A Comprehensive Review on the Role of Obesity in Functional Cognition (Part II): Cognition Impairment and Underlying Mechanisms, and Development of Neurodegenerative Diseases
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Published
Sep 30, 2023
Abstract
Epidemiological and neuroimaging studies have accumulated evidence of a significant rela-tionship between obesity and cognitive impairment. The mechanisms underlying the connec-tion between these two ostensibly unrelated domains are complex and multifactorial. First, obesity is frequently accompanied by comorbidities, such as Type 2 Diabetes and hypertension, which can contribute to cerebrovascular alterations and neuronal dysfunction, resulting in cognitive deficits. Second, chronic low-grade inflammation activates proinflammatory cyto-kines that may impair cognitive processes by affecting neuronal plasticity and synaptic func-tion. In addition, obesity-related hormonal imbalances, such as insulin resistance and dysregulation of adipokines, may disrupt neuroendocrine pathways that are essential for cog-nitive health. The gut-brain axis, which influences inflammation, metabolicsignaling, and the synthesis of neuroactive compounds, has also been linked to cognitive decline in obese indi-viduals with altered gut microbiota composition. Changes in the structure of the brain, such as a reduction in hippocampal volume and a disruption in the integrity of the white matter, have also been observed in obese individuals, further implicating the negative effects of obesity on cognition. In addition, lifestyle factors such as sedentary behavior and unfavorable dietary patterns associated with obesity can contribute independently to cognitive dysfunction.
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Keywords
Obesity, Cognition, Neuronal Plasticity, Neuroinflammation, Outcomes
References
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26. Rezaei MH, Madadizadeh E, Aminaei M, Abbaspoor M, Schierbauer J, Moser O, Khoramipour K, Chamari K. Leptin signaling could mediate hippocampal decumula-tion of beta-amyloid and tau induced by high-intensity interval training in rats with type 2 diabetes. Cell Mol Neurobiol 2023; 43(7):3465-3478. DOI: https://doi.org/10.1007/s10571-023-01357-1
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32. Pugazhenthi S, Qin L, Reddy PH. Common neuro-degenerative pathways in obesity, diabetes, and Alz-heimer's disease. Biochim Biophys Acta Mol Basis Dis 2017; 1863(5):1037-1045. DOI: https://doi.org/10.1016/j.bbadis.2016.04.017
33. Arnold SE, Arvanitakis Z, Macauley-Rambach SL, Koenig AM, Wang HY, Ahima RS, Craft S, Gandy S, Buettner C, Stoeckel LE, Holtzman DM, Nathan DM. Brain insulin resistance in type 2 diabetes and Alzheimer disease: Concepts and conundrums. Nat Rev Neurol 2018; 14(3):168-181. DOI: https://doi.org/10.1038/nrneurol.2017.185
34. Nguyen JC, Killcross AS, Jenkins TA. Obesity and cognitive decline: Role of inflammation and vascular changes. Front Neurosci 2014; 8:375. DOI: https://doi.org/10.3389/fnins.2014.00375
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36. Fruh SM. Obesity: Risk factors, complications, and strategies for sustainable long-term weight manage-ment. J Am Assoc Nurse Pract 2017; 29(S1):S3-S14. DOI: https://doi.org/10.1002/2327-6924.12510
37. Maksimovic K, Youssef M, You J, Sung HK, Park J. Evidence of metabolic dysfunction in amyotrophic lat-eral sclerosis (ALS) patients and animal models. Bio-molecules 2023; 13(5):863. DOI: https://doi.org/10.3390/biom13050863
38. Balendra R, Isaacs AM. C9orf72-mediated ALS and FTD: Multiple pathways to disease. Nat Rev Neurol 2018; 14(9):544-558. DOI: https://doi.org/10.1038/s41582-018-0047-2
