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- Snellman, Anniina, et al.
(författare)
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APOE epsilon 4 gene dose effect on imaging and blood biomarkers of neuroinflammation and beta-amyloid in cognitively unimpaired elderly
- 2023
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Ingår i: Alzheimers Research & Therapy. - 1758-9193. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNeuroinflammation, characterized by increased reactivity of microglia and astrocytes in the brain, is known to be present at various stages of the Alzheimer's disease (AD) continuum. However, its presence and relationship with amyloid pathology in cognitively normal at-risk individuals is less clear. Here, we used positron emission tomography (PET) and blood biomarker measurements to examine differences in neuroinflammation and beta-amyloid (A beta) and their association in cognitively unimpaired homozygotes, heterozygotes, or non-carriers of the APOE epsilon 4 allele, the strongest genetic risk for sporadic AD.MethodsSixty 60-75-year-old APOE epsilon 4 homozygotes (n = 19), heterozygotes (n = 21), and non-carriers (n = 20) were recruited in collaboration with the local Auria biobank. The participants underwent C-11-PK11195 PET (targeting 18-kDa translocator protein, TSPO), C-11-PiB PET (targeting A beta), brain MRI, and neuropsychological testing including a preclinical cognitive composite (APCC). C-11-PK11195 distribution volume ratios and C-11-PiB standardized uptake value ratios (SUVRs) were calculated for regions typical for early A beta accumulation in AD. Blood samples were drawn for measuring plasma glial fibrillary acidic protein (GFAP) and plasma A beta(1-42/1.40).ResultsIn our cognitively unimpaired sample, cortical C-11-PiB-binding increased according to APOE epsilon 4 gene dose (median composite SUVR 1.47 (range 1.38-1.66) in non-carriers, 1.55 (1.43-2.02) in heterozygotes, and 2.13 (1.61-2.83) in homozygotes, P = 0.002). In contrast, cortical composite C-11-PK11195-binding did not differ between the APOE epsilon 4 gene doses (P = 0.27) or between A beta-positive and A beta-negative individuals (P = 0.81) and associated with higher A beta burden only in APOE epsilon 4 homozygotes (Rho = 0.47, P = 0.043). Plasma GFAP concentration correlated with cortical C-11-PiB (Rho = 0.35, P = 0.040), but not C-11-PK11195-binding (Rho = 0.13, P = 0.47) in A beta-positive individuals. In the total cognitively unimpaired population, both higher composite C-11-PK11195-binding and plasma GFAP were associated with lower hippocampal volume, whereas elevated C-11-PiB-binding was associated with lower APCC scores.ConclusionsOnly A beta burden measured by PET, but not markers of neuroinflammation, differed among cognitively unimpaired elderly with different APOE epsilon 4 gene dose. However, APOE epsilon 4 gene dose seemed to modulate the association between neuroinflammation and A beta.
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- Snellman, Anniina, et al.
(författare)
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ASIC-E4: Interplay of Beta-Amyloid, Synaptic Density and Neuroinflammation in Cognitively Normal Volunteers With Three Levels of Genetic Risk for Late-Onset Alzheimer's Disease - Study Protocol and Baseline Characteristics
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background:& nbsp;Detailed characterization of early pathophysiological changes in preclinical Alzheimer's disease (AD) is necessary to enable development of correctly targeted and timed disease-modifying treatments. ASIC-E4 study ( "Beta-Amyloid, Synaptic loss, Inflammation and Cognition in healthy APOE epsilon 4 carriers ") combines state-of-the-art neuroimaging and fluid-based biomarker measurements to study the early interplay of three key pathological features of AD, i.e., beta-amyloid (A beta) deposition, neuroinflammation and synaptic dysfunction and loss in cognitively normal volunteers with three different levels of genetic (APOE-related) risk for late-onset AD.& nbsp;Objective:& nbsp;Here, our objective is to describe the study design, used protocols and baseline demographics of the ASIC-E4 study.& nbsp;Methods/Design:& nbsp;ASIC-E4 is a prospective observational multimodal imaging study performed in Turku PET Centre in collaboration with University of Gothenburg. Cognitively normal 60-75-year-old-individuals with known APOE epsilon 4/epsilon 4 genotype were recruited via local Auria Biobank (Turku, Finland). Recruitment of the project has been completed in July 2020 and 63 individuals were enrolled to three study groups (Group 1: APOE epsilon 4/epsilon 4, N = 19; Group 2: APOE epsilon 4/epsilon 3, N = 22; Group 3: APOE epsilon 3/epsilon 3, N = 22). At baseline, all participants will undergo positron emission tomography imaging with tracers targeted against A beta deposition (C-11-PIB), activated glia (C-11-PK11195) and synaptic vesicle glycoprotein 2A (C-11-UCB-J), two brain magnetic resonance imaging scans, and extensive cognitive testing. In addition, blood samples are collected for various laboratory measurements and blood biomarker analysis and cerebrospinal fluid samples are collected from a subset of participants based on additional voluntary informed consent. To evaluate the predictive value of the early neuroimaging findings, neuropsychological evaluation and blood biomarker measurements will be repeated after a 4-year follow-up period.& nbsp;Discussion:& nbsp;Results of the ASIC-E4 project will bridge the gap related to limited knowledge of the synaptic and inflammatory changes and their association with each other and A beta in "at-risk " individuals. Thorough in vivo characterization of the biomarker profiles in this population will produce valuable information for diagnostic purposes and future drug development, where the field has already started to look beyond A beta.
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- Hoppe, J. A., et al.
(författare)
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When do individuals choose care robots over a human caregiver? : Insights from a laboratory experiment on choices under uncertainty
- 2023
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Ingår i: Computers in Human Behavior Reports. - : Elsevier B.V.. - 2451-9588. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Demographic changes and a predicted shortage of nursing staff are progressively putting pressure on the healthcare system. Care robots may represent one part of a possible solution to this problem as they can assist care work. However, large parts of the population are reportedly skeptical about robotics in care, and field studies are difficult to conduct due to the low prevalence of real robotics in the field. Therefore, we follow an experimental approach pertaining to the question of individual decision-making. In this regard, we analyze the aspects that influence the individual's choice between a care robot and a human caregiver for assistance in their daily life. Our economic experiment is conducted in a virtual laboratory to examine specifically how quality uncertainty of care affects individual's decisions for and against robotic care. In the experiment, 162 participants fully completed the experiment in which they were asked to repeatedly choose between a human caregiver and a care robot. Our results reveal that, overall, the care robot is chosen more often than a human caregiver. At the same time, the quality uncertainty of care linked to a human caregiver barely affected the choice of participants. On the other hand, a participant's health status and their attitude toward direct interactions with care robots did partially affect their choice. Additionally, we explored causes for indecisiveness and its effect on the choice. Here, we found indecisive participants tending to choose a human caregiver more often.
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