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Meta-analysis of Alzheimer’s disease risk with obesity, diabetes, and related disorders
Open accessAbstract
Background Late-onset Alzheimer's disease (AD) is a multifactorial and heterogeneous disorder with major risk factors including advanced age, presence of an apolipoprotein E epsilon4 (APOE4) allele, and family history of AD. Other risk factors may be obesity and diabetes and related disorders, which are highly prevalent.Methods We reviewed longitudinal epidemiological studies of body mass, diabetes, metabolic syndrome, and glucose and insulin levels on risk for AD. We conducted meta-analyses of the results from these studies.Results For obesity assessed by body mass index, the pooled effect size for AD was 1.59 (95% confidence interval [CI] 1.02-2.5; z = 2.0; p = .042), and for diabetes, the pooled effect size for AD was 1.54 (95% CI 1.33-1.79; z = 5.7; p < .001). Egger's test did not find significant evidence for publication bias in the meta-analysis for obesity (t = -1.4, p = .21) or for diabetes (t = -.86, p = .42). Since these disorders are highly comorbid, we conducted a meta-analysis combining all studies of obesity, diabetes, and abnormal glucose or insulin levels, which yielded a highly significant pooled effect size for AD of 1.63 (95% CI 1.39-1.92; z = 5.9; p < .001).Conclusions Obesity and diabetes significantly and independently increase risk for AD. Though the level of risk is less than that with the APOE4 allele, the high prevalence of these disorders may result in substantial increases in future incidence of AD. Physiological changes common to obesity and diabetes plausibly promote AD.
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“Several comorbidities such as diabetes, hypertension, cardiovascular/renal/hepatic complications, hypogonadotropic hypogonadism, bronchial asthma, and Alzheimer’s disease are associated with obesity [10-13].”
From Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects (2020) · cites this paper as [13]
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“Obesity and insulin resistance are significant risk factors for Alzheimer’s disease [13] (Fig. 1).”
From Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects (2020) · cites this paper as [13]
Citations
Cites
Bias in meta-analysis detected by a simple, graphical test
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997) · BMJ · doi:10.1136/bmj.315.7109.629 · Cited by 56,722
Meta-analysis in clinical trials
DerSimonian, R., & Laird, N. (1986) · Controlled Clinical Trials · doi:10.1016/0197-2456(86)90046-2 · Cited by 39,552
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
ON ESTIMATING THE RELATION BETWEEN BLOOD GROUP AND DISEASE
Woolf, B. (1955) · Annals of Human Genetics · doi:10.1111/j.1469-1809.1955.tb01348.x · Cited by 2,724
Diabetes mellitus and the risk of dementia: The Rotterdam Study
Ott, A., Stolk, R. P., van Harskamp, F., Pols, H. A. P., Hofman, A., & Breteler, M. M. B. (1999) · Neurology · doi:10.1212/wnl.53.9.1937 · Cited by 2,175
Adipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170
Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database
Bertram, L., McQueen, M. B., Mullin, K., Blacker, D., & Tanzi, R. E. (2007) · Nature Genetics · doi:10.1038/ng1934 · Cited by 1,857
Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective
Tanzi, R. E., & Bertram, L. (2005) · Cell · doi:10.1016/j.cell.2005.02.008 · Cited by 1,849
Obesity and Vascular Risk Factors at Midlife and the Risk of Dementia and Alzheimer Disease
Kivipelto, M., Ngandu, T., Fratiglioni, L., Viitanen, M., Kåreholt, I., Winblad, B., Helkala, E.-L., Tuomilehto, J., Soininen, H., & Nissinen, A. (2005) · Archives of Neurology · doi:10.1001/archneur.62.10.1556 · Cited by 1,291
Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function
Arvanitakis, Z., Wilson, R. S., Bienias, J. L., Evans, D. A., & Bennett, D. A. (2004) · Archives of Neurology · doi:10.1001/archneur.61.5.661 · Cited by 1,258
Type 2 Diabetes, APOE Gene, and the Risk for Dementia and Related Pathologies
Peila, R., Rodriguez, B. L., & Launer, L. J. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1256 · Cited by 1,207
Yoshitake, T., Kiyohara, Y., Kato, I., Ohmura, T., Iwamoto, H., Nakayama, K., Ohmori, S., Nomiyama, K., Kawano, H., Ueda, K., et al. (1995) · Neurology · doi:10.1212/wnl.45.6.1161 · Cited by 829
