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Int J Geriatr Psychiatry. 2009 Feb;24(2):177-82. doi: 10.1002/gps.2089.

A profile of impaired insulin degradation in relation to late-life cognitive decline: a preliminary investigation.

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  • 1Division of Aging, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.



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.


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.


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).


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.

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