Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and alzheimer disease: results from the Framingham Heart Study.
OBJECTIVE
To investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A(2) levels) to the risk of developing Alzheimer disease (AD) and all-cause dementia.


METHODS
Prospective cohort study.


METHODS
Dementia-free Framingham Heart Study participants had sera measured for these biomarkers at the 19th biennial examination (1985-1988) and were followed up prospectively for the development of AD and all-cause dementia.


METHODS
Eight hundred forty (541 women, median age of 76 years) subjects participated in the study.


METHODS
We used sex-pooled and sex-specific multivariable Cox proportional hazards models adjusted for age, education, body mass index, recent change in weight, APOE ε4 allele status, and plasma docosahexaenoic acid levels to determine association of these biomarkers with the development of all-cause dementia and AD.


RESULTS
Over a mean follow-up period of 13 years, 159 persons developed dementia (including 125 with AD). After adjustment for other risk factors, only adiponectin in women was associated with an increased risk of all-cause dementia (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.00-1.66; P=.054) and AD (HR, 1.33; 95% CI, 1.00-1.76; P=.050) per 1-SD increase in adiponectin level. Women with baseline adiponectin values more than the median had a higher risk of all-cause dementia (HR, 1.63; 95% CI, 1.03-2.56; P=.04) and AD (HR, 1.87; 95% CI, 1.13-3.10; P=.01) as compared with those with values less than the median.


CONCLUSIONS
In women, increased plasma adiponectin levels are an independent risk factor for the development of both all-cause dementia and AD.
Lipid Metabolism Laboratory, Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Thomas M
TM
van Himbergen
Alexa S
AS
Beiser
Masumi
M
Ai
Sudha
S
Seshadri
Seiko
S
Otokozawa
Rhoda
R
Au
Nuntakorn
N
Thongtang
Philip A
PA
Wolf
Ernst J
EJ
Schaefer
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D052242:Adiponectin / Q000097:blood; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D001786:Blood Glucose; D002097:C-Reactive Protein / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D003704:Dementia / Q000097:blood* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D005260:Female; D005470:Fluorometry; D017127:Glycation End Products, Advanced; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D012737:Sex Factors; D000093423:Glycated Serum Albumin
D052242:Adiponectin; D001057:Apolipoproteins E; D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D007328:Insulin; D010446:Peptide Fragments; D012709:Serum Albumin; C117630:apolipoprotein E (141-155); D002097:C-Reactive Protein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000093423:Glycated Serum Albumin