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- Perez-Grijalba, V, et al.
(författare)
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Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study
- 2019
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 11:1, s. 96-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTo facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer’s disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (Aβ) levels with the presence of pathological accumulation of Aβ in the brain measured by amyloid-PET. Both plasma Aβ42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers.MethodsWe included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total Aβ40 and Aβ42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as Aβ-PET positive or negative, and the ability of TP42/40 to detect Aβ-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma Aβ biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification.ResultsEighteen (30.5%) subjects were Aβ-PET positive. TP42/40 ratio alone identified Aβ-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779–0.982). Discriminating performance of TP42/40 to detect Aβ-PET-positive subjects yielded sensitivity and specificity values at Youden’s cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of Aβ-PET scans by 64%. Combination of both FDG-PET scores and plasma Aβ biomarkers was found to be the most accurate Aβ-PET predictor, with an AUC of 0.965 (95% CI = 0.913–0.100).ConclusionsPlasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain Aβ positivity in preclinical and prodromal stages of Alzheimer’s disease.
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| 3. |
- Solomon, A, et al.
(författare)
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Multidomain interventions: state-of-the-art and future directions for protocols to implement precision dementia risk reduction. A user manual for Brain Health Services-part 4 of 6
- 2021
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1, s. 171-
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Tidskriftsartikel (refereegranskat)abstract
- Although prevention of dementia and late-life cognitive decline is a major public health priority, there are currently no generally established prevention strategies or operational models for implementing such strategies into practice. This article is a narrative review of available evidence from multidomain dementia prevention trials targeting several risk factors and disease mechanisms simultaneously, in individuals without dementia at baseline. Based on the findings, we formulate recommendations for implementing precision risk reduction strategies into new services called Brain Health Services. A literature search was conducted using medical databases (MEDLINE via PubMed and SCOPUS) to select relevant studies: non-pharmacological multidomain interventions (i.e., combining two or more intervention domains), target population including individuals without dementia, and primary outcomes including cognitive/functional performance changes and/or incident cognitive impairment or dementia. Further literature searches covered the following topics: sub-group analyses assessing potential modifiers for the intervention effect on cognition in the multidomain prevention trials, dementia risk scores used as surrogate outcomes in multidomain prevention trials, dementia risk scores in relation to brain pathology markers, and cardiovascular risk scores in relation to dementia. Multidomain intervention studies conducted so far appear to have mixed results and substantial variability in target populations, format and intensity of interventions, choice of control conditions, and outcome measures. Most trials were conducted in high-income countries. The differences in design between the larger, longer-term trials that met vs. did not meet their primary outcomes suggest that multidomain intervention effectiveness may be dependent on a precision prevention approach, i.e., successfully identifying the at-risk groups who are most likely to benefit. One such successful trial has already developed an operational model for implementing the intervention into practice. Evidence on the efficacy of risk reduction interventions is promising, but not yet conclusive. More long-term multidomain randomized controlled trials are needed to fill the current evidence gaps, especially concerning low- and middle-income countries and integration of dementia prevention with existing cerebrovascular prevention programs. A precision risk reduction approach may be most effective for dementia prevention. Such an approach could be implemented in Brain Health Services.
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- Visser, LNC, et al.
(författare)
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Dementia risk communication. A user manual for Brain Health Services-part 3 of 6
- 2021
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1, s. 170-
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Tidskriftsartikel (refereegranskat)abstract
- Growing evidence suggests dementia incidence can be reduced through prevention programs targeting risk factors. To accelerate the implementation of such prevention programs, a new generation of brain health services (BHS) is envisioned, involving risk profiling, risk communication, risk reduction, and cognitive enhancement. The purpose of risk communication is to enable individuals at risk to make informed decisions and take action to protect themselves and is thus a crucial step in tailored prevention strategies of the dementia incidence. However, communicating about dementia risk is complex and challenging.In this paper, we provide an overview of (i) perspectives on communicating dementia risk from an ethical, clinical, and societal viewpoint; (ii) insights gained from memory clinical practice; (iii) available evidence on the impact of disclosing APOE and Alzheimer’s disease biomarker test results gathered from clinical trials and observational studies; (iv) the value of established registries in light of BHS; and (v) practical recommendations regarding effective strategies for communicating about dementia risk.In addition, we identify challenges, i.e., the current lack of evidence on what to tell on an individual level—the actual risk—and on how to optimally communicate about dementia risk, especially concerning worried yet cognitively unimpaired individuals. Ideally, dementia risk communication strategies should maximize the desired impact of risk information on individuals’ understanding of their health/disease status and risk perception and minimize potential harms. More research is thus warranted on the impact of dementia risk communication, to (1) evaluate the merits of different approaches to risk communication on outcomes in the cognitive, affective and behavioral domains, (2) develop an evidence-based, harmonized dementia risk communication protocol, and (3) develop e-tools to support and promote adherence to this protocol in BHSs.Based on the research reviewed, we recommend that dementia risk communication should be precise; include the use of absolute risks, visual displays, and time frames; based on a process of shared decision-making; and address the inherent uncertainty that comes with any probability.
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