Multiple Nutritional Deficiencies Causing Dementia of the Alzheimer Type
Multiple Nutritional Deficiencies Causing Dementia of the Alzheimer Type
The purpose of the study is to compare the concentrations of Vitamin B1 (thiamine), Vitamin
 B6 (pyridoxal-5-phosphate), folate, Vitamin B12 (cobalamin), Vitamin C (ascorbic acid),
 Vitamin A (retinol), Vitamin E (alfa-tocopherol), homocystein, uric acid, F2 8-α-isoprostane,
 8-deoxyguanosine, retinoids, tau-protein and β-amyloid in spinal fluid, metabolomics,
 proteomics, m-RNA for DNA repair enzymes and DNA in patients who suffer from mild cognitive
 impairment (MCI) or mild dementia of Alzheimers type, with healthy controls.

 A second aim is to explore the association between vitamin and nutrient reductions, if any,
 and cognitive function as well as vascular score and possible changes in the MRI.
Dementia of the Alzheimer type (AD) is a serious illness affecting 60-70 000 people in Norway
 with an estimated cost of 12 Billion NOK (Norwegian kroner) per year. The Department of
 Social Affairs and Health has initiated psycho-social intervention programs for patients as
 well as caregivers, however, no research regarding etiology, pathology or prevention of the
 disease.

 In an earlier pilot study conducted on AD patients in a moderate stage, there were
 significant decrease in the concentrations of the vitamins thiamine, pyridoxal-5 phosphate,
 ascorbic acid retinol, cobalamin, and increased homocystein, compared with the control group
 of healthy elderly people. Logistic regression analysis showed that 5 models using different
 combinations of vitamins and spinal protein, all completely separating patients with dementia
 from healthy controls.

 The current study is a replication of the above mentioned study, and will include up to 120
 AD patients with mild cognitive impairment (MCI) or mild dementia (MMSE above 24/30) and up
 to 60 healthy elderly controls. Measurement of vitamines and nutrients in blood and spinal
 fluid is the central element of the study. The specimens will therefore be obtained from
 patients and controls who have abstained from supplements the last four weeks.

 Outcome measures will include biochemical analysis of nutrients, expressions of peroxidation,
 expressions of DNA damage, proteomics and metabolomics of spinal fluid, blood and urine,
 microarray analysis of different nutritional deficiency subgroups, together with the routine
 diagnostics investigations undertaken at the memory clinic, and a nutritional assessment.

 The patients and the healthy controls will only receive information about results of
 examinations that are part of the routine investigation at the memory clinic, this according
 to the Norwegian Biotechnology Law and the permission from the National Committees for
 Research Ethics in Norway.

 In addition to the vitamins listed as primary outcomes, the following measurements will be
 carried through:

 1. Isoprostane measurements: The findings of F2-α-isoprostane-increase in cerebrospinal
 fluid close to the diseased organ, and not in the plasma, makes it important to confirm
 these findings. Isoprostane measurement in CNS might become an important parameter in
 prospective treatment studies where the actual treatment at least should normalize the
 pathological finding.

 2. 8 hydroxy-2-deoxy guanosine increase in cerebrospinal fluid or urine, reveals DNA-damage
 suggesting further mechanisms for the AD development.

 3. Spinal fluid: Nutrients in spinal fluid, expressions of increased peroxidation like
 F2-α-isoprostane, tau proteins and possibly with LC/MS methodology metabolic pattern
 (metabolomics) and different proteins (proteomics).

 -  Proteomics; determination of protein profiles. The emerging technology of mass
 spectrometry (MS)-based quantitative proteomics provides a powerful tool to
 systematically and quantitatively assess quantitative differences in protein
 profiles. Discovery based proteomics compares the proteome of a diseased sample
 versus normal at a global scale, and has been widely applied to study various human
 diseases with the goal of identifying biomarkers and/or reveal the pathogenesis of
 diseases. In this study, protein samples from control and diseased will be labeled
 with different stable isotopes, digested to peptides and analyzed by LCMS.
 Quantitative differences of the proteins from these groups will be performed by
 state-of-the-art hybrid mass spectrometer, LTQ XL-Orbitrap. The Orbitrap instrument
 has extremely high resolving power, mass accuracy and sensitivity.

 -  Metabonomics: Metabonomics aims at measuring and mathematically modeling changes in
 the metabolite concentrations found in biological fluids and tissues. Nuclear
 magnetic resonance (NMR) spectroscopy allows the detection and quantification of
 compounds in large mixtures, such as the products of metabolism in biological
 fluids and tissues. There are hundreds of such metabolites to be found in
 cerebrospinal fluid, plasma, serum and urine. NMR spectroscopy offers the advantage
 of measuring their concentrations with micromolar sensitivity while conveniently
 requiring only little sample preparation. In recent studies involving large sets of
 spectra, the variation of results was shown to be as small as 2 % reflecting a high
 degree of reproducibility. By identifying patterns in the metabolic fingerprint of
 the organism, one can study the effects of diet, drugs and disease using
 multivariate statistics such as principal component analysis and partial least
 squares attempts to interpret NMR spectra.

 4. Genetic analyses: m-RNA measurement with SNP-profiles for

 -  DNA repair.

 -  Active components in processing av APP and Abeta.

 -  Will include if possible, sequencing of genome and/or GWAS.
Inclusion Criteria:

 -  Cognitive impairment with a MMSE score of 24 or better.

 -  Depression score below 9 both on MADRS and Cornell.

 Exclusion Criteria:

 -  Acute or chronic disease with CRP above 10.

 -  Lewy Body Dementia or Frontal Lobe Dementia.

 -  Dementia due to a known brain vascular disturbance, hemorrhage or thrombosis.

 -  Patients who had not stopped their intake of vitamins and food additives the last four
 weeks.