Obesity and Alzheimer’s disease





obesity, metabolic syndrome, Alzheimer’s disease, cognitive disorders


The article reviews modern information on epidemiology and risk factors for Alzheimer’s disease in obesity. The literature data on the main pathogenetic links of the development of neurodegenerative disorders in patients with obesity and metabolic syndrome are analyzed, as well as the mechanisms of mutual burden. The article deals with the results of clinical studies on the possibilities of pathogenetic correction of cognitive disorders in Alzheimer’s disease, which runs on the background of obesity.


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World Population Review. Most Obese Countries 2020. Available from: http://worldpopulationreview.com/countries/most-obese-countries/.

Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15(5):288–298. doi:10.1038/s41574-019-0176-8.

NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017;390(10113):2627–2642. doi:10.1016/S0140-6736(17)32129-3.

World Health Organization. Dementia. Available from: https://www.who.int/en/news-room/fact-sheets/detail/dementia.

Lane CA, Hardy J, Schott JM. Alzheimer's disease. Eur J Neurol. 2018;25(1):59–70. doi:10.1111/ene.13439.

Barron AM, Rosario ER, Elteriefi R, Pike CJ. Sex-specific effects of high fat diet on indices of metabolic syndrome in 3xTg-AD mice: implications for Alzheimer's disease. PLoS One. 2013;8(10):e78554. doi:10.1371/journal.pone.0078554.

Julien C, Tremblay C, Phivilay A, et al. High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model. Neurobiol Aging. 2010;31(9):1516–1531. doi:10.1016/j.neurobiolaging.2008.08.022.

Knight EM, Martins IV, Gümüsgöz S, Allan SM, Lawrence CB. High-fat diet-induced memory impairment in triple-transgenic Alzheimer's disease (3xTgAD) mice is independent of changes in amyloid and tau pathology. Neurobiol Aging. 2014;35(8):1821–1832. doi:10.1016/j.neurobiolaging.2014.02.010.

Ho AJ, Raji CA, Becker JT, et al. Obesity is linked with lower brain volume in 700 AD and MCI patients. Neurobiol Aging. 2010;31(8):1326–1339. doi:10.1016/j.neurobiolaging.2010.04.006.

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:10.1212/WNL.0b013e3182190d09.

Profenno LA, Porsteinsson AP, Faraone SV. Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders. Biol Psychiatry. 2010;67(6):505–512. doi:10.1016/j.biopsych.2009.02.013. 

Gustafson D, Rothenberg E, Blennow K, Steen B, Skoog I. An 18-year follow-up of overweight and risk of Alzheimer disease. Arch Intern Med. 2003;163(13):1524–1528. doi:10.1001/archinte.163.13.1524.

Luchsinger JA, Cheng D, Tang MX, Schupf N, Mayeux R. Central obesity in the elderly is related to late-onset Alzheimer disease. Alzheimer Dis Assoc Disord. 2012;26(2):101–105. doi:10.1097/WAD.0b013e318222f0d4.

Wotton CJ, Goldacre MJ. Age at obesity and association with subsequent dementia: record linkage study. Postgrad Med J. 2014;90(1068):547–551. doi:10.1136/postgradmedj-2014-132571.

Moser VA, Pike CJ. Obesity and sex interact in the regulation of Alzheimer's disease. Neurosci Biobehav Rev. 2016;67:102–118. doi:10.1016/j.neubiorev.2015.08.021.

Singh-Manoux A, Dugravot A, Shipley M, et al. Obesity trajectories and risk of dementia: 28 years of follow-up in the Whitehall II Study. Alzheimers Dement. 2018;14(2):178–186. doi:10.1016/j.jalz.2017.06.2637.

Fitzpatrick AL, Kuller LH, Lopez OL, et al. Midlife and late-life obesity and the risk of dementia: cardiovascular health study. Arch Neurol. 2009;66(3):336–342. doi:10.1001/archneurol.2008.582. 

Anstey KJ, Cherbuin N, Budge M, Young J. 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. doi:10.1111/j.1467-789X.2010.00825.x. 

