Albert Hofman works in Preventive Cardiology affiliated with Erasmus MC.
Albert Hofman is the Chair of the Department of Epidemiology and the Stephen B. Kay Family Professor of Public Health and Clinical Epidemiology at Harvard T.H. Chan School of Public Health. He previously served as chairman of the Department of Epidemiology at Erasmus Medical Center from 1988 to 2016. He initiated the Rotterdam Study, a large cohort study examining risk factors for cardiovascular and other age-related diseases.
2,079 pubs · 194,223 cites · h-index 208
PhD
Erasmus University Rotterdam
1983
MD
University of Groningen
1976
Chair of the Department of Epidemiology
Harvard T.H. Chan School of Public Health · 2016 - Present
Stephen B. Kay Family Professor of Public Health and Clinical Epidemiology
Harvard T.H. Chan School of Public Health · 2016 - Present
Chairman of the Department of Epidemiology
Erasmus Medical Center · 1988 - 2016
Science Director
Netherlands Institute for Health Sciences · 1990 - 2015
Senior Lecturer in Human Genetics, St George's University of London · St George's University of London
This allowed us to discover 52 regions where 67 genes are located, which we now think are involved in the functioning of the cardiac muscle. We already knew that some of these genes cause serious cardiac diseases, but we did not realise that the majority of them also play a role in the way the heart functions.
ViewHarst et al.
Prolonged QTc may heighten SCD vigilance in older adults; leaves open causal role and need for prospective trials.
Postdoctoral researcher, Respiratory Medicine, Ghent University Hospital · Ghent University Hospital
We are carrying out further research to explore the mechanisms that could explain the high risk of SCD in patients with COPD. We are also looking at the links between the causes of arrhythmias -- irregular heart beats -- and SCD and COPD.
European Heart JournalLahousse et al.
Mendelian randomization demonstrates that circulating cystatin C is a biomarker rather than a causal factor for cardiovascular disease, suggesting that therapies lowering cystatin C will not prevent CVD.
Should not yet change clinical practice; leaves open whether extracoronary imaging improves coronary risk prediction.
BACKGROUND: Compressing the duration of cognitive impairment is critical to preserve quality of life until the end. To what extent cognitive decline is compressed and cognitive resilience increases with extreme longevity is not well understood. METHODS: We used data from 13,999 deceased participants from the National Alzheimer's Coordinating Center cohort, including 8,146 with neuropathological data. Cognitive function was assessed annually (median follow-up: 4.9 years). We evaluated cognitive trajectories before death and cognitive resilience (defined as high neuropathological burden without dementia) across lifespan groups (ages 50-100+ years). RESULTS: Participants with longer lifespans, particularly centenarians, exhibited slower cognitive decline and shorter periods of cognitive impairment before death, although distinct cognitive trajectories existed among centenarians. Cognitive resilience also increased with longer lifespans, but associated factors varied. Apolipoprotein E ε2 was associated with higher cognitive resilience only in centenarians. CONCLUSION: Our findings support a general compression of cognitive decline and increased cognitive resilience in extreme longevity. HIGHLIGHTS: Individuals with longer lifespans, especially centenarians, generally exhibited better cognitive function and slower cognitive decline toward the end of life, suggesting a compression of cognitive decline in extreme longevity. Although there was a compression of cognitive decline at the group level among centenarians, heterogeneous cognitive trajectories before death were observed across individuals. The relationship between neuropathological burden and dementia risk attenuated with longer lifespans, indicating greater cognitive resilience in individuals with extreme longevity. The associations of both genetic and modifiable factors with cognitive resilience varied by lifespan.
Cohort study finds smaller ventricular volumes may indicate temperamental difficulties in infants, suggesting early brain morphology impacts behavior.
