Current Perspectives: Obesity and Neurodegeneration - Links and Risks

References

• Garnett SP, Baur LA, Jones AM, Hardy LL. Trends in the prevalence of morbid and severe obesity in Australian children aged 7-15 years, 1985–2012. PLoS One. 2016;11:e0154879. doi:10.1371/journal.pone.0154879
   PubMed Web of Science ®Google Scholar
• Beam A, Clinger E, Hao L. Effect of diet and dietary components on the composition of the Gut microbiota. Nutrients. 2021;13:2795.
   PubMed Web of Science ®Google Scholar
• Armstrong DB, Dublin LI, Wheatley GM, Marks HH. Obesity and its relation to health and disease. J Am Med Assoc. 1951;147:1007–1014. doi:10.1001/jama.1951.03670280009003
   PubMed Web of Science ®Google Scholar
• WHO. Facts about overweight and obesity [online]. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight#:~:text=Of%20these%20over%20650%20million,overweight%20or%20obese%20in%202020. Accessed December 23, 2023.
   Google Scholar
• Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet. 1997;27:325–351. doi:10.1023/A:1025635913927
   PubMed Web of Science ®Google Scholar
• Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518:197–206. doi:10.1038/nature14177
   PubMed Web of Science ®Google Scholar
• Anekwe CV, Jarrell AR, Townsend MJ, Gaudier GI, Hiserodt JM, Stanford FC. Socioeconomics of Obesity. Curr Obes Rep. 2020;9:272–279. doi:10.1007/s13679-020-00398-7
   PubMed Web of Science ®Google Scholar
• Hruby A, Hu FB. The epidemiology of obesity: a big picture. Pharmacoeconomics. 2015;33:673–689. doi:10.1007/s40273-014-0243-x
   PubMed Web of Science ®Google Scholar
• Kwarteng JL, Schulz AJ, Mentz GB, Israel BA, Perkins DW. Independent effects of neighborhood poverty and psychosocial stress on obesity over time. J Urban Health. 2017;94:791–802. doi:10.1007/s11524-017-0193-7
   PubMed Web of Science ®Google Scholar
• Donnelly JE, Honas JJ, Smith BK, et al. Aerobic exercise alone results in clinically significant weight loss for men and women: midwest exercise trial 2. Obesity (Silver Spring). 2013;21:E219–228. doi:10.1002/oby.20145
   PubMed Web of Science ®Google Scholar
• Ross R, Dagnone D, Jones PJ, et al. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Ann Intern Med. 2000;133:92–103. doi:10.7326/0003-4819-133-2-200007180-00008
   PubMed Web of Science ®Google Scholar
• Swift DL, Johannsen NM, Lavie CJ, Earnest CP, Blair SN, Church TS. Effects of clinically significant weight loss with exercise training on insulin resistance and cardiometabolic adaptations. Obesity (Silver Spring). 2016;24:812–819. doi:10.1002/oby.21404
   PubMed Web of Science ®Google Scholar
• Donnelly JE, Blair SN, Jakicic JM, et al. American College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc. 2009;41:459–471. doi:10.1249/MSS.0b013e3181949333
   PubMed Web of Science ®Google Scholar
• Flechtner-Mors M, Ditschuneit HH, Johnson TD, Suchard MA, Adler G. Metabolic and weight loss effects of long-term dietary intervention in obese patients: four-year results. Obes Res. 2000;8:399–402. doi:10.1038/oby.2000.48
   PubMedGoogle Scholar
• Foster-Schubert KE, Alfano CM, Duggan CR, et al. Effect of diet and exercise, alone or combined, on weight and body composition in overweight-to-obese postmenopausal women. Obesity (Silver Spring). 2012;20:1628–1638. doi:10.1038/oby.2011.76
   PubMed Web of Science ®Google Scholar
• Johns DJ, Hartmann-Boyce J, Jebb SA, Aveyard P; Behavioural Weight Management Review G. Diet or exercise interventions vs combined behavioral weight management programs: a systematic review and meta-analysis of direct comparisons. J Acad Nutr Diet. 2014;114:1557–1568. doi:10.1016/j.jand.2014.07.005
   PubMed Web of Science ®Google Scholar
• Messier SP, Mihalko SL, Legault C, et al. Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial. JAMA. 2013;310:1263–1273. doi:10.1001/jama.2013.277669
   PubMed Web of Science ®Google Scholar
• Capers PL, Fobian AD, Kaiser KA, Borah R, Allison DB. A systematic review and meta-analysis of randomized controlled trials of the impact of sleep duration on adiposity and components of energy balance. Obes Rev. 2015;16:771–782. doi:10.1111/obr.12296
   PubMed Web of Science ®Google Scholar
• Sperry SD, Scully ID, Gramzow RH, Jorgensen RS. Sleep duration and waist circumference in adults: a meta-analysis. Sleep. 2015;38:1269–1276. doi:10.5665/sleep.4906
   PubMed Web of Science ®Google Scholar
• Wu Y, Zhai L, Zhang D. Sleep duration and obesity among adults: a meta-analysis of prospective studies. Sleep Med. 2014;15:1456–1462. doi:10.1016/j.sleep.2014.07.018
   PubMed Web of Science ®Google Scholar
• Ahern T, O’Malley E, Dunlevy C, et al. Sleep duration and physical function in people with severe obesity: a prospective cross-sectional study. Ir J Med Sci. 2020;189:517–523. doi:10.1007/s11845-019-02110-8
   PubMed Web of Science ®Google Scholar
• Jike M, Itani O, Watanabe N, Buysse DJ, Kaneita Y. Long sleep duration and health outcomes: a systematic review, meta-analysis and meta-regression. Sleep Med Rev. 2018;39:25–36. doi:10.1016/j.smrv.2017.06.011
   PubMed Web of Science ®Google Scholar
• Messerli FH, Ventura HO, Reisin E, et al. Borderline hypertension and obesity: two prehypertensive states with elevated cardiac output. Circulation. 1982;66:55–60. doi:10.1161/01.CIR.66.1.55
   PubMed Web of Science ®Google Scholar
• Alpert MA. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am J Med Sci. 2001;321:225–236. doi:10.1097/00000441-200104000-00003
   PubMed Web of Science ®Google Scholar
• Lavie CJ, Milani RV. Obesity and cardiovascular disease: the Hippocrates paradox? J Am Coll Cardiol. 2003;42:677–679. doi:10.1016/S0735-1097(03)00784-8
   PubMed Web of Science ®Google Scholar
• Park YM, Sui X, Liu J, et al. The effect of cardiorespiratory fitness on age-related lipids and lipoproteins. J Am Coll Cardiol. 2015;65:2091–2100. doi:10.1016/j.jacc.2015.03.517
   PubMed Web of Science ®Google Scholar
• Parto P, Lavie CJ, Arena R, Bond S, Popovic D, Ventura HO. Body habitus in heart failure: understanding the mechanisms and clinical significance of the obesity paradox. Future Cardiol. 2016;12:639–653. doi:10.2217/fca-2016-0029
   PubMedGoogle Scholar
• Dart AM, Chin-Dusting JP. Lipids and the endothelium. Cardiovasc Res. 1999;43:308–322. doi:10.1016/S0008-6363(99)00150-9
   PubMed Web of Science ®Google Scholar
• Chiu JJ, Usami S, Chien S. Vascular endothelial responses to altered shear stress: pathologic implications for atherosclerosis. Ann Med. 2009;41:19–28. doi:10.1080/07853890802186921
   PubMed Web of Science ®Google Scholar
• Glass CK, Witztum JL. Atherosclerosis. the road ahead. Cell. 2001;104:503–516. doi:10.1016/S0092-8674(01)00238-0
   PubMed Web of Science ®Google Scholar
• Silverman JF, O’Brien KF, Long S, et al. Liver pathology in morbidly obese patients with and without diabetes. Am J Gastroenterol. 1990;85:1349–1355.
