title: High "normal" blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through life study.
abstract: BACKGROUND
  Type 2 diabetes is associated with cerebral atrophy, cognitive impairment and dementia. We recently showed higher glucose levels in the normal range not to be free of adverse effects and to be associated with greater hippocampal and amygdalar atrophy in older community-dwelling individuals free of diabetes.
  
  
  OBJECTIVE
  This study aimed to determine whether blood glucose levels in the normal range (<6.1 mmol/L) were associated with cerebral volumes in structures other than the hippocampus and amygdale, and whether these glucose-related regional volumes were associated with cognitive performance.
  
  
  METHODS
  210 cognitively healthy individuals (68-73 years) without diabetes, glucose intolerance or metabolic syndrome were assessed in the large, community-based Personality and Total Health Through Life (PATH) study.
  
  
  METHODS
  Baseline blood glucose levels in the normal range (3.2-6.1 mmol/l) were used to determine regional brain volumes and associated cognitive function at wave 3.
  
  
  RESULTS
  Higher blood glucose levels in the normal range were associated with lower grey/white matter regional volumes in the frontal cortices (middle frontal gyrus, inferior frontal gyrus precentral gyrus). Moreover, identified cerebral regions were associated with poorer cognitive performance and the structure-function associations were gender specific to men.
  
  
  CONCLUSIONS
  These findings stress the need to re-evaluate what is considered as healthy blood glucose levels, and consider the role of higher normal blood glucose as a risk factor for cerebral health, cognitive function and dementia. A better lifetime management of blood glucose levels may contribute to improved cerebral and cognitive health in later life and possibly protect against dementia.
authors.affiliation: Centre for Research on Ageing, Health and Wellbeing, The Australian National University, Canberra, Australia.
authors.forename: Moyra E
authors.initials: ME
authors.lastname: Mortby
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Janke
authors.forename: Kaarin J
authors.initials: KJ
authors.lastname: Anstey
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cherbuin
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D003071:Cognition; D015331:Cohort Studies; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009929:Organ Size; D012016:Reference Values; D012111:Residence Characteristics
chemical_list: D001786:Blood Glucose
references.citation: J Gerontol. 1992 May;47(3):P154-8
references.pmid: 1573197
references.citation: Stroke. 2009 Mar;40(3 Suppl):S53-5
references.pmid: 19064803
references.citation: Diab Vasc Dis Res. 2010 Oct;7(4):260-73
references.pmid: 20847109
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4703-7
references.pmid: 11930016
references.citation: Regul Pept. 2011 Feb 25;167(1):26-30
references.pmid: 21115071
references.citation: Neurobiol Dis. 2011 Nov;44(2):161-73
references.pmid: 21742034
references.citation: Neurobiol Aging. 2003 Oct;24(6):797-806
references.pmid: 12927762
references.citation: Brain. 2001 Jan;124(Pt 1):219-31
references.pmid: 11133799
references.citation: J Affect Disord. 2008 Jul;109(1-2):107-16
references.pmid: 18191459
references.citation: J Trauma. 2008 Jan;64(1):30-3; discussion 33-4
references.pmid: 18188095
references.citation: Diabetes Care. 1998 Mar;21(3):398-402
references.pmid: 9540022
references.citation: Neuroimage. 2009 Mar 1;45(1):29-37
references.pmid: 19071222
references.citation: Semin Thromb Hemost. 2009 Jul;35(5):451-7
references.pmid: 19739035
references.citation: Addiction. 1993 Jun;88(6):791-804
references.pmid: 8329970
references.citation: Biol Psychiatry. 2008 Sep 15;64(6):541-4
references.pmid: 18550031
references.citation: Circulation. 2002 Oct 15;106(16):2067-72
references.pmid: 12379575
references.citation: Stroke. 2003 Feb;34(2):392-6
references.pmid: 12574548
references.citation: IEEE Trans Med Imaging. 1998 Feb;17(1):87-97
references.pmid: 9617910
references.citation: J Neurosci. 2003 Apr 15;23(8):3295-301
references.pmid: 12716936
references.citation: Am J Cardiol. 2006 Jan 16;97(2A):3A-11A
references.pmid: 16442931
references.citation: Hippocampus. 2008;18(11):1085-8
references.pmid: 18651634
references.citation: Diabetologia. 2003 Dec;46(12):1604-10
references.pmid: 14595538
references.citation: Int J Epidemiol. 2012 Aug;41(4):951-60
references.pmid: 21349904
references.citation: Diabetes Care. 2008 Dec;31(12):2383-90
references.pmid: 19033418
references.citation: Am J Epidemiol. 2001 Oct 1;154(7):635-41
references.pmid: 11581097
references.citation: Biol Psychiatry. 2010 Nov 1;68(9):832-8
references.pmid: 20692648
references.citation: Acta Neuropathol. 1986;71(1-2):46-54
references.pmid: 3776474
references.citation: Diabetes. 2006 Jan;55(1):202-8
references.pmid: 16380494
references.citation: Neurology. 1999 Dec 10;53(9):1937-42
references.pmid: 10599761
references.citation: Arch Intern Med. 2000 Jan 24;160(2):174-80
references.pmid: 10647755
references.citation: J Am Geriatr Soc. 2002 Jan;50(1):41-8
references.pmid: 12028245
references.citation: Diabetes. 2006 Apr;55(4):1106-13
references.pmid: 16567535
references.citation: Eur J Vasc Endovasc Surg. 2007 Feb;33(2):223-33
references.pmid: 17185009
references.citation: Neuroimage. 2007 Oct 15;38(1):95-113
references.pmid: 17761438
references.citation: Neurology. 2012 Sep 4;79(10):1019-26
references.pmid: 22946113
references.citation: Neurobiol Aging. 2003 Nov;24(7):985-1003
references.pmid: 12928059
references.citation: Neuroimage. 2009 Jul 1;46(3):786-802
references.pmid: 19195496
references.citation: Neuroimage. 2005 Jul 1;26(3):839-51
references.pmid: 15955494
references.citation: Neuroradiology. 1994;36(2):101-3
references.pmid: 8183443
references.citation: J Consult Clin Psychol. 1988 Feb;56(1):123-30
references.pmid: 3346437
references.citation: J Clin Exp Neuropsychol. 2004 Nov;26(8):1044-80
references.pmid: 15590460