39. Xu WL, Atti AR, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Midlife overweight and obesity increase late-life dementia risk: A population-based twin study. Neurology 2011; 76(18):1568-1574. DOI: https://doi.org/10.1212/WNL.0b013e3182190d09
40. Martyn JA, Kaneki M, Yasuhara S. Obesity-induced insulin resistance and hyperglycemia: Etiologic factors and molecular mechanisms. Anesthesiology 2008; 109(1):137-148. DOI: https://doi.org/10.1097/ALN.0b013e3181799d45
41. Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry CP Jr, Yaffe K. Obesity in middle age and future risk of dementia: A 27-year longitudinal popula-tion-based study. BMJ 2005; 330(7504):1360. DOI: https://doi.org/10.1136/bmj.38446.466238.E0
42. Bischof GN, Park DC. Obesity and aging: Conse-quences for cognition, brain structure, and brain func-tion. Psychosom Med 2015; 77(6):697-709. DOI: https://doi.org/10.1097/PSY.0000000000000212
43. De Silva TM, Faraci FM. Contributions of aging to cerebral small vessel disease. Annu Rev Physiol 2020; 82:275-295. DOI: https://doi.org/10.1146/annurev-physiol-021119-034338
2. Duarte JM. Metabolic alterations associated to brain dysfunction in diabetes. Aging Dis 2015; 6(5):304-321. DOI: https://doi.org/10.14336/AD.2014.1104
3. Chait A, den Hartigh LJ. Adipose tissue distribution, inflammation and its metabolic consequences, includ-ing diabetes and cardiovascular disease. Front Cardi-ovasc Med 2020; 7:22. DOI: https://doi.org/10.3389/fcvm.2020.00022
4. Ungvari Z, Toth P, Tarantini S, Prodan CI, Sorond F, Merkely B, Csiszar A. Hypertension-induced cognitive impairment: From pathophysiology to public health. Nat Rev Nephrol 2021; 17(10):639-654. DOI: https://doi.org/10.1038/s41581-021-00430-6
5. Flores-Cordero JA, Pérez-Pérez A, Jimé-nez-Cortegana C, Alba G, Flores-Barragán A, Sánchez-Margalet V. Obesity as a risk factor for de-mentia and alzheimer's disease: The role of leptin. Int J Mol Sci 2022; 23(9):5202. DOI: https://doi.org/10.3390/ijms23095202
6. Zhu M, Liu X, Ye Y, Yan X, Cheng Y, Zhao L, Chen F, Ling Z. Gut microbiota: A novel therapeutic target for Parkinson’s disease. Front Immunol 2022; 13:937555. DOI: https://doi.org/10.3389/fimmu.2022.937555
7. Eichen DM, Kang Sim DE, Appleton-Knapp SL, Strong DR, Boutelle KN. Adults with overweight or obesity use less efficient memory strategies compared to adults with healthy weight on a verbal list learning task modi-fied with food words. Appetite 2023; 181:106402. DOI: https://doi.org/10.1016/j.appet.2022.106402
8. Berbegal M, Tomé M, Sánchez-SanSegundo M, Za-ragoza-Martí A, Hurtado-Sánchez JA. Memory function performance in individuals classified as overweight, obese, and normal weight. Front Nutr 2022; 9:932323. DOI: https://doi.org/10.3389/fnut.2022.932323
9. Higgs S, Spetter MS. Cognitive control of eating: The role of memory in appetite and weight gain. Curr Obes Rep 2018; 7(1):50-59. DOI: https://doi.org/10.1007/s13679-018-0296-9
10. Cheke LG, Simons JS, Clayton NS. Higher body mass index is associated with episodic memory deficits in young adults. Q J Exp Psychol (Hove) 2016; 69(11):2305-2316. DOI: https://doi.org/10.1080/17470218.2015.1099163
11. Lin X, Li H. Obesity: Epidemiology, pathophysiology, and therapeutics. Front Endocrinol (Lausanne) 2021; 12:706978. DOI: https://doi.org/10.3389/fendo.2021.706978
12. Martin AA, Davidson TL. Human cognitive function and the obesogenic environment. Physiol Behav 2014; 136:185-193. DOI: https://doi.org/10.1016/j.physbeh.2014.02.062
