Complex mechanisms linking neurocognitive dysfunction to insulin resistance and other metabolic dysfunction

F1000Research

Volumn 5, Issue , 2016, Pages

  Stoeckel, Luke E ^a   Arvanitakis, Zoe ^b   Gandy, Sam ^c   Small, Dana ^d   Kahn, C Ronald ^e   Pascual Leone, Alvaro ^e   Pawlyk, Aaron ^a   Sherwin, Robert ^d   Smith, Philip ^a  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b RUSH UNIVERSITY MEDICAL CENTER   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

^d YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADVANCED GLYCATION END PRODUCT; GLUCOSE TRANSPORTER 1; N METHYL DEXTRO ASPARTIC ACID RECEPTOR;

ALZHEIMER DISEASE; AMYLOIDOSIS; BLOOD BRAIN BARRIER; BRAIN ATROPHY; CEREBROVASCULAR DISEASE; COGNITIVE DEFECT; DEMENTIA; DISEASE ASSOCIATION; DISORDERS OF HIGHER CEREBRAL FUNCTION; EXECUTIVE FUNCTION; FOOD INTAKE; HIPPOCAMPUS; HUMAN; HYPERGLYCEMIA; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RESISTANCE; METABOLIC DISORDER; NEUROTRANSMISSION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OXIDATIVE STRESS; PATHOGENESIS; PREVALENCE; REVIEW; RISK ASSESSMENT; RISK FACTOR;

EID: 84978540597     PISSN: 20461402     EISSN: 1759796X     Source Type: Journal    
DOI: 10.12688/f1000research.8300.2     Document Type: Review

References (143)

1. Abbott RD Donahue RP MacMahon SW: Diabetes and the risk of stroke. The Honolulu Heart Program. JAMA. 1987;257(7):949-952. 3806877 10.1001/jama.1987.03390070069025
2. Abner EL Nelson PT Kryscio RJ: Diabetes is associated with cerebrovascular but not Alzheimer neuropathology. Alzheimers Dement. 2016; pii: S1552-5260(15)03030-7. 26812281 10.1016/j.jalz.2015.12.006
3. Ahtiluoto S Polvikoski T Peltonen M: Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology. 2010;75(13):1195-1202. 20739645 10.1212/WNL.0b013e3181f4d7f8
4. Alafuzoff I Aho L Helisalmi S: Beta-amyloid deposition in brains of subjects with diabetes. Neuropathol Appl Neurobiol. 2009;35(1):60-68. 18346114 10.1111/j.1365-2990.2008.00948.x
5. Alonso-Alonso M Pascual-Leone A: The right brain hypothesis for obesity. JAMA. 2007;297(16):1819-1822. 17456824 10.1001/jama.297.16.1819
6. Anstey KJ Cherbuin N Budge M: Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes Rev. 2011;12(5):e426-e437. 21348917 10.1111/j.1467-789X.2010.00825.x
7. Arvanitakis Z Schneider JA Wilson RS: Diabetes is related to cerebral infarction but not to AD pathology in older persons. Neurology. 2006a;67(11):1960-1965. 17159101 10.1212/01.wnl.0000247053.45483.4e
8. Arvanitakis Z Wilson RS Bienias JL: Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004;61(5):661-666. 15148141 10.1001/archneur.61.5.661
9. Arvanitakis Z Wilson RS Li Y: Diabetes and function in different cognitive systems in older individuals without dementia. Diabetes Care. 2006b;29(3):560-565. 16505506 10.2337/diacare.29.03.06.dc05-1901
10. Babbs RK Sun X Felsted J: Decreased caudate response to milkshake is associated with higher body mass index and greater impulsivity. Physiol Behav. 2013;121:103-111. 23562867 10.1016/j.physbeh.2013.03.025 3731396
11. Baker LD Cross DJ Minoshima S: Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch Neurol. 2011;68(1):51-57. 20837822 10.1001/archneurol.2010.225 3023149
12. Banerjee C Moon YP Paik MC: Duration of diabetes and risk of ischemic stroke: the Northern Manhattan Study. Stroke. 2012;43(5):1212-1217. 22382158 10.1161/STROKEAHA.111.641381 3336044
13. Bateman RJ Xiong C Benzinger TL: Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367(9):795-804. 22784036 10.1056/NEJMoa1202753 3474597
