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Article ; Online: The magnitude and direction of the relationship between risk factor and cognition depends on age: a pooled analysis of 5 community-based studies.

Meirelles, Osorio / Arnette, Anthony / Guðnason, Vilmundur / Launer, Lenore J

2024 Volume 39, Issue 2, Page(s) 161–169

Abstract: The mixed evidence of the association between high levels of cardiovascular risk factors (CVRF) and the risk for cognitive impairment may be due to confounding of age across studies. We pooled and harmonized individual-level data (30,967 persons, age ... ...

Abstract	The mixed evidence of the association between high levels of cardiovascular risk factors (CVRF) and the risk for cognitive impairment may be due to confounding of age across studies. We pooled and harmonized individual-level data (30,967 persons, age range 42-96 years) from five prospective cohorts to investigate by 1 year age increments to investigate whether or not there is change in slope describing the association of CVRF to a cognitive outcome (Digit Symbol Substitution Test; DSST). The CVRF included: systolic and diastolic blood pressure, total cholesterol, fasting glucose and body mass index. Linear and quadratic piecewise regression models were fit to the trajectory patterns of these slopes (betas). The pattern of yearly slope changes showed higher CVRF were associated with lower DSST, but associations attenuated toward zero as age increased for all but DBP where 1 year slopes for DBP changed direction from negative to positive from mid- to late-age. Age is not only a driver of cognitive decline-age also modifies the direction and strength of the association of cognitive function to CVRF and cohort age may be one reason why the evidence for CVRF-CD association is mixed.
MeSH term(s)	Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Prospective Studies ; Risk Factors ; Cognition ; Cognitive Dysfunction/epidemiology ; Body Mass Index
Language	English
Publishing date	2024-01-05
Publishing country	Netherlands
Document type	Meta-Analysis ; Journal Article
ZDB-ID	632614-6
ISSN	1573-7284 ; 0393-2990
ISSN (online)	1573-7284
ISSN	0393-2990
DOI	10.1007/s10654-023-01087-0
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Article: The rocky road of 55 years of change in the relationship of cardiovascular risk factors to cognition.

Meirelles, Osorio / Arnette, Anthony / Gudnason, Vilmundur / Launer, L

Research square

2023

Abstract: The mixed evidence that high levels of cardiovascular risk factors (CVRF) are associated with lower cognitive test scores of may be due to confounding of age across studies. We pooled and harmonized individual-level data (30,967 persons, age range 42-96y) ...

Abstract	The mixed evidence that high levels of cardiovascular risk factors (CVRF) are associated with lower cognitive test scores of may be due to confounding of age across studies. We pooled and harmonized individual-level data (30,967 persons, age range 42-96y) from five prospective cohorts to examine the trajectories of betas estimating 1-year-age associations of a cognitive outcome (Digit Symbol Substitution Test; DSST) to five CVRF: systolic and e blood pressure, total cholesterol, fasting glucose and body mass index. Linear and quadratic piecewise regression models were fit to the trajectory patterns of these betas. The trajectories showed with each 1-year age increment, higher CVRF were associated with lower DSST, but associations attenuated toward zero as age increased. In addition, the pattern across age of each CVRF-DSST trajectory ranged from linear to non-liner. Without accounting for participant age in cohort comparisons, conclusions about the potential benefit on cognitive function of modifiable CVRF control will continue to be mixed and lead to delays in developing prevention programs.
Language	English
Publishing date	2023-02-15
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2557208/v1
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Article ; Online: Refracture and mortality risk in the elderly with osteoporotic fractures: the AGES-Reykjavik study.

Praveen, Anitha D / Aspelund, Thor / Ferguson, Stephen J / Sigurðsson, Sigurður / Guðnason, Vilmundur / Pálsson, Halldór / Matchar, David / Helgason, Benedikt

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA

2024

Abstract: There is imminent refracture risk in elderly individuals for up to six years, with a decline thereafter except in women below 75 who face a constant elevated risk. Elderly men with fractures face the highest mortality risk, particularly those with hip ... ...

