| 1. |
- Adedeji, Dickson O., et al.
(författare)
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Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients
- 2023
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Ingår i: Brain, Behavior, and Immunity - Health. - : Elsevier. - 2666-3546. ; 28
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allostatic load (AL) is defined as the cumulative dysregulation of neuroendocrine, immunological, metabolic, and cardiovascular systems that increases the susceptibility to stress-related health problems. Several dementia and Alzheimer's disease (AD) risk factors have been identified, yet little is known about the role of AL and its associations with AD biomarkers (e.g., beta-amyloid (Aβ) or tau) and cognitive function among memory clinic patients. Hence, this study aims to assess the association between AL and AD biomarkers, cognitive performance, and cognitive decline after 3-years of follow-up.Methods: Data from 188 memory clinic patients were derived from the Cortisol and Stress in AD (Co-STAR) study in Sweden. Participants underwent baseline assessments including blood tests for AL measures (including cortisol, thyroid stimulating hormone, cobalamin, homocysteine, leukocytes, glycated hemoglobin, albumin, high-density and low-density lipoprotein cholesterol, triglycerides, and creatinine), cerebrospinal fluid (CSF) sampling for AD biomarkers and neuropsychological tests including five cognitive domains. Linear regressions were conducted, adjusting for age, sex, and education.Results: Higher AL was associated with lower CSF Aβ1-42 levels (β = −0.175, p = 0.025), reflecting higher brain levels of Aβ1-42. Stratified analyses suggested a significant association among women but not men, although the AL-sex interaction was not statistically significant. AL was not significantly associated with T-tau level (β = −0.030, p = 0.682) and P-tau level (β = 0.091, p = 0.980). There were no significant associations between AL and cognition or cognitive decline after 3 years.Conclusion: This study showed that higher AL was associated with increased brain amyloid accumulation. This suggests that AL may play a role in AD/dementia pathophysiology. Potential sex-related differences should be assessed in further larger studies.
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| 2. |
- Finkel, Deborah, et al.
(författare)
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Impact of Childhood and Adult Socioeconomic Position on Change in Functional Aging
- 2024
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Ingår i: Health Psychology. - : American Psychological Association (APA). - 0278-6133 .- 1930-7810.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To examine life-course models by investigating the roles of childhood and adult socioeconomic position (SEP) in longitudinal changes in a functional aging index. Method: Up to eight waves of testing, covering 25 years, were available from the Swedish Adoption/Twin Study of Aging: N = 654, intake age = 50-82. A two-slope latent growth curve model was applied to the data, and the impact of including childhood and adult SEP as covariates of the intercept (at age 70) and slopes (before and after age 70) was tested. Results: Both childhood and adult SEP contributed to the best-fitting model. Childhood SEP was significantly associated with intercept and Slope 1 (before age 70) of the latent growth curve model (p < .05). Association of adult SEP with Slope 2 (after age 70) trended toward significance (p < .10). There was a significant interaction effect of childhood and adult SEP on the intercept (p < .05). As a result, intercept at age 70 was highest and change after age 70 was fastest for those whose SEP decreased from childhood to adulthood. Conclusions: Both childhood and adult SEP impact change in functional abilities with age, supporting both critical period and social mobility models. The social environment is modifiable by policies at local, national, and international levels, and these policies need to recognize that early social disadvantage can have long-lasting health impacts.
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| 3. |
- Finkel, Deborah, et al.
(författare)
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Impact of Objective and Subjective Sep on Aging Trajectories of Functional Capacity
- 2022
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Ingår i: Innovation in Aging. - : Oxford University Press. - 2399-5300. ; 6:Supplement 1, s. 220-220
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Tidskriftsartikel (refereegranskat)abstract
- Long-term stress is associated with adverse health outcomes in aging. It is important to identify not only factors that influence functioning in late adulthood, such as accumulated stress, but also the timing of such factors. The aim of the current analysis was to examine how socioeconomic stressors throughout the life course are associated with aging in functional capacity. Data were available from 740 adults ranging in age from 40 to 83 at intake (mean = 62.4, SD = 8.2) who participated in up to 8 waves of data collection (mean = 3.9, SD = 2.4). A Functional Aging Index (FAI) was created by combining measures of sensory, pulmonary, gait, and grip functioning. Both childhood and adulthood measures of objective socioeconomic position (SEP) and perceived SEP (financial strain) were available. Latent growth curve models (corrected for twinness) were used to estimate the trajectory of change in FAI over age and the impact of child and adult SEP measures on the trajectories. Results indicated that both childhood and adult objective SEP independently influenced rates of change in FAI in adulthood: higher SEP was associated with higher mean functioning and slower rates of decline. In combination, model fitting indicated that if SEP is above the median in adulthood, then childhood SEP has no impact on FAI trajectories; however, if SEP is below the median in adulthood, then childhood SEP can play a role. In addition, results indicated possible long-term effects of childhood financial strain on rates of change in FAI in adulthood.
