Dieta ultraprocesada y riesgo de demencia: Mecanismos neurometabólicos del deterioro cerebral

Zoraida Flores Serrano; Daniela Rendón Coria; María Elena Hernández Aguilar; Fausto Rojas Durán; Gonzalo Aranda Abreu; Genaro Alfonso Coria Avila; Jorge Manzo Denes; Deissy Herrera Covarrubias; Rebeca Toledo Cardenas

doi:10.14198/DCN.31279

Autores/as

Zoraida Flores Serrano Instituto de Investigaciones Cerebrales, México https://orcid.org/0009-0000-2845-9639
Daniela Instituto de Investigaciones Cerebrales, México https://orcid.org/0009-0009-3802-3252
María Elena Hernández Aguilar Universidad Veracruzana, México https://orcid.org/0000-0002-1617-5636
Fausto Rojas Durán Universidad Veracruzana, México https://orcid.org/0000-0003-4497-0909
Gonzalo Aranda Abreu Universidad Veracruzana, México https://orcid.org/0000-0001-8519-5473
Genaro Alfonso Coria Avila Universidad Veracruzana, México https://orcid.org/0000-0003-1663-836X
Jorge Manzo Denes Universidad Veracruzana, México https://orcid.org/0000-0001-8659-4759
Deissy Herrera Covarrubias Universidad Veracruzana, México https://orcid.org/0000-0001-5752-4700
Rebeca Toledo Cardenas Universidad Veracruzana, México https://orcid.org/0000-0003-1273-4944

DOI:

https://doi.org/10.14198/DCN.31279

Palabras clave:

Enfermedad de Alzheimer, Neuroinflamación, Disbiosis intestinal, plasticidad sináptica, dieta ultraprocesada

Resumen

Las dietas tipo cafetería (CAF) o ultraprocesadas, con alto contenido en grasas saturadas, azúcares simples y aditivos, se asocian con alteraciones metabólicas y proinflamatorias que favorecen neurodegeneración. La evidencia indica que estas dietas inducen disfunciones sinápticas y metabólicas que favorecen el desarrollo en etapas tempranas de la enfermedad de Alzheimer (EA). El objetivo de esta revisión, es analizar los mecanismos neurometabólicos mediante los cuales la dieta CAF se asocia con una mayor vulnerabilidad cerebral, deterioro cognitivo y riesgo de demencia, incluida la enfermedad de Alzheimer. Se realizó una revisión estructurada en forma de dominios temáticos. Se buscaron artículos en PubMed con los términos “cafeteria diet”, “brain”, “Alzheimer”, “metabolic syndrome” e “insulin resistance”, se seleccionaron estudios experimentales y clínicos publicados en los últimos diez años, con acceso abierto y disponibilidad de texto completo. La evidencia analizada indica que las dietas CAF se asocian con disbiosis intestinal, resistencia a la insulina cerebral, disfunción mitocondrial y neuroinflamación glial, con alteraciones concomitantes en la plasticidad sináptica, la señalización de BDNF y promoviendo la acumulación de β-amiloide y proteína tau. Los modelos preclínicos y clínicos coinciden en que la obesidad y el metabolismo alterado aceleran el envejecimiento cerebral y la vulnerabilidad cognitiva. En conjunto, la dieta ultraprocesada se perfila como un posible modulador neurometabólico que conecta obesidad, inflamación y procesos neurodegenerativos, lo que amplía las oportunidades preventivas frente a la demencia y respalda estrategias nutricionales dirigidas a la preservación de la salud cognitiva.

Financiación

Alzheimer’s disease, Neuroinflammation, Gut dysbiosis, Synaptic plasticity, ultra-processed diet

Citas

Lalanza JF, Snoeren EMS. The cafeteria diet: A standardized protocol and its effects on behavior. Neuroscience & Biobehavioral Reviews 2021;122:92–119. https://doi.org/10.1016/j.neubiorev.2020.11.003.

De Macedo IC, De Freitas JS, Da Silva Torres IL. The Influence of Palatable Diets in Reward System Activation: A Mini Review. Advances in Pharmacological Sciences 2016;2016:1–7. https://doi.org/10.1155/2016/7238679.

Heijkoop R, Lalanza JF, Solanas M, Álvarez-Monell A, Subias-Gusils A, Escorihuela RM, et al. Changes in reward-induced neural activity upon Cafeteria Diet consumption. Physiology & Behavior 2024;276:114478. https://doi.org/10.1016/j.physbeh.2024.114478.