14. Beeri MS Schmeidler J Silverman JM: Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology. Neurology. 2008;71(10):750-757. 18765651 10.1212/01.wnl.0000324925.95210.6d 2676951
15. Beeri MS Silverman JM Davis KL: Type 2 diabetes is negatively associated with Alzheimer's disease neuropathology. J Gerontol A Biol Sci Med Sci. 2005;60(4):471-475. 15933386 10.1093/gerona/60.4.471 3163091
16. Benedict C Hallschmid M Hatke A: Intranasal insulin improves memory in humans. Psychoneuroendocrinology. 2004;29(10):1326-1334. 15288712 10.1016/j.psyneuen.2004.04.003
17. Biessels GJ Reagan LP: Hippocampal insulin resistance and cognitive dysfunction. Nat Rev Neurosci. 2015;16(11):660-671. 26462756 10.1038/nrn4019
18. Biessels GJ Strachan MW Visseren FL: Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions. Lancet Diabetes Endocrinol. 2014;2(3):246-255. 24622755 10.1016/S2213-8587(13)70088-3
19. Bingham EM Hopkins D Smith D: The role of insulin in human brain glucose metabolism: an 18fluoro-deoxyglucose positron emission tomography study. Diabetes. 2002;51(12):3384-3390. 12453890 10.2337/diabetes.51.12.3384
20. Bocarsly ME Fasolino M Kane GA: Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function. Proc Natl Acad Sci U S A. 2015;112(51):15731-15736. 26644559 10.1073/pnas.1511593112 4697408
21. Bradford HF Thomas AJ: Metabolism of glucose and glutamate by synaptosomes from mammalian cerebral cortex. J Neurochem. 1969;16(11):1495-1504. 5380010 10.1111/j.1471-4159.1969.tb09904.x
22. Brooks SJ Benedict C Burgos J: Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study. Int J Obes (Lond). 2013;37(2):230-236. 22290540 10.1038/ijo.2012.13 3572402
23. Brundel M Kappelle LJ Biessels GJ: Brain imaging in type 2 diabetes. Eur Neuropsychopharmacol. 2014;24(12):1967-1981. 24726582 10.1016/j.euroneuro.2014.01.023
24. Brüning JC Gautam D Burks DJ: Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;289(5487):2122-2125. 11000114 10.1126/science.289.5487.2122
25. Cherbuin N Sachdev P Anstey KJ: Higher normal fasting plasma glucose is associated with hippocampal atrophy: The PATH Study. Neurology. 2012;79(10):1019-1026. 22946113 10.1212/WNL.0b013e31826846de
26. Claxton A Baker LD Hanson A: Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. J Alzheimers Dis. 2015;44(3):897-906. 25374101 10.3233/JAD-141791
27. Convit A Wolf OT Tarshish C: Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly. Proc Natl Acad Sci U S A. 2003;100(4):2019-2022. 12571363 10.1073/pnas.0336073100 149951
28. Craft S Baker LD Montine TJ: Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012;69(1):29-38. 21911655 10.1001/archneurol.2011.233 3260944
29. Davidson TL Monnot A Neal AU: The effects of a high-energy diet on hippocampal-dependent discrimination performance and blood-brain barrier integrity differ for diet-induced obese and diet-resistant rats. Physiol Behav. 2012;107(1):26-33. 22634281 10.1016/j.physbeh.2012.05.015 3409296
30. Davidson TL Sample CH Swithers SE: An application of Pavlovian principles to the problems of obesity and cognitive decline. Neurobiol Learn Mem. 2014;108:172-184. 23887140 10.1016/j.nlm.2013.07.014 3899105
31. De Felice FG Lourenco MV: Brain metabolic stress and neuroinflammation at the basis of cognitive impairment in Alzheimer's disease. Front Aging Neurosci. 2015;7:94. 26042036 10.3389/fnagi.2015.00094 4436878
32. Dey A Hao S Erion JR: Glucocorticoid sensitization of microglia in a genetic mouse model of obesity and diabetes. J Neuroimmunol. 2014;269(1-2):20-27. 24534266 10.1016/j.jneuroim.2014.01.013 3989932
