| 61. |
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| 62. |
- Landgren, Sara, 1980, et al.
(författare)
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A novel ARC gene polymorphism is associated with reduced risk of Alzheimer's disease
- 2012
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 119:7, s. 833-842
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is the most common neurodegenerative disease, and is clinically characterized by cognitive disturbances and the accumulation of the amyloid beta (A beta) peptides in plaques in the brain. Recent studies have shown the links between AD and the immediate-early gene Arc (activity-regulated cytoskeleton-associated protein), involved in synaptic plasticity and memory consolidation. For example, AD mouse models show a decreased expression of Arc mRNA in the brain. In additional, acute A beta application to brain slices leads to a widespread ARC protein diffusion, unlike the normal defined localization to synapses. In this study, we investigated genetic variation in human ARC and the risk of developing AD. To this end, we genotyped 713 subjects diagnosed with AD and 841 controls without dementia. ARC was sequenced in a group of healthy individuals, and seven previously known SNPs and three novel SNPs were identified. Two of the newly found SNPs were intronic and one, +2852(G/A), was located in the 3'UTR. Three tag SNPs were selected, including the novel SNP +2852(G/A), to relate to risk of AD, Mini Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau), hyperphosphorylated tau181 (P-tau(181)) and A beta(1-42). The AA genotype of the newly found 3'-UTR SNP +2852(A/G), was associated with a decreased risk of AD (p (c) = 0.005; OR = 0.74; 95 % CI: 0.61-0.89). No associations of single SNPs or haplotypes with MMSE score or CSF biomarkers were found. Here we report a novel ARC SNP associated with a reduced risk of developing AD. To our knowledge, this is the first study associating a gene variant of ARC with any disease. The location of the SNP within the 3'UTR indicates that dendritic targeting of ARC mRNA could be involved in the molecular mechanisms underlying this protective function. However, further investigation of the importance of this SNP for ARC function, ARC processing and the pathology of AD is needed.
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| 63. |
- Li, Xuantao, et al.
(författare)
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Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV
- 2023
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Ingår i: JAMA network open. - 2574-3805. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Blood-based biomarkers associated with increased risk of Alzheimer disease (AD) are understudied in people living with and without HIV, particularly women. Objective: To determine whether baseline or 1-year changes in plasma amyloid-β40 (Aβ40), Aβ42, ratio of Aβ42 to Aβ40, total tau (t-tau), phosphorylated tau 231 (p-tau231), glial fibrillary acidic protein (GFAP), and/or neurofilament light chain (NFL) are associated with neuropsychological performance (NP) among women living with HIV (WLWH) and women living without HIV (WLWOH). Design, Setting, and Participants: This longitudinal, prospective, cohort study with 1-year repeated clinical measures (NP only measured once) and biospecimen collection occurred between 2017 and 2019. Participants were women aged 40 years or older from 10 clinical research sites in cities across the US that were part of the Women's Interagency HIV Study. Data analysis was conducted from April to December 2022. Exposure: Laboratory-confirmed HIV status and AD biomarkers. Main Outcomes and Measures: Sociodemographically adjusted NP T-scores (attention and working memory, executive function, processing speed, memory, learning, verbal fluency, motor function, and global performance) were the primary outcomes. Baseline and 1-year fasting plasma Aβ40, Aβ42, t-tau, p-tau231, GFAP, and NFL levels were measured and analyzed using multivariable linear regression. Results: The study consisted of 307 participants (294 aged ≥50 years [96%]; 164 African American or Black women [53%]; 214 women with a high school education or higher [70%]; 238 women who were current or former smokers [78%]; and 236 women [77%] who were overweight or obese [body mass index >25]) including 209 WLWH and 98 WLWOH. Compared with WLWOH at baseline, WLWH performed worse on learning (mean [SD] T-score 47.8 [11.3] vs 51.4 [10.5]), memory (mean [SD] T-score 48.3 [11.6] vs 52.4 [10.2]), verbal fluency (mean [SD] T-score 48.3 [9.8] vs 50.7 [8.5]), and global (mean [SD] T-score 49.2 [6.8] vs 51.1 [5.9]) NP assessments. Baseline median Aβ40, GFAP, and NFL levels were higher among WLWH vs WLWOH. There were no differences in 1-year biomarker change by HIV serostatus. Lower learning, memory, and motor NP were associated with 1-year Aβ40 increase; lower learning and motor with Aβ42 increase; lower motor with p-tau231 increase; and lower processing speed, verbal fluency and motor with NFL increase in the entire sample. Among WLWH, a 1-year increase in Aβ40 from baseline to follow-up was associated with worse learning, memory, and global NP; a 1-year increase in t-tau with worse executive function; and a 1-year increase in NFL with worse processing speed. Among WLWOH, a 1-year increase in Aβ40 and Aβ42 were associated with poorer memory performance and NFL was associated with poorer motor performance. Conclusions and Relevance: These findings suggest that increases in certain plasma AD biomarkers are associated with NP in WLWH and WLWOH and may be associated with later onset of AD, and measuring these biomarkers could be a pivotal advancement in monitoring aging brain health and development of AD among women with and without HIV.