Abstract	There is imminent refracture risk in elderly individuals for up to six years, with a decline thereafter except in women below 75 who face a constant elevated risk. Elderly men with fractures face the highest mortality risk, particularly those with hip and vertebral fractures. Targeted monitoring and treatment strategies are recommended. Purpose: Current management and interventions for osteoporotic fractures typically focus on bone mineral density loss, resulting in suboptimal evaluation of fracture risk. The aim of the study is to understand the progression of fractures to refractures and mortality in the elderly using multi-state models to better target those at risk. Methods: This prospective, observational study analysed data from the AGES-Reykjavik cohort of Icelandic elderly, using multi-state models to analyse the evolution of fractures into refractures and mortality, and to estimate the probability of future events in subjects based on prognostic factors. Results: At baseline, 4778 older individuals aged 65 years and older were included. Elderly men, and elderly women above 80 years of age, had a distinct imminent refracture risk that lasted between 2-6 years, followed by a sharp decline. However, elderly women below 75 continued to maintain a nearly constant refracture risk profile for ten years. Hip (30-63%) and vertebral (24-55%) fractures carried the highest 5-year mortality burden for elderly men and women, regardless of age, and for elderly men over 80, lower leg fractures also posed a significant mortality risk. Conclusion: The risk of refracture significantly increases in the first six years following the initial fracture. Elderly women, who experience fractures at a younger age, should be closely monitored to address their long-term elevated refracture risk. Elderly men, especially those with hip and vertebral fractures, face substantial mortality risk and require prioritized monitoring and treatment.
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article
ZDB-ID	1064892-6
ISSN	1433-2965 ; 0937-941X
ISSN (online)	1433-2965
ISSN	0937-941X
DOI	10.1007/s00198-024-07096-3
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Article ; Online: Creativity, leisure activities, social engagement and cognitive impairment: the AGES-Reykjavík study.

Hansdottir, Helga / Jonsdottir, María K / Fisher, Diana E / Eiriksdottir, Gudny / Jonsson, Palmi V / Gudnason, Vilmundur

Aging clinical and experimental research

2022 Volume 34, Issue 5, Page(s) 1027–1035

Abstract: Background: Participation in leisure activities and extensive social network have been associated with lower risk of cognitive impairment (CI) and dementia.: Aims: We examined whether leisure activities (cognitive solitary, cognitive group, social, ... ...

Abstract	Background: Participation in leisure activities and extensive social network have been associated with lower risk of cognitive impairment (CI) and dementia. Aims: We examined whether leisure activities (cognitive solitary, cognitive group, social, physical, or creative activities) and social involvement are associated with less incidence of CI or dementia. Methods: Analyses were performed from data of 2933 cognitively intact individuals at baseline included in the AGES-REYKJAVIK study. Odds ratios (OR) were calculated for incident CI and dementia in relation to cognitive individual, cognitive group, social, physical, and creative leisure activities as well as social networks. Models were adjusted for a number of known risk factors for cognitive decline. Results: In 5 years, 12% of the cohort were diagnosed with CI or dementia. All leisure activities were associated with reduced likelihood of cognitive decline in the raw model, but in adjusted models, cognitive solitary [OR 0.49 (Confidence Interval (CI) 0.38-0.64)], cognitive group [OR 0.50 (CI 0.30-0.82)], and creative activities [OR 0.53 (CI 0.35-0.83)] were significantly associated with less cognitive decline. Analyses examining creative leisure activities independently, controlling for all other activities, suggested individuals participating in creative activities exhibited less CI [OR 0.64 (CI 0.41-0.98)]. Among social networks variables, frequency of meeting with friends and relatives was associated with reduced likelihood of CI [OR 0.49 (CI 0.31-0.75)]. Discussion: Cognitive and creative leisure activities and frequent gatherings with friends and relatives are associated with reduced incidence of CI in this older cohort. Conclusion: Creative leisure activities might have special benefit for cognitive ability.
MeSH term(s)	Cognitive Dysfunction/complications ; Cognitive Dysfunction/epidemiology ; Dementia/diagnosis ; Humans ; Leisure Activities/psychology ; Risk Factors ; Social Participation
Language	English
Publishing date	2022-01-25
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2104785-6
ISSN	1720-8319 ; 1594-0667
ISSN (online)	1720-8319
ISSN	1594-0667
DOI	10.1007/s40520-021-02036-1
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Zs.A 3343: Show issues

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Article ; Online: Depression and Dementia: The Role of Cortisol and Vascular Brain Lesions. AGES-Reykjavik Study.

Gerritsen, Lotte / Twait, Emma L / Jonsson, Palmi V / Gudnason, Vilmundur / Launer, Lenore J / Geerlings, Mirjam I

Journal of Alzheimer's disease : JAD

2022 Volume 85, Issue 4, Page(s) 1677–1687

Abstract: Background: Late-life depression (LLD) is related to an increased risk of developing dementia; however, the biological mechanisms explaining this relationship remain unclear.: Objective: To determine whether the relationship between LLD and dementia ... ...