33. Enzinger C Fazekas F Matthews PM: Risk factors for progression of brain atrophy in aging: six-year follow-up of normal subjects. Neurology. 2005;64(10):1704-1711. 15911795 10.1212/01.WNL.0000161871.83614.BB
34. Erion JR Wosiski-Kuhn M Dey A: Obesity elicits interleukin 1-mediated deficits in hippocampal synaptic plasticity. J Neurosci. 2014;34(7):2618-2631. 24523551 10.1523/JNEUROSCI.4200-13.2014 3921429
35. Erny D Hrabě de Angelis AL Jaitin D: Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18(7):965-977. 26030851 10.1038/nn.4030
36. Ferreira ST Clarke JR Bomfim TR: Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer's disease. Alzheimers Dement. 2014;10(1 Suppl):S76-S83. 24529528 10.1016/j.jalz.2013.12.010
37. Fitzpatrick S Gilbert S Serpell L: Systematic review: are overweight and obese individuals impaired on behavioural tasks of executive functioning? Neuropsychol Rev. 2013;23(2):138-156. 23381140 10.1007/s11065-013-9224-7
38. Fotuhi M Do D Jack C: Modifiable factors that alter the size of the hippocampus with ageing. Nat Rev Neurol. 2012;8(4):189-202. 22410582 10.1038/nrneurol.2012.27
39. Francis H Stevenson R: The longer-term impacts of Western diet on human cognition and the brain. Appetite. 2013;63:119-128. 23291218 10.1016/j.appet.2012.12.018
40. Franke K Gaser C Manor B: Advanced BrainAGE in older adults with type 2 diabetes mellitus. Front Aging Neurosci. 2013;5:90. 24381557 10.3389/fnagi.2013.00090 3865444
41. Geijselaers SL Sep SJ Stehouwer CD: Glucose regulation, cognition, and brain MRI in type 2 diabetes: a systematic review. Lancet Diabetes Endocrinol. 2015;3(1):75-89. 25163604 10.1016/S2213-8587(14)70148-2
42. Germine L Nakayama K Duchaine BC: Is the Web as good as the lab? Comparable performance from Web and lab in cognitive/perceptual experiments. Psychon Bull Rev. 2012;19(5):847-857. 22829343 10.3758/s13423-012-0296-9
43. Gjedde A Crone C: Blood-brain glucose transfer: repression in chronic hyperglycemia. Science. 1981;214(4519):456-457. 7027439 10.1126/science.7027439
44. Gold M Alderton C Zvartau-Hind M: Rosiglitazone monotherapy in mild-to-moderate Alzheimer's disease: results from a randomized, double-blind, placebo-controlled phase III study. Dement Geriatr Cogn Disord. 2010;30(2):131-146. 20733306 10.1159/000318845 3214882
45. Gonzales MM Tarumi T Miles SC: Insulin sensitivity as a mediator of the relationship between BMI and working memory-related brain activation. Obesity (Silver Spring). 2010;18(11):2131-2137. 20814415 10.1038/oby.2010.183
46. Gorelick PB Scuteri A Black SE: Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(9):2672-2713. 21778438 10.1161/STR.0b013e3182299496 3778669
47. Gregor MF Hotamisligil GS: Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011;29:415-445. 21219177 10.1146/annurev-immunol-031210-101322
48. Gunstad J Paul RH Cohen RA: Elevated body mass index is associated with executive dysfunction in otherwise healthy adults. Compr Psychiatry. 2007;48(1):57-61. 17145283 10.1016/j.comppsych.2006.05.001
49. Hao S Dey A Yu X: Dietary obesity reversibly induces synaptic stripping by microglia and impairs hippocampal plasticity. Brain Behav Immun. 2016;51:230-239. 26336035 10.1016/j.bbi.2015.08.023 4679537
50. Heitner J Dickson D: Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects. A retrospective postmortem immunocytochemical and histofluorescent study. Neurology. 1997;49(5):1306-1311. 9371913 10.1212/WNL.49.5.1306
51. Higgs S Rutters F Thomas JM: Top down modulation of attention to food cues via working memory. Appetite. 2012;59(1):71-75. 22450523 10.1016/j.appet.2012.03.018
