Serum Vitamin D and Cingulate Cortex Thickness in Older Adults: Quantitative MRI of the Brain

Author(s): Gonzague Foucault, Guillaume T Duval, Romain Simon, Olivier Beauchet, Mickael Dinomais, Cédric Annweiler*, on behalf of the SOCOS group.

Journal Name: Current Alzheimer Research

Volume 16 , Issue 11 , 2019

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Background: Vitamin D insufficiency is associated with brain changes, and cognitive and mobility declines in older adults.

Objective: Our objective was to investigate in older adults whether vitamin D insufficiency<50nmol/L was associated with thinner cingulate cortex, a brain area related to cognitive functions influenced by vitamin D.

Methods: Two hundred and fifteen Caucasian older community-dwellers (mean±SD, 72.1±5.5years; 40% female) received a blood test and brain MRI. The thickness of perigenual anterior cingulate cortex, midcingulate cortex and posterior cingulate cortex was measured using FreeSurfer from T1-weighted MR images. Age, gender, education, BMI, mean arterial pressure, comorbidities, use of vitamin D supplements or anti-vascular drugs, MMSE, GDS, IADL, serum calcium and vitamin B9 concentrations, creatinine clearance were used as covariables.

Results: Participants with vitamin D insufficiency (n=80) had thinner total cingulate thickness than the others (24.6±1.9mm versus 25.3±1.4mm, P=0.001); a significant difference found for all 3 regions. Vitamin D insufficiency was cross-sectionally associated with a decreased total cingulate thickness (β=- 0.49, P=0.028). Serum 25OHD concentration correlated positively with the thickness of perigenual anterior (P=0.011), midcingulate (P=0.013) and posterior cingulate cortex (P=0.021).

Conclusion: Vitamin D insufficiency was associated with thinner cingulate cortex in the studied sample of older adults. These findings provide insight into the pathophysiology of cognitive and mobility declines in older adults with vitamin D insufficiency.

Keywords: Brain, cingulate cortex, magnetic resonance imaging, older adults, vitamin D, memory disorders.

