TY  - JOUR
AB  - BACKGROUND: Chronic inflammation is a central feature of several forms of dementia. However, few details on the associations of blood-based inflammation-related proteins with dementia incidence have been explored yet. METHODS: The Olink Target 96 Inflammation panel was measured in baseline serum samples (collected 07/2000-06/2002) of 1782 older adults from a German, population-based cohort study in a case-cohort design. Logistic regression models were used to assess the associations of biomarkers with all-cause dementia, Alzheimer's disease, and vascular dementia incidence. RESULTS: During 17 years of follow-up, 504 participants were diagnosed with dementia, including 163 Alzheimer's disease and 195 vascular dementia cases. After correction for multiple testing, 58 out of 72 tested (80.6%) biomarkers were statistically significantly associated with all-cause dementia, 22 with Alzheimer's disease, and 33 with vascular dementia incidence. We identified four biomarker clusters, among which the strongest representatives, CX3CL1, EN-RAGE, LAP TGF-beta-1, and VEGF-A, were significantly associated with dementia endpoints independently from other inflammation-related proteins. CX3CL1 (odds ratio [95% confidence interval] per 1 standard deviation increase: 1.41 [1.24-1.60]) and EN-RAGE (1.41 [1.25-1.60]) were associated with all-cause dementia incidence, EN-RAGE (1.51 [1.25-1.83]) and LAP TGF-beta-1 (1.46 [1.21-1.76]) with Alzheimer's disease incidence, and VEGF-A (1.43 [1.20-1.70]) with vascular dementia incidence. All named associations were stronger among APOE ε4-negative subjects. CONCLUSION: With this large, population-based cohort study, we show for the first time that the majority of inflammation-related proteins measured in blood samples are associated with total dementia incidence. Future studies should concentrate not only on single biomarkers but also on the complex relationships in biomarker clusters.
AU  - Trares, K.*
AU  - Bhardwaj, M.*
AU  - Perna, L.*
AU  - Stocker, H.R.*
AU  - Petrera, A.
AU  - Hauck, S.M.
AU  - Beyreuther, K.*
AU  - Brenner, H.*
AU  - Schöttker, B.*
C1  - 66151
C2  - 53092
TI  - Association of the inflammation-related proteome with dementia development at older age: Results from a large, prospective, population-based cohort study.
JO  - Alzheimers Res. Ther.
VL  - 14
IS  - 1
PY  - 2022
SN  - 1758-9193
ER  - 

TY  - JOUR
AB  - BACKGROUND: Little is known about factors influencing progression from mild cognitive impairment to Alzheimer's dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form. METHODS: We determined concentrations of selenium species in cerebrospinal fluid sampled at diagnosis in 56 participants with mild cognitive impairment of nonvascular origin. We then investigated the relation of these concentrations to subsequent conversion from mild cognitive impairment to Alzheimer's dementia. RESULTS: Twenty-one out of the 56 subjects developed Alzheimer's dementia during a median follow-up of 42 months; four subjects developed frontotemporal dementia and two patients Lewy body dementia. In a Cox proportional hazards model adjusting for age, sex, duration of sample storage, and education, an inorganic selenium form, selenate, showed a strong association with Alzheimer's dementia risk, with an adjusted hazard ratio of 3.1 (95% confidence interval 1.0-9.5) in subjects having a cerebrospinal fluid content above the median level, compared with those with lower concentration. The hazard ratio of Alzheimer's dementia showed little departure from unity for all other inorganic and organic selenium species. These associations were similar in analyses that measured exposure on a continuous scale, and also after excluding individuals who converted to Alzheimer's dementia at the beginning of the follow-up. CONCLUSIONS: These results indicate that higher amounts of a potentially toxic inorganic selenium form in cerebrospinal fluid may predict conversion from mild cognitive impairment to Alzheimer's dementia.
AU  - Vinceti, M.*
AU  - Chiari, A.*
AU  - Eichmüller, M.
AU  - Rothman, K.J.*
AU  - Filippini, T.*
AU  - Malagoli, C.*
AU  - Weuve, J.*
AU  - Tondelli, M.*
AU  - Zamboni, G.*
AU  - Nichelli, P.F.*
AU  - Michalke, B.
C1  - 52582
C2  - 44110
CY  - London
TI  - A selenium species in cerebrospinal fluid predicts conversion to Alzheimer's dementia in persons with mild cognitive impairment.
JO  - Alzheimers Res. Ther.
VL  - 9
IS  - 1
PB  - Biomed Central Ltd
PY  - 2017
SN  - 1758-9193
ER  -