| 1. |
- Marseglia, Anna, et al.
(författare)
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Metabolic Syndrome Is Associated With Poor Cognition : A Population-Based Study of 70-Year-Old Adults Without Dementia
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 76:12, s. 2275-2283
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Tidskriftsartikel (refereegranskat)abstract
- Background: Individual conditions of metabolic syndrome (MetS) have been related to dementia; however, their combined impact on the preclinical stage is unknown. We investigated the associations between MetS and domain-specific cognitive function as well as the role of sociodemographic, cardiovascular, and genetic factors.Methods: Within the Gothenburg H70 Birth Cohort Study-Birth cohort 1944, 1131 dementia-free participants (aged 70 years) were examined during 2014-2016. MetS (central obesity plus at least 2 factors [reduced HD11.-cholesterol, elevated triglycerides, blood pressure, or blood glucose]) was identified according to the International Diabetes Federation criteria. Five cognitive domains (memory, attention/perceptual speed, executive function, verbal fluency, visuospatial abilities) were generated after z-standardizing raw scores from 10 neuropsychological tests. Education, heart disease, claudication (indicating peripheral atherosclerosis), and apolipoprotein genotype were ascertained by trained staff. Data were analyzed with linear regression models.Results: Overall, 618 participants (55%) had MetS. In multiadjusted linear regressions, MetS was related to poorer performance in attention/ perceptual speed (beta -0.14 [95% CI -0.25, -0.02]), executive function (beta -0.12 [95% CI -0.23, -0.01]), and verbal fluency (beta -0.19 [95% CI -0.30, -0.08]). These associations were present only among individuals who did not carry any APOE-epsilon 4 allele or were highly educated. However, among those with MetS, high education was related to better cognitive performance. MetS together with comorbid heart disease or claudication was associated with even worse cognitive performance than each alone.Conclusions: MetS is associated with poor attention/perceptual speed, executive function, and verbal fluency performance. Education, apolipoprotein E-epsilon 4 allele, and comorbid cardiovascular disease influenced the observed associations.
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| 2. |
- Ahlner, Felicia, 1987, et al.
(författare)
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Patterns of Alcohol Consumption and Associated Factors in a Population-Based Sample of 70-Year-Olds: Data from the Gothenburg H70 Birth Cohort Study 2014-16
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601 .- 1661-7827. ; 19:14
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Tidskriftsartikel (refereegranskat)abstract
- Older adults of today consume more alcohol, yet knowledge about the factors associated with different consumption levels is limited in this age group. Based on the data from a population-based sample (n = 1156, 539 men and 617 women) in The Gothenburg H70 Birth Cohort Study 2014-16, we examined sociodemographic, social, and health-related factors associated with alcohol consumption levels in 70-year-olds, using logistic regression. Total weekly alcohol intake was calculated based on the self-reported amount of alcohol consumed. Alcohol consumption was categorized as lifetime abstention, former drinking, moderate consumption (<= 98 g/week), and at-risk consumption (>98 g/week). At-risk consumption was further categorized into lower at-risk (98-196 g/week), medium at-risk (196-350 g/week), and higher at-risk (>= 350 g/week). We found that among the 1156 participants, 3% were lifetime abstainers, 3% were former drinkers, 64% were moderate drinkers, and 30% were at-risk drinkers (20% lower, 8% medium, 2% higher). Among several factors, former drinking was associated with worse general self-rated health (OR 1.65, 95% CI 1.08-2.51) and lower health-related quality of life (measured by physical component score) (OR 0.94, 95% CI 0.91-0.97), higher illness burden (OR 1.16, 95% CI 1.07-1.27), and weaker grip strength (OR 0.96, 95% CI 0.94-0.98). Higher at-risk drinkers more often had liver disease (OR 11.41, 95% CI 3.48-37.37) and minor depression (OR 4.57, 95% CI 1.40-14.95), but less contacts with health care (OR 0.32, 95% CI 0.11-0.92). Our findings demonstrate the importance of classifications beyond abstinence and at-risk consumption, with implications for both the prevention and clinical management of unhealthy consumption patterns in older adults.
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| 3. |
- 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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| 4. |
- Fardell, Camilla, et al.
