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- Adedeji, Dickson O., et al.
(author)
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Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients
- 2023
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In: Brain, Behavior, and Immunity - Health. - : Elsevier. - 2666-3546. ; 28
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Journal article (peer-reviewed)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.
(author)
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Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients
- 2023
-
In: Brain, Behavior, and Immunity - Health. - : Elsevier BV. - 2666-3546. ; 28
-
Journal article (peer-reviewed)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. |
- Holleman, Jasper, et al.
(author)
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Cortisol, cognition and Alzheimer's disease biomarkers among memory clinic patients
- 2022
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In: BMJ Neurology Open. - : BMJ Publishing Group Ltd. - 2632-6140. ; 4:2
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Journal article (peer-reviewed)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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| 4. |
- Holleman, Jasper, et al.
(author)
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Diurnal cortisol, neuroinflammation, and neuroimaging visual rating scales in memory clinic patients
- 2024
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In: Brain, behavior, and immunity. - : Elsevier. - 0889-1591 .- 1090-2139. ; 118, s. 499-509
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Journal article (peer-reviewed)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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| 5. |
- Holleman, Jasper, et al.
(author)
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Life-course stress, cognition, and diurnal cortisol in memory clinic patients without dementia
- 2024
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In: Archives of gerontology and geriatrics (Print). - : Elsevier. - 0167-4943 .- 1872-6976. ; 119
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Journal article (peer-reviewed)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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| 6. |
- Jonell, Patrik, et al.
(author)
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Multimodal Capture of Patient Behaviour for Improved Detection of Early Dementia : Clinical Feasibility and Preliminary Results
- 2021
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In: Frontiers in Computer Science. - : Frontiers Media SA. - 2624-9898. ; 3
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Journal article (peer-reviewed)abstract
- Non-invasive automatic screening for Alzheimer's disease has the potential to improve diagnostic accuracy while lowering healthcare costs. Previous research has shown that patterns in speech, language, gaze, and drawing can help detect early signs of cognitive decline. In this paper, we describe a highly multimodal system for unobtrusively capturing data during real clinical interviews conducted as part of cognitive assessments for Alzheimer's disease. The system uses nine different sensor devices (smartphones, a tablet, an eye tracker, a microphone array, and a wristband) to record interaction data during a specialist's first clinical interview with a patient, and is currently in use at Karolinska University Hospital in Stockholm, Sweden. Furthermore, complementary information in the form of brain imaging, psychological tests, speech therapist assessment, and clinical meta-data is also available for each patient. We detail our data-collection and analysis procedure and present preliminary findings that relate measures extracted from the multimodal recordings to clinical assessments and established biomarkers, based on data from 25 patients gathered thus far. Our findings demonstrate feasibility for our proposed methodology and indicate that the collected data can be used to improve clinical assessments of early dementia.
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