52. Higgs S: Cognitive processing of food rewards. Appetite. 2015a; pii: S0195-6663(15)30054-4. 26458961 10.1016/j.appet.2015.10.003
53. Higgs S: Manipulations of attention during eating and their effects on later snack intake. Appetite. 2015b;92:287-294. 26032197 10.1016/j.appet.2015.05.033
54. Holden KF Lindquist K Tylavsky FA: Serum leptin level and cognition in the elderly: Findings from the Health ABC Study. Neurobiol Aging. 2009;30(9):1483-1489. 18358569 10.1016/j.neurobiolaging.2007.11.024
55. Horie NC Serrao VT Simon SS: Cognitive Effects of Intentional Weight Loss in Elderly Obese Individuals With Mild Cognitive Impairment. J Clin Endocrinol Metab. 2016;101(3):1104-12. 26713821 10.1210/jc.2015-2315
56. Hsu JL Chen YL Leu, JG: Microstructural white matter abnormalities in type 2 diabetes mellitus: a diffusion tensor imaging study. Neuroimage. 2012;59(2):1098-1105. 21967726 10.1016/j.neuroimage.2011.09.041
57. Hsu TM Kanoski SE: Blood-brain barrier disruption: mechanistic links between Western diet consumption and dementia. Front Aging Neurosci. 2014;6:88. 24847262 10.3389/fnagi.2014.00088 4023063
58. Ishii M Iadecola C: Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology. Biochim Biophys Acta. 2015a; pii: S0925-4439(15)00329-4. 26546479 10.1016/j.bbadis.2015.10.029
59. Ishii M Iadecola C: Metabolic and Non-Cognitive Manifestations of Alzheimer's Disease: The Hypothalamus as Both Culprit and Target of Pathology. Cell Metab. 2015b;22(5):761-776. 26365177 10.1016/j.cmet.2015.08.016 4654127
60. Ivan CS Seshadri S Beiser A: Dementia after stroke: the Framingham Study. Stroke. 2004;35(6):1264-1268. 15118167 10.1161/01.STR.0000127810.92616.78
61. Janson J Laedtke T Parisi JE: Increased risk of type 2 diabetes in Alzheimer disease. Diabetes. 2004;53(2):474-481. 14747300 10.2337/diabetes.53.2.474
62. Johnson PM Kenny PJ: Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010;13(5):635-641. 20348917 10.1038/nn.2519 2947358
63. Kanoski SE Zhang Y Zheng W: The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat. J Alzheimers Dis. 2010;21(1):207-219. 20413889 10.3233/JAD-2010-091414
64. Kenyon C Chang J Gensch E: A C. elegans mutant that lives twice as long as wild type. Nature. 1993;366(6454):461-464. 8247153 10.1038/366461a0
65. Killick R Scales G Leroy K: Deletion of Irs2 reduces amyloid deposition and rescues behavioural deficits in APP transgenic mice. Biochem Biophys Res Commun. 2009;386(1):257-262. 19523444 10.1016/j.bbrc.2009.06.032 2726921
66. Kleinridders A Cai W Cappellucci L: Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proc Natl Acad Sci U S A. 2015;112(11):3463-3468. 25733901 10.1073/pnas.1500877112 4371978
67. Knight EM Ruiz HH Kim SH: Unexpected partial correction of metabolic and behavioral phenotypes of Alzheimer's APP/PSEN1 mice by gene targeting of diabetes/Alzheimer's-related Sorcs1. Acta Neuropathol Commun. 2016;4(1):16. 26916443 10.1186/s40478-016-0282-y 4766719
68. Kumagai AK Vinores SA Pardridge WM: Pathological upregulation of inner blood-retinal barrier Glut1 glucose transporter expression in diabetes mellitus. Brain Res. 1996;706(2):313-317. 8822374 10.1016/0006-8993(95)01335-0
69. Lane RF Raines SM Steele JW: Diabetes-associated SorCS1 regulates Alzheimer's amyloid-beta metabolism: evidence for involvement of SorL1 and the retromer complex. J Neurosci. 2010;30(39):13110-13115. 20881129 10.1523/JNEUROSCI.3872-10.2010 3274732
