| 1. |
- Andersson, Carl-Henrik, et al.
(författare)
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A Genetic Variant of the Sortilin 1 Gene isAssociated with Reduced Risk ofAlzheimer's Disease
- 2016
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 53:4, s. 1353-1363
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is a neurodegenerative disorder represented by the accumulation of intracellular tau protein and extracellular deposits of amyloid-β (Aβ) in the brain. The gene sortilin 1 (SORT1) has previously been associated with cardiovascular disease in gene association studies. It has also been proposed to be involved in AD pathogenesis through facilitating Aβ clearance by binding apoE/Aβ complexes prior to cellular uptake. However, the neuropathological role of SORT1 in AD is not fully understood. To evaluate the associations between gene variants of SORT1 and risk of AD, we performed genetic analyses in a Swedish case-control cohort. Ten single nucleotide polymorphisms (SNPs), covering the whole SORT1 gene, were selected and genotyped in 620 AD patients and 1107 controls. The SNP rs17646665, located in a non-coding region of the SORT1 gene, remained significantly associated with decreased risk of AD after multiple testing (pc=0.0061). In addition, other SNPs were found to be nominally associated with risk of AD, as well as altered cognitive function and the CSF biomarker Aβ42, but these associations did not survive correction for multiple testing. The fact that SORT1 has been strongly associated with risk of cardiovascular disease is intriguing as cardiovascular disease is also regarded as a risk factor for AD. Finally, increased knowledge about SORT1 function has a potential to increase our understanding of APOE, the strongest risk factor for AD.
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| 2. |
- Arnoldussen, I. A. C., et al.
(författare)
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A 10-Year Follow-Up of Adiposity and Dementia in Swedish Adults Aged 70 Years and Older
- 2018
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 63:4, s. 1325-1335
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adiposity measured in mid-or late-life and estimated using anthropometric measures such as body mass index (BMI) and waist-to-hip ratio (WHR), or metabolic markers such as blood leptin and adiponectin levels, is associated with late-onset dementia risk. However, during later life, this association may reverse and aging- and dementia-related processes may differentially affect adiposity measures. Objective: We explored associations of concurrent BMI, WHR, and blood leptin and high molecular weight adiponectin levels with dementia occurrence. Methods: 924 Swedish community-dwelling elderly without dementia, aged 70 years and older, systematically-sampled by birth day and birth year population-based in the Gothenburg city region of Sweden. The Gothenburg Birth Cohort Studies are designed for evaluating risk and protective factors for dementia. All dementias diagnosed after age 70 for 10 years were identified. Multivariable logistic regression models were used to predict dementia occurrence between 2000-2005, 2005-2010, and 2000-2010 after excluding prevalent baseline (year 2000) dementias. Baseline levels of BMI, WHR, leptin, and adiponectin were used. Results: Within 5 years of baseline, low BMI (<20 kg/m(2)) was associated with higher odds of dementia compared to those in the healthy BMI category (>= 20-24.9 kg/m(2)). Compared to the lowest quartile, leptin levels in the second quartile were associated with lower odds of dementia in women (p < 0.05). Conclusion: In late-life, anthropometric and metabolic adiposity measures appear to be differentially associated with dementia risk. While BMI and leptin levels are highly positively correlated, our results show that their association with dementia at age >= 70 years, is asynchronous. These data suggest that with aging, the complexity of the adiposity exposure may increase and suggests metabolic dysregulation. Additional studies are needed to better understand this complexity.
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| 3. |
- Arvidsson Rådestig, Maya, et al.
(författare)
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Subtle Differences in Cognition in 70-Year-Olds with Elevated Cerebrospinal Fluid Neurofilament Light and Neurogranin: A H70 Cross-Sectional Study
- 2023
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 91:1, s. 291-303
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most research on cerebrospinal fluid (CSF) neurofilament light protein (NfL) as a marker for neurodegeneration and neurogranin (Ng) for synaptic dysfunction has largely focused on clinical cohorts rather than population-based samples. Objective: We hypothesized that increased CSF levels of NfL and Ng are associated with subtle cognitive deficits in cognitively unimpaired (CU) older adults. Methods: The sample was derived from the Gothenburg H70 Birth Cohort Studies and comprised 258 CU 70-year-olds, with a Clinical Dementia Rating score of zero. All participants underwent extensive cognitive testing. CSF levels of NfL and Ng, as well as amyloid beta(1-42), total tau, and phosphorylated tau, were measured. Results: Participants with high CSF NfL performed worse in one memory-based test (Immediate recall, p = 0.013) and a language test (FAS, p = 0.016). Individuals with high CSF Ng performed worse on the memory-based test Supra Span (p = 0.035). When stratified according to CSF tau and A beta(42) concentrations, participants with high NfL and increased tau performed worse on a memory test than participants normal tau concentrations (Delayed recall, p = 0.003). In participants with high NfL, those with pathologic A beta(42) concentrations performed worse on the Delayed recall memory (p = 0.044). In the high Ng group, participants with pathological A beta(42) concentrations had lower MMSE scores (p = 0.027). However, in regression analysis we found no linear correlations between CSF NfL or CSF Ng in relation to cognitive tests when controlled for important co-variates. Conclusion: Markers of neurodegeneration and synaptic pathology might be associated with subtle signs of cognitive decline in a population-based sample of 70-year-olds.
