years. PA was assessed with self-reported questionnaires and was categorized in low, moderate, and high PA. Cognitive function was assessed with the Mini-Mental State Examination (MMSE) and cognitive decline was defined as a decrease of three points or more on the MMSE during 3 years follow-up. We fitted logistic regression models using generalized estimating equations adjusting for age, sex, education, depressive symptoms, and number of chronic disease. Interaction between APOE and PA was tested on multiplicative and additive scale.

Results: Cohorts were similar in most aspects but InCHIANTI participants were on average older and had lower education. APOE ɛ 4 carriers had higher odds of cognitive decline (odds ratio [OR] = 1.46, 95% confidence interval [CI]: 1.29-1.64) while PA was not significantly associated with cognitive decline overall (moderate PA: OR = 0.87, 0.67-1.13; high PA: OR = 0.71, 0.36-1.40). There was no evidence for an interaction effect between PA and APOE ɛ 4 in cognitive decline in older adults (APOE × moderate PA: p = .83; APOE × high PA: p = .90).

Conclusions: Previous claims of a gene-environment interaction between APOE ɛ 4 and PA in cognitive decline are not supported by our results.
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http://dx.doi.org/10.1093/gerona/glaa054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518558PMC
September 2020

Distinct Trajectories of Individual Physical Performance Measures Across 9 Years in 60- to 70-Year-Old Adults.

J Gerontol A Biol Sci Med Sci 2020 09;75(10):1951-1959

Department of Human Movement Sciences, @AgeAmsterdam, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, the Netherlands.

Background: Physical performance is an important factor for successful aging. This study aimed to identify distinct trajectories of multiple physical performance measures over 9 years in individuals aged 60-70 years and to evaluate their characteristics and the overlap between measures.

Methods: Four physical performance measures were assessed in 440 participants of the Longitudinal Aging Study Amsterdam: tandem stand, gait speed, chair stand, and handgrip strength. Gender-specific latent class models were conducted to obtain distinct trajectories and their degree of overlap.

Results: Mean age at baseline was 67.9 (SD 1.7) years for males and 68.0 (SD 1.7) years for females. The optimal number of trajectories differed across measures. For tandem stand, no distinct trajectories were found (all 179 males, 198 females). For gait speed, three trajectories were identified, dependent on baseline speed: high-stable (47 males, 27 females), intermediate-stable (132 males, 130 females), and low-declining performance (6 males, 48 females). Two trajectories were identified for the chair stand: a stable (168 males, 150 females) and declining trajectory (10 males, 38 females). For handgrip strength, three declining trajectories were identified differing in baseline performance: high (55 males, 75 females), intermediate (111 males, 118 females), and low (17 males, 10 females). Overall, 11.9% of males and 5.7% of females were classified in similar trajectories across measures.

Conclusions: Trajectories of physical performance were heterogeneous, but showed similar patterns for males and females. Little overlap between measures was shown, suggesting different mechanisms for decline. This study emphasizes the use of multiple domains to assess physical performance.
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http://dx.doi.org/10.1093/gerona/glaa045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518554PMC
September 2020

Psychosocial and Health-Related Factors Associated With Discordance Between 13-Year Trajectories of Self-Reported Functional Limitations and Performance-Based Physical Functioning in Old Age.

J Aging Health 2020 10 5;32(9):1084-1097. Epub 2019 Nov 5.

Amsterdam UMC-Vrije Universiteit Amsterdam, The Netherlands.

The objective of this study was to examine correlates of discordance between 13-year trajectories of self-reported functional limitations and performance-based physical functioning in older adults. We included 2,135 participants from the population-based Longitudinal Aging Study Amsterdam, the Netherlands, followed across 1995-2008. Self-reported functional limitations included six (instrumental) activities of daily living. Performance-based functioning was a composite of four tests. We used latent class growth analysis and multinomial logistic regression to examine discordance and its correlates. Patterns of discordance and concordance (41% concordance, 46% "overestimation" of daily functioning, 13% "underestimation") appeared to be persistent over 13 years. Older age, male sex, cognitive impairment, absence of pain, and light alcohol use were associated with overestimation. Younger age, female sex, and lower self-rated health were associated with underestimation. Factors associated with overestimation partly differ from those associated with underestimation. Factors that are highly stable over time are particularly good indicators of persistent discordance.
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http://dx.doi.org/10.1177/0898264319884404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731649PMC
October 2020

Do Vitamin D Level and Dietary Calcium Intake Modify the Association Between Loop Diuretics and Bone Health?

