| 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
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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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| 3. |
- Aspö, Malin
(författare)
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Life changing moments : transitions and critical points in young-onset dementia
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Persons who are diagnosed with dementia before the age of 65 are commonly referred to as persons with young-onset dementia (YOD). Younger persons and their families have different needs from those in older persons with dementia. However, previous research has identified a lack of support services addressing these specific needs. Persons with YOD and their family members will experience various critical points and transitions during the disease trajectory. As we are not yet able to cure underlying diseases causing dementia, support should focus on enhancing well-being and Quality of life (QoL) / Health Related Quality of Life (HRQoL). This could be achieved by paying extra attention when persons with YOD and their family members experience critical points, to facilitate healthy transitions. Aim: The overall aim of this thesis is to enhance the knowledge and understanding of how to facilitate healthy transitions in YOD, by describing changes in QoL and HRQoL over time, and by exploring the critical points and transition processes that persons living with YOD and their family members experience in different phases of dementia. Methods: Studies I – III were part of a longitudinal project, including participants with YOD after diagnosis. Study I included data on self-reported QoL and HRQoL from 33 participants, collected every six months over a period of 24 months. We assessed changes over time and differences between ‘completers’ and ‘noncompleters’. Trajectories in self-rated QoL and HRQoL were also explored by visual inspection of scatter plots. A sub-sample of 15 participants from study I took part in yearly interviews. These interviews were conducted shortly after diagnosis (study II) and one year after diagnosis (study III) and analyzed by means of qualitative content analysis. In study II we used an inductive approach, and in study III we took on a deductive approach using the categories identified in study II as a framework for data coding. Study IV focused on the perspectives of family members. For this study, 15 family members of persons with YOD were recruited from residential care homes and one support group. To be included in the study the person had to be over 18 years of age and have a family member with YOD living in a residential care home. The family members were interviewed twice and asked to retrospectively describe their experiences of critical points and transitions throughout the disease trajectory. The interviews were analyzed with thematic analysis. Findings: Study I showed great variation in individual scores and trajectories of QoL and HRQoL over time, without identifying specific time points in need of attention. In the qualitative studies with persons with YOD (studies II and III) and family members (study IV), being diagnosed with YOD was described as a lifechanging event. Four critical points clearly emerged from the analyses. These were related to receiving the diagnosis, the premature ending of working life, not receiving formal support, and relocation to a residential care home. The critical points, especially receiving the diagnosis, consequently led to changes in roles and redefinition of identity, and for many, a withdrawal from social activities. Conclusion: Facilitating transitions in YOD is a shared responsibility between the health care sector and social service sector. Therefore, all professionals who meet persons with YOD need to have knowledge about critical points and be aware of signs of unhealthy responses to the transitions. Support for persons with YOD and their family members should focus on regaining control over the changed life situation and facilitating engagement in meaningful activities as a means of reducing the risk of social isolation. The immediate period following disclosure of diagnosis emerged as an especially vulnerable period, in which persons with YOD are likely to need more frequent contact and follow-up from the memory clinics than what is offered today. The findings also emphasize the need to improve knowledge and understanding of the specific needs in YOD, including education of employers and social service officers.
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| 4. |
- Aspö, Malin, et al.
(författare)
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Transitions : Experiences of younger persons recently diagnosed with Alzheimer-type dementia
- 2023
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Ingår i: Dementia. - : Sage Publications. - 1471-3012 .- 1741-2684. ; 22:3, s. 610-627
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Tidskriftsartikel (refereegranskat)abstract
- Receiving a diagnosis of dementia before the age of 65 has a huge impact on everyday life. Previously, the disease trajectory has mainly been described from the perspective of older persons. However, young persons with dementia are confronted with specific challenges, influencing the type of life-changing events, or 'critical points' that they may experience. The aim of this study was therefore to describe experiences of persons recently being diagnosed with young-onset dementia. In total, 14 participants with dementia due to Alzheimer's disease (10 woman/4 men) with an average age of 59 were included in the study. Interviews were conducted within 2 months after receiving the diagnosis and analyzed using qualitative content analysis with an inductive approach, resulting in three categories: (1) A life changing moment, (2) An ongoing process, and (3) Remaining in control. The findings show that receiving such a diagnosis was experienced by participants as a life changing moment, followed by them seeking to come to terms with the diagnosis and reflecting on its meaning, in which various strategies were adopted to remain in control. The current study highlights three critical points considering the diagnosis of young-onset dementia that warrant special attention and provides insight into factors related to delay in healthy transitioning after receiving the diagnosis, as well as factors that may facilitate successful transitions.
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| 5. |
- Barbera, Mariagnese, et al.
(författare)
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A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol
- 2024
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central Ltd. - 1758-9193. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Combining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer’s Disease and emerging evidence of its potential neuro-protective effects (e.g. vascular, metabolic, anti-senescence). MET-FINGER aims to test a FINGER 2.0 multimodal intervention, combining an updated FINGER multidomain lifestyle intervention with metformin, where appropriate, in an APOE ε4-enriched population of older adults (60–79 years) at increased risk of dementia.Methods: MET-FINGER is an international randomised, controlled, parallel-group, phase-IIb proof-of-concept clinical trial, where metformin is included through a trial-within-trial design. 600 participants will be recruited at three sites (UK, Finland, Sweden). Participants at increased risk of dementia based on vascular risk factors and cognitive screening, will be first randomised to the FINGER 2.0 intervention (lifestyle + metformin if eligible; active arm) or to receive regular health advice (control arm). Participants allocated to the FINGER 2.0 intervention group at risk indicators of T2D will be additionally randomised to receive metformin (2000 mg/day or 1000 mg/day) or placebo. The study duration is 2 years. The changes in global cognition (primary outcome, using a Neuropsychological Test Battery), memory, executive function, and processing speed cognitive domains; functional status; lifestyle, vascular, metabolic, and other dementia-related risk factors (secondary outcomes), will be compared between the FINGER 2.0 intervention and the control arm. The feasibility, potential interaction (between-groups differences in healthy lifestyle changes), and disease-modifying effects of the lifestyle-metformin combination will be exploratory outcomes. The lifestyle intervention is adapted from the original FINGER trial (diet, physical activity, cognitive training, monitoring of cardiovascular/metabolic risk factors, social interaction) to be consistently delivered in three countries. Metformin is administered as Glucophage®XR/SR 500, (500 mg oral tablets). The metformin/placebo treatment will be double blinded. Conclusion: MET-FINGER is the first trial combining a multimodal lifestyle intervention with a putative repurposed disease-modifying drug for cognitive impairment prevention. Although preliminary, its findings will provide crucial information for innovative precision prevention strategies and form the basis for a larger phase-III trial design and future research in this field.
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| 6. |
- 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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| 7. |
- 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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| 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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