   PubMed Web of Science ®Google Scholar
• Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140:124–131. doi:10.1053/j.gastro.2010.09.038
   PubMed Web of Science ®Google Scholar
• Zhu Y, Sidell MA, Arterburn D, et al. Racial/Ethnic Disparities in the Prevalence of Diabetes and Prediabetes by BMI: patient Outcomes Research To Advance Learning (PORTAL) Multisite Cohort of Adults in the U.S. Diabetes Care. 2019;42:2211–2219. doi:10.2337/dc19-0532
   PubMed Web of Science ®Google Scholar
• Rachdaoui N. Insulin: the friend and the Foe in the development of type 2 diabetes mellitus. Int J Mol Sci. 2020;21. doi:10.3390/ijms22010021
   PubMedGoogle Scholar
• Verdile G, Keane KN, Cruzat VF, et al. Inflammation and oxidative stress: the molecular connectivity between insulin resistance, obesity, and Alzheimer’s disease. Mediators Inflamm. 2015;2015:105828. doi:10.1155/2015/105828
   PubMed Web of Science ®Google Scholar
• Morris JK, Burns JM. Insulin: an emerging treatment for Alzheimer’s disease dementia? Curr Neurol Neurosci Rep. 2012;12:520–527. doi:10.1007/s11910-012-0297-0
   PubMed Web of Science ®Google Scholar
• Kellar D, Craft S. Brain insulin resistance in Alzheimer’s disease and related disorders: mechanisms and therapeutic approaches. Lancet Neurol. 2020;19:758–766. doi:10.1016/S1474-4422(20)30231-3
   PubMed Web of Science ®Google Scholar
• Heydenreich J, Kayser B, Schutz Y, Melzer K. Total energy expenditure, energy intake, and body composition in endurance athletes across the training season: a systematic review. Sports Med Open. 2017;3:8. doi:10.1186/s40798-017-0076-1
   PubMedGoogle Scholar
• Cerf ME. Beta cell dysfunction and insulin resistance. Front Endocrinol (Lausanne). 2013;4:37. doi:10.3389/fendo.2013.00037
   PubMedGoogle Scholar
• Petersen MC, Shulman GI. Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018;98:2133–2223. doi:10.1152/physrev.00063.2017
   PubMed Web of Science ®Google Scholar
• Goossens GH. The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol Behav. 2008;94:206–218. doi:10.1016/j.physbeh.2007.10.010
   PubMed Web of Science ®Google Scholar
• Fox CS, Massaro JM, Hoffmann U, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116:39–48. doi:10.1161/CIRCULATIONAHA.106.675355
   PubMed Web of Science ®Google Scholar
• Taksali SE, Caprio S, Dziura J, et al. High visceral and low abdominal subcutaneous fat stores in the obese adolescent: a determinant of an adverse metabolic phenotype. Diabetes. 2008;57:367–371. doi:10.2337/db07-0932
   PubMed Web of Science ®Google Scholar
• Liu J, Fox CS, Hickson DA, et al. Impact of abdominal visceral and subcutaneous adipose tissue on cardiometabolic risk factors: the Jackson Heart Study. J Clin Endocrinol Metab. 2010;95:5419–5426. doi:10.1210/jc.2010-1378
   PubMed Web of Science ®Google Scholar
• Rosenwald M, Wolfrum C. The origin and definition of brite versus white and classical brown adipocytes. Adipocyte. 2014;3:4–9. doi:10.4161/adip.26232
   PubMedGoogle Scholar
• Heaton JM. The distribution of brown adipose tissue in the human. J Anat. 1972;112:35–39.
   PubMed Web of Science ®Google Scholar
• van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360:1500–1508. doi:10.1056/NEJMoa0808718
   PubMed Web of Science ®Google Scholar
• Cheng L, Wang J, Dai H, et al. Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus. Adipocyte. 2021;10:48–65. doi:10.1080/21623945.2020.1870060
   PubMed Web of Science ®Google Scholar
• Jensen MD, Haymond MW, Rizza RA, Cryer PE, Miles JM. Influence of body fat distribution on free fatty acid metabolism in obesity. J Clin Invest. 1989;83:1168–1173. doi:10.1172/JCI113997
   PubMed Web of Science ®Google Scholar
• Boden G. Effects of free fatty acids (FFA) on glucose metabolism: significance for insulin resistance and type 2 diabetes. Exp Clin Endocrinol Diabetes. 2003;111:121–124. doi:10.1055/s-2003-39781
   PubMed Web of Science ®Google Scholar
• Manna P, Jain SK. Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: causes and therapeutic strategies. Metab Syndr Relat Disord. 2015;13:423–444. doi:10.1089/met.2015.0095
   PubMed Web of Science ®Google Scholar
• Bakker SJ, IJzerman RG, Teerlink T, Westerhoff HV, Gans RO, Heine RJ. Cytosolic triglycerides and oxidative stress in central obesity: the missing link between excessive atherosclerosis, endothelial dysfunction, and beta-cell failure? Atherosclerosis. 2000;148:17–21. doi:10.1016/S0021-9150(99)00329-9
   PubMed Web of Science ®Google Scholar
• Frontera WR, Ochala J. Skeletal muscle: a brief review of structure and function. Calcif Tissue Int. 2015;96:183–195. doi:10.1007/s00223-014-9915-y
   PubMed Web of Science ®Google Scholar
• Slentz CA, Houmard JA, Kraus WE. Exercise, abdominal obesity, skeletal muscle, and metabolic risk: evidence for a dose response. Obesity (Silver Spring). 2009;17 Suppl 3:S27–33.
   PubMed Web of Science ®Google Scholar
• Essen B, Jansson E, Henriksson J, Taylor AW, Saltin B. Metabolic characteristics of fibre types in human skeletal muscle. Acta Physiol Scand. 1975;95:153–165. doi:10.1111/j.1748-1716.1975.tb10038.x
   PubMedGoogle Scholar
• Sanchez B, Li J, Bragos R, Rutkove SB. Differentiation of the intracellular structure of slow- versus fast-twitch muscle fibers through evaluation of the dielectric properties of tissue. Phys Med Biol. 2014;59:2369–2380. doi:10.1088/0031-9155/59/10/2369
   PubMed Web of Science ®Google Scholar
• Sartori R, Romanello V, Sandri M. Mechanisms of muscle atrophy and hypertrophy: implications in health and disease. Nat Commun. 2021;12:330. doi:10.1038/s41467-020-20123-1
   PubMed Web of Science ®Google Scholar
• Tomlinson DJ, Erskine RM, Morse CI, Winwood K, Onambele-Pearson G. The impact of obesity on skeletal muscle strength and structure through adolescence to old age. Biogerontology. 2016;17:467–483. doi:10.1007/s10522-015-9626-4
   PubMed Web of Science ®Google Scholar
• Raghupathy R, McLean RR, Kiel DP, Hannan MT, Sahni S. Higher abdominal adiposity is associated with higher lean muscle mass but lower muscle quality in middle-aged and older men and women: the Framingham Heart Study. Aging Clin Exp Res. 2023;35(7):1477–1485. doi:10.1007/s40520-023-02427-6
   PubMed Web of Science ®Google Scholar
• Bohannon RW. Grip strength: an indispensable biomarker for older adults. Clin Interv Aging. 2019;14:1681–1691. doi:10.2147/CIA.S194543
   PubMed Web of Science ®Google Scholar
• Chang CY, Chu NF, Lin MH, et al. Association between grip strength, obesity, and cardiometabolic risk factors among the community-dwelling elderly population in Taiwan. Int J Environ Res Public Health. 2022;19:11359. doi:10.3390/ijerph191811359
   PubMedGoogle Scholar
• Lee MR, Jung SM, Bang H, Kim HS, Kim YB. Association between muscle strength and type 2 diabetes mellitus in adults in Korea: data from the Korea national health and nutrition examination survey (KNHANES) VI. Medicine (Baltimore). 2018;97:e10984. doi:10.1097/MD.0000000000010984
   PubMed Web of Science ®Google Scholar
• Arosio B, Calvani R, Ferri E, et al. Sarcopenia and cognitive decline in older adults: targeting the muscle-brain axis. Nutrients. 2023;15:1853.