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| 64. |
- Luchsinger, José A, et al.
(författare)
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Adiposity and Alzheimer's disease.
- 2009
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Ingår i: Current opinion in clinical nutrition and metabolic care. - 1535-3885. ; 12:1, s. 15-21
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: Alzheimer's disease is the most common form of dementia. There are no known preventive or curative measures. There is increasing evidence for the role of total adiposity, usually measured clinically as BMI, and central adiposity, in Alzheimer's disease. This topic is of enormous public health importance given the global epidemic of high adiposity and its consequences. RECENT FINDINGS: Salient publications in 2007 and 2008 showed that (a) central adiposity in middle age predicts dementia in old age; (b) the relation between high adiposity and dementia is attenuated with older age; (c) waist circumference in old age, a measure of central adiposity, may be a better predictor of dementia than BMI; (d) lower BMI predicts dementia in elderly people; and (e) weight loss may precede dementia diagnosis by decades, which may explain seemingly paradoxical findings. SUMMARY: The possibility that high adiposity increases Alzheimer's disease risk is alarming given global trends of overweight and obesity in the general population. However, prevention and manipulation of adiposity may also provide a means to prevent Alzheimer's disease. Treatment of weight loss in Alzheimer's disease may also be important but is beyond the score of this review.
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| 65. |
- Luchsinger, José A, et al.
(författare)
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Adiposity, type 2 diabetes, and Alzheimer's disease.
- 2009
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Ingår i: Journal of Alzheimer's disease : JAD. - 1387-2877. ; 16:4, s. 693-704
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Tidskriftsartikel (refereegranskat)abstract
- This manuscript provides a comprehensive review of the epidemiologic evidence linking the continuum of adiposity and type 2 diabetes (T2D) with Alzheimer's disease (AD). The mechanisms relating adiposity and T2D to AD may include hyperinsulinemia, advanced products of glycosylation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of AD but the data on this association in old age is conflicting. Several studies have shown that hyperinsulinemia, a consequence of higher adiposity and insulin resistance, is also related to a higher risk of AD. Hyperinsulinemia is a risk factor for T2D, and numerous studies have shown a relation of T2D with higher AD risk. The implication of these associations is that a large proportion of the world population may be at increased risk of AD given the trends for increasing prevalence of overweight, obesity, hyperinsulinemia, and T2D. However these associations may present a unique opportunity for prevention and treatment of AD. Several studies in the prevention and treatment of T2D are currently conducting, or have planned, cognition ancillary studies. In addition, clinical trials using insulin sensitizers in the treatment or prevention of AD are under way.
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| 66. |
- Mehlig, Kirsten, 1964, et al.
(författare)
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Alcoholic beverages and incidence of dementia: 34-year follow-up of the prospective population study of women in Goteborg.
- 2008
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Ingår i: American journal of epidemiology. - : Oxford University Press (OUP). - 1476-6256 .- 0002-9262. ; 167:6, s. 684-91
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to assess the association between different types of alcoholic beverages and 34-year incidence of dementia. Among a random sample of 1,462 women aged 38-60 years and living in Göteborg, Sweden, in 1968-1969, 164 cases of dementia were diagnosed by 2002. At baseline as well as in 1974-1975, 1980-1981, and 1992-1993, the frequency of alcohol intake, as well as other lifestyle and health factors, was recorded and related to dementia with Cox proportional hazard regression, by use of both baseline and updated covariates. Wine was protective for dementia (hazard ratio (HR) = 0.6, 95% confidence interval (CI): 0.4, 0.8) in the updated model, and the association was strongest among women who consumed wine only (HR = 0.3, 95% CI: 0.1, 0.8). After stratification by smoking, the protective association of wine was stronger among smokers. In contrast, consumption of spirits at baseline was associated with slightly increased risk of dementia (HR = 1.5, 95% CI: 1.0, 2.2). Results show that wine and spirits displayed opposing associations with dementia. Because a protective effect was not seen for the other beverages, at least part of the association for wine may be explained by components other than ethanol.
