Association of Plasma Leptin Levels With Incident Alzheimer Disease and MRI Measures of Brain Aging
Open accessAbstract
CONTEXT: The adipokine leptin facilitates long-term potentiation and synaptic plasticity in the hippocampus, promotes beta-amyloid clearance, and improves memory function in animal models of aging and Alzheimer disease (AD). OBJECTIVE: To relate baseline circulating leptin concentrations in a community-based sample of individuals without dementia to incident dementia and AD during follow-up and magnetic resonance imaging (MRI) measures of brain aging in survivors. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of plasma leptin concentrations measured in 785 persons without dementia (mean [SD] age, 79 [5] years; 62% female), who were in the Framingham original cohort at the 22nd examination cycle (1990-1994). A subsample of 198 dementia-free survivors underwent volumetric brain MRI between 1999 and 2005, approximately 7.7 years after leptin was assayed. Two measures of brain aging, total cerebral brain volume and temporal horn volume (which is inversely related to hippocampal volume) were assessed. MAIN OUTCOME MEASURE: Incidence of dementia and AD during follow-up until December 31, 2007. RESULTS: During a median follow-up of 8.3 years (range, 0-15.5 years), 111 participants developed incident dementia; 89 had AD. Higher leptin levels were associated with a lower risk of incident dementia and AD in multivariable models (hazard ratio per 1-SD increment in log leptin was 0.68 [95% confidence interval, 0.54-0.87] for all-cause dementia and 0.60 [95% confidence interval, 0.46-0.79] for AD). This corresponds to an absolute AD risk over a 12-year follow-up of 25% for persons in the lowest quartile (first quartile) vs 6% for persons in the fourth quartile of sex-specific leptin levels. In addition, a 1-SD elevation in plasma leptin level was associated with higher total cerebral brain volume and lower temporal horn volume, although the association of leptin level with temporal horn volume did not reach statistical significance. CONCLUSION: Circulating leptin was associated with a reduced incidence of dementia and AD and with cerebral brain volume in asymptomatic older adults.
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Individuals with higher leptin levels are associated with a reduced risk of dementia and Alzheimer's disease.
“individuals with higher leptin levels are associated with a reduced risk of dementia and AD.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [585]
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- Authors
- Lieb, W.
- Affiliations
- Framingham Heart Study (US)
- Corresponding author
- Lieb, Wolfgang
- ORCID
- Lieb, Wolfgang
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2009-12-16
- Volume
- 302
- Issue
- 23
- Pages
- 2565
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC2838501
- OpenAlex
- W2128828378
- Cited by
- 428
- References
- 61
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 17 · 2023: 22 · 2022: 27 · 2021: 22 · 2020: 22 · 2019: 19 · 2018: 22 · 2017: 24 · 2016: 18 · 2015: 36 · 2014: 46 · 2013: 34 · 2012: 37
- FWCI
- 19.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hc25195-41-0-1, n01hv28178-12-0-0, N01 HV28178, N01-HC 25195)
- National Institute on Aging (P30AG010129, R01AG031287, AG031287, AG08122, AG033193, R01AG016495, R01AG033193, R01AG008122)
- National Heart, Lung, and Blood Institute (N01 HV28178, N01‐HC25195, AG08122, AG031287, K24HL004334, DK080739, N01-HC-025195, N01-HV-028178, AG16495)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080739)
- National Institute of Neurological Disorders and Stroke (R01NS017950)
- 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
- leptin, Alzheimer's disease, dementia, brain aging, hippocampal volume, adipokines, incident dementia risk, older adults, Framingham cohort
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Dementia, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Prospective Studies, Leptin
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