Association of Cerebrospinal Fluid (CSF) Insulin with Cognitive Performance and CSF Biomarkers of Alzheimer's Disease
| Autor: | Frans R.J. Verhey, Lieke L. Smits, Huiberdina L. Koek, Wiesje M. van der Flier, Peter Paul De Deyn, Geert Jan Biessels, Pauline Aalten, Janne M. Papma, Inez H.G.B. Ramakers, Coen D.A. Stehouwer, Marcel Olde-Rikkert, Stefan L.C. Geijselaers, Annemieke C. Heijboer, Charlotte E. Teunissen, Fransje E. Reesink |
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| Přispěvatelé: | Neurology, Radiology & Nuclear Medicine, Molecular Neuroscience and Ageing Research (MOLAR), RS: CARIM - R3 - Vascular biology, Promovendi CD, Interne Geneeskunde, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, MUMC+: HVC Pieken Maastricht Studie (9), MUMC+: MA Interne Geneeskunde (3), MUMC+: MA Med Staf Spec Psychiatrie (9), Laboratory Medicine, AGEM - Endocrinology, metabolism and nutrition, AMS - Musculoskeletal Health, Amsterdam Movement Sciences - Rehabilitation & Development, Amsterdam Neuroscience - Neurodegeneration, APH - Personalized Medicine, APH - Methodology, Epidemiology and Data Science |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male cognition Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] medicine.medical_treatment Apolipoprotein E4 IMPAIRED OLDER-ADULTS Neuropsychological Tests Alzheimer Disease/cerebrospinal fluid 0302 clinical medicine Cerebrospinal fluid APOE*4 Allele BRAIN Apolipoprotein E4/genetics GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) RISK education.field_of_study TAU-PROTEIN biology APOE GENOTYPE General Neuroscience GLUCOSE-METABOLISM General Medicine Middle Aged Alzheimer's disease RESISTANCE SYNDROME Clinical Psychology Psychiatry and Mental health IMPROVES COGNITION Population study Female epidemiology Peptide Fragments/cerebrospinal fluid Alzheimer’s disease Signal Transduction Research Article Cognition Disorders/diagnosis medicine.medical_specialty insulin Population tau Proteins cerebrospinal fluid 03 medical and health sciences All institutes and research themes of the Radboud University Medical Center IMPAIRED INSULIN Alzheimer Disease Internal medicine medicine Humans Brain/metabolism education Aged Amyloid beta-Peptides business.industry Insulin MEMORY Insulin/cerebrospinal fluid tau Proteins/cerebrospinal fluid medicine.disease Peptide Fragments INTRANASAL INSULIN DIFFERENTIAL SENSITIVITY Amyloid beta-Peptides/cerebrospinal fluid Insulin receptor 030104 developmental biology Endocrinology biology.protein Signal Transduction/genetics Geriatrics and Gerontology Cognition Disorders business Mental Status Schedule 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease, 61, 1, pp. 309-320 Journal of Alzheimers Disease, 61(1), 309-320. IOS Press BV Journal of Alzheimer’s Disease, 61(1), 309-320. IOS Press Journal of Alzheimer's Disease, 61(1), 309-320. IOS Press Journal of Alzheimer's Disease Geijselaers, S L C, Aalten, P, Ramakers, I H G B, De Deyn, P P, Heijboer, A C, Koek, H L, Olderikkert, M G M, Papma, J M, Reesink, F E, Smits, L L, Stehouwer, C D A, Teunissen, C E, Verhey, F R J, Van Der Flier, W M & Biessels, G J 2017, ' Association of Cerebrospinal Fluid (CSF) Insulin with Cognitive Performance and CSF Biomarkers of Alzheimer's Disease ', Journal of Alzheimer's Disease, vol. 61, no. 1, pp. 309-320 . https://doi.org/10.3233/JAD-170522 Journal of Alzheimer's Disease, 61(1), 309. IOS Press Journal of Alzheimer's Disease, 61, 309-320 |
| ISSN: | 1387-2877 1875-8908 |
| DOI: | 10.3233/jad-170522 |
| Popis: | BACKGROUND: Abnormal insulin signaling in the brain has been linked to Alzheimer's disease (AD).OBJECTIVE: To evaluate whether cerebrospinal fluid (CSF) insulin levels are associated with cognitive performance and CSF amyloid-β and Tau. Additionally, we explore whether any such association differs by sex or APOE ɛ4 genotype.METHODS: From 258 individuals participating in the Parelsnoer Institute Neurodegenerative Diseases, a nationwide multicenter memory clinic population, we selected 138 individuals (mean age 66±9 years, 65.2% male) diagnosed with subjective cognitive impairment (n = 45), amnestic mild cognitive impairment (n = 44), or AD (n = 49), who completed a neuropsychological assessment, including tests of global cognition and memory performance, and who underwent lumbar puncture. We measured CSF levels of insulin, amyloid-β1-42, total (t-)Tau, and phosphorylated (p-)Tau.RESULTS: CSF insulin levels did not differ between the diagnostic groups (p = 0.136). Across the whole study population, CSF insulin was unrelated to cognitive performance and CSF biomarkers of AD, after adjustment for age, sex, body mass index, diabetes status, and clinic site (all p≥0.131). Importantly, however, we observed effect modification by sex and APOE ɛ4 genotype. Specifically, among women, higher insulin levels in the CSF were associated with worse global cognition (standardized regression coefficient -0.483; p = 0.008) and higher p-Tau levels (0.353; p = 0.040). Among non-carriers of the APOE ɛ4 allele, higher CSF insulin was associated with higher t-Tau (0.287; p = 0.008) and p-Tau (0.246; p = 0.029).CONCLUSION: Our findings provide further evidence for a relationship between brain insulin signaling and AD pathology. It also highlights the need to consider sex and APOE ɛ4 genotype when assessing the role of insulin. |
| Databáze: | OpenAIRE |
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