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| 4. |
- Hansson, Oskar, et al.
(författare)
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Evaluation of Plasma A beta as Predictor of Alzheimer's Disease in Older Individuals Without Dementia: A Population-Based Study
- 2012
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 28:1, s. 231-238
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta (A beta) pathology is a major component in the mechanisms behind Alzheimer's disease (AD). Measurement of A beta(42) in cerebrospinal fluid predicts cognitive decline in patients with mild cognitive impairment and identifies AD in patients with dementia. However, studies on A beta in plasma are contradictory. In this prospective population-based study, plasma A beta(42) and A beta(40) were measured at baseline in 730 adults aged 70 years or older and without dementia. After five years, plasma levels were analyzed again and participants were assessed for development of dementia. During follow-up, 53 individuals (7%) developed dementia of which 37 (5%) were classified as AD. No difference in baseline plasma A beta(42), A beta(40), or A beta(42)/A beta(40) ratio levels were observed between converters to dementia or AD compared to the cognitively stable individuals. However, individuals with plasma A beta(40) levels above the median level for the group at baseline had an increased risk of developing dementia and AD during the follow-up, even after adjustment for age, gender, APOE genotype, and educational level (odds ratio = 2.2, 95% confidence interval = 1.0-4.7, p < 0.05). Neither plasma A beta(42) nor the A beta(42)/A beta(40) ratio influenced the risk of developing dementia or AD. Moreover, A beta(42) and A beta(40) levels increased over the 5 years, whereas the A beta(42)/A beta(40) ratio decreased (p < 0.001). In conclusion, this study suggests that measurement of plasma A beta should not be used clinically to predict dementia or AD. However, plasma A beta(40) may possibly be regarded as a moderate risk marker comparable to other risk markers for AD such as first-degree family history of dementia.
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| 5. |
- Najar, Jenna, et al.
(författare)
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Sex Difference in the Relation Between Marital Status and Dementia Risk in Two Population-Based Cohorts
- 2021
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 83:3, s. 1269-1279
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Tidskriftsartikel (refereegranskat)abstract
- Background: The modifying effect of sex on the relation between marital status and dementia has yet to be determined. Objective: To examine if sex modifies the association between marital status and incident dementia. Methods: Population-based samples from the Mayo Clinic Study of Aging (MCSA, N = 3,471) and the Gothenburg H70 Birth Cohort Study (H70-study, N = 913) were used. A multiplicative interaction term was used to analyze the modifying effect of sex on the relation between marital status (married versus not married) and incident dementia using Cox regression models. Further, risk of dementia by marital status was also evaluated in models separated by sex. Results: In the MCSA, there was an interaction between marital status and sex in relation to dementia (p = 0.015). In contrast, in the H70-study, no significant interaction was observed (p = 0.28). Nevertheless, in both studies, not married men had increased risk of dementia compared to married men in models adjusted for age, education, and number of children (H70-study: 1.99; 1.06-3.76, MCSA: 1.43; 1.08-1.89). Associations remained similar after additional adjustment for depression, BMI, hypertension, dyslipidemia, and diabetes mellitus (H70-study: 2.00; 1.05-3.82, MCSA: 1.32; 0.99-1.76). Further, no significant association was observed between marital status and dementia in women (H70-study: 1.24; 0.82-1.89, MCSA: 0.82; 0.64-1.04). Conclusion: Sex had a modifying effect on the association between marital status and incident dementia. In analyses separated by sex, not married men had an increased risk of dementia compared to married men, while no significant association was observed between marital status and risk of dementia in women.
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| 6. |
- Schaefer, Simona, et al.
(författare)
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Screening for Mild Cognitive Impairment Using a Machine Learning Classifier and the Remote Speech Biomarker for Cognition: Evidence from Two Clinically Relevant Cohorts
- 2023
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Ingår i: JOURNAL OF ALZHEIMERS DISEASE. - 1387-2877 .- 1875-8908. ; 91:3, s. 1165-1171
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Tidskriftsartikel (refereegranskat)abstract
- Background: Modern prodromal Alzheimer's disease (AD) clinical trials might extend outreach to a general population, causing high screen-out rates and thereby increasing study time and costs. Thus, screening tools that cost-effectively detect mild cognitive impairment (MCI) at scale are needed. Objective: Develop a screening algorithm that can differentiate between healthy and MCI participants in different clinically relevant populations. Methods: Two screening algorithms based on the remote ki:e speech biomarker for cognition (ki:e SB-C) were designed on a Dutch memory clinic cohort (N= 121) and a Swedish birth cohort (N= 404). MCI classification was each evaluated on the training cohort as well as on the unrelated validation cohort. Results: The algorithms achieved a performance of AUC similar to 0.73 and AUC similar to 0.77 in the respective training cohorts and AUC similar to 0.81 in the unseen validation cohorts. Conclusion: The results indicate that a ki:e SB-C based algorithm robustly detectsMCIacross different cohorts and languages, which has the potential to make current trials more efficient and improve future primary health care.
