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Article ; Online: Erratum to: Epidemiology of Dementia: The Burden on Society, the Challenges for Research.

Wolters, Frank J / Ikram, M A

Methods in molecular biology (Clifton, N.J.)

2018 Volume 1750, Page(s) E3

Abstract: The name of the Chapter 1 author had been inadvertently mentioned as M. Arfan Ikram. ...

Abstract	The name of the Chapter 1 author had been inadvertently mentioned as M. Arfan Ikram.
Language	English
Publishing date	2018-07-04
Publishing country	United States
Document type	Journal Article ; Published Erratum
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7704-8_27
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Article ; Online: Epidemiology of Dementia: The Burden on Society, the Challenges for Research.

Wolters, Frank J / Ikram, M A

Methods in molecular biology (Clifton, N.J.)

2018 Volume 1750, Page(s) 3–14

Abstract: Dementia is among the leading causes of death and disability. Due to the ageing population, its prevalence is expected to nearly triple worldwide by 2050, urging the development of preventive and curative interventions. Various modifiable risk factors ... ...

Abstract	Dementia is among the leading causes of death and disability. Due to the ageing population, its prevalence is expected to nearly triple worldwide by 2050, urging the development of preventive and curative interventions. Various modifiable risk factors have been identified in community-based cohort studies, but insight into the underlying pathophysiological mechanisms is lacking. Clinical trials have thus far failed in the development of disease-modifying therapy in patients with dementia, thereby triggering a shift of focus toward the presymptomatic phase of disease. The extensive preclinical disease course of Alzheimer's disease warrants reliable, easily obtainable biomarkers to aid in timely application of preventive strategies, selecting participants for neuroprotective trials, and disease monitoring in trials and clinical practice. Biomarker and drug discovery may yield the fruits from technology-driven developments in the field of genomics, epigenetics, metabolomics, and brain imaging. In that context, bridging the gap between translational and population research may well prove a giant leap toward development of successful preventive and curative interventions against dementia.
MeSH term(s)	Biomarkers/analysis ; Biomedical Research/trends ; Clinical Trials as Topic ; Dementia/diagnosis ; Dementia/epidemiology ; Dementia/therapy ; Disease Progression ; Global Health ; Humans ; Risk Factors
Chemical Substances	Biomarkers
Language	English
Publishing date	2018-03-06
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7704-8_1
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Article ; Online: Air pollution and the risk of dementia

de Crom, Tosca / Oudin, Anna / Ginos, Bigina / Ikram, M.K. / Voortman, Trudy / Ikram, M.A.

Alzheimer's & Dementia

The rotterdam study

2023 Volume 19, Issue S8

Abstract: BackgroundAir pollution has been suggested to increase the risk of dementia, by triggering neuro-inflammation, oxidative stress, and cerebrovascular damage. However, studies on the association between exposure to air pollution and the risk of dementia ... ...

Abstract	BackgroundAir pollution has been suggested to increase the risk of dementia, by triggering neuro-inflammation, oxidative stress, and cerebrovascular damage. However, studies on the association between exposure to air pollution and the risk of dementia yielded inconsistent results. We therefore determined exposure to air pollution in association with the risk of dementia and cognitive decline in the population-based Rotterdam Study.MethodBetween 2009 and 2010, we determined air pollutant levels at participants residential addresses using land use regression models. Determined air pollutant levels included particulate matter with an aerodynamic diameter of less than 10 µm (PM10) and 2.5 µm (PM2.5), a proxy of elemental carbon (PM2.5 absorbance), nitrogen oxide (NOx), and nitrogen dioxide (NO2). As the individual air pollutant levels were highly correlated with each other (r = 0.71-0.98), we obtained the first unrotated component of a principal component analyses (PCA) for all air pollutants. We followed participants up for dementia until 2018 and determined cognitive performance during two subsequent examination rounds. Using Cox proportional hazard models and linear mixed models, we determined the association of exposure to air pollution with the risk of dementia and cognitive decline.ResultOf the 7511 non-demented participants at baseline (median age 68 years, 58.6% women), 545 developed dementia during a median follow-up of 7 years. Mean ± standard deviation (SD) levels per µg/m3 were 26.1 ± 1.0 for PM10, 16.8 ± 0.4 for PM2.5, 1.5 ± 0.1 for PM2.5 absorbance, 46.1 ± 12.2 for NOx, and 32.6 ± 3.4 for NO2. The individual air pollutant levels were not significantly associated with the risk of dementia, neither was the first unrotated component of a PCA for all air pollutants (hazard ratio [95% confidence interval] per SD increase: 1.04 [0.95-1.15], Figure 1). Air pollutant levels were also not associated with decline in cognitive function.ConclusionExposure to air pollution was not statistically significantly ...
Keywords	Life Science
Subject code	333
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	2211627-8
ISSN	1552-5260
ISSN	1552-5260
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Adiposity in the older population and the risk of dementia

