IntroductionWe aim to investigate the longitudinal associations between changes in body weight (BW) and declines in cognitive function and risk of mild cognitive impairment (MCI)/dementia among cognitively normal individuals 65 years or... more
IntroductionWe aim to investigate the longitudinal associations between changes in body weight (BW) and declines in cognitive function and risk of mild cognitive impairment (MCI)/dementia among cognitively normal individuals 65 years or older.MethodsData from the Age Gene/Environment Susceptibility‐Reykjavik Study (AGES‐Reykjavik Study) including 2620 participants, were examined using multiple logistic regression models. Cognitive function included speed of processing (SP), executive function (EF), and memory function (MF). Changes in BW were classified as; weight loss (WL), weight gain (WG), and stable weight (SW).ResultsMean follow‐up time was 5.2 years and 61.3% were stable weight. Participants who experienced WL (13.4%) were significantly more likely to have declines in MF and SP compared to the SW group. Weight changes were not associated with EF. WL was associated with a higher risk of MCI, while WG (25.3%) was associated with a higher dementia risk, when compared to SW.Discus...
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Background and Purpose— The differentiation of brain infarcts by region is important because their cause and clinical implications may differ. Information on the incidence of these lesions and association with cognition and dementia from... more
Background and Purpose— The differentiation of brain infarcts by region is important because their cause and clinical implications may differ. Information on the incidence of these lesions and association with cognition and dementia from longitudinal population studies is scarce. We investigated the incidence of infarcts in cortical, subcortical, cerebellar, and overall brain regions and how prevalent and incident infarcts associate with cognitive change and incident dementia. Methods— Participants (n=2612, 41% men, mean age 74.6±4.8) underwent brain magnetic resonance imaging for the assessment of infarcts and cognitive testing at baseline and on average 5.2 years later. Incident dementia was assessed according to the international guidelines. Results— Twenty-one percent of the study participants developed new infarcts. The risk of incident infarcts in men was higher than the risk in women (1.8; 95% confidence interval, 1.5–2.3). Persons with both incident and prevalent infarcts sh...
Research Interests: Dementia, Cognition, Incidence Geometry, Magnetic Resonance Imaging, Medicine, and 15 moreIceland, Humans, Cerebellum, Cerebral Cortex, Female, Male, Incidence, Clinical Sciences, Aged, Longitudinal Studies, Cognitive Decline, Confidence Interval, Cohort Studies, Cognitive dysfunction, and Cardiovascular medicine and haematology
With advancing age, an increased visibility of perivascular spaces (PVSs) on magnetic resonance imaging (MRI) is hypothesized to represent impaired drainage of interstitial fluid from the brain and may reflect underlying cerebral small... more
With advancing age, an increased visibility of perivascular spaces (PVSs) on magnetic resonance imaging (MRI) is hypothesized to represent impaired drainage of interstitial fluid from the brain and may reflect underlying cerebral small vessel disease (SVD). However, whether large perivascular spaces (L-PVSs) (>3 mm in diameter) visible on MRI are associated with SVD and cognitive deterioration in older individuals is unknown. To examine whether L-PVSs are associated with the progression of the established MRI markers of SVD, cognitive decline, and increased risk of dementia. The prospective, population-based Age, Gene/Environment Susceptibility-Reykjavik Study assessed L-PVSs at baseline (September 1, 2002, through February 28, 2006) on MRI studies of the brain in 2612 participants. Participants returned for additional MRI from April 1, 2007, through September 30, 2011, and underwent neuropsychological testing at the 2 time points a mean (SD) of 5.2 (0.2) years apart. Data analys...
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To assess the association of the number and anatomic location of cerebral microbleeds (CMBs), visible indicators of microvascular damage on MRI, with incident cognitive disease in the general population of older people. In the... more
To assess the association of the number and anatomic location of cerebral microbleeds (CMBs), visible indicators of microvascular damage on MRI, with incident cognitive disease in the general population of older people. In the longitudinal population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 2,602 participants 66 to 93 years of age and free of prevalent dementia underwent brain MRI and cognitive testing of verbal memory, processing speed, and executive function at baseline and a mean of 5.2 years later. Adjudicated incident dementia cases were diagnosed according to international guidelines. In the multiple linear regression models adjusted for demographic, genetic, cardiovascular risk, and other cerebrovascular MRI markers, the presence of CMBs located in deep or mixed (deep and lobar) areas was associated with a greater decline in all 3 cognitive domains. Mixed CMBs were the strongest correlate for decline in memory and speed. Compared to those with no CMB...