70. Lane RF Steele JW Cai D: Protein sorting motifs in the cytoplasmic tail of SorCS1 control generation of Alzheimer's amyloid-β peptide. J Neurosci. 2013;33(16):7099-7107. 23595767 10.1523/JNEUROSCI.5270-12.2013 3696125
71. Le DS Pannacciulli N Chen K: Less activation of the left dorsolateral prefrontal cortex in response to a meal: a feature of obesity. Am J Clin Nutr. 2006;84(4):725-731. 17023697
72. Li H Kang Z Qiu W: Hemoglobin A1C is independently associated with severity and prognosis of brainstem infarctions. J Neurol Sci. 2012;317(1-2):87-91. 22425018 10.1016/j.jns.2012.02.024
73. Li L Cheng WY Glicksberg BS: Identification of type 2 diabetes subgroups through topological analysis of patient similarity. Sci Transl Med. 2015;7(311):311ra174. 26511511 10.1126/scitranslmed.aaa9364 4780757
74. Linder K Schleger F Kiefer-Schmidt I: Gestational Diabetes Impairs Human Fetal Postprandial Brain Activity. J Clin Endocrinol Metab. 2015;100(11):4029-4036. 26465393 10.1210/jc.2015-2692
75. Liu S Labouèbe G Karunakaran S: Effect of insulin on excitatory synaptic transmission onto dopamine neurons of the ventral tegmental area in a mouse model of hyperinsulinemia. Nutr Diabetes. 2013;3:e97. 24336291 10.1038/nutd.2013.38 3877429
76. Macauley SL Stanley M Caesar EE: Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo. J Clin Invest. 2015;125(6):2463-7. 25938784 10.1172/JCI79742 4497756
77. MacQueen G Frodl T: The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? Mol Psychiatry. 2011;16(3):252-264. 20661246 10.1038/mp.2010.80
78. Malek-Ahmadi M Beach T Obradov A: Increased Alzheimer's disease neuropathology is associated with type 2 diabetes and ApoE ε.4 carrier status. Curr Alzheimer Res. 2013;10(6):654-659. 23627755 10.2174/15672050113109990006 4105218
79. Matsuzaki T Sasaki K Tanizaki Y: Insulin resistance is associated with the pathology of Alzheimer disease: the Hisayama study. Neurology. 2010;75(9):764-770. 20739649 10.1212/WNL.0b013e3181eee25f
80. Matthaei S Horuk R Olefsky JM: Blood-brain glucose transfer in diabetes mellitus. Decreased number of glucose transporters at blood-brain barrier. Diabetes. 1986;35(10):1181-1184. 3530847 10.2337/diab.35.10.1181
81. Mauras N Mazaika P Buckingham B: Longitudinal assessment of neuroanatomical and cognitive differences in young children with type 1 diabetes: association with hyperglycemia. Diabetes. 2015;64(5):1770-1779. 25488901 10.2337/db14-1445 4407847
82. Mazaika PK Weinzimer SA Mauras N: Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes. Diabetes. 2016;65(2):476-85. 26512024 10.2337/db15-1242 4747456
83. McNay EC Ong CT McCrimmon RJ: Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance. Neurobiol Learn Mem. 2010;93(4):546-553. 20176121 10.1016/j.nlm.2010.02.002 2878207
84. Miller AA Spencer SJ: Obesity and neuroinflammation: a pathway to cognitive impairment. Brain Behav Immun. 2014;42:10-21. 24727365 10.1016/j.bbi.2014.04.001
85. Montagne A Pa J Zlokovic BV: Vascular plasticity and cognition during normal aging and dementia. JAMA Neurol. 2015;72(5):495-496. 25751405 10.1001/jamaneurol.2014.4636 4428924
86. Moran C Beare R Phan TG: Type 2 diabetes mellitus and biomarkers of neurodegeneration. Neurology. 2015;85(13):1123-1130. 26333802 10.1212/WNL.0000000000001982
87. Musen G Simonson DC Bolo NR: Regional brain activation during hypoglycemia in type 1 diabetes. J Clin Endocrinol Metab. 2008;93(4):1450-1457. 18198228 10.1210/jc.2007-2007 2291497
88. Nandipati S Luo X Schimming C: Cognition in non-demented diabetic older adults. Curr Aging Sci. 2012;5(2):131-135. 22023096 10.2174/1874609811205020131 3659164