Calcif Tissue Int 2020 02 14;106(2):104-114. Epub 2019 Oct 14.

Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

Loop diuretics (LD) may affect bone health by inhibiting renal calcium reuptake. However, whether vitamin D status and dietary calcium intake modify the association between LD and bone outcome is unclear. Therefore, this study aimed to evaluate whether vitamin D level or calcium intake modify the association between LD and various indices of bone health including bone mineral density (BMD) and Trabecular Bone Score (TBS). From The Rotterdam Study, a prospective population-based cohort study, we used data from 6990 participants aged > 45 year with a DXA scan (2002-2008), 6908 participants with femoral neck (FN)-BMD, 6677 participants with lumbar spine (LS)-BMD and 6476 participants with LS-TBS measurements. Use of LD was available from pharmacy dispensing records. Vitamin D (25(OH)D) level was measured in serum, and dietary calcium intake was measured with a validated food frequency questionnaire. Almost eight percent of the participants used LD. The association between LD (past-users compared to never-users) and LS-TBS was significantly different by 25(OH)D concentrations (P for interaction = 0.04). A significantly lower LS-TBS among LD past-users was observed for 25(OH)D ≥ 50 nmol/l compared to ≤ 20 and 20-50 nmol/l (β = - 0.036, 95% CI - 0.060; - 0.013 vs. β = - 0.012, 95% CI - 0.036; 0.013 and β = - 0.031, 95% CI - 0.096; 0.034, respectively). However, no other significant effect modification by 25(OH)D and dietary calcium intake was found in the associations between LD use and bone health outcomes (P-interaction > 0.13). This study suggests that the association between LD use and indices of bone health is not consistently modified by vitamin D or dietary calcium intake.
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http://dx.doi.org/10.1007/s00223-019-00621-1DOI Listing
February 2020

Association Between Osteoarthritis and Social Isolation: Data From the EPOSA Study.

J Am Geriatr Soc 2020 01 17;68(1):87-95. Epub 2019 Sep 17.

National Research Council, Institute of Neuroscience-Aging Branch, Padova, Italy.

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.
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http://dx.doi.org/10.1111/jgs.16159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954097PMC
January 2020

The Longitudinal Aging Study Amsterdam: cohort update 2019 and additional data collections.

Eur J Epidemiol 2020 Jan 25;35(1):61-74. Epub 2019 Jul 25.

Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC - Location VU University Medical Center, Amsterdam, The Netherlands.

The Longitudinal Aging Study Amsterdam (LASA) is a prospective cohort study of older adults in the Netherlands, initially based on a nationally representative sample of people aged 55-84 years. The study has been ongoing since 1992, and focuses on the determinants, trajectories and consequences of physical, cognitive, emotional and social functioning. Strengths of the LASA study include its multidisciplinary character, the availability of over 25 years of follow-up, and the cohort-sequential design that allows investigations of longitudinal changes, cohort differences and time trends in functioning. The findings from LASA have been reported in over 600 publications so far (see www.lasa-vu.nl). This article provides an update of the design of the LASA study and its methods, on the basis of recent developments. We describe additional data collections, such as additional nine-monthly measurements in-between the regular three-yearly waves that have been conducted among the oldest old during 2016-2019, and the inclusion of a cohort of older Turkish and Moroccan migrants.
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http://dx.doi.org/10.1007/s10654-019-00541-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058575PMC
January 2020

Vitamin D supplementation for the prevention of depression and poor physical function in older persons: the D-Vitaal study, a randomized clinical trial.

Am J Clin Nutr 2019 11;110(5):1119-1130

Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Background: Depressive symptoms and impaired physical functioning are prevalent among older adults. Supplementation with vitamin D might improve both conditions, particularly in persons with low vitamin D status.

Objective: The D-Vitaal study primarily aimed to investigate the effect of vitamin D supplementation on depressive symptoms, functional limitations, and physical performance in a high-risk older population with low vitamin D status. Secondary aims included examining the effect of vitamin D supplementation on anxiety symptoms, cognitive functioning, mobility, handgrip strength, and health-related quality of life.

Methods: This study was a randomized placebo-controlled trial with 155 participants aged 60-80 y who had clinically relevant depressive symptoms, ≥1 functional limitations, and serum 25-hydroxyvitamin D [25(OH)D] concentrations of 15-50/70 nmol/L (depending on season). Participants received 1200 IU/d vitamin D3 (n = 77) or placebo tablets (n = 78) for 12 mo. Serum 25(OH)D was measured at baseline and 6 mo; outcomes were assessed at baseline, 6 mo, and 12 mo. Linear mixed-models analyses were conducted to assess the effect of the intervention.