Mooldijk, Sanne S. / de Crom, Tosca O.E. / Ikram, M.K. / Ikram, M.A. / Voortman, Trudy

Alzheimer's and Dementia

The Rotterdam Study

2023 Volume 19, Issue 5

Abstract: Introduction: We determined associations of total and regional adiposity with incident dementia among older adults. Methods: Within the population-based Rotterdam Study, adiposity was measured as total, android, and gynoid fat mass using dual-energy X- ... ...

Abstract	Introduction: We determined associations of total and regional adiposity with incident dementia among older adults. Methods: Within the population-based Rotterdam Study, adiposity was measured as total, android, and gynoid fat mass using dual-energy X-ray absorptiometry in 3408 men and 4563 women, every 3 to 6 years between 2002 and 2016. Incident dementia was recorded until 2020. Results: Higher adiposity measures were associated with a decreased risk of dementia in both sexes. After excluding the first 5 years of follow-up, only the association of gynoid fat among women remained significant (hazard ratio 0.85 [95% confidence interval 0.75–0.97] per standard deviation increase). No major differences in trajectories of adiposity measures were observed between dementia cases and dementia-free controls. Discussion: Higher total and regional fat mass related to a decreased risk of dementia. These results may be explained by reverse causality, although a protective effect of adiposity cannot be excluded. Highlights: Total and regional adiposity were assessed using dual-energy X-ray absorptiometry scans in 7971 older adults. All adiposity measures were associated with a decreased risk of dementia. The results suggest a beneficial effect of gynoid fat on the risk of dementia in women. Reverse causation and competing risk may explain these inverse associations.
Keywords	abdominal fat ; adiposity ; body composition ; dementia ; obesity
Subject code	360
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	2211627-8
ISSN	1552-5260
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Article ; Online: Biological Aging for Risk Prediction of First-Ever Intracerebral Hemorrhage and Cerebral Infarction in Advanced Age.

Waziry, Reem / Hofman, Albert / Ghanbari, Mohsen / Tiemeier, Henning / Ikram, M A / Viswanathan, Anand / Klap, Jaco / Ikram, M Kamran / Goudsmit, Jaap

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

2022 Volume 31, Issue 8, Page(s) 106568

Abstract: Background and objectives: successful interventions to prevent cerebrovascular disease and stroke require early identification of persons at risk before clinical manifestation of disease. The literature remains to be sparse on accessible plasma-based ... ...