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| 7. |
- Arvidsson Rådestig, Maya, et al.
(författare)
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Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer's Disease: Results from the Gothenburg H70 Birth Cohort Studies.
- 2021
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 79:1, s. 225-235
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that older adults with preclinical Alzheimer's disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology.We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology.The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n=316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories.Among participants with CDR 0 (n=259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p=0.003), object Delayed (p=0.042) and Immediate recall (p=0.033)). Among participants with CDR 0.5 (n=57), those with amyloid pathology (A+) scored worse in category fluency (p=0.003).Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.
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| 8. |
- Bjerke, Maria, 1977, et al.
(författare)
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Cerebrospinal Fluid Fatty Acid-Binding Protein 3 is Related to Dementia Development in a Population-Based Sample of Older Adult Women Followed for 8 Years.
- 2016
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 49:3, s. 733-741
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased fatty acid-binding protein 3 (FABP-3) levels have been reported in neurodegenerative diseases, including Alzheimer's disease (AD). Cerebrospinal fluid (CSF) FABP-3 has therefore been proposed as a putative marker for dementia. Population-based studies examining whether CSF FABP-3 predicts later development of dementia are lacking. OBJECTIVE: The aim of this study was to examine CSF levels of FABP-3 in relation to later development of dementia in elderly women and in relation to Aβ42, T-tau, P-tau181, and CSF: serum albumin ratio. METHODS: 86 non-demented women aged 70-84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992-93. CSF-FABP-3, Aβ42, T-tau, P-tau181, and the CSF: serum albumin ratio were measured at baseline. Participants were examined with a neuropsychiatric exam at baseline and at follow-up in 2000. Dementia was diagnosed in accordance with DSM-III-R criteria. RESULTS: Between 1992 and 2000, 8 women developed dementia (4 AD, 3 vascular dementia, 1 mixed vascular dementia and AD). Higher levels of CSF-FABP-3 at baseline were related to development of dementia (OR 1.36 CI [1.05-1.76] p=0.022) and the subtype AD (OR 1.38 CI [1.06-1.82), p=0.019) during follow-up. FABP-3 correlated with CSF T-tau (r=0.88, p< 0.001), P-tau181 (r=0.619, p< 0.001), and CSF:serum albumin ratio (r=0.233, p=0.031), but not with Aβ42 (r=-0.08, p=0.444)Conclusion: CSF FABP-3 may be an early marker for later development of dementia, probably related to neuronal degeneration, but independent of Aβ metabolism.
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| 9. |
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| 10. |
- Bäckman, Kristoffer, 1979, et al.
(författare)
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37 years of body mass index and dementia: observations from the prospective population study of women in Gothenburg, Sweden.
- 2012
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 28:1, s. 163-71
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Tidskriftsartikel (refereegranskat)abstract
- Level of adiposity is linked to dementia in epidemiological studies. Overweight and obesity in mid- and late-life may increase risk for dementia, whereas decline in body weight or body mass index (BMI) and underweight in years preceding and at the time of a dementia diagnosis may also relate to dementia. Longitudinal studies with sufficient follow-up are necessary to estimate trajectories that allow better understanding of the relationship between adiposity indices and dementia over the life course. We evaluated the natural history of BMI in relationship to clinical dementia over 37 years in the Prospective Population Study of Women (PPSW) in Sweden. PPSW is a systematic sample of 1462 women born 1908, 1914, 1918, 1922, and 1930 and aged 38-60 years at baseline. Examinations occurred in 1968, 1974, 1980, 1992, 2000, and 2005. Statistical analyses were conducted using mixed effects regression models. Trajectories of BMI over 37 years as a function of age differed between women who did versus did not develop dementia. Women developing dementia evidenced a lesser increase in BMI from age 38 to 70 years. After age 70, the BMI slope decreased similarly (no "accelerated decline") irrespective of dementia status. A lower BMI before and during dementia onset was observed. Women with similar BMI at mid-life exhibited a different pattern of BMI change as they approached late-life that was related to dementia onset. BMI may be a potential marker of dementia-related neuropathologies in the brain. Dementia is related to a common risk factor, BMI, from mid-to late-life.
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