Hukema FW, Hetty S, Kagios C, Zelleroth S, Fanni G, Pereira MJ, et al. Abundance of dopamine and its receptors in the brain and adipose tissue following diet-induced obesity or caloric restriction. Translational Research 2025;280:41–54. https://doi.org/10.1016/j.trsl.2025.05.001.

Winkler M, Schuchard J, Stölting I, Vogt FM, Barkhausen J, Thorns C, et al. The brain renin‐angiotensin system plays a crucial role in regulating body weight in diet‐induced obesity in rats. British J Pharmacology 2016;173:1602–17. https://doi.org/10.1111/bph.13461.

Neto J, Jantsch J, Rodrigues F, Squizani S, Eller S, Oliveira TF, et al. Impact of cafeteria diet and n3 supplementation on the intestinal microbiota, fatty acids levels, neuroinflammatory markers and social memory in male rats. Physiology & Behavior 2023;260:114068. https://doi.org/10.1016/j.physbeh.2022.114068.

Ramírez-Maldonado LM, Guerrero-Castro J, Rodríguez-Mejía JL, Cárdenas-Conejo Y, Bonales-Alatorre EO, Valencia-Cruz G, et al. Obesogenic cafeteria diet induces dynamic changes in gut microbiota, reduces myenteric neuron excitability, and impairs gut contraction in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology 2025;328:G32–48. https://doi.org/10.1152/ajpgi.00198.2024.

Squizani S, Jantsch J, Rodrigues FDS, Braga MF, Eller S, De Oliveira TF, et al. Zinc Supplementation Partially Decreases the Harmful Effects of a Cafeteria Diet in Rats but Does Not Prevent Intestinal Dysbiosis. Nutrients 2022;14:3921. https://doi.org/10.3390/nu14193921.

Leigh S-J, Kaakoush NO, Bertoldo MJ, Westbrook RF, Morris MJ. Intermittent cafeteria diet identifies fecal microbiome changes as a predictor of spatial recognition memory impairment in female rats. Transl Psychiatry 2020;10. https://doi.org/10.1038/s41398-020-0734-9.

Mota B, Brás AR, Araújo-Andrade L, Silva A, Pereira PA, Madeira MD, et al. High-Caloric Diets in Adolescence Impair Specific GABAergic Subpopulations, Neurogenesis, and Alter Astrocyte Morphology. IJMS 2024;25:5524. https://doi.org/10.3390/ijms25105524.

Trujillo-Villarreal LA, Romero-Díaz VJ, Marino-Martínez IA, Fuentes-Mera L, Ponce-Camacho MA, Devenyi GA, et al. Maternal cafeteria diet exposure primes depression-like behavior in the offspring evoking lower brain volume related to changes in synaptic terminals and gliosis. Transl Psychiatry 2021;11. https://doi.org/10.1038/s41398-020-01157-x.

Liśkiewicz AD, Liśkiewicz D, Marczak Ł, Przybyła M, Grabowska K, Student S, et al. Obesity-associated deterioration of the hippocampus is partially restored after weight loss. Brain, Behavior, and Immunity 2021;96:212–26. https://doi.org/10.1016/j.bbi.2021.05.030.

Morys F, for the Alzheimer’s Disease Neuroimaging Initiative, Potvin O, Zeighami Y, Vogel J, Lamontagne-Caron R, et al. Obesity-Associated Neurodegeneration Pattern Mimics Alzheimer’s Disease in an Observational Cohort Study. JAD 2023;91:1059–71. https://doi.org/10.3233/jad-220535.

Sack M, Lenz JN, Jakovcevski M, Biedermann SV, Falfán-Melgoza C, Deussing J, et al. Early effects of a high-caloric diet and physical exercise on brain volumetry and behavior: a combined MRI and histology study in mice. Brain Imaging and Behavior 2017;11:1385–96. https://doi.org/10.1007/s11682-016-9638-y.

Kim KY, Kim E, Lee J-Y, for the Alzheimer’s Disease Neuroimaging Initiative, Weiner M, Aisen P, et al. Impact of amyloid and cardiometabolic risk factors on prognostic capacity of plasma neurofilament light chain for neurodegeneration. Alz Res Therapy 2024;16. https://doi.org/10.1186/s13195-024-01564-y.

Suzuki H, Venkataraman AV, Bai W, Guitton F, Guo Y, Dehghan A, et al. Associations of Regional Brain Structural Differences With Aging, Modifiable Risk Factors for Dementia, and Cognitive Performance. JAMA Netw Open 2019;2:e1917257. https://doi.org/10.1001/jamanetworkopen.2019.17257.