   PubMed Web of Science ®Google Scholar
• Lexell J, Taylor CC, Sjostrom M. What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men. J Neurol Sci. 1988;84:275–294. doi:10.1016/0022-510X(88)90132-3
   PubMed Web of Science ®Google Scholar
• Melton LJ 3rd, Khosla S, Crowson CS, O’Connor MK, O’Fallon WM, Riggs BL. Epidemiology of sarcopenia. J Am Geriatr Soc. 2000;48:625–630. doi:10.1111/j.1532-5415.2000.tb04719.x
   PubMed Web of Science ®Google Scholar
• Ji T, Li Y, Ma L. Sarcopenic obesity: an emerging public health problem. Aging Dis. 2022;13:379–388. doi:10.14336/AD.2021.1006
   PubMed Web of Science ®Google Scholar
• Liu C, Cheng KY, Tong X, et al. The role of obesity in sarcopenia and the optimal body composition to prevent against sarcopenia and obesity. Front Endocrinol (Lausanne). 2023;14:1077255. doi:10.3389/fendo.2023.1077255
   PubMed Web of Science ®Google Scholar
• Baumgartner RN. Body composition in healthy aging. Ann N Y Acad Sci. 2000;904:437–448. doi:10.1111/j.1749-6632.2000.tb06498.x
   PubMed Web of Science ®Google Scholar
• Nishikawa H, Asai A, Fukunishi S, Nishiguchi S, Higuchi K. Metabolic syndrome and Sarcopenia. Nutrients. 2021;13:3519. doi:10.3390/nu13103519
   PubMedGoogle Scholar
• Talbot J, Maves L. Skeletal muscle fiber type: using insights from muscle developmental biology to dissect targets for susceptibility and resistance to muscle disease. Wiley Interdiscip Rev Dev Biol. 2016;5:518–534. doi:10.1002/wdev.230
   PubMed Web of Science ®Google Scholar
• Albers PH, Pedersen AJ, Birk JB, et al. Human muscle fiber type-specific insulin signaling: impact of obesity and type 2 diabetes. Diabetes. 2015;64:485–497. doi:10.2337/db14-0590
   PubMed Web of Science ®Google Scholar
• Dohm GL, Tapscott EB, Pories WJ, et al. An in vitro human muscle preparation suitable for metabolic studies. Decreased insulin stimulation of glucose transport in muscle from morbidly obese and diabetic subjects. J Clin Invest. 1988;82:486–494. doi:10.1172/JCI113622
   PubMed Web of Science ®Google Scholar
• Elton CW, Tapscott EB, Pories WJ, Dohm GL. Effect of moderate obesity on glucose transport in human muscle. Horm Metab Res. 1994;26:181–183. doi:10.1055/s-2007-1000807
   PubMed Web of Science ®Google Scholar
• Friedman JE, Caro JF, Pories WJ, Azevedo JL Jr, Dohm GL. Glucose metabolism in incubated human muscle: effect of obesity and non-insulin-dependent diabetes mellitus. Metabolism. 1994;43:1047–1054. doi:10.1016/0026-0495(94)90188-0
   PubMed Web of Science ®Google Scholar
• Tanner CJ, Barakat HA, Dohm GL, et al. Muscle fiber type is associated with obesity and weight loss. Am J Physiol Endocrinol Metab. 2002;282:E1191–1196. doi:10.1152/ajpendo.00416.2001
   PubMed Web of Science ®Google Scholar
• Akhmedov D, Berdeaux R. The effects of obesity on skeletal muscle regeneration. Front Physiol. 2013;4:371. doi:10.3389/fphys.2013.00371
   PubMed Web of Science ®Google Scholar
• Weyer C, Snitker S, Rising R, Bogardus C, Ravussin E. Determinants of energy expenditure and fuel utilization in man: effects of body composition, age, sex, ethnicity and glucose tolerance in 916 subjects. Int J Obes Relat Metab Disord. 1999;23:715–722. doi:10.1038/sj.ijo.0800910
   PubMed Web of Science ®Google Scholar
• Felber JP, Ferrannini E, Golay A, et al. Role of lipid oxidation in pathogenesis of insulin resistance of obesity and type II diabetes. Diabetes. 1987;36:1341–1350. doi:10.2337/diab.36.11.1341
   PubMed Web of Science ®Google Scholar
• Singh R, Cuervo AM. Autophagy in the cellular energetic balance. Cell Metab. 2011;13:495–504. doi:10.1016/j.cmet.2011.04.004
   PubMed Web of Science ®Google Scholar
• Yin F, Sancheti H, Patil I, Cadenas E. Energy metabolism and inflammation in brain aging and Alzheimer’s disease. Free Radic Biol Med. 2016;100:108–122. doi:10.1016/j.freeradbiomed.2016.04.200
   PubMed Web of Science ®Google Scholar
• Mirza MS. Obesity, visceral fat, and NAFLD: querying the role of adipokines in the progression of nonalcoholic fatty liver disease. ISRN Gastroenterol. 2011;2011:592404. doi:10.5402/2011/592404
   PubMedGoogle Scholar
• Brown MS, Goldstein JL. Selective versus total insulin resistance: a pathogenic paradox. Cell Metab. 2008;7:95–96. doi:10.1016/j.cmet.2007.12.009
   PubMed Web of Science ®Google Scholar
• Mavrogiannaki AN, Migdalis IN. Nonalcoholic fatty liver disease, diabetes mellitus and cardiovascular disease: newer data. Int J Endocrinol. 2013;2013:450639. doi:10.1155/2013/450639
   PubMed Web of Science ®Google Scholar
• Monsour HP, Frenette CT, Wyne K. Fatty liver: a link to cardiovascular disease--its natural history, pathogenesis, and treatment. Methodist Debakey Cardiovasc J. 2012;8:21–25. doi:10.14797/mdcj-8-3-21
   PubMedGoogle Scholar
• Asaoka Y, Terai S, Sakaida I, Nishina H. The expanding role of fish models in understanding non-alcoholic fatty liver disease. Dis Model Mech. 2013;6:905–914. doi:10.1242/dmm.011981
   PubMed Web of Science ®Google Scholar
• Luo Y, Lin H. Inflammation initiates a vicious cycle between obesity and nonalcoholic fatty liver disease. Immun Inflamm Dis. 2021;9:59–73. doi:10.1002/iid3.391
   PubMed Web of Science ®Google Scholar
• Miller AA, Spencer SJ. Obesity and neuroinflammation: a pathway to cognitive impairment. Brain Behav Immun. 2014;42:10–21. doi:10.1016/j.bbi.2014.04.001
   PubMed Web of Science ®Google Scholar
• Stanhope KL, Schwarz JM, Keim NL, et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest. 2009;119:1322–1334. doi:10.1172/JCI37385
   PubMed Web of Science ®Google Scholar
• Tappy L, Le KA. Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev. 2010;90:23–46. doi:10.1152/physrev.00019.2009
   PubMed Web of Science ®Google Scholar
• Softic S, Stanhope KL, Boucher J, et al. Fructose and hepatic insulin resistance. Crit Rev Clin Lab Sci. 2020;57:308–322. doi:10.1080/10408363.2019.1711360
   PubMed Web of Science ®Google Scholar
• Matsuura F, Yamashita S, Nakamura T, et al. Effect of visceral fat accumulation on uric acid metabolism in male obese subjects: visceral fat obesity is linked more closely to overproduction of uric acid than subcutaneous fat obesity. Metabolism. 1998;47:929–933. doi:10.1016/S0026-0495(98)90346-8
   PubMed Web of Science ®Google Scholar
• Sanchez-Lozada LG, Andres-Hernando A, Garcia-Arroyo FE, et al. Uric acid activates aldose reductase and the polyol pathway for endogenous fructose and fat production causing development of fatty liver in rats. J Biol Chem. 2019;294:4272–4281. doi:10.1074/jbc.RA118.006158
   PubMed Web of Science ®Google Scholar
• Parbo P, Ismail R, Hansen KV, et al. Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer’s disease. Brain. 2017;140:2002–2011. doi:10.1093/brain/awx120
   PubMed Web of Science ®Google Scholar
• Laurent C, Buee L, Blum D. Tau and neuroinflammation: what impact for Alzheimer’s disease and tauopathies? Biomed J. 2018;41:21–33. doi:10.1016/j.bj.2018.01.003
   PubMed Web of Science ®Google Scholar
• Song XM, Yu Q, Dong X, et al. Aldose reductase inhibitors attenuate beta-amyloid-induced TNF-alpha production in microlgia via ROS-PKC-mediated NF-kappaB and MAPK pathways. Int Immunopharmacol. 2017;50:30–37. doi:10.1016/j.intimp.2017.06.005
   PubMed Web of Science ®Google Scholar
• Yan J, Zheng K, Zhang X, Jiang Y. Fructose Consumption is associated with a higher risk of dementia and Alzheimer’s disease: a prospective cohort study. J Prev Alzheimers Dis. 2023;10:186–192. doi:10.14283/jpad.2023.7
   PubMed Web of Science ®Google Scholar
• Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci. 2013;36:587–597. doi:10.1016/j.tins.2013.07.001
   PubMed Web of Science ®Google Scholar
• Rink C, Khanna S. Significance of brain tissue oxygenation and the arachidonic acid cascade in stroke. Antioxid Redox Signal. 2011;14:1889–1903. doi:10.1089/ars.2010.3474
   PubMed Web of Science ®Google Scholar
• Hillman EM. Coupling mechanism and significance of the BOLD signal: a status report. Annu Rev Neurosci. 2014;37:161–181. doi:10.1146/annurev-neuro-071013-014111
   PubMed Web of Science ®Google Scholar
• Cipolla MJ. The cerebral circulation. San Rafael (CA); 2009.