Hossein-Nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc 88: 720-55.(2013);
DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 80: 1689S-96S.(2004);
Annweiler C, Schott AM, Berrut G, Chauviré V, Le Gall D, Inzitari M, et al. Vitamin D and ageing: neurological issues. Neuropsychobiology 62: 139-50.(2010);
Annweiler C, Montero-Odasso M, Llewellyn DJ, Richard-Devantoy S, Duque G, Beauchet O. Meta-Analysis of memory and executive dysfunctions in relation to vitamin D. J Alzh Dis 37: 147-71.(2013);
Annweiler C, Annweiler T, Montero-Odasso M, Bartha R, Beauchet O. Vitamin D and brain volumetric changes: systematic review and meta-analysis. Maturitas 78: 30-9.(2014);
Annweiler C, Beauchet O, Bartha R, Hachinsky V, Montero-Odasso M. Vitamin D and caudal primary motor cortex: a magnetic resonance spectroscopy study. PLoS One 9 e87314(2014);
Farid K, Volpe-Gillot L, Petras S, Plou C, Caillat-Vigneron N, Blacher J. Correlation between serum 25-hydroxyvitamin D concentrations and regional cerebral blood flow in degenerative dementia. Nucl Med Commun 33: 1048-52.(2012);
Bowman GL, Silbert LC, Howieson D, Dodge HH, Traber MG, Frei B, et al. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology 78: 241-9.(2012);
Annweiler C, Montero-Odasso M, Hachinsky V, Seshadri S, Bartha R, Beauchet O. Vitamin D concentration and lateral cerebral ventricle volume in older adults. Mol Nutr Food Res 57: 267-76.(2013);
Annweiler C, Bartha R, Goncalvez S, Karras SN, Millet P, Féron F, et al. Vitamin D-related changes in intracranial volume in older adults: a quantitative neuroimaging study. Maturitas 80: 312-7.(2015);
Karakis I, Pase MP, Beiser A, Booth SL, Jacques PF, Rogers G, et al. Association of serum vitamin D with the risk of incident dementia and subclinical indices of brain aging: the framingham heart study. J Alzheimers Dis 51: 451-61.(2016);
Shivakumar V, Kalmady SV, Amaresha AC, Jose D, Narayanaswamy JC, Agarwal SM, et al. Serum vitamin D and hippocampal grey matter volume in schizophrenia. Psychiatry Res 233: 175-9.(2015);
Etkin A, Egner T, Kalisch R. Emotional processing in anterior cingulate and medial prefrontal cortex. Trends Cogn Sci 15: 85-93.(2011);
Devinsky O, Morrell MJ, Vogt BA. Contributions of anterior cingulate cortex to behavior. Brain 118: 279-306.(1995);
Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 4: 215-22.(2000);
Lin YC, Shih YC, Tseng WY, Chu YH, Wu MT, Chen TF, et al. Cingulum correlates of cognitive functions in patients with mild cognitive impairment and early Alzheimer’s disease: a diffusion spectrum imaging study. Brain Topogr 27: 393-402.(2014);
Bush G. Attention-deficit/hyperactivity disorder and attention networks. Neuropsychopharmacology 35: 278-300.(2010);
Schermuly I, Fellgiebel A, Wagner S, Yakushev I, Stoeter P, Schmitt R, et al. Association between cingulum bundle structure and cognitive performance: an observational study in major depression. Eur Psychiatry 25: 355-60.(2010);
Vogt BA, Vogt L, Laureys S. Cytology and functionally correlated circuits of human posterior cingulate areas. Neuroimage 29: 452-66.(2006);
Annweiler C, Montero-Odasso M, Muir SW, Beauchet O. Vitamin D and brain imaging in the elderly: should we expect some lesions specifically related to hypovitaminosis D? Open Neuroimaging J 6: 16-8.(2012);
Annweiler C, Fantino B, Schott AM, Krolak-Salmon P, Allali G, Beauchet O. Vitamin D insufficiency and mild cognitive impairment: cross-sectional association. Eur J Neurol 19: 1023-9.(2012);
Vannier-Nitenberg C, Dauphinot V, Bongue B, Sass C, Rouch I, Beauchet O, et al. Early detection of memory impairment in people over 65 years old consulting at Health Examination Centers for the French health insurance: the EVATEM protocol. BMC Geriatr 13: 55.(2013);
Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189-98.(1975);
Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, et al. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33: 341-55.(2002);
Fischl B, Salat DH, Van Der Kouwe AJ, Makris N, Ségonne F, Quinn BT, et al. Sequence independent segmentation of magnetic resonance images. Neuroimage 23: S69-84.(2004);
Whitford TJ, Lee SW, Oh JS, De Luis-Garcia R, Savadjief P, Alvarado JL, et al. Localized abnormalities in the cingulum bundle in patients with schizophrenia: a Diffusion Tensor tractography study. Neuroimage Clin 5: 93-9.(2014);
Rosas H, Liu A, Hersch S, Glessner M, Ferrante R, Salat DH, et al. Regional and progressive thinning of the cortical ribbon in huntington’s disease. Neurology 58: 695-701.(2002);
Kuperberg GR, Broome MR, McGuire PK, David AS, Eddy M, Ozawa F, et al. Regionally localized thinning of the cerebral cortex in schizophrenia. Arch Gen Psychiatry 60: 878-88.(2003);
Salat DH, Buckner RL, Snyder AZ, Greve DN, Desikan RS, Busa E, et al. Thinning of the Cerebral Cortex in Aging. Cereb Cortex 14: 721-30.(2004);
Han X, Jovicich J, Salat DH, Van Der Kouwe A, Quinn B, Czanner S, et al. Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer. Neuroimage 32: 180-94.(2006);
Annweiler C, Souberbielle JC, Schott AM, De Decker L, Berrut G, Beauchet O, et al. Vitamin D in the elderly: 5 points to remember. Geriatr Psychol Neuropsychiatr Vieil 9: 259-67.(2011);
World Health Organization, 2003.Prevention and management of osteoporosis: report of a WHO Scientific Group World Health Organization, Geneva.
Institute of Medicine 2011.Dietary reference intakes for calcium and vitamin d committee to review dietary reference intakes for calcium and vitamin D National Academies Press, Institute of Medicine, Washington DC.
Izzo Jr JL, Sica DA, Black HR. 2008.Hypertension primer: the essentials of high blood pressure Basic Science, Population Science, and Clinical Management 4th ed. American Heart Association, Dallas.