An 18-Year Follow-up of Overweight and Risk of Alzheimer Disease
Gustafson, D., Rothenberg, E., Blennow, K., Steen, B., & Skoog, I. (2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.13.1524 · Cited by 811
Risk of Dementia among Persons with Diabetes Mellitus: A Population-based Cohort Study
Leibson, C. L., Rocca, W. A., Hanson, V. A., Cha, R., Kokmen, E., O'Brien, P. C., & Palumbo, P. J. (1997) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009106 · Cited by 700
Hyperinsulinemia and risk of Alzheimer disease
Luchsinger, J. A., Tang, M.-X., Shea, S., & Mayeux, R. (2004) · Neurology · doi:10.1212/01.wnl.0000140292.04932.87 · Cited by 683
Diabetes Mellitus and Risk of Alzheimer's Disease and Dementia with Stroke in a Multiethnic Cohort
Luchsinger, J. A. (2001) · American Journal of Epidemiology · doi:10.1093/aje/154.7.635 · Cited by 682
Stewart, R., Masaki, K., Xue, Q.-L., Peila, R., Petrovitch, H., White, L. R., & Launer, L. J. (2005) · Archives of Neurology · doi:10.1001/archneur.62.1.55 · Cited by 478
Body Mass Index in Midlife and Risk of Alzheimer Disease and Vascular Dementia
Whitmer, R., Gunderson, E., Quesenberry, C., Zhou, J., & Yaffe, K. (2007) · Current Alzheimer Research · doi:10.2174/156720507780362047 · Cited by 430
Diabetes mellitus and risk of dementia in the Kungsholmen project
Xu, W., Qiu, C., Wåhlin, Å., Winblad, B. G., & Fratiglioni, L. (2004) · Neurology · doi:10.1212/01.wnl.0000140291.86406.d1 · Cited by 418
Kalmijn, S., Foley, D., White, L., Burchfiel, C. M., Curb, J. D., Petrovitch, H., Ross, G. W., Havlik, R. J., & Launer, L. J. (2000) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.20.10.2255 · Cited by 417
Change in body mass index and risk of incident Alzheimer disease
Buchman, A. S., Wilson, R. S., Bienias, J. L., Shah, R. C., Evans, D. A., & Bennett, D. A. (2005) · Neurology · doi:10.1212/01.wnl.0000176061.33817.90 · Cited by 407
Accelerated Weight Loss May Precede Diagnosis in Alzheimer Disease
Johnson, D. K., Wilkins, C. H., & Morris, J. C. (2006) · Archives of Neurology · doi:10.1001/archneur.63.9.1312 · Cited by 350
Intracerebroventricular insulin enhances memory in a passive-avoidance task
Park, C. R., Seeley, R. J., Craft, S., & WOODS, S. (2000) · Physiology & Behavior · doi:10.1016/s0031-9384(99)00220-6 · Cited by 343
Culmsee, C., monnig, J., Kemp, B. E., & Mattson, M. P. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:17:1:45 · Cited by 340
MacKnight, C., Rockwood, K., Awalt, E., & McDowell, I. (2002) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000064928 · Cited by 313
Obesity‐related leptin regulates Alzheimer's Aβ
Fewlass, D. C., Noboa, K., Pi‐Sunyer, F. X., Johnston, J. M., Yan, S. D., & Tezapsidis, N. (2004) · The FASEB Journal · doi:10.1096/fj.04-2572com · Cited by 308
Vascular Risk Factors for Incident Alzheimer Disease and Vascular Dementia: The Cache County Study
Hayden, K. M., Zandi, P. P., Lyketsos, C. G., Khachaturian, A. S., Bastian, L. A., Charoonruk, G., Tschanz, J. T., Norton, M. C., Pieper, C. F., Munger, R. G., et al. (2006) · Alzheimer Disease & Associated Disorders · doi:10.1097/01.wad.0000213814.43047.86 · Cited by 293
Diabetes Mellitus and Risk of Developing Alzheimer Disease
Akomolafe, A., Beiser, A., Meigs, J. B., Au, R., Green, R. C., Farrer, L. A., Wolf, P. A., & Seshadri, S. S. (2006) · Archives of Neurology · doi:10.1001/archneur.63.11.1551 · Cited by 287
Weight Loss Precedes Dementia in Community‐Dwelling Older Adults
Barrett-Connor, E. L., Edelstein, S. L., Corey‐Bloom, J., & Wiederholt, W. C. (1996) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1996.tb01362.x · Cited by 266
Cellular signaling roles of TGFβ, TNFα and βAPP in brain injury responses and Alzheimer's disease
Mattson, M. P., Barger, S. W., Furukawa, K., Bruce‐Keller, A. J., Wyss‐Coray, T., Mark, R. J., & Mucke, L. (1997) · Brain Research Reviews · doi:10.1016/s0165-0173(96)00014-8 · Cited by 243
Measures of Adiposity and Dementia Risk in Elderly Persons
Luchsinger, J. A., Patel, B. N., Tang, M., Schupf, N., & Mayeux, R. P. (2007) · Archives of Neurology · doi:10.1001/archneur.64.3.392 · Cited by 237
Longitudinal association of vascular and Alzheimer’s dementias, diabetes, and glucose tolerance
Curb, J. D., Rodríguez, B. L., Abbott, R. D., Petrovitch, H., Ross, G. W., Masaki, K., Foley, D. J., Blanchette, P. L., Harris, T. B., Chen, R., et al. (1999) · Neurology · doi:10.1212/wnl.52.5.971 · Cited by 231