Research Interests: Cognitive Science, Dementia, Cognition, Incidence Geometry, Magnetic Resonance Imaging, and 15 moreMedicine, Linear models, Executive Function, Iceland, Brain, Humans, Female, Male, Incidence, Clinical Sciences, Aged, Longitudinal Studies, Cognitive Decline, Cerebral Hemorrhage, and Cognitive dysfunction
studies on the association of dementia with specific body composition (BC) components are scarce. Our aim was to investigate associations of BC measures with different levels of cognitive function in late-life. we studied 5,169... more
studies on the association of dementia with specific body composition (BC) components are scarce. Our aim was to investigate associations of BC measures with different levels of cognitive function in late-life. we studied 5,169 participants (mean age 76 years, 42.9% men) in the AGES-Reykjavik Study of whom 485 (9.4%) were diagnosed with mild cognitive impairment (MCI) and 307 (5.9%) with dementia. Visceral fat, abdominal and thigh subcutaneous fat, and thigh muscle were assessed by computed tomography. MCI and dementia were based on clinical assessment and a consensus meeting; those without MCI or dementia were categorised as normal. Multinomial regression models assessed the associations stratified by sex and in additional analyses by midlife body mass index (BMI). among women, there was a decreased likelihood of dementia per SD increase in abdominal subcutaneous fat (OR 0.72; 95% CI: 0.59-0.88), thigh subcutaneous fat (0.81; 0.67-0.98) and thigh muscle (0.63; 0.52-0.76), but not v...
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Research Interests: Ophthalmology, Aging, Mortality, Medicine, Comorbidity, and 15 moreProspective studies, Humans, Diabetes mellitus, Diabetic Retinopathy, Female, Male, Clinical Sciences, Aged, Optometry and Ophthalmology, Public health systems and services research, Age Factors, Cardiovascular Diseases, Ger, Retinal Diseases, and Cohort Studies
Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity... more
Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, ...
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Research Interests: Depression, Medicine, Iceland, Humans, Female, and 15 moreMale, Risk factors, Clinical Sciences, Aged, Geriatric Depression Scale, Middle Aged, Longitudinal Studies, Odds ratio, Age Factors, Ger, Geriatric Assessment, Risk Factors, Confidence Interval, Motor activity, and Psychiatric Status Rating Scales
Arterial stiffness may contribute to depression via cerebral microvascular damage, but evidence for this is scarce. We therefore investigated whether arterial stiffness is associated with depressive symptoms and whether cerebral small... more
Arterial stiffness may contribute to depression via cerebral microvascular damage, but evidence for this is scarce. We therefore investigated whether arterial stiffness is associated with depressive symptoms and whether cerebral small vessel disease contributes to this association. This cross-sectional study included a subset of participants from the AGES-Reykjavik study second examination round, which was conducted from 2007 to 2011. Arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]), depressive symptoms (15-item geriatric depression scale [GDS-15]) and cerebral small vessel disease (MRI) were determined. Manifestations of cerebral small vessel disease included higher white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces and lower total brain parenchyma volume. We included 2058 participants (mean age 79.6 yr; 59.0% women) in our analyses. Higher CFPWV was associated with a higher GDS-15 score, after adjustment for potenti...