Beauchet O, Hélard L, Montero-Odasso M, De Decker L, Berrut G, Annweiler C. Hypovitaminosis D in geriatric impatients: a marker of severity of chronic diseases. Aging Clin Exp Res 24: 188-92.(2012);
Pérès K, Chrysostome V, Fabrigoule C, Orgogozo JM, Dartigues JF, Barberger-Gateau P. Restriction in complex activities of daily living in MCI: impact on outcome. Neurology 67: 461-6.(2006);
Rochon J, Gondan M, Kieser M. To test or not to test: preliminary assessment of normality when comparing two independent samples. BMC Med Res Methodol 12: 81.(2012);
Kočovská E, Gaughran F, Krivoy A, Meier UC. Vitamin-D deficiency as a potential environmental risk factor in multiple sclerosis, schizophrenia, and autism. Front Psychiatry 8: 47.(2017);
Tot Babberich Ede N, Gourdeau C, Pointel S, Lemarchant B, Beauchet O, Annweiler C. Biology of subjective cognitive complaint amongst geriatric patients: vitamin D involvement. Curr Alzheimer Res 12: 173-8.(2015);
Annweiler C, Doineau L, Gerigne L, Provendier A, Karras SN, Beauchet O, et al. Vitamin D and subjective memory complaint in community-dwelling older adults. Curr Alzheimer Res 15: 664-70.(2018);
Goodwill AM, Szoeke C. A Systematic review and meta-analysis of the effect of low vitamin D on cognition. J Am Geriatr Soc 65: 2161-8.(2017);
Annweiler C, Llewellyn DJ, Beauchet O. Low serum vitamin D concentrations in Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis 33: 659-74.(2013);
Alharbi FM. Update in vitamin D and multiple sclerosis. Neurosciences 20: 329-35.(2015);
Parker GB, Brotchie H, Graham RK. Vitamin D and depression. J Affect Disord 208: 56-61.(2017);
Annweiler C, Rastmanesh R, Richard-Devantoy S, Beauchet O. The role of vitamin D in depression: from a curious idea to a therapeutic option. J Clin Psychiatry 74: 1121-2.(2013);
Brouwer-Brolsma EM. Higher serum 25-hydroxyvitamin d and lower plasma glucose are associated with larger gray matter volume but not with white matter or total brain volume in dutch community-dwelling older adults. J Nutr 145: 1817-23.(2015);
Buell JS, Dawson-Hugues B, Scott TM, Wiener DE, Dallal GE, Qui WQ, et al. 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 74: 18-26.(2010);
Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 341: c3666.(2010);
Schmidt R, Enzinger C, Ropele S, Schmidt H, Fazekas F. Progression of cerebral white matter lesions: 6-year results of the Austrian Stroke Prevention Study. Lancet 361: 2046-8.(2003);
Willey JZ, Scarmeas N, Provenzano FA, Luchsinger JA, Mayeux R, Brickman AM. White matter hyperintensity volume and impaired mobility among older adults. J Neurol 260: 884-90.(2013);
Wion D, Macgrogan D, Neveu I, Jehan F, Houlgatte R, Brachet P. 1,25 Dihydroxyvitamin-D3 is a potent inducer of nerve growth-factor synthesis. J Neurosci Res 28: 110-4.(1991);
Naveilhan P, Neveu I, Wion D, Brachet P. 1,25-Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic factor. Neuroreport 7: 2171-5.(1996);
Brown J, Bianco JI, McGrath JJ, Eyles DW. 1,25-Dihydroxyvitamin D-3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett 343: 139-43.(2003);
Nishida Y, Ito S, Ohtsuki S, Yamamoto N, Takahashi T, Iwata N, et al. Depletion of vitamin E increases amyloid β accumulation by decreasing its clearances from brain and blood in a mouse model of Alzheimer disease. J Biol Chem 284: 33400-8.(2009);
Ho R, Ortiz D, Shea TB. Amyloid-beta promotes calcium influx and neurodegeneration via stimulation of L voltage-sensitive calcium channels rather than NMDA channels in cultured neurons. J Alzheimer Dis 3: 479-83.(2011);
Cheng J, Rui Y, Qin L, Xu J, Han S, Yuan L, et al. Vitamin D combined with resveratrol prevents cognitive decline in SAMP8 mice. Curr Alzheimer Res 14: 820-33.(2017);
Masoumi A, Goldenson B, Ghirmai S, Avagyan H, Zaghi J, Abel K, et al. 1Alpha,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer’s disease patients. J Alzheimers Dis 17: 703-17.(2009);
Ito S, Ohtsuki S, Nezu Y, Koitabashi Y, Murata S, Terasaki T. 1a,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-b peptide (1-40) from mouse brain across the blood-brain barrier. Fluids Barriers CNS 8: 20.(2011);
SanMartin CD, Henriquez M, Chacon C, Ponce DP, Salech F, Rogers NK, et al. Vitamin D increases Aβ140 plasma levels and protects lymphocytes from oxidative death in mild cognitive impairment patients. Curr Alzheimer Res 15: 561-9.(2018);
Dursun E, Gezen-Ak D, Yilmazer S. A novel perspective for Alzheimer’s disease: vitamin D receptor suppression by amyloid- induced alterations by vitamin D in cortical neurons. J Alzheimers Dis 23: 207-19.(2011);
Schram MT, Trompet S, Kamper AM, de Craen AJ, Hofman A, Euser SM, et al. Serum calcium and cognitive function in old age. J Am Geriatr Soc 55: 1786-92.(2007);
Wong SK, Chin KY, Soelaiman I. Vitamin D and depression: the evidence from an indirect clue to treatment strategy. Curr Drug Targets 19(8): 888-97.(2018);
Chiang M, Natarajan R, Fan X. Vitamin D in schizophrenia: a clinical review. Evid Based Ment Health 19: 6-9.(2016);
Sharif MR, Madani M, Tabatabaei F, Tabatabaee Z. The relationship between serum vitamin d level and attention deficit hyperactivity disorder. Iran J Child Neurol 9: 48-53.(2015);
Martin KR, Reid DM. Is there a role for vitamin D in the treatment of chronic pain? Ther Adv Musculoskelet Dis 9: 131-5.(2017);
Fjell AM, Walhovd KB, Fennema-Notestine C, McEvoy LK, Hagler DJ, Holland D, et al. One year brain atrophy evident in healthy aging. J Neurosci 29: 15223-31.(2009);
Heaney RP. Vitamin d in health and disease. Clin J Am Soc Nephrol 3: 1535-41.(2008);
Vieth R. Vitamin D supplementation, 25-hydroxyvitamin d concentrations, and safety. Am J Clin Nutr 69: 842-56.(1999);

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Year: 2019
Page: [1063 - 1071]
Pages: 9
DOI: 10.2174/1567205016666191113124356
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