Acetylcholinesterase inhibitors normalise circulating vitamin D2 levels in Alzheimer's disease: an observational study

Shah, Iltaf, Petroczi, Andrea, Tabet, Naji, Klugman, Anthony, Mokhtar, Isaac and Naughton, Declan (2011) Acetylcholinesterase inhibitors normalise circulating vitamin D2 levels in Alzheimer's disease: an observational study. In: St. George’s Research Day, School of Life Sciences, Kingston University London,; 30 Nov 2011, London, UK. (Unpublished)


Background: Insufficient vitamin D levels have been linked to a wide range of diseases including several major neurological conditions, including the putative roles and levels of vitamin D in dementia. Owing to inter laboratory, inter method variations, overlapping peaks and identical masses of epimers and isobars, considerable discrepancies in results are frequent. The primary aim of this study was to accurately identify and quantitate vitamin D metabolites through chromatographic separation from its epimers and isobars and to investigate the relationships or differences between vitamin D forms and cognitive state (MMSE scores), along with calcium levels. Methods: Blood samples were collected from 5 healthy male Caucasian volunteers and vitamin D metabolites along with co-eluting epimers and analogues were quantified. AD subjects were grouped as A: untreated (n= 26) and B: treated with acetylcholinesterase inhibitors (AChEI) (n= 44) and C: control (n= 35), based on the cognitive function and treatment. Levels of vitamin D metabolites along with epimers and isobars were measured using liquid chromatography-mass spectrometry (LC-MS) and calcium measurements were conducted using inductively coupled plasma-mass spectrometry (ICP-MS). Results: The new method allowed chromatographic separation and quantification of vitamin D metabolites, along with their epimer 3-epi-25OHD3 and isobars 1-∝-hydroxyvitamin-D3 (1∝OHD3), and 7∝hydroxy-4-cholesten-3-one (7∝C4). In AD subjects, no relationship was observed between MMSE score, calcium and any form of vitamin D. There was no significant difference in calcium levels among the three groups. For Group A, the levels of both total 25-hydroxtvitamin-D (25OHD) (14.79 +/- 13.31 nmol/mL,) and 25-hydroxyvitamin-D2 (25OHD2) (undetected) were lower compared to the control (40.50 +/- 23.46 and 9.58 +/- 6.23 nmol/mL) and treated groups (32.89 +/- 28.58 and 6.84 +/- 7.86 nmol/mL) p=0.004 and p<0.001, respectively. No significant differences were found in the levels of the primary forms vitamin D2 and vitamin D3. Conclusions: This specific, reliable, reproducible and robust method provided valuable insight into the vitamin D status of AD sufferers with 25OHD being significantly lower in patients suffering from AD arising from extremely low levels of 25OHD2 along with low levels of 25OHD3. Treatment with AChEI appears to reverse this deficit.

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