   Google Scholar
• Claassen J, Thijssen DHJ, Panerai RB, Faraci FM. Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation. Physiol Rev. 2021;101:1487–1559. doi:10.1152/physrev.00022.2020
   PubMed Web of Science ®Google Scholar
• Mizee MR, de Vries HE. Blood-brain barrier regulation: environmental cues controlling the onset of barrier properties. Tissue Barriers. 2013;1:e26882. doi:10.4161/tisb.26882
   PubMedGoogle Scholar
• Nehlig A. Brain uptake and metabolism of ketone bodies in animal models. Prostaglandins Leukot Essent Fatty Acids. 2004;70:265–275. doi:10.1016/j.plefa.2003.07.006
   PubMed Web of Science ®Google Scholar
• Xue X, Liu B, Hu J, Bian X, Lou S. The potential mechanisms of lactate in mediating exercise-enhanced cognitive function: a dual role as an energy supply substrate and a signaling molecule. Nutr Metab (Lond). 2022;19:52. doi:10.1186/s12986-022-00687-z
   PubMed Web of Science ®Google Scholar
• Kacem K, Lacombe P, Seylaz J, Bonvento G. Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia. 1998;23:1–10. doi:10.1002/(SICI)1098-1136(199805)23:1<1::AID-GLIA1>3.0.CO;2-B
   PubMed Web of Science ®Google Scholar
• Watanabe T, Matsushima S, Okazaki M, et al. Localization and ontogeny of GLUT3 expression in the rat retina. Brain Res Dev Brain Res. 1996;94:60–66. doi:10.1016/0165-3806(96)00044-2
   PubMedGoogle Scholar
• Leloup C, Arluison M, Kassis N, et al. Discrete brain areas express the insulin-responsive glucose transporter GLUT4. Brain Res Mol Brain Res. 1996;38:45–53. doi:10.1016/0169-328X(95)00306-D
   PubMedGoogle Scholar
• Kobayashi M, Nikami H, Morimatsu M, Saito M. Expression and localization of insulin-regulatable glucose transporter (GLUT4) in rat brain. Neurosci Lett. 1996;213:103–106. doi:10.1016/0304-3940(96)12845-7
   PubMed Web of Science ®Google Scholar
• Maher F. Immunolocalization of GLUT1 and GLUT3 glucose transporters in primary cultured neurons and glia. J Neurosci Res. 1995;42:459–469. doi:10.1002/jnr.490420404
   PubMed Web of Science ®Google Scholar
• Vannucci SJ, Maher F, Simpson IA. Glucose transporter proteins in brain: delivery of glucose to neurons and glia. Glia. 1997;21:2–21. doi:10.1002/(SICI)1098-1136(199709)21:1<2::AID-GLIA2>3.0.CO;2-C
   PubMed Web of Science ®Google Scholar
• Alosco ML, Spitznagel MB, Raz N, et al. Obesity interacts with cerebral hypoperfusion to exacerbate cognitive impairment in older adults with heart failure. Cerebrovasc Dis Extra. 2012;2:88–98. doi:10.1159/000343222
   PubMedGoogle Scholar
• Selim M, Jones R, Novak P, Zhao P, Novak V. The effects of body mass index on cerebral blood flow velocity. Clin Auton Res. 2008;18:331–338. doi:10.1007/s10286-008-0490-z
   PubMed Web of Science ®Google Scholar
• Willeumier KC, Taylor DV, Amen DG. Elevated BMI is associated with decreased blood flow in the prefrontal cortex using SPECT imaging in healthy adults. Obesity (Silver Spring). 2011;19:1095–1097. doi:10.1038/oby.2011.16
   PubMed Web of Science ®Google Scholar
• Pegueroles J, Pane A, Vilaplana E, et al. Obesity impacts brain metabolism and structure independently of amyloid and tau pathology in healthy elderly. Alzheimers Dement (Amst). 2020;12:e12052.
   PubMedGoogle Scholar
• Ishibashi K, Onishi A, Fujiwara Y, Ishiwata K, Ishii K. Relationship between Alzheimer disease-like pattern of 18F-FDG and fasting plasma glucose levels in cognitively normal volunteers. J Nucl Med. 2015;56:229–233. doi:10.2967/jnumed.114.150045
   PubMed Web of Science ®Google Scholar
• Burns CM, Chen K, Kaszniak AW, et al. Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions. Neurology. 2013;80:1557–1564. doi:10.1212/WNL.0b013e31828f17de
   PubMed Web of Science ®Google Scholar
• Honea RA, John CS, Green ZD, et al. Relationship of fasting glucose and longitudinal Alzheimer’s disease imaging markers. Alzheimers Dement (N Y). 2022;8:e12239. doi:10.1002/trc2.12239
   PubMedGoogle Scholar
• Park HS, Park JY, Yu R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabet Res Clin Pract. 2005;69:29–35. doi:10.1016/j.diabres.2004.11.007
   PubMed Web of Science ®Google Scholar
• Matulewicz N, Karczewska-Kupczewska M. Insulin resistance and chronic inflammation. Postepy Hig Med Dosw (Online). 2016;70:1245–1258.
   PubMedGoogle Scholar
• Mauer J, Denson JL, Bruning JC. Versatile functions for IL-6 in metabolism and cancer. Trends Immunol. 2015;36:92–101. doi:10.1016/j.it.2014.12.008
   PubMed Web of Science ®Google Scholar
• Lyngso D, Simonsen L, Bulow J. Interleukin-6 production in human subcutaneous abdominal adipose tissue: the effect of exercise. J Physiol. 2002;543:373–378. doi:10.1113/jphysiol.2002.019380
   PubMed Web of Science ®Google Scholar
• van Hall G, Steensberg A, Sacchetti M, et al. Interleukin-6 stimulates lipolysis and fat oxidation in humans. J Clin Endocrinol Metab. 2003;88:3005–3010. doi:10.1210/jc.2002-021687
   PubMed Web of Science ®Google Scholar
• Wedell-Neergaard AS, Lang Lehrskov L, Christensen RH, et al. Exercise-induced changes in visceral adipose tissue mass are regulated by IL-6 signaling: a randomized controlled trial. Cell Metab. 2019;29:844–855 e843. doi:10.1016/j.cmet.2018.12.007
   PubMed Web of Science ®Google Scholar
• Cai D, Yuan M, Frantz DF, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005;11:183–190. doi:10.1038/nm1166
   PubMed Web of Science ®Google Scholar
• Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest. 1995;95:2111–2119. doi:10.1172/JCI117899
   PubMed Web of Science ®Google Scholar
• Remels AH, Langen RC, Gosker HR, et al. PPARgamma inhibits NF-kappaB-dependent transcriptional activation in skeletal muscle. Am J Physiol Endocrinol Metab. 2009;297:E174–183. doi:10.1152/ajpendo.90632.2008
   PubMed Web of Science ®Google Scholar
• Wascher TC, Lindeman JH, Sourij H, Kooistra T, Pacini G, Roden M. Chronic TNF-alpha neutralization does not improve insulin resistance or endothelial function in ”healthy” men with metabolic syndrome. Mol Med. 2011;17:189–193. doi:10.2119/molmed.2010.00221
   PubMed Web of Science ®Google Scholar
• Bernstein LE, Berry J, Kim S, Canavan B, Grinspoon SK. Effects of etanercept in patients with the metabolic syndrome. Arch Intern Med. 2006;166:902–908. doi:10.1001/archinte.166.8.902
   PubMed Web of Science ®Google Scholar
• Stanley TL, Zanni MV, Johnsen S, et al. TNF-alpha antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. J Clin Endocrinol Metab. 2011;96:E146–150. doi:10.1210/jc.2010-1170
   PubMed Web of Science ®Google Scholar
• Watts G. Nobel prize is awarded to doctors who discovered H pylori. BMJ. 2005;331:795. doi:10.1136/bmj.331.7520.795
   PubMedGoogle Scholar
• Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med. 2016;8:51. doi:10.1186/s13073-016-0307-y
   PubMed Web of Science ®Google Scholar
• Al-Lahham SH, Peppelenbosch MP, Roelofsen H, Vonk RJ, Venema K. Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms. Biochim Biophys Acta. 2010;1801:1175–1183. doi:10.1016/j.bbalip.2010.07.007
   PubMed Web of Science ®Google Scholar
• Yao Y, Cai X, Fei W, Ye Y, Zhao M, Zheng C. The role of short-chain fatty acids in immunity, inflammation and metabolism. Crit Rev Food Sci Nutr. 2022;62:1–12. doi:10.1080/10408398.2020.1854675
   PubMed Web of Science ®Google Scholar
• Koliada A, Syzenko G, Moseiko V, et al. Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiol. 2017;17:120. doi:10.1186/s12866-017-1027-1
   PubMed Web of Science ®Google Scholar
• Duncan SH, Lobley GE, Holtrop G, et al. Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes Lond. 2008;32:1720–1724. doi:10.1038/ijo.2008.155
   PubMed Web of Science ®Google Scholar