Abstract	Background and objectives: successful interventions to prevent cerebrovascular disease and stroke require early identification of persons at risk before clinical manifestation of disease. The literature remains to be sparse on accessible plasma-based biomarkers for monitoring brain health and cerebrovascular disease in advanced age. We assessed the predictive value of biological age (BA) as an early indicator for cerebrovascular disease and risk of first-ever intracerebral hemorrhage (ICH) and cerebral infarction (CI) in advanced age and compared these relationships with chronological age (CA) and commonly used biomarkers including tau and Aβ40 and Aβ42. Methods: The study included Individuals who consented for blood draw and follow-up. We computed biological age using structural equation modelling. The criteria for the biomarkers included their representability of the various body systems; their availability in the Rotterdam study and their pre-hypothesized reflection of aging in other populations. The algorithm integrates biomarkers that represent six body systems involved in overall cerebrovascular health including metabolic function, cardiac function, lung function, kidney function, liver function, immunity, and inflammation. Time to event analysis was conducted using Cox-regression models. Prediction analysis was conducted using Harrel's C and Area under the receiver operating characteristic curve. Results: The sample included a total of 1699 individuals at baseline followed up over a median of 11 years. During a period of 15, 780 and 16, 172 person-years, a total of 17 first-ever intracerebral hemorrhage and 83 cerebral infarction cases occurred. In time-to-event analysis, BA showed higher magnitude of associations with ICH compared to CA (HR Conclusions: Biological aging (delta biological aging) based on integrated physiology biomarkers provides a novel tool for monitoring and identification of persons at highest risk of cerebrovascular disease in advanced age with varying degrees of precision and magnitude for stroke subtypes. These variations are likely related to differences in pathophysiology of intracerebral hemorrhage and cerebral infarction. Wider validation and applicability require extension of these findings in other comparable samples and in clinical settings.
MeSH term(s)	Aging ; Biomarkers ; Cerebral Hemorrhage ; Cerebral Infarction/complications ; Cerebral Infarction/etiology ; Cerebrovascular Disorders/complications ; Humans ; Stroke/complications
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-06-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1131675-5
ISSN	1532-8511 ; 1052-3057
ISSN (online)	1532-8511
ISSN	1052-3057
DOI	10.1016/j.jstrokecerebrovasdis.2022.106568
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Article ; Online: MIND diet and the risk of dementia a population-based study

de Crom, Tosca O.E. / Mooldijk, Sanne S. / Ikram, M.K. / Ikram, M.A. / Voortman, Trudy

Alzheimer's Research and Therapy

2022 Volume 14

Abstract: Background: Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has been linked to a decreased risk of dementia, but reverse causality and residual confounding by lifestyle may partly account for this link. We aimed ... ...

Abstract	Background: Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has been linked to a decreased risk of dementia, but reverse causality and residual confounding by lifestyle may partly account for this link. We aimed to address these issues by studying the associations over cumulative time periods, which may provide insight into possible reverse causality, and by using both historical and more contemporary dietary data as this could give insight into confounding since historical data may be less affected by lifestyle factors. Methods: In the population-based Rotterdam Study, dietary intake was assessed using validated food frequency questionnaires in 5375 participants between 1989 and 1993 (baseline I) and in a largely non-overlapping sample in 2861 participants between 2009 and 2013 (baseline II). We calculated the MIND diet score and studied its association with the risk of all-cause dementia, using Cox models. Incident all-cause dementia was recorded until 2018. Results: During a mean follow-up of 15.6 years from baseline I, 1188 participants developed dementia. A higher MIND diet score at baseline I was associated with a lower risk of dementia over the first 7 years of follow-up (hazard ratio (HR) [95% confidence interval (CI)] per standard deviation (SD) increase, 0.85 [0.74, 0.98]), but associations disappeared over longer follow-up intervals. The mean follow-up from baseline II was 5.9 years during which 248 participants developed dementia. A higher MIND diet score at baseline II was associated with a lower risk of dementia over every follow-up interval, but associations slightly attenuated over time (HR [95% CI] for 7 years follow-up per SD increase, 0.76 [0.66, 0.87]). The MIND diet score at baseline II was more strongly associated with the risk of dementia than the MIND diet score at baseline I. Conclusion: Better adherence to the MIND diet is associated with a decreased risk of dementia within the first years of follow-up, but this may in part be explained by ...
Keywords	Dementia ; Dietary pattern ; Epidemiology ; MIND diet ; Population-based
Subject code	360
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	2506521-X
ISSN	1758-9193
ISSN	1758-9193
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Article ; Online: Cognitive and physical impairment and the risk of stroke - A prospective cohort study.

Heshmatollah, A / Mutlu, U / Koudstaal, P J / Ikram, M A / Ikram, M K

Scientific reports

2020 Volume 10, Issue 1, Page(s) 6274

Abstract: The manifestation of cognitive and physical impairment in stroke patients before the acute event suggests accumulating subclinical vascular pathology in the brain. We investigated whether impairments in cognitive and physical functioning were associated ... ...