Research Interests: Cognitive Science, Cardiology, Depression, Magnetic Resonance Imaging, Medicine, and 15 moreBrain, Humans, Internal Medicine, Female, Male, Arterial stiffness, Clinical Sciences, Aged, Atrophy, Cross sectional Study, Cross Sectional Studies, Cerebral Hemorrhage, Neurosciences, Femoral Artery, and Carotid Arteries
Background/Objectives:Low intake of long chain polyunsaturated fatty acids (PUFAs) are associated with physical disability; however, prospective studies of circulating PUFAs are scarce. We examined associations between plasma phospholipid... more
Background/Objectives:Low intake of long chain polyunsaturated fatty acids (PUFAs) are associated with physical disability; however, prospective studies of circulating PUFAs are scarce. We examined associations between plasma phospholipid n-3 and n-6 PUFAs with risk of incident mobility disability and gait speed decline.Subjects/Methods:Data are from a subgroup of the Age, Gene/Environment Susceptibility-Reykjavik Study, a population-based study of risk factors for disease and disability in old age. In this subgroup (n=556, mean age 75.1±5.0 years, 47.5% men), plasma phospholipid PUFAs were assessed at baseline using gas chromatography. Mobility disability and usual gait speed were assessed at baseline and after 5.2±0.2 years. Mobility disability was defined as the following: having much difficulty, or being unable to walk 500 m or climb up 10 steps; decline in gait speed was defined as change ⩾0.10 m/s. Logistic regression analyses were performed to determine associations between s...
Research Interests: Geography, Nutrition and Dietetics, Medicine, Multivariate Analysis, Gait, and 15 moreHumans, OMEGA, Fatty acids, Female, Male, Body Mass Index, Aged, Odds ratio, Food Sciences, Cross Sectional Studies, Environment, Logistic Models, Motor activity, Mobility limitation, and Human Movement and Sports Sciences
Research Interests: Depression, Dementia, Magnetic Resonance Imaging, Brain, Humans, and 15 moreInternal Medicine, Cerebral Cortex, Female, Male, Depressive Disorder, Incidence, Aged, Geriatric Depression Scale, Longitudinal Studies, American J of Psychiatry, Cerebral Infarction, Cohort Studies, brain size, Medical and Health Sciences, and Genetic predisposition to disease
There are several lines of evidence pointing to fetal and other early origins of diseases of the aging brain, but there are no data directly addressing the hypotheses in an older population. We investigated the association of fetal size... more
There are several lines of evidence pointing to fetal and other early origins of diseases of the aging brain, but there are no data directly addressing the hypotheses in an older population. We investigated the association of fetal size to late-age measures of brain structure and function in a large cohort of older men and women and explored the modifying effect of education on these associations. Within the AGES (Age Gene/Environment Susceptibility)-Reykjavik population-based cohort (born between 1907 and 1935), archived birth records were abstracted for 1254 men and women who ∼75 years later underwent an examination that included brain MRI and extensive cognitive assessment. Adjustment for intracranial volume, demographic and medical history characteristics, and lower Ponderal index at birth (per kg/m(3)), an indicator of third-trimester fetal wasting, was significantly associated with smaller volumes of total brain and white matter; βs (95% confidence intervals) were -1.0 (-1.9 t...
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Studies in type 2 diabetes report both increased mortality for normal weight and no evidence of an obesity paradox. We aimed to examine whether adipose tissue, muscle size, and physical function, which are known to vary by weight, mediate... more
Studies in type 2 diabetes report both increased mortality for normal weight and no evidence of an obesity paradox. We aimed to examine whether adipose tissue, muscle size, and physical function, which are known to vary by weight, mediate associations between BMI and mortality. The AGES-Reykjavik cohort comprised participants aged 66-96 years with diabetes defined by fasting glucose, medications, or self-report. BMI was determined from measured height and weight and classified as normal (18.5-24.9 kg/m(2), n = 117), overweight (25.0-29.9 kg/m(2), n = 293, referent group) or obese (≥30.0 kg/m(2), n = 227). Thigh muscle area and intermuscular, visceral, and subcutaneous adipose tissues were assessed with computed tomography. Function was assessed from gait speed and knee extensor strength. Hazard ratios (HRs) and 95% CIs were estimated by Cox proportional hazards regression adjusted for demographics and diabetes-related risk factors. The median follow-up was 6.66 years, and there were...