The Effect of Borderline Diabetes on the Risk of Dementia and Alzheimer’s Disease
Xu, W., Qiu, C., Winblad, B. G., & Fratiglioni, L. (2006) · Diabetes · doi:10.2337/db06-0879 · Cited by 221
Spranger, J., Verma, S., Göhring, I., Bobbert, T., Seifert, J., Sindler, A. L., Pfeiffer, A. F. H., Hileman, S. M., Tschöp, M. H., & Banks, W. A. (2006) · Diabetes · doi:10.2337/diabetes.55.01.06.db05-1077 · Cited by 220
Leptin and its role in hippocampal synaptic plasticity
HARVEY, J., SOLOVYOVA, N., & IRVING, A. (2006) · Progress in Lipid Research · doi:10.1016/j.plipres.2006.03.001 · Cited by 202
Corticosteroids and Hippocampal Plasticity
McEwen, B. S. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb39223.x · Cited by 155
Han, B. H., Zhou, M.-L., Abousaleh, F., Brendza, R. P., Dietrich, H. H., Koenigsknecht-Talboo, J., Cirrito, J. R., Milner, E., Holtzman, D. M., & Zipfel, G. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4686-08.2008 · Cited by 138
The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing
Tschäpe, J., Hammerschmied, C., Mühlig‐Versen, M., Athenstaedt, K., Daum, G., & Kretzschmar, D. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf636 · Cited by 129
Alzoubi, K., Gerges, N. Z., & Alkadhi, K. (2005) · Experimental Neurology · doi:10.1016/j.expneurol.2005.05.007 · Cited by 115
Beydoun, M. A., Lhotsky, A., Wang, Y., Forno, G. D., An, Y., Metter, E. J., Ferrucci, L., O’Brien, R., & Zonderman, A. B. (2008) · American Journal of Epidemiology · doi:10.1093/aje/kwn229 · Cited by 111
Xu, X.-H., & Zhang, Z.-G. (2006) · Life Science · doi:10.1016/j.lfs.2006.04.020 · Cited by 88
Maher, F. O., Clarke, R. M., Kelly, A. M., Nally, R. E., & Lynch, M. A. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03664.x · Cited by 81
Utter, S., Tamboli, I. Y., Walter, J., Upadhaya, A. R., Birkenmeier, G., Pietrzik, C. U., Ghebremedhin, E., & Thal, D. R. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181836a71 · Cited by 80
Sathiavageeswaran, M., Burman, P., Lawrence, D., Harris, A. G., Downing, M. G., Maruff, P. T., & Wass, J. A. H. (2007) · European Journal of Endocrinology · doi:10.1530/eje.1.02346 · Cited by 65
Diabetes and overweight associate with non‐APOE4 genotype in an alzheimer's disease population
Profenno, L. A., & Faraone, S. V. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30694 · Cited by 39
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Talbot, K., Wang, H.-Y., Kazi, H., Han, L.-Y., Bakshi, K. P., Stucky, A., Fuino, R. L., Kawaguchi, K. R., Samoyedny, A. J., Wilson, R. S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59903 · Cited by 1,871
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Epidemiology of Alzheimer disease
Reitz, C., Brayne, C., & Mayeux, R. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.2 · Cited by 1,675
Baumgart, M., Snyder, H. M., Carrillo, M. C., Fazio, S., Kim, H., & Johns, H. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.05.016 · Cited by 1,660
Metadata
- Authors
- Profenno, L. A., Porsteinsson, A. P., & Faraone, S. V.
- Affiliations
- SUNY Upstate Medical University (US)
- University of Rochester Medicine (US)
- Corresponding author
- Profenno, Louis A.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 67
- Issue
- 6
- Pages
- 505-512
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2032605307
- Cited by
- 718
- References
- 45
- Citations by year
- 2026: 19 · 2025: 41 · 2024: 55 · 2023: 51 · 2022: 44 · 2021: 47 · 2020: 55 · 2019: 65 · 2018: 39 · 2017: 43 · 2016: 41 · 2015: 52 · 2014: 50 · 2013: 46 · 2012: 44
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- SUNY Digital Repository Support (State University of New York System) (submittedVersion, cc-by-nc-nd)
- Funders
- U.S. Department of Veterans Affairs
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- Alzheimer's disease, obesity, diabetes mellitus, metabolic syndrome, body mass index, glucose concentration, insulin levels, disease risk factors, APOE ε4, comorbidities
- MeSH terms
- Aged, Alzheimer Disease, Female, Glucose, Humans, Insulin, Longitudinal Studies, Male, Mental Status Schedule, Middle Aged, Obesity, Retrospective Studies, Risk Factors, Body Mass Index, Proportional Hazards Models, PubMed, Diabetes Complications, Overweight, Apolipoprotein E4
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