Abstract	Background: Late-life depression (LLD) is related to an increased risk of developing dementia; however, the biological mechanisms explaining this relationship remain unclear. Objective: To determine whether the relationship between LLD and dementia can be best explained by the glucocorticoid cascade or vascular hypothesis. Methods: Data are from 4,354 persons (mean age 76±5 years) without dementia at baseline from the AGES-Reykjavik Study. LLD was assessed with the MINI diagnostic interview (current and remitted major depressive disorder [MDD]) and the Geriatric Depression Scale-15. Morning and evening salivary cortisol were collected (glucocorticoid cascade hypothesis). White matter hyperintensities (WMH; vascular hypothesis) volume was assessed using 1.5T brain MRI. Using Cox proportional hazard models, we estimated the associations of LLD, cortisol levels, and WMH volume with incident all-cause dementia, AD, and non-AD dementia. Results: During 8.8±3.2 years of follow-up, 843 persons developed dementia, including 397 with AD. Current MDD was associated with an increased risk of developing all-cause dementia (HR = 2.17; 95% CI 1.66-2.67), with risks similar for AD and non-AD, while remitted MDD was not (HR = 1.02; 95% CI 0.55-1.49). Depressive symptoms were also associated with increased risk of dementia, in particular non-AD dementias. Higher levels of evening cortisol increased risk of dementia, but this was independent of MDD. WMH partially explained the relation between current MDD and dementia risk but remained increased (HR = 1.71; 95% CI 1.34-2.08). Conclusion: The current study highlights the importance of LLD in developing dementia. However, neither the glucocorticoid cascade nor the vascular hypotheses fully explained the relation between depression and dementia.
MeSH term(s)	Aged ; Brain/pathology ; Dementia/diagnosis ; Depressive Disorder, Major/epidemiology ; Female ; Humans ; Hydrocortisone/analysis ; Iceland ; Interviews as Topic ; Longitudinal Studies ; Magnetic Resonance Imaging ; Male ; Risk Factors ; White Matter/pathology
Chemical Substances	Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2022-01-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-215241
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Zs.A 6084: Show issues

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Article ; Online: Late-life depression, allostatic load, and risk of dementia: The AGES-Reykjavik study.

Twait, Emma L / Basten, Maartje / Gerritsen, Lotte / Gudnason, Vilmundur / Launer, Lenore J / Geerlings, Mirjam I

Psychoneuroendocrinology

2022 Volume 148, Page(s) 105975

Abstract: Background: The current study aimed to assess if the relation between depression and dementia could be explained by allostatic load (AL) profiles, as well as assessing their risk on incident all-cause dementia, Alzheimer's disease (AD), and non-AD ... ...

Abstract	Background: The current study aimed to assess if the relation between depression and dementia could be explained by allostatic load (AL) profiles, as well as assessing their risk on incident all-cause dementia, Alzheimer's disease (AD), and non-AD dementias. Methods: The study included individuals without dementia at baseline from the population-based AGES-Reykjavik Study. Depressive symptoms assessed with the Geriatric Depression Scale-15 and AL markers were collected at baseline. Latent profile analysis (LPA) was performed on the AL markers. Incident dementia was measured during 12-years of follow-up. Cox regressions adjusted for AL profiles were performed to evaluate if AL could explain the relation between depressive symptoms and incident dementia. Additional Cox regressions exploring the interaction with depressive symptoms and AL profiles were also performed. Results: LPA revealed four profiles based on AL factors: 'Low cardiovascular dysregulation' (43 %), 'Average' (42 % prevalence), 'High cardiovascular dysregulation' (11 %), and 'Multisystem dysregulation' (4 %). Cox regression analyses found an increased risk for dementia in the 'Multisystem dysregulation' group (HR 1.72; 95 % CI 1.26-2.33), as well as for AD (HR 1.75; 95 % CI: 1.12-2.71) and non-AD dementias (HR 1.87; 95 % CI: 1.23-2.84). AL profiles did not mediate the risk of all-cause dementia with depressive symptoms; however, there was evidence of additive interaction with depressive symptoms and the 'Multisystem dysregulation' profile and all-cause dementia (RERI 0.15; 95 % CI 0.03-0.26). Conclusion: AL profiles and depressive symptoms were independently related to dementia. Individuals with multisystem dysregulation could be more susceptible to the negative effects of depressive symptomology on incident dementia.
MeSH term(s)	Humans ; Aged ; Depression/epidemiology ; Allostasis/physiology ; Alzheimer Disease/epidemiology ; Risk Factors
Language	English
Publishing date	2022-11-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	197636-9
ISSN	1873-3360 ; 0306-4530
ISSN (online)	1873-3360
ISSN	0306-4530
DOI	10.1016/j.psyneuen.2022.105975
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Article ; Online: Associations of plasma NfL, GFAP, and t-tau with cerebral small vessel disease and incident dementia: longitudinal data of the AGES-Reykjavik Study.

van Gennip, April C E / Satizabal, Claudia L / Tracy, Russell P / Sigurdsson, Sigurdur / Gudnason, Vilmundur / Launer, Lenore J / van Sloten, Thomas T

GeroScience

2023 Volume 46, Issue 1, Page(s) 505–516

Abstract: We investigated the associations of plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and total tau (t-tau) with markers of cerebral small vessel disease (SVD) and with incident dementia. We also investigated whether associations ... ...