Lee CM, Woodward M, Batty GD, et al. Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia. Obes Rev. 2020;10.1111/obr.12989. doi:10.1111/obr.12989.

Li XY, Zhang M, Xu W, et al. Midlife Modifiable Risk Factors for Dementia: A Systematic Review and Meta-analysis of 34 Prospective Cohort Studies. Curr Alzheimer Res. 2019;16(14):1254–1268. doi:10.2174/1567205017666200103111253.

Borshchev YY, Uspensky YP, Galagudza MM. Pathogenetic pathways of cognitive dysfunction and dementia in metabolic syndrome. Life Sci. 2019;237:116932. doi:10.1016/j.lfs.2019.116932.

Silva MVF, Loures CMG, Alves LCV, de Souza LC, Borges KBG, Carvalho MDG. Alzheimer's disease: risk factors and potentially protective measures. J Biomed Sci. 2019;26(1):33. doi:10.1186/s12929-019-0524-y.

Folch J, Olloquequi J, Ettcheto M, et al. The Involvement of Peripheral and Brain Insulin Resistance in Late Onset Alzheimer's Dementia. Front Aging Neurosci. 2019;11:236. doi:10.3389/fnagi.2019.00236.

Pashkovska NV, Pankiv VI, Grinko NV, Pashkovska OV. Diabetes mellitus and and Alzheimer’s disease. Mìžnarodnij endokrinologìčnij žurnal. 2019;15(3):188-195. doi: 10.22141/2224-0721.15.3.2019.172103.

Gudala K, Bansal D, Schifano F, Bhansali A. Diabetes mellitus and risk of dementia: A meta-analysis of prospective observational studies. J Diabetes Investig. 2013;4(6):640–650. doi:10.1111/jdi.12087.

Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999;53(9):1937–1942. doi:10.1212/wnl.53.9.1937.

Cheng G, Huang C, Deng H, Wang H. Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies. Intern Med J. 2012;42(5):484–491. doi:10.1111/j.1445-5994.2012.02758.x.

Dodd GT, Tiganis T. Insulin action in the brain: Roles in energy and glucose homeostasis. J Neuroendocrinol. 2017;29(10):10.1111/jne.12513. doi:10.1111/jne.12513.

Costello DA, Claret M, Al-Qassab H, et al. Brain deletion of insulin receptor substrate 2 disrupts hippocampal synaptic plasticity and metaplasticity. PLoS One. 2012;7(2):e31124. doi:10.1371/journal.pone.0031124.

Crane PK, Walker R, Hubbard RA, et al. Glucose levels and risk of dementia. N Engl J Med. 2013;369(6):540–548. doi:10.1056/NEJMoa1215740.

Laws SM, Gaskin S, Woodfield A, et al. Insulin resistance is associated with reductions in specific cognitive domains and increases in CSF tau in cognitively normal adults. Sci Rep. 2017;7(1):9766. doi:10.1038/s41598-017-09577-4.

Bernstein LH. Brain and Cognition. Available from: https://pharmaceuticalintelligence.com/2015/10/14/brain-and-cognition/.

de la Monte SM, Tong M. Brain metabolic dysfunction at the core of Alzheimer's disease. Biochem Pharmacol. 2014;88(4):548–559. doi:10.1016/j.bcp.2013.12.012.

Derakhshan F, Toth C. Insulin and the brain. Curr Diabetes Rev. 2013;9(2):102–116.

Shpakov A, Chistyakova O, Derkach K, Bondareva V, autors; Chang RCC, editor. Hormonal signaling systems of the brain in diabetes mellitus. Rijeka (Croatia): Intech Open Access Publisher; 2011. 349-386 pp. doi: 10.5772/28930.

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:10.2337/db14-0568.

Leszek J, Trypka E, Tarasov VV, Ashraf GM, Aliev G. Type 3 Diabetes Mellitus: A Novel Implication of Alzheimers Disease. Curr Top Med Chem. 2017;17(12):1331–1335. doi:10.2174/1568026617666170103163403.