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| 4. |
- Forouzanfar, Mohammad H, et al.
(författare)
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Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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| 5. |
- Hampel, Harald, et al.
(författare)
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Advances in the therapy of Alzheimer's disease : targeting amyloid beta and tau and perspectives for the future
- 2015
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Ingår i: Expert Review of Neurotherapeutics. - : Informa UK Limited. - 1473-7175 .- 1744-8360. ; 15:1, s. 83-105
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Forskningsöversikt (refereegranskat)abstract
- Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD.
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| 6. |
- Holleman, Jasper, et al.
(författare)
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Cortisol, cognition and Alzheimer's disease biomarkers among memory clinic patients
- 2022
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Ingår i: BMJ Neurology Open. - : BMJ Publishing Group Ltd. - 2632-6140. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThis study aims to investigate the relationship between diurnal cortisol patterns, cognition and Alzheimer's disease (AD) biomarkers in memory clinic patients.MethodMemory clinic patients were recruited from Karolinska University Hospital in Sweden (n=155). Diurnal cortisol patterns were assessed using five measures: awakening levels, cortisol awakening response, bedtime levels, the ratio of awakening to bedtime levels (AM/PM ratio) and total daily output. Cognition was measured in five domains: memory, working memory, processing speed, perceptual reasoning and overall cognition. AD biomarkers A beta(42), total tau and phosphorylated tau were assessed from cerebrospinal fluid (CSF). Cognition was measured at follow-up (average 32 months) in a subsample of participants (n=57).ResultsIn assessing the associations between cortisol and cognition, higher awakening cortisol levels were associated with greater processing speed at baseline. No relationship was found between diurnal cortisol patterns and change in cognition over time or CSF AD biomarkers in the total sample. After stratification by CSF A beta(42) levels, higher awakening cortisol levels were associated with worse memory performance in amyloid-positive participants. In amyloid-negative participants, higher bedtime cortisol levels and a lower AM/PM ratio were associated with lower overall cognition, greater awakening cortisol levels were associated with better processing speed, and a higher AM/PM ratio was associated with better perceptual reasoning. Additionally, higher awakening cortisol levels were associated with lower CSF A beta(42) levels in amyloid-positive participants, while higher bedtime cortisol levels and a lower AM/PM ratio were associated with higher CSF total tau in amyloid-negative participants.ConclusionsOur findings suggest that diurnal cortisol patterns are associated with cognitive function and provide new insights into the association between diurnal cortisol patterns and AD-related CSF biomarkers. Further research is needed to examine the complex relationship between cortisol, cognition and brain pathology.
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| 7. |
- Holleman, Jasper, et al.
(författare)
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Diurnal cortisol, neuroinflammation, and neuroimaging visual rating scales in memory clinic patients
- 2024
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Ingår i: Brain, behavior, and immunity. - : Elsevier. - 0889-1591 .- 1090-2139. ; 118, s. 499-509
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neuroinflammation is a hallmark of the Alzheimer's disease (AD) pathogenic process. Cortisol dysregulation may increase AD risk and is related to brain atrophy. This cross-sectional study aims to examine interactions of cortisol patterns and neuroinflammation markers in their association with neuroimaging correlates.METHOD: 134 participants were recruited from the Karolinska University Hospital memory clinic (Stockholm, Sweden). Four visual rating scales were applied to magnetic resonance imaging or computed tomography scans: medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), white matter lesions (WML), and posterior atrophy. Participants provided saliva samples for assessment of diurnal cortisol patterns, and underwent lumbar punctures for cerebrospinal fluid (CSF) sampling. Three cortisol measures were used: the cortisol awakening response, total daily output, and the ratio of awakening to bedtime levels. Nineteen CSF neuroinflammation markers were categorized into five composite scores: proinflammatory cytokines, other cytokines, angiogenesis markers, vascular injury markers, and glial activation markers. Ordinal logistic regressions were conducted to assess associations between cortisol patterns, neuroinflammation scores, and visual rating scales, and interactions between cortisol patterns and neuroinflammation scores in relation to visual rating scales.RESULT: Higher levels of angiogenesis markers were associated with more severe WML. Some evidence was found for interactions between dysregulated diurnal cortisol patterns and greater neuroinflammation-related biomarkers in relation to more severe GCA and WML. No associations were found between cortisol patterns and visual rating scales.CONCLUSION: This study suggests an interplay between diurnal cortisol patterns and neuroinflammation in relation to brain structure. While this cross-sectional study does not provide information on causality or temporality, these findings suggest that neuroinflammation may be involved in the relationship between HPA-axis functioning and AD.
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| 8. |
- Holleman, Jasper, et al.