BACKGROUND: MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally and show differential expression in various tissues with aging phenotypes. Detectable in circulation, extracellular microRNAs reflect (patho)physiological processes and hold promise as biomarkers for healthy aging and age-related diseases. This study aimed to explore plasma extracellular microRNAs as a biological aging indicator and their associations with health outcomes using population-level data. METHODS: We quantified plasma expression levels of 2083 extracellular microRNAs using targeted RNA-sequencing in 2684 participants from the population-based Rotterdam Study cohort. The training and test sets included 1930 participants from the advanced-aged initial and second subcohort (RS-I/RS-II; median age: 70.6), while the validation set comprised 754 participants from the middle-aged fourth subcohort (RS-IV; median age: 53.5). Based on 591 microRNAs well-expressed in plasma, we examined differential expression of microRNAs with chronological age, PhenoAge-a composite score of age and nine multi-system blood biomarkers-the frailty index, and mortality. Next, elastic net models were employed to construct composite microRNA-based aging biomarkers predicting chronological age (mirAge), PhenoAge (mirPA), frailty index (mirFI), and mortality (mirMort). The association of these aging biomarkers with different age-related health outcomes was assessed using Cox Proportional Hazard, linear regression, and logistic regression models in the test and validation sets. Moreover, 227 miRNAs showed robust associations with PhenoAge, 61 with FI, and 16 with 10-year mortality independent of chronological age. Subsequently, we constructed four plasma microRNA-based aging biomarkers: mirAge with 108, mirPA with 153, mirFI with 81, and mirMort with 50 miRNAs. Elevated scores on these microRNA-based aging biomarkers were associated with unfavorable health outcomes, including lower subjective physical functioning and self-reported health and increased mortality and frailty risk, but not with first- or multi-morbidity. Overall, larger effect estimates were observed for mirPA, mirFI, and mirMort compared to mirAge. CONCLUSIONS: This study describes distinct plasma microRNA-aging signatures and introduces four microRNA-based aging biomarkers with the potential to identify accelerated aging and age-related decline, providing insights into the intricate process of human aging.
China accounts for 1/5 of the global population and China faces a particularly heavy dementia burden due to its rapidly ageing population. Unique historical events, genetic background, sociocultural factors, lifestyle, and the COVID-19 pandemic further influence cognitive outcomes in the Chinese population. We searched PubMed, Web of Science, and Embase for community-based cohort studies related to dementia in the Chinese population, and summarized the characteristics, methodologies, and major findings published over the last 25 years from 39 cohorts. We identified critical research gaps and propose future directions, including enhancing sample representativeness, investigating China-specific risk factors, expanding exposure measurements to the whole life-span, collecting objective data, conducting administer-friendly domain-specific cognitive assessments, adopting pathological diagnostic criteria, standardizing biobank construction, verifying multi-modal biomarkers, examining social and genetic-environmental aspects, and monitoring post-COVID cognitive health, to approach high quality of dementia studies that can provide solid evidence to policy making and promote global brain health research.
Impaired baroreflex sensitivity may flag higher dementia risk in untreated older adults; leaves open its incremental value for prediction or prevention.
BACKGROUND: Cerebral hypoperfusion is associated with vascular brain injury and neurodegeneration, but their longitudinal relationship is largely unknown, especially in healthy older adults. METHODS: We investigated the longitudinal relationship between cerebral hemodynamics and subclinical vascular brain disease in community-dwelling older adults without stroke or dementia at baseline. Participants underwent brain magnetic resonance imaging scans every 3 to 4 years between 2005 and 2016. Cerebral blood flow (CBF) was measured through 2-dimensional phase-contrast magnetic resonance imaging; the cerebrovascular resistance index (CVRi) was defined as the ratio of mean arterial blood pressure to total CBF. Simultaneous progression in subclinical brain disease was evaluated through repeated magnetic resonance imaging assessment of white matter hyperintensities (WMH), cerebral microbleeds, lacune, and brain atrophy. The longitudinal relationship was estimated using generalized estimating equations, with adjustment for age, sex, smoking habits, body mass index, systolic blood pressure (for CBF measures), lipid level, history of diabetes and cardiovascular disease, and the baseline burden of magnetic resonance imaging markers. RESULTS: Among 3623 older adults (mean age, 61.4±9.3 years; 54.6% women), large decreases and increases in CBF and increases in CVRi over time were associated with white matter hyperintensity progression. The risk ratios for white matter hyperintensity progression were 1.36 (95% CI, 1.19-1.55) for large decreases in total CBF (lowest quartile), 1.02 (95% CI, 0.91-1.14) for moderate decreases (second quartile), and 1.28 (95% CI, 1.14-1.45) for large increases (highest quartile), compared with stable CBF (third quartile). The corresponding risk ratios for changes in CVRi were 1.13 (95% CI, 1.00-1.30), 1.25 (95% CI, 1.09-1.43), and 1.33 (95% CI, 1.16-1.52) for the second to fourth (versus lowest) quartiles, respectively, showing a dose-response relationship. The changes in CBF also demonstrate a similar U-shaped association with the progression of brain atrophy and incident microbleeds, whereas increases in CVRi were associated with lower microbleed risk. CONCLUSIONS: Longitudinal changes in CBF and CVRi may capture distinct pathophysiologies linking cerebral hemodynamics to subclinical brain disease, extending beyond single-time point measurements.