• Zhang Q, Hu N. Effects of metformin on the gut microbiota in obesity and type 2 diabetes mellitus. Diabetes Metab Syndr Obes. 2020;13:5003–5014. doi:10.2147/DMSO.S286430
   PubMed Web of Science ®Google Scholar
• Trikha SRJ, Lee DM, Ecton KE, et al. Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance. Gut Microbes. 2021;13:1940791. doi:10.1080/19490976.2021.1940791
   PubMed Web of Science ®Google Scholar
• Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913–916 e917. doi:10.1053/j.gastro.2012.06.031
   PubMed Web of Science ®Google Scholar
• Kootte RS, Levin E, Salojarvi J, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab. 2017;26:611–619 e616. doi:10.1016/j.cmet.2017.09.008
   PubMed Web of Science ®Google Scholar
• Nogal A, Valdes AM, Menni C. The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health. Gut Microbes. 2021;13:1–24. doi:10.1080/19490976.2021.1897212
   PubMed Web of Science ®Google Scholar
• D’Alessio DA, Kahn SE, Leusner CR, Ensinck JW. Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. J Clin Invest. 1994;93:2263–2266. doi:10.1172/JCI117225
   PubMed Web of Science ®Google Scholar
• Puddu A, Sanguineti R, Montecucco F, Viviani GL. Evidence for the gut microbiota short-chain fatty acids as key pathophysiological molecules improving diabetes. Mediators Inflamm. 2014;2014:162021. doi:10.1155/2014/162021
   PubMed Web of Science ®Google Scholar
• Morris JK, John CS, Green ZD, et al. Characterization of the meal-stimulated incretin response and relationship with structural brain outcomes in aging and Alzheimer’s Disease. Front Neurosci. 2020;14:608862. doi:10.3389/fnins.2020.608862
   PubMed Web of Science ®Google Scholar
• Pizzino G, Irrera N, Cucinotta M, et al. Oxidative stress: harms and benefits for human health. Oxid Med Cell Longev. 2017;2017:8416763. doi:10.1155/2017/8416763
   PubMed Web of Science ®Google Scholar
• Hancock JT, Desikan R, Neill SJ. Role of reactive oxygen species in cell signalling pathways. Biochem Soc Trans. 2001;29:345–350. doi:10.1042/bst0290345
   PubMed Web of Science ®Google Scholar
• Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol. 2014;24:R453–462. doi:10.1016/j.cub.2014.03.034
   PubMed Web of Science ®Google Scholar
• Tirichen H, Yaigoub H, Xu W, Wu C, Li R, Li Y. Mitochondrial reactive oxygen species and their contribution in chronic kidney disease progression through oxidative stress. Front Physiol. 2021;12:627837. doi:10.3389/fphys.2021.627837
   PubMed Web of Science ®Google Scholar
• Guo C, Sun L, Chen X, Zhang D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res. 2013;8:2003–2014. doi:10.3969/j.issn.1673-5374.2013.21.009
   PubMed Web of Science ®Google Scholar
• Wang X, Wang W, Li L, Perry G, Lee HG, Zhu X. Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease. Biochim Biophys Acta. 2014;1842:1240–1247. doi:10.1016/j.bbadis.2013.10.015
   PubMed Web of Science ®Google Scholar
• Subramaniam SR, Chesselet MF. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog Neurobiol. 2013;106–107:17–32. doi:10.1016/j.pneurobio.2013.04.004
   PubMed Web of Science ®Google Scholar
• Heiss C, Rodriguez-Mateos A, Kelm M. Central role of eNOS in the maintenance of endothelial homeostasis. Antioxid Redox Signal. 2015;22:1230–1242. doi:10.1089/ars.2014.6158
   PubMed Web of Science ®Google Scholar
• Arora D, Jain P, Singh N, Kaur H, Bhatla SC. Mechanisms of nitric oxide crosstalk with reactive oxygen species scavenging enzymes during abiotic stress tolerance in plants. Free Radic Res. 2016;50:291–303. doi:10.3109/10715762.2015.1118473
   PubMed Web of Science ®Google Scholar
• Haruna Y, Morita Y, Komai N, et al. Endothelial dysfunction in rat adjuvant-induced arthritis: vascular superoxide production by NAD(P)H oxidase and uncoupled endothelial nitric oxide synthase. Arthritis Rheum. 2006;54:1847–1855. doi:10.1002/art.21891
   PubMedGoogle Scholar
• Zhang C. The role of inflammatory cytokines in endothelial dysfunction. Basic Res Cardiol. 2008;103:398–406. doi:10.1007/s00395-008-0733-0
   PubMed Web of Science ®Google Scholar
• Anderson TJ. Assessment and treatment of endothelial dysfunction in humans. J Am Coll Cardiol. 1999;34:631–638. doi:10.1016/S0735-1097(99)00259-4
   PubMed Web of Science ®Google Scholar
• Venturelli M, Pedrinolla A, Boscolo Galazzo I, et al. Impact of nitric oxide bioavailability on the progressive cerebral and peripheral circulatory impairments during aging and Alzheimer’s disease. Front Physiol. 2018;9:169. doi:10.3389/fphys.2018.00169
   PubMed Web of Science ®Google Scholar
• Smith KJ, Kapoor R, Felts PA. Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol. 1999;9:69–92. doi:10.1111/j.1750-3639.1999.tb00212.x
   PubMed Web of Science ®Google Scholar
• Yang K, Wu Z, Long J, et al. White matter changes in Parkinson’s disease. NPJ Parkinsons Dis. 2023;9:150. doi:10.1038/s41531-023-00592-z
   PubMed Web of Science ®Google Scholar
• Kloppenborg RP, Nederkoorn PJ, Geerlings MI, van den Berg E. Presence and progression of white matter hyperintensities and cognition: a meta-analysis. Neurology. 2014;82:2127–2138. doi:10.1212/WNL.0000000000000505
   PubMed Web of Science ®Google Scholar
• Bouhrara M, Khattar N, Elango P, Resnick SM, Ferrucci L, Spencer RG. Evidence of association between obesity and lower cerebral myelin content in cognitively unimpaired adults. Int J Obes Lond. 2021;45:850–859. doi:10.1038/s41366-021-00749-x
   PubMed Web of Science ®Google Scholar
• Laporte JP, Faulkner ME, Gong Z, et al. Hypertensive adults exhibit lower myelin content: a multicomponent relaxometry and diffusion magnetic resonance imaging study. Hypertension. 2023;80:1728–1738. doi:10.1161/HYPERTENSIONAHA.123.21012
   PubMed Web of Science ®Google Scholar
• Burzynska AZ, Anderson C, Arciniegas DB, et al. Metabolic syndrome and adiposity: risk factors for decreased myelin in cognitively healthy adults. Cereb Circ Cogn Behav. 2023;5:100180. doi:10.1016/j.cccb.2023.100180
   PubMedGoogle Scholar
• Hindle JV. Ageing, neurodegeneration and Parkinson’s disease. Age Ageing. 2010;39:156–161. doi:10.1093/ageing/afp223
   PubMed Web of Science ®Google Scholar
• Pagano G, Polychronis S, Wilson H, et al. Diabetes mellitus and Parkinson disease. Neurology. 2018;90:e1654–e1662. doi:10.1212/WNL.0000000000005475
   PubMed Web of Science ®Google Scholar
• Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004;61:661–666. doi:10.1001/archneur.61.5.661
   PubMed Web of Science ®Google Scholar
• Ismail Z, Malick A, Smith EE, Schweizer T, Fischer C. Depression versus dementia: is this construct still relevant? Neurodegener Dis Manag. 2014;4:119–126. doi:10.2217/nmt.14.5
   PubMedGoogle Scholar
• Djamshidian A, Friedman JH. Anxiety and depression in Parkinson’s disease. Curr Treat Options Neurol. 2014;16:285. doi:10.1007/s11940-014-0285-6
   PubMed Web of Science ®Google Scholar
• Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261:921–923. doi:10.1126/science.8346443
   PubMed Web of Science ®Google Scholar
• Linton MF, Gish R, Hubl ST, et al. Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation. J Clin Invest. 1991;88:270–281. doi:10.1172/JCI115288
   PubMed Web of Science ®Google Scholar
• Martinez-Morillo E, Hansson O, Atagi Y, et al. Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer’s disease patients and controls. Acta Neuropathol. 2014;127:633–643. doi:10.1007/s00401-014-1266-2
   PubMed Web of Science ®Google Scholar
• Serrano-Pozo A, Das S, Hyman BT. APOE and Alzheimer’s disease: advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol. 2021;20:68–80. doi:10.1006/exnr.1994.1044
   PubMed Web of Science ®Google Scholar
• Triebswetter C, Kiely M, Khattar N, et al. Differential associations between apolipoprotein E alleles and cerebral myelin content in normative aging. Neuroimage. 2022;251:118988. doi:10.1016/j.neuroimage.2022.118988
