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- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 3. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 5. |
- Malzbender, K., et al.
(författare)
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Validation, Deployment, and Real-World Implementation of a Modular Toolbox for Alzheimer’s Disease Detection and Dementia Risk Reduction: The AD-RIDDLE Project
- 2024
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Ingår i: Journal of Prevention of Alzheimer's Disease. - 2274-5807 .- 2426-0266. ; 11:2, s. 329 - 338
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Tidskriftsartikel (refereegranskat)abstract
- The Real-World Implementation, Deployment, and Validation of Early Detection Tools and Lifestyle Enhancement (AD-RIDDLE) project, recently launched with the support of the EU Innovative Health Initiative (IHI) public-private partnership and UK Research and Innovation (UKRI), aims to develop, test, and deploy a modular toolbox platform that can reduce existing barriers to the timely detection, and therapeutic approaches in Alzheimer’s disease (AD), thus accelerating AD innovation. By focusing on health system and health worker practices, AD-RIDDLE seeks to improve and smooth AD management at and between each key step of the clinical pathway and across the disease continuum, from at-risk asymptomatic stages to early symptomatic ones. This includes innovation and improvement in AD awareness, risk reduction and prevention, detection, diagnosis, and intervention. The 24 partners in the AD-RIDDLE interdisciplinary consortium will develop and test the AD-RIDDLE toolbox platform and its components individually and in combination in six European countries. Expected results from this cross-sectoral research collaboration include tools for earlier detection and accurate diagnosis; validated, novel digital cognitive and blood-based biomarkers; and improved access to individualized preventative interventions (including multimodal interventions and symptomatic/disease-modifying therapies) across diverse populations, within the framework of precision medicine. Overall, AD-RIDDLE toolbox platform will advance management of AD, improving outcomes for patients and their families, and reducing costs.
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| 6. |
- Feliziani, FT, et al.
(författare)
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Cognitive performance in elderly patients undergoing carotid endarterectomy or carotid artery stenting: a twelve-month follow-up study
- 2010
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Ingår i: Cerebrovascular diseases (Basel, Switzerland). - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 30:3, s. 244-251
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> It is still a matter of debate if and to what extent carotid endarterectomy (CEA) and carotid artery stenting (CAS) impair cognitive functioning in the elderly. <i>Methods:</i> We conducted a nonrandomized clinical trial on subjects with asymptomatic carotid artery stenosis comparing CEA (n = 28; 24 males and 4 females; 72.6 ± 5.8 years old) with CAS (n = 29; 17 males and 12 females; 75.1 ± 5.7 years old). Cognition, mood and functional status were evaluated by a broad spectrum of tests performed on the day prior to carotid reopening as well as 3 and 12 months after. <i>Results:</i> No significant differences in scores on cognitive tests including the Babcock story recall test and Rey’s auditory verbal learning test (memory), category naming test (verbal fluency), trail-making test parts A and B (attention and executive function) and controlled oral word association test (executive functioning) were observed 3 and 12 months after carotid reopening independent of the technique used. Only scores on the copy drawing test (visuospatial and constructional abilities) slightly but significantly (p < 0.05) worsened in the CAS group 12 months after the intervention. No significant differences between the CEA and CAS groups were detected regarding mood and functional status after 3 and 12 months. <i>Conclusions:</i> CEA and CAS seem to be safe procedures in elderly patients in terms of cognitive, mood and functional status in the short and long term. CAS might be preferred for the shorter hospital stay, but further studies with a larger number of old and oldest old subjects with a longer follow-up are needed to better understand the cost-effectiveness of both treatments.
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| 10. |
- Maggio, D, et al.
(författare)
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Emotional and psychological distress of persons involved in the care of patients with Alzheimer disease predicts falls and fractures in their care recipients
- 2010
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 30:1, s. 33-38
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Elderly patients with dementia have a higher risk of falls and fractures as compared to cognitively intact elderly subjects. To investigate whether psychological distress of the caregiver might predispose older persons with Alzheimer disease (AD) to falls and fractures, we performed a prospective cohort study. <i>Methods:</i> A consecutive series of 110 subjects with dementia underwent baseline and follow-up clinical and functional evaluations. The burden of the caregivers was recorded at baseline. Any intervening fall or fracture was ascertained at the 1-year follow-up. <i>Results:</i> The caregiver burden was significantly higher in persons involved in the care of patients with AD who subsequently fell. In a multivariate regression model, the caregiver burden score predicted falls and fractures. <i>Conclusion:</i> Part of the increased risk of falls and fractures in AD might be due to the distress of caregivers, a factor potentially amenable to treatment.
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