Cummings JL, Atri A, Feldman HH, Hansson O, Sano M, Knop FK, et al. evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer’s disease. Alz Res Therapy 2025;17. https://doi.org/10.1186/s13195-024-01666-7.

Levakov G, Kaplan A, Yaskolka Meir A, Rinott E, Tsaban G, Zelicha H, et al. The effect of weight loss following 18 months of lifestyle intervention on brain age assessed with resting-state functional connectivity. eLife 2023;12. https://doi.org/10.7554/elife.83604.

Luiza Rolim Bezerra M, Gouveia-Nhanca M, D’ Angelo Da Silva Andrade A, Oliveira Pinheiro R, Francisco Alves A, Carolina De Paiva Sousa M, et al. Malicia honey (Mimosa quadrivalvis L.) produced by the jandaíra bee (Melipona subnitida D.) improves depressive-like behaviour, somatic, biochemical and inflammatory parameters of obese rats. Food Research International 2023;164:112391. https://doi.org/10.1016/j.foodres.2022.112391.

Heininger K. A unifying hypothesis of Alzheimer’s disease. III. Risk factors. Hum Psychopharmacol Clin Exp 2000;15:1–70. https://doi.org/10.1002/(SICI)1099-1077(200001)15:1<1::AID-HUP153>3.0.CO;2-1.

Hayes AMR, Lauer LT, Kao AE, Sun S, Klug ME, Tsan L, et al. Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling. Brain, Behavior, and Immunity 2024;118:408–22. https://doi.org/10.1016/j.bbi.2024.03.015.

Fock E, Parnova R. Mechanisms of Blood–Brain Barrier Protection by Microbiota-Derived Short-Chain Fatty Acids. Cells 2023;12:657. https://doi.org/10.3390/cells12040657.

Feng Z, Fang C, Ma Y, Chang J. Obesity-induced blood-brain barrier dysfunction: phenotypes and mechanisms. J Neuroinflammation 2024;21:110. https://doi.org/10.1186/s12974-024-03104-9.

Fülling C, Lach G, Bastiaanssen TFS, Fouhy F, O’Donovan AN, Ventura-Silva A-P, et al. Adolescent dietary manipulations differentially affect gut microbiota composition and amygdala neuroimmune gene expression in male mice in adulthood. Brain, Behavior, and Immunity 2020;87:666–78. https://doi.org/10.1016/j.bbi.2020.02.013.

McWhinney SR, Abé C, Alda M, Benedetti F, Bøen E, Del Mar Bonnin C, et al. Association between body mass index and subcortical brain volumes in bipolar disorders–ENIGMA study in 2735 individuals. Mol Psychiatry 2021;26:6806–19. https://doi.org/10.1038/s41380-021-01098-x.

Patel V, Edison P. Cardiometabolic risk factors and neurodegeneration: a review of the mechanisms underlying diabetes, obesity and hypertension in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2024;95:581–9. https://doi.org/10.1136/jnnp-2023-332661.

Mielke MM, Evans JK, Neiberg RH, Molina-Henry DP, Marcovina SM, Johnson KC, et al. Alzheimer Disease Blood Biomarkers and Cognition Among Individuals With Diabetes and Overweight or Obesity. JAMA Netw Open 2025;8:e2458149. https://doi.org/10.1001/jamanetworkopen.2024.58149.

Corlier F, Hafzalla G, Faskowitz J, Kuller LH, Becker JT, Lopez OL, et al. Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk. NeuroImage 2018;172:118–29. https://doi.org/10.1016/j.neuroimage.2017.12.027.

Head E, T. Lott I, M. Wilcock D, A. Lemere C. Aging in Down Syndrome and the Development of Alzheimer’s Disease Neuropathology. CAR 2015;13:18–29. https://doi.org/10.2174/1567205012666151020114607.

Sordo L, Du A, Sandadi V, Dustagheer FB, Pascual J, Ngo P, et al. Leptin levels are associated with body mass index and Alzheimer’s disease in Down syndrome. Alzheimer’s & Dementia 2025;21:e70448. https://doi.org/10.1002/alz.70448.

Ngandu T, Lehtisalo J, Solomon A, Levälahti E, Ahtiluoto S, Antikainen R, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. The Lancet 2015;385:2255–63. https://doi.org/10.1016/S0140-6736(15)60461-5.