title: Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Circulating leptin was associated with a reduced incidence of dementia and AD and with cerebral brain volume in asymptomatic older adults.
authors.affiliation: Framingham Heart Study, Framingham, Massachusetts, USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Beiser
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Zaldy S
authors.initials: ZS
authors.lastname: Tan
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: Ronenn
authors.initials: R
authors.lastname: Roubenoff
authors.forename: Sanford
authors.initials: S
authors.lastname: Auerbach
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology / Q000502:physiology; D000544:Alzheimer Disease / Q000097:blood* / Q000473:pathology*; D001921:Brain / Q000473:pathology* / Q000502:physiology; D003704:Dementia / Q000097:blood / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020738:Leptin / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D011446:Prospective Studies
chemical_list: D020738:Leptin