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| 2. |
- Blom, Elin Susanne, et al.
(författare)
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Does APOE explain the linkage of Alzheimer’s disease to chromosome 19q13?
- 2008
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Ingår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-485X. ; 147B:6, s. 778-83
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the impact of the apolipoprotein E gene (APOE) on the chromosome 19 linkage peak from an analysis of sib-pairs affected by Alzheimer's disease. We genotyped 417 affected sib-pairs (ASPs) collected in Sweden and Norway (SWE), the UK and the USA for 10 microsatellite markers on chromosome 19. The highest Zlr (3.28, chromosome-wide P-value 0.036) from the multi-point linkage analysis was located approximately 1 Mb from APOE, at marker D19S178. The linkage to chromosome 19 was well explained by APOE in the whole sample as well as in the UK and USA subsamples, as identity by descent (IBD) increased with the number of epsilon 4 alleles in ASPs. There was a suggestion from the SWE subsample that linkage was higher than would be expected from APOE alone, although the test for this did not reach formal statistical significance. There was also a significant age at onset (aao) effect on linkage to chromosome 19q13 in the whole sample, which manifested itself as increased IBD sharing in relative pairs with lower mean aao. This effect was partially, although not completely, explained by APOE. The aao effect varied considerably between the different subsamples, with most of the effect coming from the UK sample. The other samples showed smaller effects in the same direction, but these were not significant.
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| 3. |
- Brommelhoff, Jessica A, et al.
(författare)
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Depression as a risk factor or prodromal feature for dementia? Findings in a population-based sample of Swedish twins.
- 2009
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Ingår i: Psychology and aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 24:2, s. 373-84
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Tidskriftsartikel (refereegranskat)abstract
- This study tested whether history of depression is associated with an increased likelihood of dementia, and whether a first depressive episode earlier in life is associated with increased dementia risk, or whether only depressive episodes close in time to dementia onset are related to dementia. Depression information came from national hospital discharge registries, medical history, and medical records. Dementia was diagnosed clinically. In case-control results, individuals with recent registry-identified depression were 3.9 times more likely than those with no registry-identified depression history to have dementia, whereas registry-identified depression earlier in life was not associated with dementia risk. Each 1-year increase in time between depression onset and dementia onset or equivalent age decreased the likelihood of dementia by 8.4%. In co-twin control analyses, twins with prior depression were 3.0 times more likely to have dementia than their nondepressed twin partners, with a similar age of depression gradient. These findings suggest that after partially controlling for genetic influences, late-life depression for many individuals may be a prodrome rather than a risk factor for dementia.
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| 8. |
- Hefling, L A, et al.
(författare)
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Cancer as a risk factor for long-term cognitive deficits and dementia.
- 2005
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 97:11, s. 854-856
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that cancer survivors frequently experience short-term cognitive deficits, but it is unknown how long these deficits last or whether they worsen over time. Using a co-twin control design, the cognitive function of 702 cancer survivors aged 65 years and older was compared with that of their cancer-free twins. Dementia rates were also compared in 486 of the twin pairs discordant for cancer. Cancer survivors overall, as well as individuals who had survived cancer for 5 or more years before cognitive testing, were more likely than their co-twins to have cognitive dysfunction (odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.36 to 3.24; P<.001; and OR = 2.71, 95% CI = 1.47 to 5.01; P<.001, respectively). Cancer survivors were also twice as likely to be diag-nosed with dementia as their co-twins, but this odds ratio did not reach statisti-cal significance (OR = 2.0, 95% CI = 0.86 to 4.67; P = .10). These results suggest that cancer patients are at increased risk for long-term cognitive dysfunction compared with individuals who have never had cancer, even after controlling for the influence of genetic factors and rearing environment.
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| 9. |
- Hong, Mun-Gwan, et al.
(författare)
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Evidence that the gene encoding insulin degrading enzyme influences human lifespan.
- 2008
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 17:15, s. 2370-8
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Tidskriftsartikel (refereegranskat)abstract
- Studies in model organisms have demonstrated that components of insulin and insulin-like signaling pathways are involved in the regulation of lifespan but the relevance of those findings to humans has remained obscure. Here we provide evidence suggesting that variants of the gene encoding insulin-degrading enzyme (IDE) may be influencing human lifespan. We have employed a variety of models and diverse samples that reproducibly indicate the relative change in IDE genotype frequency across the age spectrum as well as allow the detection of association with age-at-death. A tenable molecular basis of this is suggested by the observation of genetic association with both fasting plasma insulin levels and IDE mRNA expression. Across populations the emergent genetic model is indicative of over-dominance, where heterozygotes of critical markers have increased IDE mRNA expression and insulin levels, and this is reflected in diminished heterozygosity at advanced age. A critical and replicating feature of this study is that change in IDE genotype frequency with advancing age appears to be occurring only in men, and this is supported in that insulin levels are only associated with IDE in men. Results suggest a relationship between a gene that is intimately involved in insulin metabolism and the determination of lifespan in humans, but over-dominance and gender specificity will be important parameters to consider clarifying the biological importance of these findings.
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