The role of IGF-I, IGF-II, and IGFBP-3 in male cognitive aging and dementia risk: the Caerphilly Prospective Study.
BACKGROUND
The increasing incidence of cognitive impairment and dementia in an aging population poses a significant burden on healthcare. Consequently, identifying modifiable physiological factors which may influence the onset of cognitive decline are becoming increasingly important. Previous studies have suggested an association between levels of insulin-like growth factors and cognitive function.


OBJECTIVE
To investigate whether low IGF-I, IGF-II, and IGF molar ratio is associated with greater cognitive decline and increased risk of dementia.


METHODS
We examined prospective associations between IGF-I, IGF-II, and IGFBP-3 and cognitive function in the Caerphilly Prospective Study (CaPS) (n = 746 men) from samples obtained around 1986, with assessment in around 2003 for clinical diagnosis of cognitive impairment but no dementia (CIND) or dementia, as well as with CAMCOG scores at three phases.


RESULTS
A one standard deviation increase in IGF-II was associated with a reduced odds ratio for CIND (0.76, 95% CI 0.60, 0.96) which hardly altered after further adjustment for confounders. A one standard deviation increase in IGFBP-3 among participants without dementia or CIND was associated with greater decline in cognition (p = 0.002) equivalent to 2.4 years difference in age. All the associations between IGF-I and our outcomes were consistent with chance.


CONCLUSIONS
In this study of men, we found that both IGF-II and IGFBP-3 are associated with normal age-related cognitive decline and clinical pathology associated with CIND, but we failed to replicate previous associations with IGF-I. Assuming these findings are replicated, they may provide new insights into potential biological mechanisms that underlie age-related cognitive changes and development of dementia.
School of Social and Community Medicine, University of Bristol, UK.
Christopher J
CJ
Green
School of Clinical Sciences, University of Bristol, UK.
Jeffrey M P
JM
Holly
Institute of Primary Care and Public Health, School of Medicine, Cardiff University, UK.
Antony
A
Bayer
Department of Neurology, Musgrove Park Hospital, Taunton, UK.
Mark
M
Fish
London School of Hygiene and Tropical Medicine, UK.
Shah
S
Ebrahim
Institute of Primary Care and Public Health, School of Medicine, Cardiff University, UK.
John
J
Gallacher
School of Social and Community Medicine, University of Bristol, UK.
Yoav
Y
Ben-Shlomo
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000097:blood*; D015331:Cohort Studies; D003704:Dementia / Q000097:blood*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D016017:Odds Ratio; D011446:Prospective Studies; D012306:Risk
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II
Dementia; insulin-like growth factors; mild cognitive impairment; prospective cohort study