Results: The supplementation increased serum 25(OH)D concentrations in the intervention group to a mean ± SD of 85 ± 16 nmol/L compared with 43 ± 18 nmol/L in the placebo group after 6 mo (P < 0.001). No relevant differences between the treatment groups were observed regarding depressive symptoms, functional limitations, physical performance, or any of the secondary outcomes.

Conclusions: Supplementation with 1200 IU/d vitamin D for 12 mo had no effect on depressive symptoms and physical functioning in older persons with relatively low vitamin D status, clinically relevant depressive symptoms, and poor physical functioning. This trial is registered with the Netherlands Trial Register (www.trialregister.nl) under NTR3845.
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http://dx.doi.org/10.1093/ajcn/nqz141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821546PMC
November 2019

Development of a clinical prediction model for the onset of functional decline in people aged 65-75 years: pooled analysis of four European cohort studies.

BMC Geriatr 2019 06 27;19(1):179. Epub 2019 Jun 27.

Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081, BT, Amsterdam, The Netherlands.

Background: Identifying those people at increased risk of early functional decline in activities of daily living (ADL) is essential for initiating preventive interventions. The aim of this study is to develop and validate a clinical prediction model for onset of functional decline in ADL in three years of follow-up in older people of 65-75 years old.

Methods: Four population-based cohort studies were pooled for the analysis: ActiFE-ULM (Germany), ELSA (United Kingdom), InCHIANTI (Italy), LASA (Netherlands). Included participants were 65-75 years old at baseline and reported no limitations in functional ability in ADL at baseline. Functional decline was assessed with two items on basic ADL and three items on instrumental ADL. Participants who reported at least some limitations at three-year follow-up on any of the five items were classified as experiencing functional decline. Multiple logistic regression analysis was used to develop a prediction model, with subsequent bootstrapping for optimism-correction. We applied internal-external cross-validation by alternating the data from the four cohort studies to assess the discrimination and calibration across the cohorts.

Results: Two thousand five hundred sixty community-dwelling people were included in the analyses (mean age 69.7 ± 3.0 years old, 47.4% female) of whom 572 (22.3%) reported functional decline at three-year follow-up. The final prediction model included 10 out of 22 predictors: age, handgrip strength, gait speed, five-repeated chair stands time (non-linear association), body mass index, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, arthritis, and depressive symptoms. The optimism-corrected model showed good discrimination with a C statistic of 0.72. The calibration intercept was 0.06 and the calibration slope was 1.05. Internal-external cross-validation showed consistent performance of the model across the four cohorts.

Conclusions: Based on pooled cohort data analyses we were able to show that the onset of functional decline in ADL in three years in older people aged 65-75 years can be predicted by specific physical performance measures, age, body mass index, presence of depressive symptoms, and chronic conditions. The prediction model showed good discrimination and calibration, which remained stable across the four cohorts, supporting external validity of our findings.
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http://dx.doi.org/10.1186/s12877-019-1192-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595632PMC
June 2019

The Effect of a Screening and Treatment Program for the Prevention of Fractures in Older Women: A Randomized Pragmatic Trial.

J Bone Miner Res 2019 11 1;34(11):1993-2000. Epub 2019 Aug 1.

Amsterdam UMC, Vrije Universiteit Amsterdam, General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, Amsterdam, Netherlands.

