Fasting plasma insulin, C-peptide and cognitive change in older men without diabetes: results from the Physicians' Health Study II.
BACKGROUND
Type 2 diabetes has been associated with diminished late-life cognition; less is known about relations of insulin levels and insulin secretion to cognitive change among persons without diabetes. We examined prospectively relations of fasting insulin levels and insulin secretion to cognitive decline among healthy, community-dwelling older men without diabetes.


METHODS
Fasting plasma insulin and C-peptide (insulin secretion) levels were measured in 1,353 nondiabetic men, aged 60-92 years (mean = 71.3 years), in the Physicians' Health Study II, who participated in cognitive testing an average of 3.3 years later. Two assessments were administered 2 years apart (range = 1.5-4.0 years) using telephone-based tests (general cognition, verbal memory and category fluency). Primary outcomes were the Telephone Interview for Cognitive Status (TICS), global cognition (averaging all tests) and verbal memory (averaging 4 verbal tests). Multivariable linear regression models were used to estimate the relations of insulin and C-peptide to cognitive decline.


RESULTS
Higher fasting insulin was associated with a greater decline on all tests, after adjustment. Findings were statistically significant for the TICS and category fluency, e.g. the multivariable-adjusted mean difference (95% CI) in decline for men with the highest versus lowest insulin levels was -0.62 (-1.15, -0.09) points on the TICS (p for trend = 0.04); this difference was similar to that between men 7 years apart in age. Similarly, there was a greater decline across all tests with increasing C-peptide, but the findings were statistically significant only for the global score (p for trend = 0.03).


CONCLUSIONS
Higher fasting insulin and greater insulin secretion in older men may be related to overall cognitive decline, even in the absence of diabetes.
Okereke
Olivia I
OI
Divisions of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. ookereke@partners.org
Kurth
Tobias
T
Pollak
Michael N
MN
Gaziano
J Michael
JM
Grodstein
Francine
F
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D002096:C-Peptide / Q000097:blood*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000097:blood / Q000503:physiopathology*; D005215:Fasting; D006304:Health Status; D006306:Health Surveys; D006801:Humans; D007328:Insulin / Q000097:blood*; D007407:Interviews as Topic; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011863:Radioimmunoassay; D012016:Reference Values; D011795:Surveys and Questionnaires
D002096:C-Peptide; D007328:Insulin