   PubMed Web of Science ®Google Scholar
• Belvisi D, Pellicciari R, Fabbrini A, et al. Risk factors of Parkinson disease: simultaneous assessment, interactions, and etiologic subtypes. Neurology. 2020;95:e2500–e2508. doi:10.1212/WNL.0000000000010813
   PubMed Web of Science ®Google Scholar
• Ettle B, Kerman BE, Valera E, et al. alpha-Synuclein-induced myelination deficit defines a novel interventional target for multiple system atrophy. Acta Neuropathol. 2016;132:59–75. doi:10.1007/s00401-016-1572-y
   PubMed Web of Science ®Google Scholar
• Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature. 1997;388:839–840. doi:10.1038/42166
   PubMed Web of Science ®Google Scholar
• Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997;276:2045–2047. doi:10.1126/science.276.5321.2045
   PubMed Web of Science ®Google Scholar
• Peng C, Gathagan RJ, Covell DJ, et al. Cellular milieu imparts distinct pathological alpha-synuclein strains in alpha-synucleinopathies. Nature. 2018;557:558–563. doi:10.1038/s41586-018-0104-4
   PubMed Web of Science ®Google Scholar
• de Bem AF, Krolow R, Farias HR, et al. Animal models of metabolic disorders in the study of neurodegenerative diseases: an overview. Front Neurosci. 2020;14:604150. doi:10.3389/fnins.2020.604150
   PubMed Web of Science ®Google Scholar
• Wieckowska-Gacek A, Mietelska-Porowska A, Wydrych M, Wojda U. Western diet as a trigger of Alzheimer’s disease: from metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration. Ageing Res Rev. 2021;70:101397. doi:10.1016/j.arr.2021.101397
   PubMed Web of Science ®Google Scholar
• Amelianchik A, Sweetland-Martin L, Norris EH. The effect of dietary fat consumption on Alzheimer’s disease pathogenesis in mouse models. Transl Psychiatry. 2022;12:293. doi:10.1038/s41398-022-02067-w
   PubMed Web of Science ®Google Scholar
• Sparks DL, Scheff SW, Hunsaker JC 3rd, Liu H, Landers T, Gross DR. Induction of Alzheimer-like beta-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol. Exp Neurol. 1994;126:88–94.
   PubMed Web of Science ®Google Scholar
• Refolo LM, Malester B, LaFrancois J, et al. Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model. Neurobiol Dis. 2000;7:321–331. doi:10.1006/nbdi.2000.0304
   PubMed Web of Science ®Google Scholar
• Ullrich C, Pirchl M, Humpel C. Hypercholesterolemia in rats impairs the cholinergic system and leads to memory deficits. Mol Cell Neurosci. 2010;45:408–417. doi:10.1016/j.mcn.2010.08.001
   PubMed Web of Science ®Google Scholar
• Moreira EL, de Oliveira J, Engel DF, et al. Hypercholesterolemia induces short-term spatial memory impairments in mice: up-regulation of acetylcholinesterase activity as an early and causal event? J Neural Transm (Vienna). 2014;121:415–426. doi:10.1007/s00702-013-1107-9
   PubMed Web of Science ®Google Scholar
• Ho L, Qin W, Pompl PN, et al. Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer’s disease. FASEB J. 2004;18:902–904. doi:10.1096/fj.03-0978fje
   PubMed Web of Science ®Google Scholar
• Wang X, Zheng W, Xie JW, et al. Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model. Mol Neurodegener. 2010;5:46. doi:10.1186/1750-1326-5-46
   PubMed Web of Science ®Google Scholar
• Hascup ER, Broderick SO, Russell MK, et al. Diet-induced insulin resistance elevates hippocampal glutamate as well as VGLUT1 and GFAP expression in AbetaPP/PS1 mice. J Neurochem. 2019;148:219–237. doi:10.1111/jnc.14634
   PubMed Web of Science ®Google Scholar
• Yekollu SK, Thomas R, O’Sullivan B. Targeting curcusomes to inflammatory dendritic cells inhibits NF-kappaB and improves insulin resistance in obese mice. Diabetes. 2011;60:2928–2938. doi:10.2337/db11-0275
   PubMed Web of Science ®Google Scholar
• Hasegawa Y, Saito T, Ogihara T, et al. Blockade of the nuclear factor-kappaB pathway in the endothelium prevents insulin resistance and prolongs life spans. Circulation. 2012;125:1122–1133. doi:10.1161/CIRCULATIONAHA.111.054346
   PubMed Web of Science ®Google Scholar
• Wang C, Fan L, Khawaja RR, et al. Microglial NF-kappaB drives tau spreading and toxicity in a mouse model of tauopathy. Nat Commun. 2022;13:1969. doi:10.1038/s41467-022-29552-6
   PubMed Web of Science ®Google Scholar
• Sandhu M, Irfan HM, Shah SA, et al. Friedelin attenuates neuronal dysfunction and memory impairment by inhibition of the activated JNK/NF-kappaB signalling pathway in scopolamine-induced mice model of neurodegeneration. Molecules. 2022;27. doi:10.3390/molecules28010027
   PubMed Web of Science ®Google Scholar
• Dye L, Boyle NB, Champ C, Lawton C. The relationship between obesity and cognitive health and decline. Proc Nutr Soc. 2017;76:443–454. doi:10.1017/S0029665117002014
   PubMed Web of Science ®Google Scholar
• Pugazhenthi S, Qin L, Reddy PH. Common neurodegenerative pathways in obesity, diabetes, and Alzheimer’s disease. Biochim Biophys Acta Mol Basis Dis. 2017;1863:1037–1045. doi:10.1016/j.bbadis.2016.04.017
   PubMed Web of Science ®Google Scholar
• Garcia-Ptacek S, Faxen-Irving G, Cermakova P, Eriksdotter M, Religa D. Body mass index in dementia. Eur J Clin Nutr. 2014;68:1204–1209. doi:10.1038/ejcn.2014.199
   PubMed Web of Science ®Google Scholar
• Lung T, Jan S, Tan EJ, Killedar A, Hayes A. Impact of overweight, obesity and severe obesity on life expectancy of Australian adults. Int J Obes Lond. 2019;43:782–789. doi:10.1038/s41366-018-0210-2
   PubMed Web of Science ®Google Scholar
• Buchman AS, Capuano AW, VanderHorst V, et al. Brain beta-amyloid links the association of change in body mass index with cognitive decline in community-dwelling older adults. J Gerontol a Biol Sci Med Sci. 2023;78:277–285. doi:10.1093/gerona/glab320
   PubMed Web of Science ®Google Scholar
• Clark LR, Koscik RL, Allison SL, et al. Hypertension and obesity moderate the relationship between beta-amyloid and cognitive decline in midlife. Alzheimers Dement. 2019;15:418–428. doi:10.1016/j.jalz.2018.09.008
   PubMed Web of Science ®Google Scholar
• Herrmann MJ, Tesar AK, Beier J, Berg M, Warrings B. Grey matter alterations in obesity: a meta-analysis of whole-brain studies. Obes Rev. 2019;20:464–471. doi:10.1111/obr.12799
   PubMed Web of Science ®Google Scholar
• Papageorgiou I, Astrakas LG, Xydis V, et al. Abnormalities of brain neural circuits related to obesity: a diffusion tensor imaging study. Magn Reson Imaging. 2017;37:116–121. doi:10.1016/j.mri.2016.11.018
   PubMed Web of Science ®Google Scholar
• Repple J, Opel N, Meinert S, et al. Elevated body-mass index is associated with reduced white matter integrity in two large independent cohorts. Psychoneuroendocrinology. 2018;91:179–185. doi:10.1016/j.psyneuen.2018.03.007
   PubMed Web of Science ®Google Scholar
• Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997;278:1349–1356. doi:10.1001/jama.1997.03550160069041
   PubMed Web of Science ®Google Scholar
• Gustafson D, Lissner L, Bengtsson C, Bjorkelund C, Skoog I. A 24-year follow-up of body mass index and cerebral atrophy. Neurology. 2004;63:1876–1881. doi:10.1212/01.WNL.0000141850.47773.5F
   PubMed Web of Science ®Google Scholar
• Zhu D, Chung HF, Pandeya N, et al. Body mass index and age at natural menopause: an international pooled analysis of 11 prospective studies. Eur J Epidemiol. 2018;33:699–710. doi:10.1007/s10654-018-0367-y
   PubMed Web of Science ®Google Scholar
• Lu W, Guo W, Hou K, et al. Grey matter differences associated with age and sex hormone levels between premenopausal and perimenopausal women: a voxel-based morphometry study. J Neuroendocrinol. 2018;30:e12655. doi:10.1111/jne.12655
   PubMed Web of Science ®Google Scholar
