A profile of impaired insulin degradation in relation to late-life cognitive decline: a preliminary investigation.
OBJECTIVE
Insulin degradation pathways may be related to Alzheimer's disease pathology. In preliminary analyses, we considered the relation of combined lower insulin secretion (c-peptide) and higher insulin--possibly a phenotype for impaired insulin degradation--to cognitive decline.


METHODS
Fasting plasma c-peptide and insulin were measured in 1,187 non-diabetic Nurses' Health Study participants (mean age = 64 years). Cognitive testing began 10 years later. Participants completed three repeated assessments (over an average span of 4.4 years) of verbal memory, a strong predictor of Alzheimer disease development. C-peptide and insulin distributions were dichotomized at their medians to create four cross-tabulated categories. Multivariable linear mixed effects models were used to relate c-peptide/insulin categories to cognitive decline.


RESULTS
Compared to the lower c-peptide/lower insulin group, women with lower c-peptide/higher insulin had a significantly faster rate of verbal memory decline: the mean difference was -0.05 units/year (95% CI -0.09,-0.01). This mean difference was similar to that which we found for women 5 years apart in age, indicating that having a profile of lower c-peptide/higher insulin appeared cognitively equivalent to aging by five years on tests of verbal memory. For women with higher c-peptide/higher insulin, the estimated mean difference in decline compared to those in the lower c-peptide/lower insulin group was statistically significant, but slightly lower, at -0.04 units/year (95% CI: -0.07,-0.02).


CONCLUSIONS
These preliminary analyses of a possible phenotype of impaired insulin degradation provide supportive evidence that deficits in insulin degradation may be related to late-life verbal memory decline.
Okereke
Olivia I
OI
Division of Aging, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ookereke@partners.org
Selkoe
Dennis J
DJ
Pollak
Michael N
MN
Stampfer
Meir J
MJ
Hu
Frank B
FB
Hankinson
Susan E
SE
Grodstein
Francine
F
D000368:Aged; D000375:Aging / Q000097:blood* / Q000523:psychology; D000544:Alzheimer Disease / Q000097:blood* / Q000523:psychology; D002096:C-Peptide / Q000097:blood*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype
D002096:C-Peptide; D007328:Insulin