(författare)
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Life-course stress, cognition, and diurnal cortisol in memory clinic patients without dementia
- 2024
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Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier. - 0167-4943 .- 1872-6976. ; 119
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To examine associations of life-course stress with cognition and diurnal cortisol patterns in older adulthood, as well as potential mediation effects of diurnal cortisol patterns and perceived stress on the association between life-course stress and cognition.METHODS: 127 participants without dementia were selected from a cohort of Swedish memory clinic patients. Cross-sectional associations between scores on two chronic stress questionnaires (perceived stress, stressful life events (SLEs)), five cognitive domains (overall cognition, memory, working memory, processing speed, perceptual reasoning), and two measures of diurnal cortisol patterns (total daily output, diurnal cortisol slope), as well as potential mediation effects of diurnal cortisol patterns and perceived stress on associations between life-course stress and cognition, were assessed using linear regressions.RESULTS: Greater lifetime exposure to SLEs was associated with worse memory, working memory, and processing speed performance, but not with diurnal cortisol patterns. A greater number of SLEs in late childhood was associated with worse working memory and processing speed, while a greater number of SLEs in non-recent adulthood were associated with better overall cognition and perceptual reasoning. Greater perceived stress was associated with a flattened diurnal cortisol slope, but not with cognition. No evidence for interplay between self-reported and physiological stress markers was found in relation to cognition, although there appeared to be a significant positive indirect association between economic/legal SLEs and the diurnal cortisol slope via perceived stress.CONCLUSIONS: The associations between SLEs and cognition depend on the period during which SLEs occur, but seem independent of late-life cortisol dysregulation.
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| 9. |
- Hooshmand, Babak, et al.
(författare)
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Serum Insulin and Cognitive Performance in Older Adults : A Longitudinal Study
- 2019
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Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 132:3, s. 367-373
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe aim of this study was to examine the association of serum glucose, insulin, and insulin resistance with cognitive functioning 7 years later in a longitudinal population-based study of Finnish older adults.MethodsSerum glucose and insulin were measured at baseline in 269 dementia-free individuals aged 65-79 years, from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study. Insulin resistance was estimated with the homeostasis model assessment (HOMA-IR). Participants were reexamined 7 years later, and global cognition, episodic memory, executive functioning, verbal expression, and psychomotor speed were assessed, both at baseline and at follow-up. Multiple linear regression was used to investigate the associations with cognitive performance at follow-up, after adjusting for several potential confounders, including common vascular risk factors.ResultsIn the multivariable-adjusted linear regression models, no associations of insulin resistance with cognitive functioning were observed. After excluding 19 incident dementia cases, higher baseline HOMA-IR values were related to worse performance in global cognition (beta [standard error (SE)] -.050 [0.02]; P =.043) and psychomotor speed (beta [SE] -.064 [. 03]; P = [.043]) 7 years later. Raised serum insulin levels were associated with lower scores on global cognition (b [SE] -.054 [.03]; P =.045) and tended to relate to poorer performance in psychomotor speed (beta [SE] -.061 [.03]; P =.070).ConclusionsSerum insulin and insulin resistance may be independent predictors of cognitive performance 7 years later in elderly individuals without dementia. Randomized controlled trials are needed to determine this issue.
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| 10. |
- Kåreholt, Ingemar, 1960-, et al.
(författare)
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Mid-life financial stress and cognitive and physical problems in older age : The role of potentially modifying factors
- 2023
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Ingår i: Innovation in Aging. - : Oxford University Press. - 2399-5300. ; 7:Supplement 1, s. 377-377
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Financial stress is an important source of chronic stress and has been associated with cognitive and physical impairments. This study investigates whether midlife financial stress is associated with the combination of cognitive and physical impairment, the role of potentially modifiable factors, and sex differences.Methods: The Cardiovascular Risk Factors, Aging, and Dementia population-based cohort study from Finland was used (n=1497) (baseline collected 1972-1987, mean age 50 years). There were two late-life re-examinations (mean total follow-up 25 years). Midlife financial stress was measured using two questions on financial situation. Cognitive impairment was based on six cognitive domains. Physical impairment was self-reported. Potential modifying factors investigated were smoking, alcohol, physical activity, cohabiting/not, non-manual work, and sleep disturbances. Sex differences were investigated. We used path analyses with full information maximum likelihood estimation.Results: Among women and men, midlife financial stress associated with cognitive impairment, physical impairment and their combination. Smoking and sleep disturbances mediated associations between financial stress, physical impairment, and combined impairments. Among men: manual/non-manual work mediated the association to cognitive impairments; cohabitation mediated to cognitive impairment; financial stress was associated with cognitive impairment only among smokers and stress had a stronger association to physical and combined impairments among non-drinkers. Among women, sleep seems to have role in the association between financial stress and cognitive impairment.Conclusions: Midlife financial stress associates with late-life impairments, and lifestyle/sociodemographic factors may modify these associations. Sex differences were observed. Interventions promoting healthier lifestyle and psychosocial factors may buffer against the deleterious role of financial stress.
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