Abstract	The manifestation of cognitive and physical impairment in stroke patients before the acute event suggests accumulating subclinical vascular pathology in the brain. We investigated whether impairments in cognitive and physical functioning were associated with an increased stroke risk. Between 2002 and 2008, 8,519 stroke-free non-demented participants from the population-based Rotterdam Study underwent cognition and physical assessments including Mini-Mental State Examination, 15-word learning test, Stroop test, letter-digit substitution test, verbal fluency test, Purdue pegboard test and questionnaires on basic and instrumental activities of daily living (BADL; IADL). Principal component analysis was used to derive global cognition (G-factor). Incident stroke was assessed through continuous monitoring of medical records until 2016. Among 8,519 persons (mean age 66.0 years; 57.8% women), 489 suffered a stroke during mean follow-up of 8.7 years (SD: 2.9). Worse G-factor was associated with higher stroke risk (Hazard Ratio 1.21, 95% CI: 1.06-1.38), largely driven by unspecified stroke. Likewise, worse scores on 15-word learning test, Stroop test, Purdue pegboard test, IADL, and BADL were associated with higher risk of stroke. Thus both worse cognitive and physical functioning were associated with a higher stroke risk, in particular unspecified stroke and persons with worse memory, information processing, executive function, and motor function.
MeSH term(s)	Aged ; Cognitive Dysfunction/diagnosis ; Early Diagnosis ; Female ; Humans ; Male ; Mental Processes ; Middle Aged ; Physical Functional Performance ; Prospective Studies ; Risk Factors ; Stroke/diagnosis
Language	English
Publishing date	2020-04-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-63295-y
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Article ; Online: Sexual dimorphisms in serum calcium and phosphate concentrations in the Rotterdam Study.

Bosman, Ariadne / Koek, W Nadia H / Campos-Obando, Natalia / van der Eerden, Bram C J / Ikram, M A / Uitterlinden, André G / van Leeuwen, Johannes P T M / Zillikens, M C

Scientific reports

2023 Volume 13, Issue 1, Page(s) 8310

Abstract: Sex differences in serum phosphate and calcium have been reported but the exact nature and underlying regulatory mechanisms remain unclear. We aimed to compare calcium and phosphate concentrations between sexes, and explore potential covariates to ... ...

Abstract	Sex differences in serum phosphate and calcium have been reported but the exact nature and underlying regulatory mechanisms remain unclear. We aimed to compare calcium and phosphate concentrations between sexes, and explore potential covariates to elucidate underlying mechanisms of sex differences in a prospective, population-based cohort study. Pooled data of subjects > 45 years from three independent cohorts of the Rotterdam Study (RS) were used: RS-I-3 (n = 3623), RS-II-1 (n = 2394), RS-III-1 (n = 3241), with separate analyses from an additional time point of the first cohort RS-I-1 (n = 2688). Compared to men, women had significantly higher total serum calcium and phosphate concentrations which was not explained by BMI, kidney function nor smoking. Adjustment for serum estradiol diminished sex differences in serum calcium while adjustment for serum testosterone diminished sex differences in serum phosphate. Adjustment for vitamin D and alkaline phosphatase did not change the association between sex and calcium or phosphate in RS-I-1. In the sex-combined group, both serum calcium and phosphate decreased with age with a significant interaction for sex differences for serum calcium but not phosphate. In sex-stratified analyses, serum estradiol but not testosterone was inversely associated with serum calcium in both sexes. Serum estradiol was inversely associated with serum phosphate in both sexes to a similar degree, while serum testosterone was inversely associated with serum phosphate in both sexes with an apparent stronger effect in men than in women. Premenopausal women had lower serum phosphate compared to postmenopausal women. Serum testosterone was inversely associated with serum phosphate in postmenopausal women only. In conclusion, women > 45 years have higher serum calcium and phosphate concentrations compared to men of similar age, not explained by vitamin D or alkaline phosphatase concentrations. Serum estradiol but not testosterone was inversely associated with serum calcium while serum testosterone was inversely associated with serum phosphate in both sexes. Serum testosterone may in part explain sex differences in serum phosphate while estradiol could partly explain sex differences in serum calcium.
MeSH term(s)	Female ; Humans ; Male ; Sex Characteristics ; Calcium ; Phosphates ; Alkaline Phosphatase ; Cohort Studies ; Prospective Studies ; Calcium, Dietary ; Vitamins ; Vitamin D ; Coloring Agents ; Estradiol ; Testosterone
Chemical Substances	Calcium (SY7Q814VUP) ; Phosphates ; Alkaline Phosphatase (EC 3.1.3.1) ; Calcium, Dietary ; Vitamins ; Vitamin D (1406-16-2) ; Coloring Agents ; Estradiol (4TI98Z838E) ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2023-05-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-34800-w
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Article ; Online: Air Pollution and the Risk of Dementia