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Total brain volume is an integrated measure of health and may be an independent indicator of mortality risk independent of any one clinical or subclinical disease state. We investigate the association of brain volume to total and... more
Total brain volume is an integrated measure of health and may be an independent indicator of mortality risk independent of any one clinical or subclinical disease state. We investigate the association of brain volume to total and cause-specific mortality in a large nondemented stroke-free community-based cohort. The analysis includes 3,543 men and women (born 1907-1935) participating in the Age, Gene, Environment Susceptibility-Reykjavik Study. Participants with a known brain-related high risk for mortality (cognitive impairment or stroke) were excluded from these analyses. Quantitative estimates of total brain volume, white matter, white matter lesions, total gray matter (GM; cortical GM and subcortical GM separately), and focal cerebral vascular disease were generated from brain magnetic resonance imaging. Brain atrophy was expressed as brain tissue volume divided by total intracranial volume, yielding a percentage. Mean follow-up duration was 7.2 (0-10) years, with 647 deaths. Co...
Research Interests: Demography, Epidemiology, Magnetic Resonance Imaging, Aging, Iceland, and 15 moreBrain, Humans, Internal Medicine, Female, Cohort, Clinical Sciences, Aged, Atrophy, Cardiovascular Diseases, Brain Aging, Cerebrovascular Disorders, health status indicators, Cause of death, brain size, and hazard ratio
Background and Purpose— Cerebral infarcts increase the risk for cognitive impairment. The relevance of location and number of infarcts with respect to cognitive function is less clear. Methods— We studied the cross-sectional association... more
Background and Purpose— Cerebral infarcts increase the risk for cognitive impairment. The relevance of location and number of infarcts with respect to cognitive function is less clear. Methods— We studied the cross-sectional association between number and location of infarcts and cognitive performance in 4030 nondemented participants of the Age Gene/Environment Susceptibility-Reykjavik Study. Composite scores for memory, processing speed, and executive function were created from a neuropsychological battery. Subcortical, cortical, and cerebellar infarcts were identified on brain MRI. We performed linear regression analyses adjusted for demographic and vascular risk factors, depression, white matter lesions, and atrophy. Results— Compared to participants with no infarcts, those with infarcts in multiple locations (n=287, 7%) had slower processing speed (β=−0.19; P <0.001) and poorer memory (β=−0.16; P <0.001) and executive function (β=−0.12; P =0.003). Compared to no infarcts, ...
Research Interests: Cardiology, Dementia, Cognition, Cardiovascular disease, Executive Function, and 15 moreIceland, Humans, Female, Health Science, Cognitive Performance, Clinical Sciences, Brain atrophy, Aged, Cognitive impairment, Cross Section, Cognitive Function, Cardiovascular Diseases, Cognition disorders, Cerebral Infarction, and Cardiovascular medicine and haematology
Significance Understanding loci nominated by genome-wide association studies (GWASs) is challenging. Here, we show, using the specific example of Parkinson disease, that identification of protein–protein interactions can help determine... more
Significance Understanding loci nominated by genome-wide association studies (GWASs) is challenging. Here, we show, using the specific example of Parkinson disease, that identification of protein–protein interactions can help determine the most likely candidate for several GWAS loci. This result illustrates a significant general principle that will likely apply across multiple diseases.
Research Interests: Genetics, Computational Biology, Mass Spectrometry, Biology, Confocal Microscopy, and 15 moreMedicine, Multidisciplinary, Western blotting, Brain, Humans, Disease, Cell Fractionation, Plasmids, Immunoprecipitation, Analysis of Variance, Genetic Association, Golgi Apparatus, Parkinson´s Disease, Parkinson Disease, and Genetic predisposition to disease
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Research Interests: Cognitive Science, Cardiology, Dementia, Cognition, Magnetic Resonance Imaging, and 15 moreAging, Microcirculation, Medicine, Executive Function, Iceland, Brain, Humans, Female, Male, Confidence intervals, Clinical Sciences, Aged, Cross Sectional Studies, Cerebral Hemorrhage, and Confidence Interval
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Research Interests: Geriatrics, Epidemiology, Biostatistics, Cognition, Health Services Research, and 15 moreExecutive Function, Cognitive Complexity, Brain, Humans, Female, Male, Cognitive Performance, Clinical Sciences, Aged, Cognitive Ability, Cognitive Function, Confidence Interval, Cognition disorders, Brain Diseases, and Leisure Activities
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To assess whether markers of micro- and macrostructural brain abnormalities are associated with slower gait in older men and women independent of each other, and also independent of health-related conditions and of behavioral, cognitive... more
To assess whether markers of micro- and macrostructural brain abnormalities are associated with slower gait in older men and women independent of each other, and also independent of health-related conditions and of behavioral, cognitive and peripheral function.