13. Jangmo A, Stålhandske A, Chang Z, Chen Q, Almqvist C, Feldman I, Bulik CM, Lichtenstein P, D'Onofrio B, Kuja-Halkola R, Larsson H. Atten-tion-deficit/hyperactivity disorder, school performance, and effect of medication. J Am Acad Child Adolesc Psychiatry 2019; 58(4):423-432. DOI: https://doi.org/10.1016/j.jaac.2018.11.014
14. Tronieri JS, Alamuddin N, Wadden TA. Behavioral Ap-proaches to Obesity Management. [Updated 2022 Oct 13]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. Available at: https://www.ncbi.nlm.nih.gov/books/NBK278952/
15. Dol A, van Gemert-Pijnen L, Schwartz LM, Velthuijsen H, Bode C. Exploring tailored virtual emotion regulation approaches for individuals with emotional eating. J Eat Disord 2023; 11(1):134. DOI: https://doi.org/10.1186/s40337-023-00856-2
16. Dakanalis A, Mentzelou M, Papadopoulou SK, Papan-dreou D, Spanoudaki M, Vasios GK, Pavlidou E, Man-tzorou M, Giaginis C. The association of emotional eating with overweight/obesity, depression, anxie-ty/stress, and dietary patterns: A review of the current clinical evidence. Nutrients 2023; 15(5):1173. DOI: https://doi.org/10.3390/nu15051173
17. Liang J, Matheson BE, Kaye WH, Boutelle KN. Neu-rocognitive correlates of obesity and obesity-related behaviors in children and adolescents. Int J Obes (Lond) 2014; 38(4):494-506. DOI: https://doi.org/10.1038/ijo.2013.142
18. Sripetchwandee J, Chattipakorn N, Chattipakorn SC. Links between obesity-induced brain insulin resistance, brain mitochondrial dysfunction, and dementia. Front Endocrinol (Lausanne) 2018; 9:496. DOI: https://doi.org/10.3389/fendo.2018.00496
19. Vinuesa A, Pomilio C, Gregosa A, Bentivegna M, Presa J, Bellotto M, Saravia F, Beauquis J. Inflammation and insulin resistance as risk factors and potential thera-peutic targets for Alzheimer's Disease. Front Neurosci 2021; 15:653651. DOI: https://doi.org/10.3389/fnins.2021.653651
20. Cacciatore M, Grasso EA, Tripodi R, Chiarelli F. Impact of glucose metabolism on the developing brain. Front Endocrinol (Lausanne) 2022; 13:1047545. DOI: https://doi.org/10.3389/fendo.2022.1047545
21. Kraft AD, Harry GJ. Features of microglia and neu-roinflammation relevant to environmental exposure and neurotoxicity. Int J Environ Res Public Health 2011; 8(7):2980-3018. DOI: https://doi.org/10.3390/ijerph8072980
22. Kleinridders A, Ferris HA, Cai W, Kahn CR. Insulin action in brain regulates systemic metabolism and brain function. Diabetes 2014; 63(7):2232-2243. DOI: https://doi.org/10.2337/db14-0568
23. Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis 2015; 26:26191. DOI: https://doi.org/10.3402/mehd.v26.26191
24. Picó C, Palou M, Pomar CA, Rodríguez AM, Palou A. Leptin as a key regulator of the adipose organ. Rev Endocr Metab Disord 2022; 23(1):13-30. DOI: https://doi.org/10.1007/s11154-021-09687-5
25. Hamilton K, Harvey J. The neuronal actions of leptin and the implications for treating Alzheimer’s disease. Pharmaceuticals (Basel) 2021; 14(1):52. DOI: https://doi.org/10.3390/ph14010052
26. Rezaei MH, Madadizadeh E, Aminaei M, Abbaspoor M, Schierbauer J, Moser O, Khoramipour K, Chamari K. Leptin signaling could mediate hippocampal decumula-tion of beta-amyloid and tau induced by high-intensity interval training in rats with type 2 diabetes. Cell Mol Neurobiol 2023; 43(7):3465-3478. DOI: https://doi.org/10.1007/s10571-023-01357-1
27. Seminara RS, Jeet C, Biswas S, Kanwal B, Iftikhar W, Sakibuzzaman M, Rutkofsky IH. The neurocognitive effects of ghrelin-induced signaling on the hippocampus: a promising approach to Alzheimer’s disease. Cureus 2018; 10(9):e3285. DOI: https://doi.org/10.7759/cureus.3285
28. Kim C, Kim S, Park S. Neurogenic effects of ghrelin on the hippocampus. Int J Mol Sci 2017; 18(3):588. DOI: https://doi.org/10.3390/ijms18030588