• Mosconi L, Rahman A, Diaz I, et al. Increased Alzheimer’s risk during the menopause transition: a 3-year longitudinal brain imaging study. PLoS One. 2018;13:e0207885. doi:10.1371/journal.pone.0207885
   PubMed Web of Science ®Google Scholar
• Franz CE, Xian H, Lew D, et al. Body mass trajectories and cortical thickness in middle-aged men: a 42-year longitudinal study starting in young adulthood. Neurobiol Aging. 2019;79:11–21. doi:10.1016/j.neurobiolaging.2019.03.003
   PubMed Web of Science ®Google Scholar
• Morys F, Dadar M, Dagher A. Association between midlife obesity and its metabolic consequences, cerebrovascular disease, and cognitive decline. J Clin Endocrinol Metab. 2021;106:e4260–e4274. doi:10.1210/clinem/dgab135
   PubMed Web of Science ®Google Scholar
• Maffei M, Halaas J, Ravussin E, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995;1:1155–1161. doi:10.1038/nm1195-1155
   PubMed Web of Science ®Google Scholar
• Alexander C, Cochran CJ, Gallicchio L, Miller SR, Flaws JA, Zacur H. Serum leptin levels, hormone levels, and hot flashes in midlife women. Fertil Steril. 2010;94:1037–1043. doi:10.1016/j.fertnstert.2009.04.001
   PubMed Web of Science ®Google Scholar
• Banks WA, Kastin AJ, Huang W, Jaspan JB, Maness LM. Leptin enters the brain by a saturable system independent of insulin. Peptides. 1996;17:305–311. doi:10.1016/0196-9781(96)00025-3
   PubMed Web of Science ®Google Scholar
• Garza JC, Guo M, Zhang W, Lu XY. Leptin increases adult hippocampal neurogenesis in vivo and in vitro. J Biol Chem. 2008;283:18238–18247. doi:10.1074/jbc.M800053200
   PubMed Web of Science ®Google Scholar
• Narita K, Kosaka H, Okazawa H, Murata T, Wada Y. Relationship between plasma leptin level and brain structure in elderly: a voxel-based morphometric study. Biol Psychiatry. 2009;65:992–994. doi:10.1016/j.biopsych.2008.10.006
   PubMed Web of Science ®Google Scholar
• Obradovic M, Sudar-Milovanovic E, Soskic S, et al. Leptin and obesity: role and clinical implication. Front Endocrinol (Lausanne). 2021;12:585887. doi:10.3389/fendo.2021.585887
   PubMed Web of Science ®Google Scholar
• Witte AV, Kobe T, Graunke A, et al. Impact of leptin on memory function and hippocampal structure in mild cognitive impairment. Hum Brain Mapp. 2016;37:4539–4549. doi:10.1002/hbm.23327
   PubMed Web of Science ®Google Scholar
• Savica R, Rocca WA, Ahlskog JE. When does Parkinson disease start? Arch Neurol. 2010;67:798–801. doi:10.1001/archneurol.2010.135
   PubMed Web of Science ®Google Scholar
• Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001;50:537–546.
   PubMed Web of Science ®Google Scholar
• Gallego M, Setien R, Izquierdo MJ, Casis O, Casis E. Diabetes-induced biochemical changes in central and peripheral catecholaminergic systems. Physiol Res. 2003;52:735–741. doi:10.33549/physiolres.930334
   PubMed Web of Science ®Google Scholar
• Shimomura Y, Shimizu H, Takahashi M, et al. Changes in ambulatory activity and dopamine turnover in streptozotocin-induced diabetic rats. Endocrinology. 1988;123:2621–2625. doi:10.1210/endo-123-6-2621
   PubMed Web of Science ®Google Scholar
• Jones KT, Woods C, Zhen J, Antonio T, Carr KD, Reith ME. Effects of diet and insulin on dopamine transporter activity and expression in rat caudate-putamen, nucleus accumbens, and midbrain. J Neurochem. 2017;140:728–740. doi:10.1111/jnc.13930
   PubMed Web of Science ®Google Scholar
• Anitha M, Abraham PM, Paulose CS. Striatal dopamine receptors modulate the expression of insulin receptor, IGF-1 and GLUT-3 in diabetic rats: effect of pyridoxine treatment. Eur J Pharmacol. 2012;696:54–61. doi:10.1016/j.ejphar.2012.09.006
   PubMed Web of Science ®Google Scholar
• Choi JY, Jang EH, Park CS, Kang JH. Enhanced susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in high-fat diet-induced obesity. Free Radic Biol Med. 2005;38:806–816. doi:10.1016/j.freeradbiomed.2004.12.008
   PubMed Web of Science ®Google Scholar
• Morris JK, Bomhoff GL, Stanford JA, Geiger PC. Neurodegeneration in an animal model of Parkinson’s disease is exacerbated by a high-fat diet. Am J Physiol Regul Integr Comp Physiol. 2010;299:R1082–1090. doi:10.1152/ajpregu.00449.2010
   PubMed Web of Science ®Google Scholar
• Sharma S, Taliyan R. High fat diet feeding induced insulin resistance exacerbates 6-OHDA mediated neurotoxicity and behavioral abnormalities in rats. Behav Brain Res. 2018;351:17–23. doi:10.1016/j.bbr.2018.05.025
   PubMed Web of Science ®Google Scholar
• Bousquet M, St-Amour I, Vandal M, Julien P, Cicchetti F, Calon F. High-fat diet exacerbates MPTP-induced dopaminergic degeneration in mice. Neurobiol Dis. 2012;45:529–538. doi:10.1016/j.nbd.2011.09.009
   PubMed Web of Science ®Google Scholar
• Griffioen KJ, Rothman SM, Ladenheim B, et al. Dietary energy intake modifies brainstem autonomic dysfunction caused by mutant alpha-synuclein. Neurobiol Aging. 2013;34:928–935. doi:10.1016/j.neurobiolaging.2012.07.008
   PubMed Web of Science ®Google Scholar
• Rotermund C, Truckenmuller FM, Schell H, Kahle PJ. Diet-induced obesity accelerates the onset of terminal phenotypes in alpha-synuclein transgenic mice. J Neurochem. 2014;131:848–858. doi:10.1111/jnc.12813
   PubMed Web of Science ®Google Scholar
• Morris JK, Bomhoff GL, Gorres BK, et al. Insulin resistance impairs nigrostriatal dopamine function. Exp Neurol. 2011;231:171–180. doi:10.1016/j.expneurol.2011.06.005
   PubMed Web of Science ®Google Scholar
• Hebert MA, Gerhardt GA. Normal and drug-induced locomotor behavior in aging: comparison to evoked DA release and tissue content in Fischer 344 rats. Brain Res. 1998;797:42–54. doi:10.1016/S0006-8993(98)00370-9
   PubMed Web of Science ®Google Scholar
• Bharath S, Hsu M, Kaur D, Rajagopalan S, Andersen JK. Glutathione, iron and Parkinson’s disease. Biochem Pharmacol. 2002;64:1037–1048. doi:10.1016/S0006-2952(02)01174-7
   PubMed Web of Science ®Google Scholar
• Ma D, Shuler JM, Raider KD, et al. Effects of discontinuing a high-fat diet on mitochondrial proteins and 6-hydroxydopamine-induced dopamine depletion in rats. Brain Res. 2015;1613:49–58. doi:10.1016/j.brainres.2015.03.053
   PubMed Web of Science ®Google Scholar
• Hirsch L, Jette N, Frolkis A, Steeves T, Pringsheim T. The incidence of Parkinson’s disease: a systematic review and meta-analysis. Neuroepidemiology. 2016;46:292–300. doi:10.1159/000445751
   PubMed Web of Science ®Google Scholar
• Wright Willis A, Evanoff BA, Lian M, Criswell SR, Racette BA. Geographic and ethnic variation in Parkinson disease: a population-based study of US Medicare beneficiaries. Neuroepidemiology. 2010;34:143–151. doi:10.1159/000275491
   PubMed Web of Science ®Google Scholar
• Narayan S, Liew Z, Bronstein JM, Ritz B. Occupational pesticide use and Parkinson’s disease in the Parkinson Environment Gene (PEG) study. Environ Int. 2017;107:266–273. doi:10.1016/j.envint.2017.04.010
   PubMed Web of Science ®Google Scholar
• Dannawi M, Riachi ME, Haddad AF, et al. Influence of intermittent fasting on prediabetes-induced neuropathy: insights on a novel mechanistic pathway. Metabol Open. 2022;14:100175. doi:10.1016/j.metop.2022.100175
   PubMedGoogle Scholar
• Schonknecht YB, Crommen S, Stoffel-Wagner B, et al. Acute effects of three different meal patterns on postprandial metabolism in older individuals with a risk phenotype for cardiometabolic diseases: a randomized controlled crossover trial. Mol Nutr Food Res. 2020;64:e1901035. doi:10.1002/mnfr.201901035
   PubMed Web of Science ®Google Scholar
• Schonknecht YB, Crommen S, Stoffel-Wagner B, et al. APOE varepsilon4 is associated with postprandial inflammation in older adults with metabolic syndrome traits. Nutrients. 2021;13:3924.