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Research Interests: Cardiology, Calcium, Medicine, Iceland, Gait, and 15 moreHumans, Internal Medicine, Female, Male, Aged, Coronary Angiography, Calcinosis, Odds ratio, Age Factors, Calcium Metabolism, Coronary Artery Disease, Motor activity, Multidetector Computed Tomography, Cardiovascular medicine and haematology, and Coronary Vessels
OBJECTIVE To examine the association of glycemic status to magnetic resonance imaging indicators of brain pathological changes. RESEARCH DESIGN AND METHODS This was a cross-sectional, population-based study of 4,415 men and women without... more
OBJECTIVE To examine the association of glycemic status to magnetic resonance imaging indicators of brain pathological changes. RESEARCH DESIGN AND METHODS This was a cross-sectional, population-based study of 4,415 men and women without dementia (mean age 76 years) participating in the Age Gene/Environment Susceptibility–Reykjavik Study. Glycemic status groups included the following: type 2 diabetes (self-report of diabetes, use of diabetes medications, or fasting blood glucose ≥7.0 mmol/l [11.1%]); impaired fasting glucose (IFG) (fasting blood glucose 5.6–6.9 mmol/l [36.2%]); and normoglycemic (52.7%). Outcomes were total brain volume, white and gray matter volume, white matter lesion (WML) volume, and presence of cerebral infarcts. RESULTS After adjustment for demographic and cardiovascular risk factors, participants with type 2 diabetes had significantly lower total brain volume (72.2 vs. 71.5%; P < 0.001) and lower gray and white matter volumes (45.1 vs. 44.9%, P < 0.01 a...
Research Interests: Disease susceptibility, Humans, Diabetes mellitus, Female, Health Science, and 15 moreBrain injury, Brain atrophy, Aged, Atrophy, Cross Section, Cardiovascular Risk Factor, Age Factors, AGE FACTOR, Gray Matter, Diabetes Care, Fasting Blood Glucose, Cerebral Infarction, Cumulant, Brain injuries, and brain size
ObjectiveTo investigate whether the severity and location of cerebral white matter hyperintensities (WMHs) and brain infarcts are correlated with the signs of retinal microvascular abnormalities in the elderly.MethodsThe study included... more
ObjectiveTo investigate whether the severity and location of cerebral white matter hyperintensities (WMHs) and brain infarcts are correlated with the signs of retinal microvascular abnormalities in the elderly.MethodsThe study included 4,176 men and women (mean age, 76 years) who participated in the Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study. Digital retinal images of both dilated eyes were taken and evaluated for the presence of retinal focal arteriolar signs (focal arteriolar narrowing and arteriovenous nicking) and retinopathy lesions (retinal blot hemorrhages and microaneurysms). Brain magnetic resonance imaging scans were acquired and evaluated for the presence and distribution of cerebral infarcts and WMHs. Logistic and multinomial logistic models were constructed to estimate the association of retinal microvascular signs to brain lesions.ResultsControlling for demographic and major cardiovascular risk factors, we found that retinal focal arteriolar signs, but...
