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Cited by 86Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAdipokines, Inflammation, and Metabolic Diseases

Obesity, Insulin Resistance, and Alzheimer's Disease

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Hildreth, Kerry L., Van Pelt, Rachael E., Schwartz, Robert S.·2012·Obesity
DOI 10.1038/oby.2012.19PMC PMC4314950
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Abstract

Obesity has reached epidemic proportions in our society, affecting over one-third of US adults, with two-thirds overweight or obese (1). Trends toward overweight and obesity among younger age groups are alarming; 27.5% of men and 34.0% of women ages 20–39 are obese (1), and 11.3% of children 2–19 years of age are at or above the 97th percentile for 2000 BMI-for-age growth charts (2). The majority of overweight or obese individuals are also insulin resistant (3). The adverse health consequences of obesity and insulin resistance (IR) are well-documented, particularly with respect to cardiovascular disease and type 2 diabetes mellitus (T2DM). More recently, these conditions have also been linked to an increased risk of cognitive impairment and Alzheimer’s disease (AD) (4). AD is the most common cause of dementia, and the fifth leading cause of death in the United States among those 65 and older (5). The number of patients affected by AD in the United States is projected to increase from 5.3 million currently, to 16 million in 2050 as the population ages (5), imposing extraordinary monetary and non-monetary costs on patients, caregivers, and the healthcare system. Currently approved therapies for AD provide modest symptomatic benefits to some patients, but do not affect the underlying pathology. Identification of modifiable risk factors to delay or prevent progression to clinical dementia and functional impairment could have a dramatic impact on the prevalence and costs associated with AD. Although there is currently insufficient evidence to firmly link any modifiable risk factor with AD, substantial empirical evidence supports a role for several cardiovascular risk factors, including obesity, hypertension, dyslipidemia, diabetes, and IR (6). All of these factors have been implicated in the development and progression of AD, both individually and in aggregate (i.e., the metabolic syndrome) (7,8). A growing body of literature has demonstrated insulin dysregulation as a risk factor for both AD and its prodrome, mild cognitive impairment (4,9,10). Furthermore, IR represents a preclinical stage on the path to diabetes during which efforts at intervention are likely to have maximal effect. We focus here on the potential role of IR in the pathogenesis of AD, and discuss interventions that target IR as possible approaches to prevent or delay progression of AD.

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  • Dyslipidemias are associated with obesity, which has been linked to insulin resistance/hyperinsulinemia in the development of Alzheimer's disease.

    “Dyslipidemias are also associated with obesity, which has been linked to insulin resistance/hyperinsulinemia in the development of AD [108,109].”

    From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [109]

    The Introduction identifies obesity, dyslipidemia, and insulin resistance as cardiovascular risk factors implicated in AD, and the section ‘Obesity, Peripheral Insulin, and AD’ links obesity, insulin resistance, and hyperinsulinemia to increased AD risk. However, our copy does not explicitly say that dyslipidemia is associated with obesity; it lists them as separate factors that may act in aggregate. (LLM, conf=0.83)

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2 of the 101 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. [26]Luchsinger JA Patel B Tang MX Schupf N Mayeux R Measures of adiposity and dementia risk in elderly persons Arch Neurol 2007 64 392 398 17353383 PMC1821350
  2. [45]Hörsch D Kahn CR Region-specific mRNA expression of phosphatidylinositol 3-kinase regulatory isoforms in the central nervous system of C57BL/6J mice J Comp Neurol 1999 415 105 120 10540361
  3. [69]Snowdon DA Greiner LH Mortimer JA Brain infarction and the clinical expression of Alzheimer disease. The Nun Study JAMA 1997 277 813 817 9052711

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Authors
Hildreth, K. L., Van Pelt, R. E., & Schwartz, R. S.
Affiliations
University of Colorado Anschutz (US)
ORCID
Hildreth, Kerry L.
Venue
Obesity
Publisher
Wiley
Published
2012-08
Volume
20
Issue
8
Pages
1549-1557
ISSN
  • 1930-7381 (ISSN-L)
  • 1930-739X
DOI
10.1038/oby.2012.19
PMC
PMC4314950
OpenAlex
W2086598037
Cited by
86
References
101
Citations by year
2026: 2 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 11 · 2021: 9 · 2020: 7 · 2019: 1 · 2018: 4 · 2017: 8 · 2016: 5 · 2015: 3 · 2014: 13 · 2013: 8 · 2012: 2
FWCI
1.12
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 77 d)
Locations
  • Obesity (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (R01AG028746, AG028746, AG-000279, AG019339, R01AG019339, T32AG000279)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
insulin resistance, Alzheimer's disease, mild cognitive impairment, metabolic syndrome, cardiovascular risk factors, type 2 diabetes, dementia risk factors, Alzheimer's disease pathogenesis, insulin dysregulation, obesity intervention
MeSH terms
Alzheimer Disease, Brain, Female, Humans, Insulin, Insulin Resistance, Male, Obesity

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