Population screening for fracture risk may reduce the fracture incidence. In this randomized pragmatic trial, the SALT Osteoporosis Study (SOS), we studied whether screening for fracture risk and subsequent treatment in primary care can reduce fractures compared with usual care. A total of 11,032 women aged 65 to 90 years with ≥1 clinical risk factor for fractures were individually randomized to screening (n = 5575) or usual care (n = 5457). Participants in the screening group underwent a screening program, including bone densitometry and vertebral fracture assessment. Participants with a high 10-year fracture probability (FRAX) or a vertebral fracture were offered treatment with anti-osteoporosis medication by their general practitioner. Incident fractures as reported by questionnaires were verified with medical records. Follow-up was completed by 94% of the participants (mean follow-up = 3.7 years). Of the 5575 participants in the screening group, 1417 (25.4%) had an indication for anti-osteoporosis medication. Screening and subsequent treatment had no statistically significant effect on the primary outcome fracture (hazard ratio [HR] = 0.97; 95% confidence interval [CI] 0.87-1.08), nor on the secondary outcomes osteoporotic fractures (HR = 0.91; 95% CI 0.81-1.03), major osteoporotic fractures (HR = 0.91; 95% CI 0.80-1.04), hip fractures (HR = 0.91; 95% CI 0.71-1.15), falls (odds ratio [OR] = 0.91; 95% CI 0.72-1.15), or mortality (HR = 1.03; 95% CI 0.91-1.17). Post hoc explorative finding suggested that screening might be most effective after a recent fracture (HR = 0.65; 95% CI 0.44-0.96 for major osteoporotic fractures and HR = 0.38; 95% CI 0.18-0.79 for hip fractures). The results of this study might have been compromised by nonparticipation and medication nonadherence in the screening group. Overall, this study does not provide sufficient indications to consider screening for fracture prevention. However, we cannot exclude its clinical relevance to reduce (major) osteoporotic fractures and hip fractures because of the relatively small number of women with a treatment indication in the intervention group. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jbmr.3815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900199PMC
November 2019

A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

Acta Neuropathol 2019 08 27;138(2):237-250. Epub 2019 May 27.

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.
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http://dx.doi.org/10.1007/s00401-019-02026-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660501PMC
August 2019

Minimal clinically important decline in physical function over one year: EPOSA study.

BMC Musculoskelet Disord 2019 May 17;20(1):227. Epub 2019 May 17.

National Research Council, Neuroscience Institute - Aging Branch, Via Giustiniani 2, ,35128, Padova, Italy.

Background: The Australian/Canadian hand Osteoarthritis Index (AUSCAN) and the Western Ontario and McMaster Universities knee and hip Osteoarthritis Index (WOMAC) are the most commonly used clinical tools to manage and monitor osteoarthritis (OA). Few studies have as yet reported longitudinal changes in the AUSCAN index regarding the hand. While there are published data regarding WOMAC assessments of the hip and the knee, the two sites have always evaluated separately. The current study therefore sought to determine the minimal clinically important difference (MCID) in decline in the AUSCAN hand and WOMAC hip/knee physical function scores over 1 year using anchor-based and distribution-based methods.

Methods: The study analysed data collected by the European Project on Osteoarthritis, a prospective observational study investigating six adult cohorts with and without OA by evaluating changes in the AUSCAN and WOMAC physical function scores at baseline and 12-18 months later. Pain and stiffness scores, the performance-based grip strength and walking speed and health-related quality of life measures were used as the study's anchors. Receiver operating characteristic curves and distribution-based methods were used to estimate the MCID in the AUSCAN and WOMAC physical function scores; only the data of those participants who possessed paired (baseline and follow up-measures) AUSCAN and WOMAC scores were included in the analysis.

Results: Out of the 1866 participants who were evaluated, 1842 had paired AUSCAN scores and 1845 had paired WOMAC scores. The changes in the AUSCAN physical function score correlated significantly with those in the AUSCAN pain score (r = 0.31). Anchor- and distribution-based approaches converged identifying 4 as the MCID for decline in the AUSCAN hand physical function. Changes in the WOMAC hip/knee physical function score were significantly correlated with changes in both the WOMAC pain score (r = 0.47) and the WOMAC stiffness score (r = 0.35). The different approaches converged identifying two as the MCID for decline in the WOMAC hip/knee physical function.

Conclusions: The most reliable MCID estimates of decline over 1 year in the AUSCAN hand and WOMAC hip/knee physical function scores were 4 and 2 points, respectively.
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http://dx.doi.org/10.1186/s12891-019-2593-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525447PMC
May 2019

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis.

Nat Commun 2019 05 15;10(1):2176. Epub 2019 May 15.

School of Pathology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, 2000, South Africa.

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.
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http://dx.doi.org/10.1038/s41467-019-09976-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520353PMC
May 2019

B-vitamins and body composition: integrating observational and experimental evidence from the B-PROOF study.

Eur J Nutr 2020 Apr 10;59(3):1253-1262. Epub 2019 May 10.

Department of Epidemiology, Erasmus University Medical Center, Postbus 2040, 3000 CA, Rotterdam, The Netherlands.

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 lower BMI (95% CI - 0.039; - 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m higher FMI (95% CI 0.262; 1.647), and higher MMA (per μgmol/L) was associated with a 1.108 kg/m 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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http://dx.doi.org/10.1007/s00394-019-01985-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098930PMC
April 2020

Trends across 20 years in multiple indicators of functioning among older adults in the Netherlands.