(författare)
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S100B polymorphisms are associated with age of onset of Parkinson's disease
- 2018
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Ingår i: Bmc Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 19:42
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Tidskriftsartikel (refereegranskat)abstract
- Background: In this study we investigated the association between SNPs in the S100B gene and Parkinson's disease (PD) in two independent Swedish cohorts. The SNP rs9722 has previously been shown to be associated with higher S100B concentrations in serum and frontal cortex in humans. S100B is widely expressed in the central nervous system and has many functions such as regulating calcium homeostasis, inflammatory processes, cytoskeleton assembly/disassembly, protein phosphorylation and degradation, and cell proliferation and differentiation. Several of these functions have been suggested to be of importance for the pathophysiology of PD. Methods: The SNPs rs9722, rs2239574, rs881827, rs9984765, and rs1051169 of the S100B gene were genotyped using the KASPar (R) PCR SNP genotyping system in a case-control study of two populations (431 PD patients and 465 controls, 195 PD patients and 378 controls, respectively). The association between the genotype and allelic distributions and PD risk was evaluated using Chi-Square and Cox proportional hazards test, as well as logistic regression. Linear regression and Cox proportional hazards tests were applied to assess the effect of the rs9722 genotypes on age of disease onset. Results: The S100B SNPs tested were not associated with the risk of PD. However, in both cohorts, the T allele of rs9722 was significantly more common in early onset PD patients compared to late onset PD patients. The SNP rs9722 was significantly related to age of onset, and each T allele lowered disease onset with 4.9 years. In addition, allelic variants of rs881827, rs9984765, and rs1051169, were significantly more common in early-onset PD compared to late-onset PD in the pooled population. Conclusions: rs9722, a functional SNP in the 3'-UTR of the S100B gene, was strongly associated with age of onset of PD.
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| 5. |
- Henningsson, Susanne, 1977, et al.
(författare)
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Association between polymorphisms in NOS3 and KCNH2 and social memory
- 2015
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Social memory, including the ability to recognize faces and voices, is essential for social relationships. It has a large heritable component, but the knowledge about the contributing genes is sparse. The genetic variation underlying inter-individual differences in social memory was investigated in an exploratory sample (n = 55), genotyped with a chip comprising approximately 200,000 single nucleotide polymorphisms (SNPs), and in a validation sample (n = 582), where 30 SNPs were targeted. In the exploratory study face identity recognition was measured. The validation study also measured vocal sound recognition, as well as recognition of faces and vocal sounds combined (multimodal condition). In the exploratory study, the 30 SNPs that were associated with face recognition at puncorrected < 0.001 and located in genes, were chosen for further study. In the validation study two of these SNPs showed significant associations with recognition of faces, vocal sounds, and multimodal stimuli: rs1800779 in the gene encoding nitric oxide synthase 3 (NOS3) and rs3807370 in the gene encoding the voltage-gated channel, subfamily H, member 2 (KCNH2), in strong linkage disequilibrium with each other. The uncommon alleles were associated with superior performance, and the effects were present for men only (p < 0.0002). The exploratory study also showed a weaker but significant association with (non-emotional) word recognition, an effect that was independent of the effect on face recognition. This study demonstrates evidence for an association between NOS3 and KCNH2SNPs and social memory.
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| 6. |
- Hovey, Daniel, et al.
(författare)
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Emotion recognition associated with polymorphism in oxytocinergic pathway gene ARNT2
- 2018
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Ingår i: Social Cognitive & Affective Neuroscience. - : Oxford University Press (OUP). - 1749-5024 .- 1749-5016. ; 13:2, s. 173-181
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Tidskriftsartikel (refereegranskat)abstract
- The ability to correctly understand the emotional expression of another person is essential for social relationships and appears to be a partly inherited trait. The neuropeptides oxytocin and vasopressin have been shown to influence this ability as well as face processing in humans. Here, recognition of the emotional content of faces and voices, separately and combined, was investigated in 492 subjects, genotyped for 25 single nucleotide polymorphisms (SNPs) in eight genes encoding proteins important for oxytocin and vasopressin neurotransmission. The SNP rs4778599 in the gene encoding aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), a transcription factor that participates in the development of hypothalamic oxytocin and vasopressin neurons, showed an association that survived correction for multiple testing with emotion recognition of audio-visual stimuli in women (). This study demonstrates evidence for an association that further expands previous findings of oxytocin and vasopressin involvement in emotion recognition.
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| 7. |
- Karlsson, Sara, 1980, et al.