89. Nelson PT Smith CD Abner EA: Human cerebral neuropathology of Type 2 diabetes mellitus. Biochim Biophys Acta. 2009;1792(5):454-469. 18789386 10.1016/j.bbadis.2008.08.005 2834412
90. Norton S Matthews FE Barnes DE: Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. Lancet Neurol. 2014;13(8):788-794. 25030513 10.1016/S1474-4422(14)70136-X
91. Novak V Milberg W Hao Y: Enhancement of vasoreactivity and cognition by intranasal insulin in type 2 diabetes. Diabetes Care. 2014;37(3):751-759. 24101698 10.2337/dc13-1672 3931384
92. Nunley KA Rosano C Ryan CM: Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes. Diabetes Care. 2015a;38(9):1768-1776. 26153270 10.2337/dc15-0041 4542271
93. Nunley KA Ryan CM Orchard TJ: White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes. Neurology. 2015b;84(20):2062-2069. 25904692 10.1212/WNL.0000000000001582 4442104
94. Oberman L Pascual-Leone A: Changes in plasticity across the lifespan: cause of disease and target for intervention. Prog Brain Res. 2013;207:91-120. 24309252 10.1016/B978-0-444-63327-9.00016-3 4392917
95. Pannacciulli N Del Parigi A Chen K: Brain abnormalities in human obesity: a voxel-based morphometric study. Neuroimage. 2006;31(4):1419-1425. 16545583 10.1016/j.neuroimage.2006.01.047
96. Pascual-Leone A Freitas C Oberman L: Characterizing brain cortical plasticity and network dynamics across the age-span in health and disease with TMS-EEG and TMS-fMRI. Brain Topogr. 2011;24(3-4):302-315. 21842407 10.1007/s10548-011-0196-8 3374641
97. Peila R Rodriguez BL Launer LJ: Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes. 2002;51(4):1256-1262. 11916953 10.2337/diabetes.51.4.1256
98. Poldrack RA Laumann TO Koyejo O: Long-term neural and physiological phenotyping of a single human. Nat Commun. 2015;6: 8885. 26648521 10.1038/ncomms9885 4682164
99. Raber J: Detrimental effects of chronic hypothalamic-pituitary-adrenal axis activation. From obesity to memory deficits. Mol Neurobiol. 1998;18(1):1-22. 9824846 10.1007/BF02741457
100. Raji CA Ho AJ Parikshak NN: Brain structure and obesity. Hum Brain Mapp. 2010;31(3):353-364. 19662657 10.1002/hbm.20870 2826530
101. Ramirez A Wolfsgruber S Lange C: Elevated HbA 1c is associated with increased risk of incident dementia in primary care patients. J Alzheimers Dis. 2015;44(4):1203-1212. 25524954 10.3233/JAD-141521
102. Rivera EJ Goldin A Fulmer N: Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine. J Alzheimers Dis. 2005;8(3):247-268. 16340083
103. Rivera HM Kievit P Kirigiti MA: Maternal high-fat diet and obesity impact palatable food intake and dopamine signaling in nonhuman primate offspring. Obesity (Silver Spring). 2015;23(11):2157-2164. 26530932 10.1002/oby.21306 4636015
104. Roberts RO Knopman DS Cha RH: Diabetes and elevated hemoglobin A1c levels are associated with brain hypometabolism but not amyloid accumulation. J Nucl Med. 2014;55(5):759-764. 24652830 10.2967/jnumed.113.132647 4011952
105. Ruiz HH Chi T Lindtner C: Increased susceptibility to metabolic dysregulation in a mouse model of Alzheimer's disease is associated with impaired hypothalamic insulin signaling and elevated BCAA levels. Alzheimers Dement. 2016; pii: S1552-5260(16)00049-2. 26928090 10.1016/j.jalz.2016.01.008
106. Ryan JP Aizenstein HJ Orchard TJ: Age of Childhood Onset in Type 1 Diabetes and Functional Brain Connectivity in Midlife. Psychosom Med. 2015;77(6):622-630. 26163816 10.1097/PSY.0000000000000206 4503367
107. Sabia S Kivimaki M Shipley MJ: Body mass index over the adult life course and cognition in late midlife: the Whitehall II Cohort Study. Am J Clin Nutr. 2009;89(2):601-607. 19073790 10.3945/ajcn.2008.26482 2714395