   PubMed Web of Science ®Google Scholar
• Witte AV, Fobker M, Gellner R, Knecht S, Floel A. Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A. 2009;106:1255–1260. doi:10.1073/pnas.0808587106
   PubMed Web of Science ®Google Scholar
• Prehn K, Jumpertz von schwartzenberg R, Mai K, et al. Caloric restriction in older adults-differential effects of weight loss and reduced weight on brain structure and function. Cereb Cortex. 2017;27:1765–1778. doi:10.1093/cercor/bhw008
   PubMed Web of Science ®Google Scholar
• Owen OE, Felig P, Morgan AP, Wahren J, Cahill GF Jr. Liver and kidney metabolism during prolonged starvation. J Clin Invest. 1969;48:574–583. doi:10.1172/JCI106016
   PubMed Web of Science ®Google Scholar
• Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimers Res Ther. 2021;13:51. doi:10.1186/s13195-021-00783-x
   PubMed Web of Science ®Google Scholar
• Ota M, Matsuo J, Ishida I, et al. Effects of a medium-chain triglyceride-based ketogenic formula on cognitive function in patients with mild-to-moderate Alzheimer’s disease. Neurosci Lett. 2019;690:232–236. doi:10.1016/j.neulet.2018.10.048
   PubMed Web of Science ®Google Scholar
• Phillips MCL, Murtagh DKJ, Gilbertson LJ, Asztely FJS, Lynch CDP. Low-fat versus ketogenic diet in Parkinson’s disease: a pilot randomized controlled trial. Mov Disord. 2018;33:1306–1314. doi:10.1002/mds.27390
   PubMed Web of Science ®Google Scholar
• Myers J, Kokkinos P, Nyelin E. Physical activity, cardiorespiratory fitness, and the metabolic syndrome. Nutrients. 2019;11:1652.
   PubMed Web of Science ®Google Scholar
• Lavie CJ, Ozemek C, Carbone S, Katzmarzyk PT, Blair SN. Sedentary behavior, exercise, and cardiovascular health. Circ Res. 2019;124:799–815. doi:10.1161/CIRCRESAHA.118.312669
   PubMed Web of Science ®Google Scholar
• Hotting K, Roder B. Beneficial effects of physical exercise on neuroplasticity and cognition. Neurosci Biobehav Rev. 2013;37:2243–2257. doi:10.1016/j.neubiorev.2013.04.005
   PubMed Web of Science ®Google Scholar
• Chodzko-Zajko WJ, Proctor DN; American College of Sports M. American College of Sports Medicine position stand. Exercise and physical activity for older adults. Med Sci Sports Exerc. 2009;41:1510–1530. doi:10.1249/MSS.0b013e3181a0c95c
   PubMed Web of Science ®Google Scholar
• Goodpaster BH, Wolfe RR, Kelley DE. Effects of obesity on substrate utilization during exercise. Obes Res. 2002;10:575–584. doi:10.1038/oby.2002.78
   PubMedGoogle Scholar
• Morris JK, Vidoni ED, Johnson DK, et al. Aerobic exercise for Alzheimer’s disease: a randomized controlled pilot trial. PLoS One. 2017;12:e0170547. doi:10.1371/journal.pone.0170547
   PubMed Web of Science ®Google Scholar
• Dauwan M, Begemann MJH, Slot MIE, Lee EHM, Scheltens P, Sommer IEC. Physical exercise improves quality of life, depressive symptoms, and cognition across chronic brain disorders: a transdiagnostic systematic review and meta-analysis of randomized controlled trials. J Neurol. 2021;268:1222–1246. doi:10.1007/s00415-019-09493-9
   PubMed Web of Science ®Google Scholar
• Schenkman M, Moore CG, Kohrt WM, et al. Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson disease: a Phase 2 randomized clinical trial. JAMA Neurol. 2018;75:219–226. doi:10.1001/jamaneurol.2017.3517
   PubMed Web of Science ®Google Scholar
• Motiani KK, Collado MC, Eskelinen JJ, et al. Exercise training modulates gut microbiota profile and improves endotoxemia. Med Sci Sports Exerc. 2020;52:94–104. doi:10.1249/MSS.0000000000002112
   PubMed Web of Science ®Google Scholar
• Numakawa T, Odaka H. The Role of neurotrophin signaling in age-related cognitive decline and cognitive diseases. Int J Mol Sci. 2022;23:7726. doi:10.3390/ijms23147726
   PubMed Web of Science ®Google Scholar
• Kim CS, Cha L, Sim M, et al. Probiotic supplementation improves cognitive function and mood with changes in gut microbiota in community-dwelling older adults: a randomized, double-blind, placebo-controlled, multicenter trial. J Gerontol a Biol Sci Med Sci. 2021;76:32–40. doi:10.1093/gerona/glaa090
   PubMed Web of Science ®Google Scholar
• Berchtold NC, Chinn G, Chou M, Kesslak JP, Cotman CW. Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience. 2005;133:853–861. doi:10.1016/j.neuroscience.2005.03.026
   PubMed Web of Science ®Google Scholar
• Kim DM, Leem YH. Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction. Neuroscience. 2016;324:271–285. doi:10.1016/j.neuroscience.2016.03.019
   PubMed Web of Science ®Google Scholar
• Gaitan JM, Moon HY, Stremlau M, et al. Effects of aerobic exercise training on systemic biomarkers and cognition in late middle-aged adults at risk for Alzheimer’s disease. Front Endocrinol (Lausanne). 2021;12:660181. doi:10.3389/fendo.2021.660181
   PubMed Web of Science ®Google Scholar
• Atrooz F, Salim S. Sleep deprivation, oxidative stress and inflammation. Adv Protein Chem Struct Biol. 2020;119:309–336.
   PubMed Web of Science ®Google Scholar
• Hargens TA, Kaleth AS, Edwards ES, Butner KL. Association between sleep disorders, obesity, and exercise: a review. Nat Sci Sleep. 2013;5:27–35. doi:10.2147/NSS.S34838
   PubMedGoogle Scholar
• Lucey BP, Hicks TJ, McLeland JS, et al. Effect of sleep on overnight cerebrospinal fluid amyloid beta kinetics. Ann Neurol. 2018;83:197–204. doi:10.1002/ana.25117
   PubMed Web of Science ®Google Scholar
• Curcio G, Ferrara M, De Gennaro L. Sleep loss, learning capacity and academic performance. Sleep Med Rev. 2006;10:323–337. doi:10.1016/j.smrv.2005.11.001
   PubMed Web of Science ®Google Scholar
• Gillen-O’Neel C, Huynh VW, Fuligni AJ. To study or to sleep? The academic costs of extra studying at the expense of sleep. Child Dev. 2013;84:133–142. doi:10.1111/j.1467-8624.2012.01834.x
   PubMed Web of Science ®Google Scholar
• Krause AJ, Simon EB, Mander BA, et al. The sleep-deprived human brain. Nat Rev Neurosci. 2017;18:404–418. doi:10.1038/nrn.2017.55
   PubMed Web of Science ®Google Scholar
• Rothman SM, Herdener N, Frankola KA, Mughal MR, Mattson MP. Chronic mild sleep restriction accentuates contextual memory impairments, and accumulations of cortical Abeta and pTau in a mouse model of Alzheimer’s disease. Brain Res. 2013;1529:200–208. doi:10.1016/j.brainres.2013.07.010
   PubMed Web of Science ®Google Scholar
• Reutrakul S, Van Cauter E. Sleep influences on obesity, insulin resistance, and risk of type 2 diabetes. Metabolism. 2018;84:56–66. doi:10.1016/j.metabol.2018.02.010
   PubMed Web of Science ®Google Scholar