29. Litwiniuk A, Bik W, Kalisz M, Baranowska-Bik A. In-flammasome NLRP3 potentially links obesi-ty-associated low-grade systemic inflammation and insulin resistance with Alzheimer’s disease. Int J Mol Sci 2021; 22(11):5603. DOI: https://doi.org/10.3390/ijms22115603
30. Rizzo MR, Fasano R, Paolisso G. Adiponectin and cognitive decline. Int J Mol Sci. 2020; 21(6):2010. DOI: https://doi.org/10.3390/ijms21062010
31. Achari AE, Jain SK. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int J Mol Sci 2017; 18(6):1321. DOI: https://doi.org/10.3390/ijms18061321
32. Pugazhenthi S, Qin L, Reddy PH. Common neuro-degenerative pathways in obesity, diabetes, and Alz-heimer's disease. Biochim Biophys Acta Mol Basis Dis 2017; 1863(5):1037-1045. DOI: https://doi.org/10.1016/j.bbadis.2016.04.017
33. Arnold SE, Arvanitakis Z, Macauley-Rambach SL, Koenig AM, Wang HY, Ahima RS, Craft S, Gandy S, Buettner C, Stoeckel LE, Holtzman DM, Nathan DM. Brain insulin resistance in type 2 diabetes and Alzheimer disease: Concepts and conundrums. Nat Rev Neurol 2018; 14(3):168-181. DOI: https://doi.org/10.1038/nrneurol.2017.185
34. Nguyen JC, Killcross AS, Jenkins TA. Obesity and cognitive decline: Role of inflammation and vascular changes. Front Neurosci 2014; 8:375. DOI: https://doi.org/10.3389/fnins.2014.00375
35. Kouli A, Torsney KM, Kuan WL. Parkinson’s Disease: Etiology, Neuropathology, and Pathogenesis. In: Stoker TB, Greenland JC, editors. Parkinson’s Disease: Pathogenesis and Clinical Aspects [Internet]. Brisbane (AU): Codon Publications; 2018 Dec 21. Chapter 1. DOI: https://doi.org/10.15586/codonpublications.parkinsonsdisease.2018.ch1
36. Fruh SM. Obesity: Risk factors, complications, and strategies for sustainable long-term weight manage-ment. J Am Assoc Nurse Pract 2017; 29(S1):S3-S14. DOI: https://doi.org/10.1002/2327-6924.12510
37. Maksimovic K, Youssef M, You J, Sung HK, Park J. Evidence of metabolic dysfunction in amyotrophic lat-eral sclerosis (ALS) patients and animal models. Bio-molecules 2023; 13(5):863. DOI: https://doi.org/10.3390/biom13050863
38. Balendra R, Isaacs AM. C9orf72-mediated ALS and FTD: Multiple pathways to disease. Nat Rev Neurol 2018; 14(9):544-558. DOI: https://doi.org/10.1038/s41582-018-0047-2
39. Xu WL, Atti AR, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Midlife overweight and obesity increase late-life dementia risk: A population-based twin study. Neurology 2011; 76(18):1568-1574. DOI: https://doi.org/10.1212/WNL.0b013e3182190d09
40. Martyn JA, Kaneki M, Yasuhara S. Obesity-induced insulin resistance and hyperglycemia: Etiologic factors and molecular mechanisms. Anesthesiology 2008; 109(1):137-148. DOI: https://doi.org/10.1097/ALN.0b013e3181799d45
41. Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry CP Jr, Yaffe K. Obesity in middle age and future risk of dementia: A 27-year longitudinal popula-tion-based study. BMJ 2005; 330(7504):1360. DOI: https://doi.org/10.1136/bmj.38446.466238.E0
42. Bischof GN, Park DC. Obesity and aging: Conse-quences for cognition, brain structure, and brain func-tion. Psychosom Med 2015; 77(6):697-709. DOI: https://doi.org/10.1097/PSY.0000000000000212
43. De Silva TM, Faraci FM. Contributions of aging to cerebral small vessel disease. Annu Rev Physiol 2020; 82:275-295. DOI: https://doi.org/10.1146/annurev-physiol-021119-034338
How to Cite
Callaghan, R. (2023). A Comprehensive Review on the Role of Obesity in Functional Cognition (Part II): Cognition Impairment and Underlying Mechanisms, and Development of Neurodegenerative Diseases. Science Insights, 43(3), 1049–1057. https://doi.org/10.15354/si.23.re701
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