Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging

Wolfgang Lieb, Alexa S. Beiser, Ramachandran S. Vasan, Zaldy S. Tan, Rhoda Au, Tamara B. Harris, Ronenn Roubenoff, Sanford Auerbach, Charles DeCarli, Philip A. Wolf, Sudha Seshadri

Research output: Contribution to journalArticle

260 Citations (Scopus)

Abstract

Context: The adipokine leptin facilitates long-term potentiation and synaptic plasticity in the hippocampus, promotes β-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.

Original languageEnglish (US)
Pages (from-to)2565-2572
Number of pages8
JournalJAMA - Journal of the American Medical Association
Volume302
Issue number23
DOIs
StatePublished - Dec 16 2009

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Leptin
Alzheimer Disease
Dementia
Magnetic Resonance Imaging
Brain
Temporal Lobe
Survivors
Confidence Intervals
Neuronal Plasticity
Adipokines
Long-Term Potentiation
Incidence
Proportional Hazards Models
Amyloid
Hippocampus
Animal Models
Outcome Assessment (Health Care)
Prospective Studies

ASJC Scopus subject areas

  • Medicine(all)

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Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. / Lieb, Wolfgang; Beiser, Alexa S.; Vasan, Ramachandran S.; Tan, Zaldy S.; Au, Rhoda; Harris, Tamara B.; Roubenoff, Ronenn; Auerbach, Sanford; DeCarli, Charles; Wolf, Philip A.; Seshadri, Sudha.

In: JAMA - Journal of the American Medical Association, Vol. 302, No. 23, 16.12.2009, p. 2565-2572.

Research output: Contribution to journalArticle

Lieb, W, Beiser, AS, Vasan, RS, Tan, ZS, Au, R, Harris, TB, Roubenoff, R, Auerbach, S, DeCarli, C, Wolf, PA & Seshadri, S 2009, 'Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging', JAMA - Journal of the American Medical Association, vol. 302, no. 23, pp. 2565-2572. https://doi.org/10.1001/jama.2009.1836
Lieb, Wolfgang ; Beiser, Alexa S. ; Vasan, Ramachandran S. ; Tan, Zaldy S. ; Au, Rhoda ; Harris, Tamara B. ; Roubenoff, Ronenn ; Auerbach, Sanford ; DeCarli, Charles ; Wolf, Philip A. ; Seshadri, Sudha. / Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. In: JAMA - Journal of the American Medical Association. 2009 ; Vol. 302, No. 23. pp. 2565-2572.
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abstract = "Context: The adipokine leptin facilitates long-term potentiation and synaptic plasticity in the hippocampus, promotes β-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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AU - Lieb, Wolfgang

AU - Beiser, Alexa S.

AU - Vasan, Ramachandran S.

AU - Tan, Zaldy S.

AU - Au, Rhoda

AU - Harris, Tamara B.

AU - Roubenoff, Ronenn

AU - Auerbach, Sanford

AU - DeCarli, Charles

AU - Wolf, Philip A.

AU - Seshadri, Sudha

PY - 2009/12/16

Y1 - 2009/12/16

N2 - Context: The adipokine leptin facilitates long-term potentiation and synaptic plasticity in the hippocampus, promotes β-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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