Jackson K, Barisone GA, Diaz E, Jin LW, DeCarli C, Despa F. Amylin deposition in the brain: A second amyloid in Alzheimer disease?. Ann Neurol. 2013;74(4):517–526. doi:10.1002/ana.23956.

Xie L, Helmerhorst E, Taddei K, Plewright B, Van Bronswijk W, Martins R. Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor. J Neurosci. 2002;22(10):RC221. doi:10.1523/JNEUROSCI.22-10-j0001.2002.

Pivovarova O, Höhn A, Grune T, Pfeiffer AF, Rudovich N. Insulin-degrading enzyme: new therapeutic target for diabetes and Alzheimer's disease?. Ann Med. 2016;48(8):614–624. doi:10.1080/07853890.2016.1197416.

Kimura N. Diabetes Mellitus Induces Alzheimer's Disease Pathology: Histopathological Evidence from Animal Models. Int J Mol Sci. 2016;17(4):503. doi:10.3390/ijms17040503.

Abbatecola AM, Rizzo MR, Barbieri M, et al. Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics. Neurology. 2006;67(2):235–240. doi:10.1212/01.wnl.0000224760.22802.e8.

Macauley SL, Stanley M, Caesar EE, et al. Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo. J Clin Invest. 2015;125(6):2463–2467. doi:10.1172/JCI79742.

Stanley M, Macauley SL, Holtzman DM. Changes in insulin and insulin signaling in Alzheimer's disease: cause or consequence?. J Exp Med. 2016;213(8):1375–1385. doi:10.1084/jem.20160493.

Ko SY, Ko HA, Chu KH, et al. The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer's Disease. PLoS One. 2015;10(11):e0143345. doi:10.1371/journal.pone.0143345. 

Li XH, Du LL, Cheng XS, et al. Glycation exacerbates the neuronal toxicity of β-amyloid. Cell Death Dis. 2013;4(6):e673. doi:10.1038/cddis.2013.180. 

Wu JH, Haan MN, Liang J, Ghosh D, Gonzalez HM, Herman WH. Impact of antidiabetic medications on physical and cognitive functioning of older Mexican Americans with diabetes mellitus: a population-based cohort study. Ann Epidemiol. 2003;13(5):369–376. doi:10.1016/s1047-2797(02)00464-7.

Weinstock RS, Teresi JA, Goland R, et al. Glycemic control and health disparities in older ethnically diverse underserved adults with diabetes: five-year results from the Informatics for Diabetes Education and Telemedicine (IDEATel) study. Diabetes Care. 2011;34(2):274–279. doi:10.2337/dc10-1346.

Launer LJ, Miller ME, Williamson JD, et al. Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): a randomised open-label substudy. Lancet Neurol. 2011;10(11):969–977. doi:10.1016/S1474-4422(11)70188-0.

Feinkohl I, Aung PP, Keller M, et al. Severe hypoglycemia and cognitive decline in older people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetes Care. 2014;37(2):507–515. doi:10.2337/dc13-1384.

de Galan BE, Zoungas S, Chalmers J, et al. Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Diabetologia. 2009;52(11):2328–2336. doi:10.1007/s00125-009-1484-7.

Shukla V, Shakya AK, Perez-Pinzon MA, Dave KR. Cerebral ischemic damage in diabetes: an inflammatory perspective. J Neuroinflammation. 2017;14(1):21. doi:10.1186/s12974-016-0774-5.

Roostaei T, Nazeri A, Felsky D, et al. Genome-wide interaction study of brain beta-amyloid burden and cognitive impairment in Alzheimer's disease. Mol Psychiatry. 2017;22(2):287–295. doi:10.1038/mp.2016.35.

Zhu H, Xue X, Wang E, et al. Amylin receptor ligands reduce the pathological cascade of Alzheimer's disease. Neuropharmacology. 2017;119:170–181. doi:10.1016/j.neuropharm.2017.03.030.