(författare)
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Social memory associated with estrogen receptor polymorphisms in women
- 2016
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Ingår i: Social Cognitive & Affective Neuroscience. - : Oxford University Press (OUP). - 1749-5016 .- 1749-5024. ; 11:6, s. 877-883
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Tidskriftsartikel (refereegranskat)abstract
- The ability to recognize the identity of faces and voices is essential for social relationships. Although the heritability of social memory is high, knowledge about the contributing genes is sparse. Since sex differences and rodent studies support an influence of estrogens and androgens on social memory, polymorphisms in the estrogen and androgen receptor genes (ESR1, ESR2, AR) are candidates for this trait. Recognition of faces and vocal sounds, separately and combined, was investigated in 490 subjects, genotyped for 10 single nucleotide polymorphisms (SNPs) in ESR1, four in ESR2 and one in the AR. Four of the associations survived correction for multiple testing: women carrying rare alleles of the three ESR2 SNPs, rs928554, rs1271572 and rs1256030, in linkage disequilibrium with each other, displayed superior face recognition compared with non-carriers. Furthermore, the uncommon genotype of the ESR1 SNP rs2504063 was associated with better recognition of identity through vocal sounds, also specifically in women. This study demonstrates evidence for associations in women between face recognition and variation in ESR2, and recognition of identity through vocal sounds and variation in ESR1. These results suggest that estrogen receptors may regulate social memory function in humans, in line with what has previously been established in mice.
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| 8. |
- Le Guen, Yann, et al.
(författare)
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Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
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Tidskriftsartikel (refereegranskat)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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| 9. |
- Westberg, Lars, 1973, et al.
(författare)
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Variation in the Oxytocin Receptor Gene Is Associated with Face Recognition and its Neural Correlates
- 2016
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Ingår i: Frontiers in Behavioral Neuroscience. - : Frontiers Media SA. - 1662-5153. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The ability to recognize faces is crucial for daily social interactions. Recent studies suggest that intranasal oxytocin administration improves social recognition in humans. Oxytocin signaling in the amygdala plays an essential role for social recognition in mice, and oxytocin administration has been shown to influence amygdala activity in humans. It is therefore possible that the effects of oxytocin on human social recognition depend on mechanisms that take place in the amygdala a central region for memory processing also in humans. Variation in the gene encoding the oxytocin receptor (OXTR) has been associated with several aspects of social behavior. The present study examined the potential associations between nine OXTR polymorphisms, distributed across the gene, and the ability to recognize faces, as well as face-elicited amygdala activity measured by functional magnetic resonance imaging (fMRI) during incidental encoding of faces. The OXTR 3' polymorphism rs7632287, previously related to social bonding behavior and autism risk, was associated with participants ability to recognize faces. Carriers of the GA genotype, associated with enhanced memory, displayed higher amygdala activity during face encoding compared to carriers of the GG genotype. In line with work in rodents, these findings suggest that, in humans, naturally occurring endogenous modulation of OXTR function affects social recognition through an amygdala-dependent mechanism. These findings contribute to the understanding of how oxytocin regulates human social behaviors.
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| 10. |
- Wetterberg, Hanna, et al.
(författare)
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Decreasing Incidence and Prevalence of Dementia Among Octogenarians: A Population-Based Study on 3 Cohorts Born 30 Years Apart
- 2023
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Ingår i: Journals of Gerontology Series a-Biological Sciences and Medical Sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 78:6, s. 1069-1077
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Tidskriftsartikel (refereegranskat)abstract
- Background Recent studies suggest a decline in the age-specific incidence and prevalence of dementia. However, results are mixed regarding trends among octogenarians. We investigated time trends in the prevalence and incidence of dementia in 3 population-based cohorts of 85-90-year olds. We also examined if there were different time trends for men and women. Methods We examined population-based birth cohorts within the Gothenburg H70 Birth Cohort Studies born 1901-02, 1923-24, and 1930, at ages 85 (N = 1481) and 88 (N = 840) years. The first 2 cohorts were also examined at age 90 (N = 450). The incidence was examined in 1 109 individuals free from dementia at baseline using information from the examination at age 88 or register data. All 3 cohorts were examined with identical methods. Results The prevalence of dementia decreased from 29.8% in 1986-87 to 21.5% in 2008-10 and 24.5% in 2015-16 among 85-year olds, and from 41.9% in 1989-90 to 28.0% in 2011-12 to 21.7% in 2018-19 among 88-year olds, and from 41.5% in 1991-92 to 37.2% in 2013-14 among 90-year olds. The decline was most accentuated among women. The incidence of dementia per 1 000 risk-years from ages 85 to 89 declined from 48.8 among those born 1901-02 to 37.9 in those born 1923-24 to 22.5 among those born 1930. Conclusions The prevalence and incidence of dementia decreased substantially over 3 decades among octogenarians. This might slow down the projected increase in cases of dementia expected by the increasing number of octogenarians during the following decades.
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