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| 67. |
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| 68. |
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| 69. |
- Mielke, Michelle M., et al.
(författare)
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The 32-year relationship between cholesterol and dementia from midlife to late life.
- 2010
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Ingår i: Neurology. - 0028-3878. ; 75:21, s. 1888-95
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cellular and animal studies suggest that hypercholesterolemia contributes to Alzheimer disease (AD). However, the relationship between cholesterol and dementia at the population level is less clear and may vary over the lifespan. Methods: The Prospective Population Study of Women, consisting of 1,462 women without dementia aged 38–60 years, was initiated in 1968–1969 in Gothenburg, Sweden. Follow-ups were conducted in 1974–1975, 1980–1981, 1992–1993, and 2000–2001. All-cause dementia was diagnosed according to DSM-III-R criteria and AD according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria. Cox proportional hazards regression examined baseline, time-dependent, and change in cholesterol levels in relation to incident dementia and AD among all participants. Analyses were repeated among participants who survived to the age of 70 years or older and participated in the 2000–2001 examination. Results: Higher cholesterol level in 1968 was not associated with an increased risk of AD (highest vs lowest quartile: hazard ratio [HR] 2.82, 95% confidence interval [CI] 0.94–8.43) among those who survived to and participated in the 2000–2001 examination. While there was no association between cholesterol level and dementia when considering all participants over 32 years, a time-dependent decrease in cholesterol over the follow-up was associated with an increased risk of dementia (HR 2.35, 95% CI 1.22–4.58). Conclusion: These data suggest that midlife cholesterol level is not associated with an increased risk of AD. However, there may be a slight risk among those surviving to an age at risk for dementia. Declining cholesterol levels from midlife to late life may better predict AD risk than levels obtained at one timepoint prior to dementia onset. Analytic strategies examining this and other risk factors across the lifespan may affect interpretation of results.
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| 70. |
- Murphy, K., et al.
(författare)
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Association of self-reported race with AIDS death in continuous HAART users in a cohort of HIV-infected women in the United States
- 2013
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Ingår i: Aids. - : Ovid Technologies (Wolters Kluwer Health). - 0269-9370. ; 27:15, s. 2413-2423
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To assess the association of race with clinical outcomes in HIV-positive women on continuous HAART.Design:Prospective study that enrolled women from 1994 to 1995 and 2001 to 2002.Setting:Women's Interagency HIV Study, a community-based cohort in five US cities.Participants:One thousand, four hundred and seventy-one HIV-positive continuous HAART users.Main outcome measures:Times to AIDS and non-AIDS death and incident AIDS-defining illness (ADI) after HAART initiation.Results:In adjusted analyses, black vs. white women had higher rates of AIDS death [adjusted hazard ratio (aHR) 2.14, 95% confidence interval (CI) 1.30, 3.50; P=0.003] and incident ADI (aHR 1.58, 95% CI 1.08, 2.32; P=0.02), but not non-AIDS death (aHR 0.91, 95% CI 0.59, 1.39; P=0.65). Cumulative AIDS death incidence at 10 years was 17.3 and 8.3% for black and white women, respectively. Other significant independent pre-HAART predictors of AIDS death included peak viral load (aHR 1.70 per log(10), 95% CI 1.34, 2.16; P<0.001), nadir CD4(+) cell count (aHR 0.65 per 100cells/l, 95% CI 0.56, 0.76; P<0.001), depressive symptoms by Center for Epidemiology Studies Depression score at least 16 (aHR 2.10, 95% CI 1.51, 2.92; P<0.001), hepatitis C virus infection (aHR 1.57, 95% CI 1.02, 2.40; P=0.04), and HIV acquisition via transfusion (aHR 2.33, 95% CI 1.21, 4.49; P=0.01). In models with time-updated HAART adherence, association of race with AIDS death remained statistically significant (aHR 3.09, 95% CI 1.38, 6.93; P=0.006).Conclusion:In continuous HAART-using women, black women more rapidly died from AIDS or experienced incident ADI than their white counterparts after adjusting for confounders. Future studies examining behavioral and biologic factors in these women may further the understanding of HAART prognosis.
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