Abstract	We investigated the associations of plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and total tau (t-tau) with markers of cerebral small vessel disease (SVD) and with incident dementia. We also investigated whether associations of NfL, GFAP, and t-tau with incident dementia were explained by SVD. Data are from a random subsample (n = 1069) of the population-based AGES-Reykjavik Study who underwent brain MRI and in whom plasma NfL, GFAP, and t-tau were measured at baseline (76.1 ± 5.4 years/55.9% women/baseline 2002-2006/follow-up until 2015). A composite SVD burden score was calculated using white matter hyperintensity volume (WMHV), subcortical infarcts, cerebral microbleeds, and large perivascular spaces. Dementia was assessed in a 3-step process and adjudicated by specialists. Higher NfL was associated with a higher SVD burden score. Dementia occurred in 225 (21.0%) individuals. The SVD burden score significantly explained part of the association between NfL and incident dementia. WMHV mostly strongly contributed to the explained effect. GFAP was not associated with the SVD burden score, but was associated with WMHV, and WMHV significantly explained part of the association between GFAP and incident dementia. T-tau was associated with WMHV, but not with incident dementia. In conclusion, the marker most strongly related to SVD is plasma NfL, for which the association with WMHV appeared to explain part of its association with incident dementia. This study suggests that plasma NfL may reflect the contribution of co-morbid vascular disease to dementia. However, the magnitude of the explained effect was relatively small, and further research is required to investigate the clinical implications of this finding.
MeSH term(s)	Female ; Humans ; Male ; Cerebral Small Vessel Diseases/epidemiology ; Dementia/epidemiology ; Glial Fibrillary Acidic Protein ; Intermediate Filaments ; Magnetic Resonance Imaging ; tau Proteins/metabolism
Chemical Substances	Glial Fibrillary Acidic Protein ; neurofilament protein L ; tau Proteins ; GFAP protein, human
Language	English
Publishing date	2023-08-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-023-00888-1
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Zs.A 1502: Show issues

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Article ; Online: Exposure factors associated with dementia among older adults in Iceland: the AGES-Reykjavik study.

Valsdóttir, Vaka / Magnúsdóttir, Brynja Björk / Gylfason, Haukur Freyr / Chang, Milan / Aspelund, Thor / Gudnason, Vilmundur / Launer, Lenore J / Jónsdóttir, María K

GeroScience

2023 Volume 45, Issue 3, Page(s) 1953–1965

Abstract: The study aimed to assess whether factors related to cognitive performance were associated with the development of dementia. Additionally, the study aimed to establish whether cognitive performance at baseline or change in cognition between baseline and ... ...

Abstract	The study aimed to assess whether factors related to cognitive performance were associated with the development of dementia. Additionally, the study aimed to establish whether cognitive performance at baseline or change in cognition between baseline and follow-up (five-year period) had a stronger association with whether an individual would fulfill a dementia criterion at follow-up. The data was collected from 2002 to 2011. Logistic regression was applied to the AGES-Reykjavik Study epidemiological data. The analysis, which builds upon previous data analyses of the same dataset, included 1,491 participants between the ages of 66 and 90. All those included were considered to have normal cognition at baseline; 8.2% (n = 123) of them fulfilled a dementia criterion at follow-up five years later. The study's results indicated that being high on cognitive reserve factors reduced the risk of developing dementia. Compared to other known dementia risk factors, cognitive reserve factors (education level, participation in leisure activities, and self-reported health) were more likely than others to have an association with dementia. Additionally, the study's findings showed that cognitive performance at baseline, rather than change in cognition between baseline and follow-up five years later, had a stronger association with dementia at the follow-up assessment. Together, these findings support the notion that promoting high cognitive reserve throughout the lifespan and reaching high cognitive performance is important in reducing dementia risk.
MeSH term(s)	Humans ; Aged ; Aged, 80 and over ; Dementia/epidemiology ; Iceland/epidemiology ; Cognition ; Risk Factors ; Educational Status
Language	English
Publishing date	2023-05-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-023-00804-7
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Article ; Online: Comparative study of machine learning methods for modeling associations between risk factors and future dementia cases.