Background. In this article the results are presented of a four part study on the effect of screening for scoliosis and (repeated) well-care visits and freely accessible consultation hours at secondary schools, on the incidence and prevalence of (para)suicide, mental health, adolescent health compromising behaviour and lastly obesity. Methods. An ecologic case-referent study design was used with data from the Netherlands Bureau of Statistics, the Ministry of Defence, the 1992 High-School Student Study, all of the youth health care departments in The Netherlands and relevant censuses. Results. Attention to mental and physical health and health compromising behaviour, either during screening, open consultation hours or during well-care visits seems to be ineffective and in some instances even detrimental to youth health. Of the 18 different outcome measurements, 5 were significantly negative and none were significantly positive. Conclusions. This four part study does not support the hypothesis that on a population level, the preventive activities of youth health care departments such as screening for scoliosis, (more) frequent well-care visits or offering open consultation hours at secondary schools, have a beneficial effect on prevention of (para)suicide, poor mental health, health compromising behaviour or obesity.
The brain and its health are essential for our (physical mental, social, and spiritual) wellbeing, for being able to realize our potential as individuals, and also for a fair, well-functioning, and productive society. However, today the world is facing a healthcare crisis related to the very high (and increasing) burden of brain disorders. As a response to this crisis, the “Swiss Brain Health Plan” (SBHP) was conceptualized in the context of other initiatives launched to value, promote, and protect brain health over the entire life course. In the first section of this position paper, the following fundamental considerations of the SBHP are discussed: (1) the high (and increasing) burden of brain disorders in terms of prevalence (>50% of the population suffers from a brain disorder), disability, mortality, and costs; (2) the prevention of brain disorders; (3) the operational definition of brain health; (4) determinants of brain health; (5) international initiatives to promote brain (including mental) health including the World Health Organization (WHO) intersectorial global action plan on epilepsy and other neurological disorders (NDs) (IGAP) and the WHO comprehensive mental health action plan. In the second section of the paper, the five strategic objectives of the SBHP, which has the vision of promoting brain health for all across the entire life course, are presented: (1) to raise awareness; (2) strengthen cross-disciplinary and interprofessional training/educational programs for healthcare professionals; (3) foster research on brain health determinants and individualized prevention of brain disorders; (4) prioritize a holistic (non-disease-specific), integrated, person-centered public health approach to promote brain health and prevent brain disorders through collaborations across scientific, health care, commercial, societal and governmental stakeholders and insurance providers; (5) support, empower, and engage patients, caregivers, and patient organizations, and reduce the stigma and discrimination related to brain disorders. In the third section of the paper, the first (2024) steps in the implementation of the SHBP, which will be officially launched in Zurich on 22 November 2023, are presented: (1) a definition of the overall organization, governance, specific targets, and action areas of the SBHP; (2) the patronage and/or co-organization of events on such specific topics as brain research (Lausanne), dementia (Geneva), stroke (Basel), neurohumanities (Bellinzona), sleep (Lugano), and psychiatry (Zurich); (3) the conduction of a new study on the global burden of brain disorders in Switzerland; (4) the launching of an international Certificate of Advanced Studies (CAS) on Brain Health at the University of Bern. In the fourth section of the paper, there is a concise executive summary of the SBHP.
Abrupt drops in systolic blood pressure within the first minute of standing are associated with a higher long-term risk of developing dementia.
Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.