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Research Interests: Cardiology, Geriatrics, Epidemiology, Brain Imaging, Biostatistics, and 15 moreCognition, Executive Function, Cerebrospinal Fluid, Female, Cohort Study, Clinical Sciences, Aged, Cognitive impairment, Annals, General Population, Confidence Interval, Cognition disorders, Cohort Studies, brain size, and Elderly Person
Research Interests: Executive Function, Humans, Blood Glucose, Fasting, Diabetes mellitus, and 15 moreFemale, Cohort Study, American, Glycemic Index, Cognitive Performance, Aged, Cognitive impairment, Cross Section, Cognitive Ability, Environment, Fasting Blood Glucose, Cognition disorders, Cohort Studies, Cognitive dysfunction, and Genetic predisposition to disease
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Intracranial volume, measured through magnetic resonance imaging and/or estimated from head circumference, is heritable and correlates with cognitive traits and several neurological disorders. We performed a genome-wide association study... more
Intracranial volume, measured through magnetic resonance imaging and/or estimated from head circumference, is heritable and correlates with cognitive traits and several neurological disorders. We performed a genome-wide association study meta-analysis of intracranial volume (n = 79 174) and found 64 associating sequence variants explaining 5.0% of its variance. We used coding variation, transcript and protein levels, to uncover 12 genes likely mediating the effect of these variants, including GLI3 and CDK6 that affect cranial synostosis and microcephaly, respectively. Intracranial volume correlates genetically with volumes of cortical and sub-cortical regions, cognition, learning, neonatal and neurological traits. Parkinson’s disease cases have greater and attention deficit hyperactivity disorder cases smaller intracranial volume than controls. Our Mendelian randomization studies indicate that intracranial volume associated variants either increase the risk of Parkinson’s disease an...
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Objective: To investigate the association between 25-hydroxy vitamin D (25OHD) and cognitive function with particular consideration of physical activity (PA) in Icelandic older adults. Design: Cross-sectional study. Setting: Iceland.... more
Objective: To investigate the association between 25-hydroxy vitamin D (25OHD) and cognitive function with particular consideration of physical activity (PA) in Icelandic older adults. Design: Cross-sectional study. Setting: Iceland. Participants: Old adults aged 65-96. The final analytical sample included 4304 non-demented participants. Measurements: Serum 25OHD was categorized into deficient (≤ 30 nmol/L, 8%), insufficient (31-49 nmol/L, 25%) and normal-high levels (>50 nmol/L, 67%). Cognitive function assessments included measurements of memory function (MF), speed of processing (SP) and executive function (EF) all categorized as low and high (divided by 50th percentile). Multivariate logistic regression analysis was used to calculate the odds ratio (OR) for having high cognitive function. Results: Serum 25OHD was positively associated with cognitive function. Adjustment for PA and other potential confounders diminished this association only partially. Compared to participants...
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Late onset Alzheimer’s disease (AD) is the most common form of dementia with more than 35 million people affected worldwide, and no curative treatment available. AD is highly heritable and recent genome-wide meta-analyses have identified... more
Late onset Alzheimer’s disease (AD) is the most common form of dementia with more than 35 million people affected worldwide, and no curative treatment available. AD is highly heritable and recent genome-wide meta-analyses have identified over 20 genomic loci associated with AD, yet only explaining a small proportion of the genetic variance indicating that undiscovered loci exist. Here, we performed the largest genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 AD cases, 383,378 controls). AD-by-proxy status is based on parental AD diagnosis, and showed strong genetic correlation with AD (rg=0.81). Genetic meta analysis identified 29 risk loci, of which 9 are novel, and implicating 215 potential causative genes. Independent replication further supports these novel loci in AD. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver and microglia). Furthermore, gene-set analyses indicate the genetic contribution of b...
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Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more... more
Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. The association signal was robust to the exclusion of GBA, and consistent results were obtained in two independent replication cohorts, including 436 cases and 169 controls with whole exome sequencing and an additional 6713 cases and 5964 controls with exome-wide genotyping. In secondary analyses designed to highlight the...
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Research Interests: Gerontology, Aging, Comparative Study, Activities of Daily Living, Elderly, and 15 moreEurope, Female, Care, Health Status, Cognitive Performance, Aged, Cross Section, Cancer Patient, Geriatric Assessment, Binary Logistic Regression, Cross sectional Study, Cross Sectional Studies, Ernæring, Cognition disorders, and Health services for the aged
Neðst á síðuni er hægt er að nálgast greinina í heild sinni með því að smella á hlekkinn View/Open OBJECTIVE: Complex functional decline and comorbid state is an important indicator of outcome for hospital care of older adults. In today... more
Neðst á síðuni er hægt er að nálgast greinina í heild sinni með því að smella á hlekkinn View/Open OBJECTIVE: Complex functional decline and comorbid state is an important indicator of outcome for hospital care of older adults. In today acute care it is important to quickly be able to target those who might benefit from geriatric assessment. The MDS-AC is an evaluation system for geriatric acute care patients that records functional impairment and co-morbid states. The object of this study was to compare the MDS-AC registration with the traditional nurses and doctors records for chosen variables important to older patient care in Iceland and other Nordic countries. METHODS: This was a randomised prospective Nordic study. The study took place in Reykjavík, Copenhagen, Umeå, Oslo and Helsinki. Participants in each country were chosen from 75 year old and older patients admitted to acute care medical wards, 160 patients from each country. The results presented here show data from selec...
