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Association of Cerebrospinal Fluid (CSF) Insulin with Cognitive Performance and CSF Biomarkers of Alzheimer's Disease.
J Alzheimers Dis 2018; 61(1):309-320JA

Abstract

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.

Authors+Show Affiliations

Departments of Neurology and Geriatrics Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, the Netherlands. Department of Internal Medicine and Cardiovascular Research Institute, Maastricht University Medical Centre +, Maastricht, the Netherlands.Alzheimer Centre Limburg, School for Mental Health and Neuroscience (MHeNS), Maastricht University Medical Centre +, Maastricht, the Netherlands.Alzheimer Centre Limburg, School for Mental Health and Neuroscience (MHeNS), Maastricht University Medical Centre +, Maastricht, the Netherlands.Department of Neurology and Alzheimer Research Centre, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Centre, Amsterdam, the Netherlands.Departments of Neurology and Geriatrics Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, the Netherlands.Radboudumc Alzheimer Centre, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands.Departments of Neurology and Radiology, Erasmus University Medical Centre, Rotterdam, the Netherlands.Department of Neurology and Alzheimer Research Centre, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.Alzheimer Centre Amsterdam, VU University Medical Centre, Amsterdam, the Netherlands.Department of Internal Medicine and Cardiovascular Research Institute, Maastricht University Medical Centre +, Maastricht, the Netherlands.Department of Clinical Chemistry, Neurochemistry Laboratory and Biobank, VU University Medical Centre, Amsterdam, the Netherlands.Alzheimer Centre Limburg, School for Mental Health and Neuroscience (MHeNS), Maastricht University Medical Centre +, Maastricht, the Netherlands.Alzheimer Centre Amsterdam, VU University Medical Centre, Amsterdam, the Netherlands.Department of Internal Medicine and Cardiovascular Research Institute, Maastricht University Medical Centre +, Maastricht, the Netherlands.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29154275

Citation

Geijselaers, Stefan L C., et al. "Association of Cerebrospinal Fluid (CSF) Insulin With Cognitive Performance and CSF Biomarkers of Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 61, no. 1, 2018, pp. 309-320.
Geijselaers SLC, Aalten P, Ramakers IHGB, et al. Association of Cerebrospinal Fluid (CSF) Insulin with Cognitive Performance and CSF Biomarkers of Alzheimer's Disease. J Alzheimers Dis. 2018;61(1):309-320.
Geijselaers, S. L. C., Aalten, P., Ramakers, I. H. G. B., De Deyn, P. P., Heijboer, A. C., Koek, H. L., ... Biessels, G. J. (2018). Association of Cerebrospinal Fluid (CSF) Insulin with Cognitive Performance and CSF Biomarkers of Alzheimer's Disease. Journal of Alzheimer's Disease : JAD, 61(1), pp. 309-320. doi:10.3233/JAD-170522.
Geijselaers SLC, et al. Association of Cerebrospinal Fluid (CSF) Insulin With Cognitive Performance and CSF Biomarkers of Alzheimer's Disease. J Alzheimers Dis. 2018;61(1):309-320. PubMed PMID: 29154275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Cerebrospinal Fluid (CSF) Insulin with Cognitive Performance and CSF Biomarkers of Alzheimer's Disease. AU - Geijselaers,Stefan L C, AU - Aalten,Pauline, AU - Ramakers,Inez H G B, AU - De Deyn,Peter Paul, AU - Heijboer,Annemieke C, AU - Koek,Huiberdina L, AU - OldeRikkert,Marcel G M, AU - Papma,Janne M, AU - Reesink,Fransje E, AU - Smits,Lieke L, AU - Stehouwer,Coen D A, AU - Teunissen,Charlotte E, AU - Verhey,Frans R J, AU - van der Flier,Wiesje M, AU - Biessels,Geert Jan, AU - ,, PY - 2017/11/21/pubmed PY - 2018/7/14/medline PY - 2017/11/21/entrez KW - Alzheimer’s disease KW - cerebrospinal fluid KW - cognition KW - epidemiology KW - insulin SP - 309 EP - 320 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 61 IS - 1 N2 - 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/29154275/Association_of_Cerebrospinal_Fluid__CSF__Insulin_with_Cognitive_Performance_and_CSF_Biomarkers_of_Alzheimer's_Disease_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-170522 DB - PRIME DP - Unbound Medicine ER -