title: The negative effects of obesity and poor glycemic control on cognitive function: a proposed model for possible mechanisms.
abstract: Obesity has reached epidemic proportions and is a contributor to many adverse health outcomes, including increased risk for dementia and adverse structural and functional brain changes. Milder forms of cognitive impairment in multiple domains can also be found in obese individuals of all ages that are believed to stem from brain abnormalities long prior to onset of neurologic conditions such as dementia. However, the mechanisms for adverse brain changes and subsequent cognitive dysfunction in obesity are complex and poorly understood. This paper proposes a possible etiologic model for obesity associated cognitive impairment with emphasis on the role of poor glycemic control and conditions like type 2 diabetes mellitus. Clinical implications associated with treatment of obesity in persons with cognitive deficits in addition to the cognitive promoting effects of weight loss surgery are also discussed.
authors.affiliation: Department of Psychology, Kent State University, 238 Kent Hall Addition, Kent, OH, 44242, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Alosco
authors.forename: John
authors.initials: J
authors.lastname: Gunstad
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003071:Cognition; D060825:Cognitive Dysfunction / Q000097:blood / Q000209:etiology*; D003704:Dementia / Q000097:blood / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000523:psychology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000523:psychology; D012307:Risk Factors; D040242:Risk Reduction Behavior
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
references.citation: Int J Obes (Lond). 2014 Mar;38(3):388-96
references.pmid: 23801147
references.citation: Obesity (Silver Spring). 2011 May;19(5):1095-7
references.pmid: 21311507
references.citation: Ann Neurol. 1999 Apr;45(4):466-72
references.pmid: 10211471
references.citation: J Clin Endocrinol Metab. 2001 Dec;86(12):5992
references.pmid: 11739476
references.citation: Curr Gerontol Geriatr Res. 2012;2012:384094
references.pmid: 22654904
references.citation: Pharmacol Ther. 2012 Feb;133(2):159-76
references.pmid: 22079549
references.citation: Arch Gen Psychiatry. 2010 Mar;67(3):220-9
references.pmid: 20194822
references.citation: Clin Neuropathol. 2009 Jan-Feb;28(1):40-5
references.pmid: 19216219
references.citation: Int J Neurosci. 2008 Nov;118(11):1582-93
references.pmid: 18853335
references.citation: J Nutr Health Aging. 2011 Jun;15(6):445-9
references.pmid: 21623465
references.citation: Diabetes Care. 2006 Jul;29(7):1529-34
references.pmid: 16801574
references.citation: Prog Cardiovasc Dis. 2014 Jan-Feb;56(4):448-56
references.pmid: 24438737
references.citation: Br J Sports Med. 2011 Dec;45(15):1208-15
references.pmid: 20558529
references.citation: J Clin Endocrinol Metab. 2012 Jul;97(7):E1197-201
references.pmid: 22508715
references.citation: Cerebrovasc Dis Extra. 2012 Jan;2(1):88-98
references.pmid: 23272007
references.citation: Surg Obes Relat Dis. 2011 Jul-Aug;7(4):465-72
references.pmid: 21145295
references.citation: Neurology. 2002 Aug 13;59(3):371-8
references.pmid: 12177370
references.citation: Br J Ophthalmol. 2001 Jun;85(6):746-53
references.pmid: 11371498
references.citation: Brain Res. 2008 Sep 16;1230:233-6
references.pmid: 18675793
references.citation: Diabetes Care. 2009 Feb;32(2):287-94
references.pmid: 19017771