Moreno-Gonzalez I, Edwards Iii G, Salvadores N, Shahnawaz M, Diaz-Espinoza R, Soto C. Molecular interaction between type 2 diabetes and Alzheimer's disease through cross-seeding of protein misfolding. Mol Psychiatry. 2017;22(9):1327–1334. doi:10.1038/mp.2016.230.

Jackson K, Barisone GA, Diaz E, Jin LW, DeCarli C, Despa F. Amylin deposition in the brain: A second amyloid in Alzheimer disease?. Ann Neurol. 2013;74(4):517–526. doi:10.1002/ana.23956.

Zhu H, Stern RA, Tao Q, et al. An amylin analog used as a challenge test for Alzheimer's disease. Alzheimers Dement (N Y). 2017;3(1):33–43. doi:10.1016/j.trci.2016.12.002.

Skoog I, Lernfelt B, Landahl S, et al. 15-year longitudinal study of blood pressure and dementia. Lancet. 1996;347(9009):1141–1145. doi:10.1016/s0140-6736(96)90608-x. 

Staessen JA, Richart T, Birkenhäger WH. Less atherosclerosis and lower blood pressure for a meaningful life perspective with more brain. Hypertension. 2007;49(3):389–400. doi:10.1161/01.HYP.0000258151.00728.d8. 

Skoog I, Gustafson D. Update on hypertension and Alzheimer's disease. Neurol Res. 2006;28(6):605–611. doi:10.1179/016164106X130506. 

Popp J, Meichsner S, Kölsch H, et al. Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer's disease. Biochem Pharmacol. 2013;86(1):37–42. doi:10.1016/j.bcp.2012.12.007. 

Xue-Shan Z, Juan P, Qi W, et al. Imbalanced cholesterol metabolism in Alzheimer's disease. Clin Chim Acta. 2016;456:107–114. doi:10.1016/j.cca.2016.02.024. 

Ricciarelli R, Canepa E, Marengo B, et al. Cholesterol and Alzheimer's disease: a still poorly understood correlation. IUBMB Life. 2012;64(12):931–935. doi:10.1002/iub.1091. 

Ullrich C, Pirchl M, Humpel C. Hypercholesterolemia in rats impairs the cholinergic system and leads to memory deficits. Mol Cell Neurosci. 2010;45(4):408–417. doi:10.1016/j.mcn.2010.08.001. 

Hendrie HC, Hake A, Lane K, et al. Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans. Ethn Dis. 2015;25(3):345–354. doi:10.18865/ed.25.3.345. 

Lin FC, Chuang YS, Hsieh HM, et al. Early Statin Use and the Progression of Alzheimer Disease: A Total Population-Based Case-Control Study. Medicine (Baltimore). 2015;94(47):e2143. doi:10.1097/MD.0000000000002143. 

Song Y, Nie H, Xu Y, Zhang L, Wu Y. Association of statin use with risk of dementia: a meta-analysis of prospective cohort studies. Geriatr Gerontol Int. 2013;13(4):817–824. doi:10.1111/ggi.12044. 

McGuinness B, Craig D, Bullock R, Passmore P. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2016;(1):CD003160. doi:10.1002/14651858.CD003160.pub3.

Jiang C, Li G, Huang P, Liu Z, Zhao B. The Gut Microbiota and Alzheimer's Disease. J Alzheimers Dis. 2017;58(1):1–15. doi:10.3233/JAD-161141.

Solas M, Milagro FI, Ramírez MJ, Martínez JA. Inflammation and gut-brain axis link obesity to cognitive dysfunction: plausible pharmacological interventions. Curr Opin Pharmacol. 2017;37:87–92. doi:10.1016/j.coph.2017.10.005.

Kuehn BM. In Alzheimer Research, Glucose Metabolism Moves to Center Stage. JAMA. 2020;10.1001/jama.2019.20939. doi:10.1001/jama.2019.20939.




How to Cite

Pashkovska, N., Pankiv, V., & Pashkovska, O. (2021). Obesity and Alzheimer’s disease. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), 16(1), 3–9. https://doi.org/10.22141/2224-0721.16.1.2020.199121



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