Eur J Public Health 2019 12;29(6):1096-1102

Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC - Location VU University Medical Center, Amsterdam, The Netherlands.

Background: Monitoring of trends in functioning of older adults provides indispensable information for health care policy. This study examined trends in multiple indicators of functioning among Dutch older adults across a period of 20 years.

Methods: Data from the Longitudinal Aging Study Amsterdam were used. We included 10 870 observations of 3803 respondents aged 64-84 years across seven waves (1992-12) and 931 observations of 603 respondents aged 85-94 years across four waves (2001-12). At each wave, 8 indicators of functioning were measured: multimorbidity, severe functional limitations, depression, anxiety, cognitive impairment, physical inactivity, loneliness and social isolation. In addition, a sum score (range: 0-8) of these indicators was calculated, with a score of ≥5 indicating 'multiple problems.' Trends in functioning over time were assessed using Generalized Estimating Equation analyses.

Results: In the 64-84-years-olds, the prevalence of multimorbidity increased over time [OR(year) = 1.06, 95% CI = 1.05-1.06], whereas the prevalence of the other indicators decreased [i.e. cognitive impairment, physical inactivity (in women) and loneliness (in women)] or remained stable [i.e. severe functional limitations, depression, anxiety, physical inactivity (in men), loneliness (in men) and social isolation]. In the 85-94-year-olds, the prevalence of severe functional limitations increased over time [OR(year) = 1.08, 95% CI = 1.02-1.13], whereas the prevalence of the other indicators remained stable. In both age groups, the prevalence of 'multiple problems' remained stable.

Conclusion: Unfavorable trends were observed in multimorbidity among 64-84-years-olds and in severe functional limitations among 85-94-year-olds. Favorable trends were found in cognitive impairment, physical inactivity (in women) and loneliness (in women) among 64-84-years-olds.
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http://dx.doi.org/10.1093/eurpub/ckz065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896978PMC
December 2019

Relative importance of four functional measures as predictors of 15-year mortality in the older Dutch population.

BMC Geriatr 2019 03 25;19(1):92. Epub 2019 Mar 25.

Department of Epidemiology and Biostatistics/LASA, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers location VU University Medical Center, Van der Boechorststraat 7, 1081, BT, Amsterdam, The Netherlands.

Background: Decreased physical function is known to raise mortality risk. Little is known about how different physical function measures compare in predicting mortality risk in older men and women. The objective of this study was to compare four, objective and self-reported, physical function measures in predicting 15-year mortality risk in older men and women.

Methods: Data were used from the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study in a population-based sample of the older Dutch population, sampled from municipal records. The 1995-96 cycle, including 727 men and 778 women aged 65-88 years, was considered as the baseline. Mortality was followed up through September 1, 2011. Physical function measures were: lower-body performance (chair stands test, walk test and tandem stand); handgrip strength (grip strength dynamometer); lung function (peak expiratory flow rate); functional limitations (self-report of difficulties in performing six activities of daily living). Cox proportional hazard models were used to determine the predictive value of each physical function measure for 15-year mortality risk, adjusted for demographic, lifestyle and health variables as potential confounders.

Results: 1031 participants (68.5%) had died. After adjustments for confounders, in models assessing single functional measures, peak flow was the strongest predictor of all-cause mortality in men (HR 1.76, CI 1.38-2.26, CI) and lower-body performance in women (HR 1.97,CI 1.40-2.76, CI). In a model including all four functional measures only peak flow was statistically significant in predicting mortality in both genders (men HR 1.54,CI 1.18-2.01 and women HR 1.45,CI 1.08-1.94). In women, lower-body performance (HR 1.66, CI 1.15-2.41) followed by grip strength (HR 1.38, CI 1.02-1.89), and in men, functional limitations (HR 1.43, CI 1.14-1.8) were the other significant predictors of all-cause mortality.

Conclusion: Both objective and self-reported measures of physical functioning predicted all-cause mortality in a representative sample of the older Dutch population to different extents in men and women. Peak flow contributed important unique predictive value for mortality in both men and women. In women, however, lower-body performance tests had better predictive ability. A second-best predictor in men was self-reported functional limitations. Peak flow, and possibly one of the other measures, may be used in clinical practice for assessment in the context of time constraints.
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http://dx.doi.org/10.1186/s12877-019-1092-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434808PMC
March 2019