Valsdóttir, Vaka / Jónsdóttir, María K / Magnúsdóttir, Brynja Björk / Chang, Milan / Hu, Yi-Han / Gudnason, Vilmundur / Launer, Lenore J / Stefánsson, Hlynur

GeroScience

2023 Volume 46, Issue 1, Page(s) 737–750

Abstract: A substantial portion of dementia risk can be attributed to modifiable risk factors that can be affected by lifestyle changes. Identifying the contributors to dementia risk could prove valuable. Recently, machine learning methods have been increasingly ... ...

Abstract	A substantial portion of dementia risk can be attributed to modifiable risk factors that can be affected by lifestyle changes. Identifying the contributors to dementia risk could prove valuable. Recently, machine learning methods have been increasingly applied to healthcare data. Several studies have attempted to predict dementia progression by using such techniques. This study aimed to compare the performance of different machine-learning methods in modeling associations between known cognitive risk factors and future dementia cases. A subset of the AGES-Reykjavik Study dataset was analyzed using three machine-learning methods: logistic regression, random forest, and neural networks. Data were collected twice, approximately five years apart. The dataset included information from 1,491 older adults who underwent a cognitive screening process and were considered to have healthy cognition at baseline. Cognitive risk factors included in the models were based on demographics, MRI data, and other health-related data. At follow-up, participants were re-evaluated for dementia using the same cognitive screening process. Various performance metrics for all three machine learning algorithms were assessed. The study results indicate that a random forest algorithm performed better than neural networks and logistic regression in predicting the association between cognitive risk factors and dementia. Compared to more traditional statistical analyses, machine-learning methods have the potential to provide more accurate predictions about which individuals are more likely to develop dementia than others.
MeSH term(s)	Humans ; Aged ; Dementia/diagnosis ; Dementia/epidemiology ; Dementia/etiology ; Machine Learning ; Risk Factors ; Cognition ; Logistic Models
Language	English
Publishing date	2023-12-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-023-01040-9
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Article ; Online: Proteomic associations with forced expiratory volume: a Mendelian randomisation study.

Axelsson, Gisli Thor / Jonmundsson, Thorarinn / Woo, Youngjae / Frick, Elisabet Alexandra / Aspelund, Thor / Loureiro, Joseph J / Orth, Anthony P / Jennings, Lori L / Gudmundsson, Gunnar / Emilsson, Valur / Gudmundsdottir, Valborg / Gudnason, Vilmundur

Respiratory research

2024 Volume 25, Issue 1, Page(s) 44

Abstract: Background: A decline in forced expiratory volume (FEV1) is a hallmark of respiratory diseases that are an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic ... ...

Abstract	Background: A decline in forced expiratory volume (FEV1) is a hallmark of respiratory diseases that are an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic analysis of causal relations of biomarkers with FEV1. Methods: Data from the population-based AGES-Reykjavik study were used. Serum proteomic measurements were done using 4782 DNA aptamers (SOMAmers). Data from 1479 participants with spirometric data were used to assess the association of SOMAmer measurements with FEV1 using linear regression. Bi-directional two-sample Mendelian randomisation (MR) analyses were done to assess causal relations of observationally associated SOMAmers with FEV1, using genotype and SOMAmer data from 5368 AGES-Reykjavik participants and genetic associations with FEV1 from a publicly available GWAS (n = 400,102). Results: In observational analyses, 530 SOMAmers were associated with FEV1 after multiple testing adjustment (FDR < 0.05). The most significant were Retinoic Acid Receptor Responder 2 (RARRES2), R-Spondin 4 (RSPO4) and Alkaline Phosphatase, Placental Like 2 (ALPPL2). Of the 257 SOMAmers with genetic instruments available, eight were associated with FEV1 in MR analyses. Three were directionally consistent with the observational estimate, Thrombospondin 2 (THBS2), Endoplasmic Reticulum Oxidoreductase 1 Beta (ERO1B) and Apolipoprotein M (APOM). THBS2 was further supported by a colocalization analysis. Analyses in the reverse direction, testing whether changes in SOMAmer levels were caused by changes in FEV1, were performed but no significant associations were found after multiple testing adjustments. Conclusions: In summary, this large scale proteogenomic analyses of FEV1 reveals circulating protein markers of FEV1, as well as several proteins with potential causality to lung function.
MeSH term(s)	Humans ; Female ; Pregnancy ; Aged ; Forced Expiratory Volume/genetics ; Lung ; Proteomics ; Placenta ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-023-02587-z
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