Nutritional requirements in AlzHEimer’s disease

 

Specific nutritional needs

The link between nutrition and the risk of developing Alzheimer’s disease is supported by an increasing level of epidemiological evidence. This evidence highlights distinct nutritional requirements that originate from low levels of several key nutrients, metabolic alterations related to absorption of nutrients and endogenous production of various intermediates from nutrients, and increased nutrient requirements for synapse formation.

If the distinct nutritional requirements of people with Alzheimer’s disease are not addressed, this can aggravate known risk factors such as circulating homocysteine levels, oxidative stress, diminished blood flow to the brain and neuronal membrane health, all of which contribute to the pathophysiology of Alzheimer’s disease.

Low levels of several key nutrients

A systematic review and meta-analysis conducted by Lopes da Silva et al [1] demonstrated that people with Alzheimer’s disease have significantly lower plasma levels of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), vitamins A, C, E, folate and vitamin B12 compared with cognitively intact elderly controls. Furthermore, these nutritional deficiencies are observed in the absence of any signs of protein and energy malnutrition, which is known to be a common occurrence in Alzheimer’s disease, and therefore suggests that compromised nutritional status in Alzheimer’s disease patients may precede protein and energy malnutrition.

Altered nutrient absorption and metabolism

The compromised nutritional status observed in Alzheimer’s disease patients typically cannot be met by the diet alone, and occur because of physiological and metabolic disturbances.

Endogenous DHA synthesis in the liver is reduced in people with Alzheimer’s disease, which may be attributable to age related decline in liver function [2,3]. DHA and uridine monophosphate synthesis may be further impaired by accelerated age related liver dysfunction due to increased oxidative stress, which is often observed in people with Alzheimer’s disease [4].

Choline uptake from the circulation into the brain decreases with age [5], which may result in increased degradation of membrane phosphatidylcholine (main phospholipid present in neuronal cell membranes) in order to produce sufficient amounts of acetylcholine [6], an important neurotransmitter in learning and memory processes. It is suggested that this contributes to the increased degradation of neuronal cell membrane observed in Alzheimer’s disease patients [7].

A decrease in B vitamins is associated with increased plasma homocysteine levels [8], which is associated with decreased mobilisation of DHA from the liver into plasma [9,10], and increased metabolic use of choline [11]. Elevated homocysteine levels has been associated with increased brain atrophy in elderly subjects, but is even more prominent in people with mild cognitive impairment and Alzheimer’s disease [12-16].

 

References

  1. Lopes da Silva, S, Vellas, B, Elemans, S, Luchsinger, J, Kamphuis, P, Yaffe, K, & Stijnen, T. Plasma nutrient status of patients with Alzheimer’s disease: Systematic review and meta-analysis. Alzheimer’s & Dementia, 2014; 10(4): 485-502
  2. Astarita G, Jung KM, Berchtold NC, Nguyen VQ, Gillen DL, Head E, Cotman CW, Piomelli D (2010) Deficient liver biosynthesis of docosahexaenoic Acid correlates with cognitive impairment in Alzheimer’s disease. PLoS One 5, e12538
  3. Rapoport SI, Igarashi M, Gao F (2010) Quantitative contributions of diet and liver synthesis to docosahexaenoic acid homeostasis. Prostaglandins Leukot Essent Fatty Acids 82, 273-276
  4. Youssef J, Badr M (1999) Biology of senescent liver peroxisomes: role in hepatocellular aging and disease. Environ Health Perspect 107, 791-797
  5. Nitsch RM, Blusztajn JK, Pittas AG, Slack BE, Growdon JH, Wurtman RJ (1992) Evidence for a membrane defect in Alzheimer disease brain. Proc Natl Acad Sci U S A 89, 1671-1675
  6. Ulus IH, Watkins CJ, Cansev M, Wurtman RJ (2006) Cytidine and Uridine Increase Striatal CDP-Choline Levels Without Decreasing Acetylcholine Synthesis or Release. Cell Mol Neurobiol
  7. Blusztajn JK, Holbrook PG, Lakher M, Liscovitch M, Maire JC, Mauron C, Richardson UI, Tacconi M, Wurtman RJ (1986) “Autocannibalism” of membrane choline-phospholipids: physiology and pathology. Psychopharmacol Bull 22, 781-786
  8. Van Dam F, Van Gool WA (2009) Hyperhomocysteinemia and Alzheimer’s disease: A systematic review. Arch Gerontol Geriatr 48, 425-430
  9. Selley ML (2007) A metabolic link between S-adenosylhomocysteine and polyunsaturated fatty acid metabolism in Alzheimer’s disease. Neurobiol Aging 28, 1834-1839
  10. Li D, Mann NJ, Sinclair AJ (2006) A significant inverse relationship between concentrations of plasma homocysteine and phospholipid docosahexaenoic acid in healthy male subjects. Lipids 41, 85-89
  11. van Wijk N, Watkins CJ, Bohlke M, Maher TJ, Hageman RJ, Kamphuis PJ, Broersen LM, Wurtman RJ (2011) Plasma choline concentration varies with different dietary levels of vitamins B6, B12 and folic acid in rats maintained on choline-adequate diets. Br J Nutr, 1-5
  12. den Heijer T, Vermeer SE, Clarke R, Oudkerk M, Koudstaal PJ, Hofman A, Breteler MM (2003) Homocysteine and brain atrophy on MRI of non-demented elderly. Brain 126, 170-175
  13. Sachdev PS (2005) Homocysteine and brain atrophy. Prog Neuropsychopharmacol Biol Psychiatry 29, 1152-1161.
  14. Herrmann W, Obeid R (2011) Homocysteine: a biomarker in neurodegenerative diseases. CCLM / FESCC 49, 435-441.
  15. Rajagopalan P, Hua X, Toga AW, Jack, Weiner MW, Thompson PM (2011) Homocysteine effects on brain volumes mapped in 732 elderly individuals. Neuroreport 22, 391-395
  16. Tangney CC, Aggarwal NT, Li H, Wilson RS, Decarli C, Evans DA, Morris MC (2011) Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination. Neurology 77, 1276-1282