de Crom, Tosca O.E. / Ginos, Bigina N.R. / Oudin, Anna / Ikram, M.K. / Voortman, Trudy / Ikram, M.A.

Journal of Alzheimer's Disease

The Rotterdam Study

2023 Volume 91, Issue 2

Abstract: Background: Exposure to air pollution has been suggested to increase the risk of dementia, but studies on this link often lack a detailed screening for dementia and data on important confounders. Objective: To determine the association of exposure to air ...

Abstract	Background: Exposure to air pollution has been suggested to increase the risk of dementia, but studies on this link often lack a detailed screening for dementia and data on important confounders. Objective: To determine the association of exposure to air pollution with the risk of dementia and cognitive decline in the population-based Rotterdam Study. Methods: Between 2009 and 2010, we determined air pollutant concentrations at participants residential addresses using land use regression models. Determined air pollutants include particulate matter Results: Of the 7,511 non-demented participants at baseline, 545 developed dementia during a median follow-up of 7 years. The general marker of all air pollutants was not associated with the risk of dementia (hazard ratio [95% confidence interval]: 1.04 [0.95–1.15]), neither were the individual air pollutants. Also, the general marker of all air pollutants or the individual air pollutant levels were not associated with cognitive decline. Conclusion: In this study, we found no clear evidence for an association between exposure to air pollution and the risk of dementia or cognitive decline.
Keywords	Life Science
Subject code	333
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Gait speed reference values in community-dwelling older adults - Cross-sectional analysis from the Rotterdam Study.

Dommershuijsen, L J / Ragunathan, J / Ruiter, R / Groothof, D / Mattace-Raso, F U S / Ikram, M A / Polinder-Bos, H A

Experimental gerontology

2021 Volume 158, Page(s) 111646

Abstract: Background: Gait speed is a simple, inexpensive and clinically useful marker of physical function in older adults. We aimed to establish gait speed reference values for community-dwelling older adults. To this end, we further explored the association of ...

Abstract	Background: Gait speed is a simple, inexpensive and clinically useful marker of physical function in older adults. We aimed to establish gait speed reference values for community-dwelling older adults. To this end, we further explored the association of age, sex and height with gait speed. Methods: This study included community-dwelling participants aged 50 years and over enrolled in the Rotterdam Study. Participants completed the gait protocol between 2009 and 2016. The mean gait speed was calculated for age and height groups, stratified by sex. Reference values for gait speed were calculated using a quantile regression model adjusted for sex, the non-linear effects of age and height, as well as the interaction between age and sex plus the interaction between age and height. Results: The study population included 4656 Dutch participants with a mean (standard deviation) age of 67.7 (9.5) years, comprising 2569 (55.2%) women. The mean height of the participants was 1.69 (0.10) meters and the mean gait speed was 1.20 (0.20) m/s. Gait speed was lower with older age and greater with taller stature, but the effect of height disappeared above the age of 80 years. Sex did not affect gait speed after accounting for age and height. Age-, sex-, and height-specific reference values for gait speed are available for use at https://emcbiostatistics.shinyapps.io/GaitSpeedReferenceValues/. Conclusions: We found that height explains the commonly noted difference in usual gait speed between sexes and that neither height nor sex impacts gait speed in the very oldest adults. We developed reference values for usual gait speed in Western European community-dwelling older adults.
MeSH term(s)	Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Female ; Gait ; Humans ; Independent Living ; Middle Aged ; Reference Values ; Walking Speed
Language	English
Publishing date	2021-11-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	390992-x
ISSN	1873-6815 ; 0531-5565
ISSN (online)	1873-6815
ISSN	0531-5565
DOI	10.1016/j.exger.2021.111646
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