108. Schneider JA Arvanitakis Z Bang W: Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69(24):2197-2204. 17568013 10.1212/01.wnl.0000271090.28148.24
109. Schubert M Gautam D Surjo D: Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci U S A. 2004;101(9):3100-3105. 14981233 10.1073/pnas.0308724101 365750
110. Sellbom KS Gunstad J: Cognitive function and decline in obesity. J Alzheimers Dis. 2012;30(Suppl 2):S89-S95. 22258511 10.3233/JAD-2011-111073
111. Semenkovich K Patel PP Pollock AB: Academic abilities and glycaemic control in children and young people with Type 1 diabetes mellitus. Diabet Med. 2015. 26173465 10.1111/dme.12854 4713372
112. Sevgi M Rigoux L Kühn AB: An Obesity-Predisposing Variant of the FTO Gene Regulates D2R-Dependent Reward Learning. J Neurosci. 2015;35(36):12584-12592. 26354923 10.1523/JNEUROSCI.1589-15.2015
113. Sharkey RJ Karama S Dagher A: Overweight is not associated with cortical thickness alterations in children. Front Neurosci. 2015;9:24. 25698918 10.3389/fnins.2015.00024 4316697
114. Shimizu F Sano Y Tominaga O: Advanced glycation end-products disrupt the blood-brain barrier by stimulating the release of transforming growth factor-β by pericytes and vascular endothelial growth factor and matrix metalloproteinase-2 by endothelial cells in vitro. Neurobiol Aging. 2013;34(7):1902-1912. 23428182 10.1016/j.neurobiolaging.2013.01.012
115. Small DM Zatorre RJ Jones-Gotman M: Increased intensity perception of aversive taste following right anteromedial temporal lobe removal in humans. Brain. 2001;124(Pt 8):1566-1575. 11459748 10.1093/brain/124.8.1566
116. Snyder HM Corriveau RA Craft S: Vascular contributions to cognitive impairment and dementia including Alzheimer's disease. Alzheimers Dement. 2015;11(6):710-717. 25510382 10.1016/j.jalz.2014.10.008 4731036
117. Sonnen JA Larson EB Brickell K: Different patterns of cerebral injury in dementia with or without diabetes. Arch Neurol. 2009;66(3):315-322. 19139294 10.1001/archneurol.2008.579 2766529
118. Sperling RA Amariglio RE Marshall GA: Establishing Clinical Relevance in Preclinical Alzheimer's Disease. J Prev Alzheimers Dis. 2015;2(2):85-87. 26247003 10.14283/jpad.2015.56 4523117
119. Steculorum SM Solas M Brüning JC: The paradox of neuronal insulin action and resistance in the development of aging-associated diseases. Alzheimers Dement. 2014;10(1 Suppl):S3-11. 24529522 10.1016/j.jalz.2013.12.008
120. Stice E Spoor S Bohon C: Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science. 2008;322(5900):449-452. 18927395 10.1126/science.1161550 2681095
121. Stouffer MA Woods CA Patel JC: Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward. Nat Commun. 2015;6: 8543. 26503322 10.1038/ncomms9543 4624275
122. Stranahan AM Arumugam TV Cutler RG: Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat Neurosci. 2008;11(3):309-317. 18278039 10.1038/nn2055 2927988
123. Sun X Kroemer NB Veldhuizen MG: Basolateral amygdala response to food cues in the absence of hunger is associated with weight gain susceptibility. J Neurosci. 2015;35(20):7964-7976. 25995480 10.1523/JNEUROSCI.3884-14.2015 4438134
124. Suzuki R Ferris HA Chee MJ: Reduction of the Cholesterol Sensor SCAP in the Brains of Mice Causes Impaired Synaptic Transmission and Altered Cognitive Function. PLoS Biol. 2013;11(4):e1001532. 23585733 10.1371/journal.pbio.1001532 3621654
125. Suzuki R Lee K Jing E: Diabetes and insulin in regulation of brain cholesterol metabolism. Cell Metab. 2010;12(6):567-579. 21109190 10.1016/j.cmet.2010.11.006 3205997
