Metabolically healthy obesity and lipids may be protective factors for pathological changes of alzheimer's disease in cognitively normal adults.
Aged
Alzheimer Disease
/ prevention & control
Apolipoprotein E4
/ genetics
Biomarkers
/ cerebrospinal fluid
Body Mass Index
China
Cholesterol
/ blood
Cognition
/ physiology
Databases, Factual
Female
Health Status
Humans
Life Style
Lipid Metabolism
/ physiology
Lipoproteins, LDL
/ cerebrospinal fluid
Male
Middle Aged
Obesity
/ metabolism
Protective Factors
tau Proteins
/ cerebrospinal fluid
Alzheimer's disease
cerebrospinal fluid biomarkers
metabolically healthy obesity
preclinical stage
serum lipid
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
13
09
2021
received:
20
07
2020
accepted:
13
01
2021
pubmed:
19
1
2021
medline:
22
6
2021
entrez:
18
1
2021
Statut:
ppublish
Résumé
The associations between obesity and Alzheimer's disease (AD) at different ages have been debated. Recent evidence implied the protective effects of metabolically healthy obesity on AD. We hypothesized that obesity and lipids could mitigate the detrimental impacts of AD pathological changes among metabolically healthy individuals in late life. In this study, a total of 604 metabolically healthy participants with normal cognition were included from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Multiple linear regression models were used to test the associations of body mass index (BMI) or lipids with cerebrospinal fluid (CSF) biomarkers after adjustment for age, gender, education, and Apolipoprotein E-ɛ4 (APOE-ɛ4). The results showed the lower CSF levels of total tau protein (t-tau: p = .0048) and phosphorylated tau protein (p-tau: p = .0035) in obese participants than in non-obese participants, even after correcting for covariates. Moreover in late life, higher BMI was associated with decreased CSF t-tau (β: -0.15, p = .0145) and p-tau (β: -0.17, p = .0052). As for lipids, higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were associated with decreased CSF t-tau (TC: β: -0.16, p = .0115; LDL-C: β: -0.16, p = .0082) and p-tau (TC: β: -0.15, p = .0177; LDL-C: β: -0.14, p = .0225) in obese participants. Furthermore, these associations were only significant in participants with late-life obesity and APOE-ɛ4 non-carriers. Overall, in a cognitively normal population, we found metabolically healthy obesity and lipids in late life might be protective factors for neurodegenerative changes.
Substances chimiques
Apolipoprotein E4
0
Biomarkers
0
Lipoproteins, LDL
0
MAPT protein, human
0
tau Proteins
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
834-845Informations de copyright
© 2021 International Society for Neurochemistry.
Références
Aguilar-Salinas, C. A., García, E. G., Robles, L., Riaño, D., Ruiz-Gomez, D. G., García-Ulloa, A. C., Melgarejo, M. A., Zamora, M., Guillen-Pineda, L. E., Mehta, R., Canizales-Quinteros, S., Tusie Luna, M. T., & Gómez-Pérez, F. J. (2008). High adiponectin concentrations are associated with the metabolically healthy obese phenotype. Journal of Clinical Endocrinology and Metabolism, 93, 4075-4079. https://doi.org/10.1210/jc.2007-2724
Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., Snyder, P. J., Carrillo, M. C., Thies, B., & Phelps, C. H. (2011). The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 7, 270-279. https://doi.org/10.1016/j.jalz.2011.03.008
Al-Delaimy, W. K., von Muhlen, D., & Barrett-Connor, E. (2009). Insulinlike growth factor-1, insulinlike growth factor binding protein-1, and cognitive function in older men and women. Journal of the American Geriatrics Society, 57, 1441-1446. https://doi.org/10.1111/j.1532-5415.2009.02343.x