High adiposity in midlife might increase risk for late-life brain pathology, including dementia. Using data from the prospective Age, Gene/Environment Susceptibility-Reykjavik Study of men and women (born 1907-1935), we studied the... more
High adiposity in midlife might increase risk for late-life brain pathology, including dementia. Using data from the prospective Age, Gene/Environment Susceptibility-Reykjavik Study of men and women (born 1907-1935), we studied the associations of overweight and obesity at midlife (mean age, 50 (standard deviation, 4.7) years) with 1.5-T brain magnetic resonance imaging measures of infarct-like brain lesions, cerebral microbleeds, total brain volume, and white matter lesions volume, as well as dementia, in late life (mean age, 76 (standard deviation, 5.2) years). We used linear and Poisson models to estimate associations in 3,864 persons after adjustment for sociodemographic, health, and lifestyle characteristics. In midlife, the prevalence of overweight was 39% and that of obesity was 8%. After a mean follow-up of 26.2 (standard deviation, 4.9) years, midlife overweight and obesity were not associated with infarct-like brain lesions (relative risk (RR) = 0.82, 95% confidence interv...
Research Interests: Dementia, Obesity, Magnetic Resonance Imaging, Medicine, Iceland, and 15 moreBrain, Overweight, Humans, Internal Medicine, Mathematical Sciences, Female, Male, Follow-up studies, Body Mass Index, Aged, Middle Aged, Cerebral Hemorrhage, Confidence Interval, brain size, and Medical and Health Sciences
We conducted a search for rare, functional variants altering susceptibility to Alzheimer's disease that exploited knowledge of common variants associated with the same disease. We found that loss-of-function variants in ABCA7 confer... more
We conducted a search for rare, functional variants altering susceptibility to Alzheimer's disease that exploited knowledge of common variants associated with the same disease. We found that loss-of-function variants in ABCA7 confer risk of Alzheimer's disease in Icelanders (odds ratio (OR) = 2.12, P = 2.2 × 10(-13)) and discovered that the association replicated in study groups from Europe and the United States (combined OR = 2.03, P = 6.8 × 10(-15)).
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Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic... more
Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10(-11)), cholesterol transport (P = 2.96 × 10(-9)), and proteasome-ubiquitin activity (P = 1.34 × 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). The immune response, regulation of endocytosis, cholesterol tran...
Research Interests: Algorithms, Epidemiology, Dementia, Computational Biology, Biology, and 15 moreDevelopmental neuroscience, Health Policy, Brain, Humans, Endocytosis, Disease, Gene, Clinical Sciences, Cellular and Molecular Neuroscience, Elsevier, Cholesterol Metabolism, Alzheimer Disease, Geriatrics and Gerontology, HUMAN MEDICINE, and Genetic predisposition to disease
Complex functional decline and comorbid state is an important indicator of outcome for hospital care of older adults. In today acute care it is important to quickly be able to target those who might benefit from geriatric assessment. The... more
Complex functional decline and comorbid state is an important indicator of outcome for hospital care of older adults. In today acute care it is important to quickly be able to target those who might benefit from geriatric assessment. The MDS-AC is an evaluation system for geriatric acute care patients that records functional impairment and co-morbid states. The object of this study was to compare the MDS-AC registration with the traditional nurses and doctors records for chosen variables important to older patient care in Iceland and other Nordic countries. This was a randomised prospective Nordic study. The study took place in Reykjavík, Copenhagen, Umeå, Oslo and Helsinki. Participants in each country were chosen from 75 year old and older patients admitted to acute care medical wards, 160 patients from each country. The results presented here show data from selected variables collected with the MDS-AC instrument version 1,1 in the first 24 hours of admission, compared with hospit...