126. Sweetnam D Holmes A Tennant KA: Diabetes impairs cortical plasticity and functional recovery following ischemic stroke. J Neurosci. 2012;32(15):5132-5143. 22496559 10.1523/JNEUROSCI.5075-11.2012
127. Talbot K Wang HY Kazi H: Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest. 2012;122(4):1316-1338. 22476197 10.1172/JCI59903 3314463
128. Thaler JP Schwartz MW: Minireview: Inflammation and obesity pathogenesis: the hypothalamus heats up. Endocrinology. 2010;151(9):4109-4115. 20573720 10.1210/en.2010-0336 2940486
129. Thompson PM Stein JL Medland SE: The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data. Brain Imaging Behav. 2014;8(2):153-182. 24399358 10.1007/s11682-013-9269-5 4008818
130. Trollor JN Smith E Agars E: The association between systemic inflammation and cognitive performance in the elderly: the Sydney Memory and Ageing Study. Age (Dordr). 2012;34(5):1295-1308. 21853262 10.1007/s11357-011-9301-x 3448981
131. Vainik U Dagher A Dubé L: Neurobehavioural correlates of body mass index and eating behaviours in adults: a systematic review. Neurosci Biobehav Rev. 2013;37(3):279-299. 23261403 10.1016/j.neubiorev.2012.11.008 4017079
132. Val-Laillet D Layec S Guérin S: Changes in brain activity after a diet-induced obesity. Obesity (Silver Spring). 2011;19(4):749-756. 21212769 10.1038/oby.2010.292
133. Vogt MC Paeger L Hess S: Neonatal insulin action impairs hypothalamic neurocircuit formation in response to maternal high-fat feeding. Cell. 2014;156(3):495-509. 24462248 10.1016/j.cell.2014.01.008 4101521
134. Wang D Buckner RL Fox MD: Parcellating cortical functional networks in individuals. Nat Neurosci. 2015;18(12):1853-1860. 26551545 10.1038/nn.4164 4661084
135. Watson GS Cholerton BA Reger MA: Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am J Geriatr Psychiatry. 2005;13(11):950-958. 16286438 10.1097/00019442-200511000-00005
136. Wosiski-Kuhn M Erion JR Gomez-Sanchez EP: Glucocorticoid receptor activation impairs hippocampal plasticity by suppressing BDNF expression in obese mice. Psychoneuroendocrinology. 2014;42:165-177. 24636513 10.1016/j.psyneuen.2014.01.020 4426342
137. Yaffe K Lindquist K Schwartz AV: Advanced glycation end product level, diabetes, and accelerated cognitive aging. Neurology. 2011;77(14):1351-1356. 21900628 10.1212/WNL.0b013e3182315a56 3182758
138. Yaffe K: Metabolic syndrome and cognitive disorders: is the sum greater than its parts? Alzheimer Dis Assoc Disord. 2007;21(2):167-171. 17545744 10.1097/WAD.0b013e318065bfd6
139. Yarchoan M Arnold SE: Repurposing diabetes drugs for brain insulin resistance in Alzheimer disease. Diabetes. 2014;63(7):2253-2261. 24931035 10.2337/db14-0287 4066335
140. Yarchoan M Toledo JB Lee EB: Abnormal serine phosphorylation of insulin receptor substrate 1 is associated with tau pathology in Alzheimer's disease and tauopathies. Acta Neuropathol. 2014;128(5):679-689. 25107476 10.1007/s00401-014-1328-5 4304658
141. Yau PL Castro MG Tagani A: Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. Pediatrics. 2012;130(4):e856-e864. 22945407 10.1542/peds.2012-0324 3457620
142. Yau PL Kang EH Javier DC: Preliminary evidence of cognitive and brain abnormalities in uncomplicated adolescent obesity. Obesity (Silver Spring). 2014;22(8):1865-1871. 24891029 10.1002/oby.20801 4114991
143. Yeo BT Krienen FM Eickhoff SB: Functional Specialization and Flexibility in Human Association Cortex. Cereb Cortex. 2016;26(1):465. 26508334 10.1093/cercor/bhv260 4677986