references.citation: Neurobiol Aging. 2010 Aug;31(8):1326-39
references.pmid: 20570405
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11704-8
references.pmid: 7972128
references.citation: Eur J Neurol. 2013 Jun;20(6):899-906, e76-7
references.pmid: 23323838
references.citation: Arch Med Res. 2012 Nov;43(8):615-21
references.pmid: 23085449
references.citation: Psychoneuroendocrinology. 2013 Nov;38(11):2493-501
references.pmid: 23786881
references.citation: Curr Alzheimer Res. 2007 Apr;4(2):147-52
references.pmid: 17430239
references.citation: Ann Neurol. 2005 Jun;57(6):789-94
references.pmid: 15929050
references.citation: Psychosom Med. 2013 Sep;75(7):632-9
references.pmid: 23873714
references.citation: Popul Health Metr. 2010 Oct 22;8:29
references.pmid: 20969750
references.citation: Neurology. 2005 May 24;64(10):1704-11
references.pmid: 15911795
references.citation: Lancet Neurol. 2011 Nov;10(11):969-77
references.pmid: 21958949
references.citation: J Clin Neurosci. 2006 Jun;13(5):540-6
references.pmid: 16723232
references.citation: J Neural Transm (Vienna). 1998;105(4-5):423-38
references.pmid: 9720972
references.citation: Neurology. 2003 Jul 8;61(1):76-80
references.pmid: 12847160
references.citation: Curr Alzheimer Res. 2007 Apr;4(2):111-6
references.pmid: 17430232
references.citation: Int J Obes (Lond). 2012 May;36(5):656-64
references.pmid: 21894161
references.citation: CNS Neurol Disord Drug Targets. 2014 Mar;13(2):283-9
references.pmid: 24074446
references.citation: J Nutr Health Aging. 2006 Jul-Aug;10(4):293-5
references.pmid: 16886099
references.citation: Psychosom Med. 2012 Nov-Dec;74(9):965-73
references.pmid: 23115344
references.citation: Obesity (Silver Spring). 2009 Jan;17(1):60-5
references.pmid: 18948965
references.citation: Am J Epidemiol. 1990 Sep;132(3):501-13
references.pmid: 2389754
references.citation: Circulation. 2013 Jan 1;127(1):e6-e245
references.pmid: 23239837
references.citation: Neurology. 2001 Jan 9;56(1):42-8
references.pmid: 11148234
references.citation: Med J Aust. 2003 May 5;178(9):427-32
references.pmid: 12720507
references.citation: Brain Res. 2002 Aug 16;946(2):221-31
references.pmid: 12137925
references.citation: Obesity (Silver Spring). 2011 Mar;19(3):500-4
references.pmid: 21183934
references.citation: J Clin Invest. 2000 Jul;106(2):171-6
references.pmid: 10903330
references.citation: Stroke. 1987 Jan-Feb;18(1):52-8
references.pmid: 2949400
references.citation: J Alzheimers Dis. 2011;26(1):127-34
references.pmid: 21593560
references.citation: Neurosci Med. 2011 Mar 1;2(1):34-42
references.pmid: 21691448
references.citation: Surg Obes Relat Dis. 2009 Sep-Oct;5(5):547-52
references.pmid: 19766958
references.citation: Curr Opin Neurol. 1998 Dec;11(6):673-7
references.pmid: 9870136
references.citation: Eat Weight Disord. 2006 Mar;11(1):e15-9
references.pmid: 16801734
references.citation: Annu Rev Med. 1995;46:223-34
references.pmid: 7598459
references.citation: J Alzheimers Dis. 2012;30 Suppl 2:S185-98
references.pmid: 22433668
references.citation: Int J Obes (Lond). 2007 Jul;31(7):1068-73
references.pmid: 17471298
references.citation: Neurology. 2006 Oct 10;67(7):1208-14
references.pmid: 17030754
references.citation: Arch Neurol. 2005 Oct;62(10):1545-8
references.pmid: 16216937
references.citation: BMJ. 1996 Oct 19;313(7063):953-4
references.pmid: 8892401
references.citation: J Alzheimers Dis. 2012;30(2):299-309
references.pmid: 22426020
references.citation: Neurology. 1999 Dec 10;53(9):1937-42