INTRODUCTION: Lower education is associated with higher burden of vascular risk factors in mid-life and higher risk of dementia in late life. We aim to understand the causal mechanism through which vascular risk factors potentially mediate the relationship between education and dementia. METHODS: In a cohort of 13,368 Black and White older adults in the Atherosclerosis Risk in Communities Study, we assessed the relationship between education (grade school, high school without graduation, high school graduate or equivalent, college, graduate/professional school) and dementia among all participants and among those with incident stroke. Cox models were adjusted for age, race-center (a variable stratified by race and field center), sex, apolipoprotein E (APOE) ε4 genotype, and family history of cardiovascular disease. Causal mediation models assessed mediation by mid-life systolic blood pressure, fasting blood glucose, body mass index, and smoking. RESULTS: More education was associated with 8 to 44% lower risk of dementia compared to grade school-level education in a dose-response pattern, while the relationship between education and post-stroke dementia was not statistically significant. Up to 25% of the association between education and dementia was mediated through mid-life vascular risk factors, with a smaller percentage mediated for lower levels of education. INTERPRETATION: A substantial proportion of the relationship between education and dementia was mediated through mid-life vascular risk factors. However, risk factor modification is unlikely to fully address the large educational disparities in dementia risk. Prevention efforts must also address disparities in socioeconomic resources leading to divergent early-life education and other structural determinants of mid-life vascular risk factors. ANN NEUROL 2023;94:13-26.
Systematic review analyzes dementia predictors in ischemic stroke survivors, suggesting key monitoring factors.
Plasma levels of fibrinogen, coagulation factors VII and VIII and von Willebrand factor (vWF) are four intermediate phenotypes that are heritable and have been associated with the risk of clinical thrombotic events. To identify rare and low-frequency variants associated with these hemostatic factors, we conducted whole-exome sequencing in 10 860 individuals of European ancestry (EA) and 3529 African Americans (AAs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and the National Heart, Lung and Blood Institute's Exome Sequencing Project. Gene-based tests demonstrated significant associations with rare variation (minor allele frequency < 5%) in fibrinogen gamma chain (FGG) (with fibrinogen, P = 9.1 × 10-13), coagulation factor VII (F7) (with factor VII, P = 1.3 × 10-72; seven novel variants) and VWF (with factor VIII and vWF; P = 3.2 × 10-14; one novel variant). These eight novel rare variant associations were independent of the known common variants at these loci and tended to have much larger effect sizes. In addition, one of the rare novel variants in F7 was significantly associated with an increased risk of venous thromboembolism in AAs (Ile200Ser; rs141219108; P = 4.2 × 10-5). After restricting gene-based analyses to only loss-of-function variants, a novel significant association was detected and replicated between factor VIII levels and a stop-gain mutation exclusive to AAs (rs3211938) in CD36 molecule (CD36). This variant has previously been linked to dyslipidemia but not with the levels of a hemostatic factor. These efforts represent the largest integration of whole-exome sequence data from two national projects to identify genetic variation associated with plasma hemostatic factors.
BACKGROUND AND AIMS: We aimed to determine associations of plasma amyloid-β40 (Aβ40) with subclinical atherosclerosis and risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. METHODS: Between 2002 and 2005, plasma Aβ40 was measured by single molecule array (SiMoA®) in 3879 participants of the population-based Rotterdam Study (mean age: 71 years, 61% female). Subclinical atherosclerosis was quantified as computed tomography-assessed calcification volumes. We determined the association of Aβ40 with calcification volumes and clinical ASCVD event risk, and repeated the analyses for ASCVD in a replication cohort of 1467 individuals. RESULTS: Higher levels of Aβ40 were associated with increased volumes of calcification in the coronary arteries and to a lesser extent extracranial carotid arteries, independent of traditional cardiovascular risk factors. Of all 3879 participants, 748 developed ASCVD during a median 9.7 years of follow-up. In age- and sex-adjusted models, higher Aβ40 predisposed to a minor increase in ASCVD risk (HR [95%CI]: 1.11[1.02-1.21] per 1-SD increase in Aβ40), driven by coronary heart disease (HR: 1.17[1.05-1.29]) rather than stroke (HR: 1.04[0.93-1.16]). However, excess risk of clinical outcomes was largely explained by baseline differences in cardiovascular risk factors and attenuated after further adjustment (for ASCVD- HR: 1.05[0.96-1.15] and for CHD- HR: 1.08[0.96-1.20]). Results were similar in the replication cohort, with highest risk estimates for CHD (HR: 1.24[1.04-1.48]) in age- and sex-adjusted models, attenuated after adjustment for cardiovascular risk factors (HR: 1.15[0.96-1.39]). CONCLUSIONS: In this population-based study, higher plasma amyloid-β40 is associated with subclinical atherosclerosis, but not risk of first-ever ASCVD after accounting for traditional cardiovascular risk factors.