Arold, S., Sullivan, P., Bilousova, T., Teng, E., Miller, C. A., Poon, W. W., Vinters, H. V., Cornwell, L. B., Saing, T., Cole, G. M., & Gylys, K. H. (2012). Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex. Acta Neuropathologica, 123, 39-52. https://doi.org/10.1007/s00401-011-0892-1
Atti, A. R., Palmer, K., Volpato, S., Winblad, B., De Ronchi, D., & Fratiglioni, L. (2008). Late-life body mass index and dementia incidence: Nine-year follow-up data from the Kungsholmen Project. Journal of the American Geriatrics Society, 56, 111-116. https://doi.org/10.1111/j.1532-5415.2007.01458.x
Barupal, D. K., Baillie, R., Fan, S., Saykin, A. J., Meikle, P. J., Arnold, M., Nho, K., Fiehn, O., & Kaddurah-Daouk, R. (2019a). Sets of coregulated serum lipids are associated with Alzheimer's disease pathophysiology. Alzheimer's & Dementia (Amsterdam, Netherlands), 11, 619-627. https://doi.org/10.1016/j.dadm.2019.07.002
Barupal, D. K., Baillie, R., Fan, S., Saykin, A. J., Meikle, P. J., Arnold, M., Nho, K., Fiehn, O., & Kaddurah-Daouk, R. (2019b). Sets of coregulated serum lipids are associated with Alzheimer's disease pathophysiology. Alzheimers Dement (Amst), 11, 619-627. https://doi.org/10.1016/j.dadm.2019.07.002
Beccano-Kelly, D., & Harvey, J. (2012). Leptin: A novel therapeutic target in Alzheimer's disease? International Journal of Alzheimer's Disease, 2012, 594137. https://doi.org/10.1155/2012/594137
Brochu, M., Tchernof, A., Dionne, I. J., Sites, C. K., Eltabbakh, G. H., Sims, E. A., & Poehlman, E. T. (2001). What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women? Journal of Clinical Endocrinology and Metabolism, 86, 1020-1025.
Buchman, A. S., Wilson, R. S., Bienias, J. L., Shah, R. C., Evans, D. A., & Bennett, D. A. (2005). Change in body mass index and risk of incident Alzheimer disease. Neurology, 65, 892-897. https://doi.org/10.1212/01.wnl.0000176061.33817.90
Chang, C. C., & Roberts, B. L. (2008). Feeding difficulty in older adults with dementia. Journal of Clinical Nursing, 17, 2266-2274. https://doi.org/10.1111/j.1365-2702.2007.02275.x
Corazon, B., Tommaso, C. S., Jeffery, C., & Ian D.H. (2004). Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet (London, England), 363, 157-163.
Dahl, A. K., Lopponen, M., Isoaho, R., Berg, S., & Kivela, S. L. (2008). Overweight and obesity in old age are not associated with greater dementia risk. Journal of the American Geriatrics Society, 56, 2261-2266. https://doi.org/10.1111/j.1532-5415.2008.01958.x
Djordjevic, J., Jones-Gotman, M., De Sousa, K., & Chertkow, H. (2008). Olfaction in patients with mild cognitive impairment and Alzheimer's disease. Neurobiology of Aging, 29, 693-706. https://doi.org/10.1016/j.neurobiolaging.2006.11.014
Expert Panel on Detection, E. and Treatment of High Blood Cholesterol in Adults (2001). Executive summary of the third report of The National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA, 285, 2486-2497. https://doi.org/10.1001/jama.285.19.2486
Fitzpatrick, A. L., Kuller, L. H., Lopez, O. L., Diehr, P., O'Meara, E. S., Longstreth, W. T. Jr, & Luchsinger, J. A. (2009). Midlife and late-life obesity and the risk of dementia: Cardiovascular health study. Archives of Neurology, 66, 336-342. https://doi.org/10.1001/archneurol.2008.582
Hughes, T. F., Borenstein, A. R., Schofield, E., Wu, Y., & Larson, E. B. (2009). Association between late-life body mass index and dementia: The Kame Project. Neurology, 72, 1741-1746. https://doi.org/10.1212/WNL.0b013e3181a60a58