references.pmid: 10599761
references.citation: Neuroendocrinology. 2009;90(4):383-90
references.pmid: 19672057
references.citation: Diabetes. 2010 Nov;59(11):2928-35
references.pmid: 20713684
references.citation: Obesity (Silver Spring). 2014 Jan;22(1):32-8
references.pmid: 23625587
references.citation: Obesity (Silver Spring). 2013 Dec;21(12):2530-7
references.pmid: 23512884
references.citation: Proc Natl Acad Sci U S A. 2010 May 4;107(18):8404-9
references.pmid: 20404173
references.citation: Arch Intern Med. 2006 May 8;166(9):1003-8
references.pmid: 16682574
references.citation: Diabetes Res Clin Pract. 2005 Jul;69(1):29-35
references.pmid: 15955385
references.citation: Curr Alzheimer Res. 2007 Apr;4(2):185-9
references.pmid: 17430245
references.citation: Nat Neurosci. 2003 Jul;6(7):736-42
references.pmid: 12796784
references.citation: BMJ. 2010 Jul 26;341:c3666
references.pmid: 20660506
references.citation: Diabetes Care. 1994 Sep;17(9):961-9
references.pmid: 7988316
references.citation: Diabetes. 1990 Apr;39(4):437-40
references.pmid: 2318347
references.citation: Surg Obes Relat Dis. 2013 Jul-Aug;9(4):580-5
references.pmid: 23791534
references.citation: Health Psychol. 2010 Jan;29(1):50-5
references.pmid: 20063935
references.citation: Ann N Y Acad Sci. 2011 Dec;1243:15-29
references.pmid: 22211890
references.citation: Circulation. 2004 Jul 27;110(4):466-70
references.pmid: 15249512
references.citation: Obes Surg. 2013 Nov;23(11):1790-8
references.pmid: 23832521
references.citation: Dtsch Arztebl Int. 2009 Oct;106(40):641-8
references.pmid: 19890430
references.citation: Congest Heart Fail. 2013 Jul-Aug;19(4):E29-34
references.pmid: 23517434
references.citation: Obes Facts. 2013;6(2):185-92
references.pmid: 23594505
references.citation: Diabetes. 2004 Mar;53(3):687-92
references.pmid: 14988253
references.citation: Diabetes. 1988 Jun;37(6):667-87
references.pmid: 3289989
references.citation: Neurology. 2004 Aug 24;63(4):658-63
references.pmid: 15326238
references.citation: J Diabet Complications. 1990 Oct-Dec;4(4):170-4
references.pmid: 2151229
references.citation: Diabetes. 2002 Apr;51(4):1256-62
references.pmid: 11916953
references.citation: Curr Alzheimer Res. 2007 Apr;4(2):103-9
references.pmid: 17430231
references.citation: Int Psychogeriatr. 2004 Sep;16(3):327-36
references.pmid: 15559756
references.citation: Am J Prev Med. 2010 Apr;38(4):403-9
references.pmid: 20307809
references.citation: Diabetologia. 2010 Nov;53(11):2298-306
references.pmid: 20668831
references.citation: Compr Psychiatry. 2007 Jan-Feb;48(1):57-61
references.pmid: 17145283
references.citation: J Am Coll Nutr. 2012 Apr;31(2):79-86
references.pmid: 22855912
references.citation: Arch Neurol. 2009 Mar;66(3):336-42
references.pmid: 19273752
references.citation: Hum Brain Mapp. 2013 Jul;34(7):1737-46
references.pmid: 22419507
references.citation: BMC Med. 2011 Jun 08;9:71
references.pmid: 21651756
references.citation: Neuromolecular Med. 2011 Dec;13(4):217-22
references.pmid: 21898045
references.citation: Nat Neurosci. 2006 Mar;9(3):381-8
references.pmid: 16491079
references.citation: Alzheimer Dis Assoc Disord. 2012 Apr-Jun;26(2):101-5
references.pmid: 21666429
references.citation: J Clin Exp Neuropsychol. 2004 Nov;26(8):1044-80
references.pmid: 15590460
references.citation: Nat Med. 2007 Sep;13(9):1029-31
references.pmid: 17694066
references.citation: Ann Surg. 2013 Oct;258(4):628-36; discussion 636-7
references.pmid: 24018646