| 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. |
- 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
-
Ingår i: Brain, Behavior, and Immunity - Health. - : Elsevier BV. - 2666-3546. ; 28
-
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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| 3. |
- Delaby, Constance, et al.
(författare)
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Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.
- 2022
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 18:10, s. 1868-1879
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Tidskriftsartikel (refereegranskat)abstract
- The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests.We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients.The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis.This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- Kalaria, Raj, et al.
(författare)
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The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.
- 2024
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.
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| 8. |
- Yerramalla, Manasa S., et al.
(författare)
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Cognitive reserve, cortisol, and Alzheimer's disease biomarkers : A memory clinic study
- 2024
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Ingår i: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279. ; 20:7, s. 4486-4498
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Cognitive reserve might mitigate the risk of Alzheimer's dementia among memory clinic patients. No study has examined the potential modifying role of stress on this relation.METHODS: We examined cross-sectional associations of the cognitive reserve index (CRI; education, occupational complexity, physical and leisure activities, and social health) with cognitive performance and AD-related biomarkers among 113 memory clinic patients. The longitudinal association between CRI and cognition over a 3-year follow-up was assessed. We examined whether associations were influenced by perceived stress and five measures of diurnal salivary cortisol.RESULTS: Higher CRI scores were associated with better cognition. Adjusting for cortisol measures reduced the beneficial association of CRI on cognition. A higher CRI score was associated with better working memory in individuals with higher (favorable) cortisol AM/PM ratio, but not among individuals with low cortisol AM/PM ratio. No association was found between CRI and AD-related biomarkers.DISCUSSION: Physiological stress reduces the neurocognitive benefits of cognitive reserve among memory clinic patients. Highlights: Physiological stress may reduce the neurocognitive benefits accrued from cognitively stimulating and enriching life experiences (cognitive reserve [CR]) in memory clinic patients. Cortisol awakening response modified the relation between CR and P-tau181, a marker of Alzheimer's disease (AD). Effective stress management techniques for AD and related dementia prevention are warranted.
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