Jack, C. R. Jr, & Holtzman, D. M. (2013). Biomarker modeling of Alzheimer's disease. Neuron, 80, 1347-1358. https://doi.org/10.1016/j.neuron.2013.12.003
Jack, C. R., Knopman, D. S., Weigand, S. D., Wiste, H. J., Vemuri, P., Lowe, V., Kantarci, K., Gunter, J. L., Senjem, M. L., Ivnik, R. J., Roberts, R. O., Rocca, W. A., Boeve, B. F., & Petersen, R. C. (2012). An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Annals of Neurology, 71, 765-775. https://doi.org/10.1002/ana.22628
Jang, H., Kim, J. H., Choi, S. H., Lee, Y., Hong, C. H., Jeong, J. H., Han, H. J., Moon, S. Y., Park, K. W., Han, S.-H., Park, K. H., Kim, H. J., Na, D. L., & Seo, S. W. (2015). Body mass index and mortality rate in Korean patients with Alzheimer's disease. Journal of Alzheimer's Disease, 46, 399-406. https://doi.org/10.3233/JAD-142790
Karelis, A. D., Faraj, M., Bastard, J. P., St-Pierre, D. H., Brochu, M., Prud'homme, D., & Rabasa-Lhoret, R. (2005). The metabolically healthy but obese individual presents a favorable inflammation profile. Journal of Clinical Endocrinology and Metabolism, 90, 4145-4150. https://doi.org/10.1210/jc.2005-0482
Kivipelto, M., Ngandu, T., Fratiglioni, L., Viitanen, M., Kåreholt, I., Winblad, B., Helkala, E.-L., Tuomilehto, J., Soininen, H., & Nissinen, A. (2005). Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Archives of Neurology, 62, 1556-1560. https://doi.org/10.1001/archneur.62.10.1556
Knopman, D. S., Jack, C. R., Wiste, H. J., Weigand, S. D., Vemuri, P., Lowe, V. J., Kantarci, K., Gunter, J. L., Senjem, M. L., Mielke, M. M., Roberts, R. O., Boeve, B. F., & Petersen, R. C. (2013). Brain injury biomarkers are not dependent on β-amyloid in normal elderly. Annals of Neurology, 73, 472-480. https://doi.org/10.1002/ana.23816
Lee, E. B. (2011). Obesity, leptin, and Alzheimer's disease. Annals of the New York Academy of Sciences, 1243, 15-29. https://doi.org/10.1111/j.1749-6632.2011.06274.x
Lee, J.-Y., Han, K., Han, E., Kim, G., Cho, H., Kim, K. J., Lee, B. W., Kang, E. S., Cha, B.-S., Brayne, C., & Lee, Y.-H. (2019). Risk of incident dementia according to metabolic health and obesity status in late life: A population-based cohort study. The Journal of Clinical Endocrinology and Metabolism, 104, 2942-2952. https://doi.org/10.1210/jc.2018-01491
Ma, L.-Z., Huang, Y.-Y., Wang, Z.-T., Li, J.-Q., Hou, X.-H., Shen, X.-N., Ou, Y.-N., Dong, Q., Tan, L., Yu, J.-T., & Initiative, A. D. N. (2019). Metabolically healthy obesity reduces the risk of Alzheimer's disease in elders: A longitudinal study. Aging, 11, 10939-10951. https://doi.org/10.18632/aging.102496
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., Mohs, R. C., Morris, J. C., Rossor, M. N., Scheltens, P., Carrillo, M. C., Thies, B., Weintraub, S., & Phelps, C. H. (2011). The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 7, 263-269. https://doi.org/10.1016/j.jalz.2011.03.005
Nazare, J. A., Smith, J. D., Borel, A. L., Haffner, S. M., Balkau, B., Ross, R., Massien, C., Almeras, N., & Despres, J. P. (2012). Ethnic influences on the relations between abdominal subcutaneous and visceral adiposity, liver fat, and cardiometabolic risk profile: The International Study of Prediction of intra-abdominal adiposity and its relationship with cardiometabolic risk/intra-abdominal adiposity. American Journal of Clinical Nutrition, 96, 714-726. https://doi.org/10.3945/ajcn.112.035758
