| 1. |
- Escott-Price, Valentina, et al.
(författare)
-
Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
|
|
| 2. |
- Jones, Lesley, et al.
(författare)
-
Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
-
Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
|
|
| 3. |
- Wu, Yu-Tzu, et al.
(författare)
-
The changing prevalence and incidence of dementia over time - current evidence.
- 2017
-
Ingår i: Nature reviews. Neurology. - : Springer Science and Business Media LLC. - 1759-4766 .- 1759-4758. ; 13:6, s. 327-339
-
Tidskriftsartikel (refereegranskat)abstract
- Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.
|
|
| 4. |
- Freak-Poli, Rosanne, et al.
(författare)
-
Loneliness, Not Social Support, Is Associated with Cognitive Decline and Dementia Across Two Longitudinal Population-Based Cohorts
- 2022
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 85:1, s. 295-308
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Poor social health is likely associated with cognitive decline and risk of dementia; however, studies show inconsistent results. Additionally, few studies separate social health components or control for mental health.Objective: To investigate whether loneliness and social support are independently associated with cognitive decline and risk of dementia, and whether depressive symptoms confound the association.Methods: We included 4,514 participants from the population-based Rotterdam Study (RS; aged 71 +/- 7SD years) followed up to 14 years (median 10.8, interquartile range 7.4-11.6), and 2,112 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; aged 72 +/- 10SD years) followed up to 10 years (mean 5.9 +/- 1.6SD). At baseline, participants were free of major depression and scored on the Mini-Mental State Examination (MMSE) >= 26 for RS and >= 25 for SNAC-K. We investigated loneliness, perceived social support, and structural social support (specifically marital status and number of children). In both cohorts, dementia was diagnosed and cognitive function was repeatedly assessed with MMSE and a global cognitive factor (g-factor).Results: Loneliness was prospectively associated with a decline in the MMSE in both cohorts. Consistently, persons who were lonely had an increased risk of developing dementia (RS: HR 1.34, 95% CI 1.08-1.67; SNAC-K: HR 2.16, 95% CI 1.12-4.17). Adjustment for depressive symptoms and exclusion of the first 5 years of follow-up did not alter results. Neither perceived or structural social support was associated with cognitive decline or dementia risk.Conclusion: Loneliness, not social support, predicted cognitive decline and incident dementia independently of depressive symptoms.
|
|
| 5. |
- Lenart-Bugla, Marta, et al.
(författare)
-
What Do We Know about Social and Non-Social Factors Influencing the Pathway from Cognitive Health to Dementia? A Systematic Review of Reviews
- 2022
-
Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 12:9
-
Forskningsöversikt (refereegranskat)abstract
- The heterogeneous and multi-factorial nature of dementia requires the consideration of all health aspects when predicting the risk of its development and planning strategies for its prevention. This systematic review of reviews provides a comprehensive synthesis of those factors associated with cognition in the context of dementia, identifying the role of social aspects and evidencing knowledge gaps in this area of research. Systematic reviews and meta-analyses from 2009–2021 were searched for within Medline, PsycINFO, CINAHL Complete, Cochrane, and Epistemonikos. Reviewers independently screened, reviewed, and assessed the records, following the PRISMA-2020 guidelines. From 314 included studies, 624 cognitive-related factors were identified, most of them risk factors (61.2%), mainly belonging to the group of ‘somatic comorbidities’ (cardiovascular disease and diabetes) and ‘genetic predispositions’. The protective factors (20%) were mainly related to lifestyle, pointing to the Mediterranean diet, regular physical activity, and cognitively stimulating activities. Social factors constituted 9.6% of all identified factors. Research on biological and medical factors dominates the reviewed literature. Greater social support and frequent contact may confer some protection against cognitive decline and dementia by delaying its onset or reducing the overall risk; however, overall, our findings are inconsistent. Further research is needed in the fields of lifestyle, psychology, social health, and the protective factors against cognitive decline and dementia.
|
|
| 6. |
- Vernooij-Dassen, Myrra, et al.
(författare)
-
Recognition of social health : A conceptual framework in the context of dementia research
- 2022
-
Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The recognition of dementia as a multifactorial disorder encourages the exploration of new pathways to understand its origins. Social health might play a role in cognitive decline and dementia, but conceptual clarity is lacking and this hinders investigation of associations and mechanisms. The objective is to develop a Conceptual framework for social health to advance conceptual clarity in future studies.Process: We use the following steps: underpinning for concept advancement, concept advancement by the development of a conceptual model, and exploration of its potential feasibility. An iterative consensus-based process was used within the international multidisciplinary SHARED project.Conceptual framework: Underpinning of the concept drew from a synthesis of theoretical, conceptual and epidemiological work, and resulted in a definition of social health as wellbeing that relies on capacities both of the individual and the social environment. Consequently, domains in the conceptual framework are on both the individual (e.g., social participation) and the social environmental levels (e.g., social network). We hypothesize that social health acts as a driver for use of cognitive reserve which can then slow cognitive impairment or maintain cognitive functioning. The feasibility of the conceptual framework is demonstrated in its practical use in identifying and structuring of social health markers within the SHARED project.Discussion: The conceptual framework provides guidance for future research and facilitates identification of modifiable risk and protective factors, which may in turn shape new avenues for preventive interventions. We highlight the paradigm of social health in dementia as a priority for dementia research.
|
|
