Alzheimer's Disease Biomarkers in Cerebrospinal Fluid in Insulin-resistant Men
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Study type: Observational [Patient Registry]

Summary: 
      Type 2 diabetes mellitus has been associated with an about 2-fold increase in risk of
      Alzheimer's disease (AD). Patients with AD have been reported to have reduced insulin
      sensitivity. It may be hypothesized that, compared to insulin sensitive subjects otherwise
      similar in general health and body habitus, insulin resistant subjects are more likely to
      have cerebrospinal fluid (CSF) indicators of incipient AD pathology, abnormalities in CSF
      peptides related to insulin signaling and glucose homeostasis, and possibly other metabolites
      that are associated with a risk of AD. The objective of this study is to examine the relation
      of insulin resistance and the concentrations of CSF biomarkers. The results of this study may
      be useful in the detection of the subjects who are at risk for cognitive decline and AD.
    

Detailed description: 
      Type 2 diabetes mellitus has been associated with an approximately 2-fold increase in risk of
      Alzheimer's disease (AD). Patients with AD have been reported to have reduced insulin
      sensitivity, and to have insulin concentrations that are elevated in plasma and decreased in
      cerebrospinal fluid (CSF). Cognitively normal individuals with insulin resistance are thus of
      interest in our effort to gain an understanding of the antecedents of this problem. It may be
      hypothesized that, compared to insulin sensitive subjects otherwise similar in general health
      and body habitus, insulin resistant subjects are more likely to have CSF indicators of
      incipient Alzheimer pathology, abnormalities in CSF peptides related to insulin signaling and
      glucose homeostasis, and possibly other metabolites that are associated with a risk of AD.

      The objectives are to 1) assess the concentrations of biomarkers of Alzheimer pathology in
      the CSF of cognitively normal men with and without insulin resistance, and 2) assess the
      concentrations of other CSF biomarkers of potential relevance to insulin resistance and AD in
      the CSF of cognitively normal men with and without insulin resistance.

      All subjects with eligibility will have had an oral glucose tolerance test performed within
      the past 3 months that revealed a normal fasting blood level and normal glucose tolerance. In
      addition, they will have had no history of significant cognitive disorders, no prior
      diagnosis of diabetes mellitus, and will not be receiving insulin or oral hypoglycemic.
      Eligibility for inclusion in the insulin-resistant group will be defined by scores on the
      Matsuda Index; non-insulin resistant controls will have normal values on the Matsuda Index.
      An effort will be made to ensure that both groups (i.e., those with insulin resistance and
      those without insulin resistance) will be similar in age, weight, BMI, and Apo E4 genotype
      (APOE).

      All procedures will be performed on a single visit. The subjects will undergo a Mini-Mental
      Status Examination (MMSE) performed by a qualified examiner. In addition, a blood sample will
      be obtained for measurements of basic blood chemistry (electrolytes, creatinine, glucose,
      total protein, and albumin), hematology, thyroid function, metabolic function (e.g. fasting
      plasma glucose and insulin levels) and for proteomic analysis. The APOE genotype will be
      determined from the blood samples, if it has not been assessed earlier. A lumbar puncture
      will be performed to obtain CSF samples that will be used to determine concentrations of
      biomarkers of AD pathology and to find out new biomarkers that may reflect AD pathology.

      All materials will be used according to national ethical guidelines for Good Clinical
      Practice. Analyses of the CSF for levels of beta-Amyloid biomarkers, total tau and
      phosphorylated tau will be done using a sandwich ELISA. Descriptive statistics will be
      provided for each analyte, comparing the 2 groups of subjects.

      All participants will provide written informed consent. Blood and CSF samples will be
      analysed also by collaborators in other European countries. Before analysis and sending data
      and blood/CSF samples to partners of the project, all clinical information and sample
      information will be made anonymous (coded data). Personal information, i.e., name and
      personal identity number, is removed from data/samples, and separate codes are given to them
      before delivering them to other partners for the purposes of the project. Methods for
      database maintenance and data delivery will be used that have proved to be functional in
      previous research projects. A formal description of the different data formats, access
      routines and tools for basic processing will be created at the start of the project.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        the research data sources of METSIM study (METabolic Syndrome In Men; professor Markku
        Laakso) performed in the Department of Internal Medicine, University of Eastern Finland
      
Biospecimen description: 
      whole blood, serum, plasma, white cells, urine, cerebrospinal fluid
    
Keywords: Alzheimer's disease, CSF biomarkers, Insulin resistance