Nourhashemi, F., Andrieu, S., Gillette-Guyonnet, S., Reynish, E., Albarede, J. L., Grandjean, H., & Vellas, B. (2002). Is there a relationship between fat-free soft tissue mass and low cognitive function? Results from a study of 7,105 women. Journal of the American Geriatrics Society, 50, 1796-1801. https://doi.org/10.1046/j.1532-5415.2002.50507.x
Pedditzi, E., Peters, R., & Beckett, N. (2016). The risk of overweight/obesity in mid-life and late life for the development of dementia: A systematic review and meta-analysis of longitudinal studies. Age and Ageing, 45, 14-21. https://doi.org/10.1093/ageing/afv151
Proitsi, P., Lupton, M. K., Velayudhan, L., Newhouse, S., Fogh, I., Tsolaki, M., Daniilidou, M., Pritchard, M., Kloszewska, I., Soininen, H., Mecocci, P., Vellas, B., Williams, J., Stewart, R., Sham, P., Lovestone, S., & Powell, J. F. (2014). Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease: A Mendelian randomization analysis. PLoS Med, 11, e1001713. https://doi.org/10.1371/journal.pmed.1001713
Snijder, M. B., Dekker, J. M., Visser, M., Bouter, L. M., Stehouwer, C. D., Yudkin, J. S., Heine, R. J., Nijpels, G., & Seidell, J. C. (2004). Trunk fat and leg fat have independent and opposite associations with fasting and postload glucose levels: The Hoorn study. Diabetes Care, 27, 372-377. https://doi.org/10.2337/diacare.27.2.372
Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., Park, D. C., Reiman, E. M., Rowe, C. C., Siemers, E., Stern, Y., Yaffe, K., Carrillo, M. C., Thies, B., Morrison-Bogorad, M., … Phelps, C. H. (2011). Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia: the Journal of the Alzheimer's Association, 7, 280-292. https://doi.org/10.1016/j.jalz.2011.03.003
Watanabe, T., Miyazaki, A., Katagiri, T., Yamamoto, H., Idei, T., & Iguchi, T. (2005). Relationship between serum insulin-like growth factor-1 levels and Alzheimer's disease and vascular dementia. Journal of the American Geriatrics Society, 53, 1748-1753. https://doi.org/10.1111/j.1532-5415.2005.53524.x
West, N. A., & Haan, M. N. (2009). Body adiposity in late life and risk of dementia or cognitive impairment in a longitudinal community-based study. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 64, 103-109. https://doi.org/10.1093/gerona/gln006
Whitmer, R. A., Gunderson, E. P., Barrett-Connor, E., Quesenberry, C. P. Jr, & Yaffe, K. (2005). Obesity in middle age and future risk of dementia: A 27 year longitudinal population based study. BMJ, 330, 1360. https://doi.org/10.1136/bmj.38446.466238.E0
Wimo, A., Guerchet, M., Ali, G. C., Wu, Y. T., Prina, A. M., Winblad, B., Jonsson, L., Liu, Z., & Prince, M. (2017). The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimer's & Dementia: the Journal of the Alzheimer's Association, 13, 1-7. https://doi.org/10.1016/j.jalz.2016.07.150
Wingo, T. S., Cutler, D. J., Wingo, A. P., Le, N. A., Rabinovici, G. D., Miller, B. L., Lah, J. J., & Levey, A. I. (2019). Association of early-onset Alzheimer disease with elevated low-density lipoprotein cholesterol levels and rare genetic coding variants of APOB. JAMA Neurology, 76, 809-817.
Xu, W., Tan, L., Su, B. J., Yu, H., Bi, Y. L., Yue, X. F., Dong, Q., & Yu, J. T. (2020). Sleep characteristics and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact older adults: The CABLE study. Alzheimer's & Dementia, 16(8), 1146-1152.
Ye, B. S., Jang, E. Y., Kim, S. Y., Kim, E. J., Park, S. A., Lee, Y., Hong, C. H., Choi, S. H., Yoon, B., Yoon, S. J., & Na, H. R. (2016). Unstable body mass index and progression to probable Alzheimer's disease dementia in patients with amnestic mild cognitive impairment. Journal of Alzheimer's Disease, 49, 483-491.