Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease

There is increasing interest in interactions between metabolic syndromes and neurodegeneration. Diabetes mellitus (DM) contributes to cognitive impairment in the elderly but its effect in Parkinson disease (PD) is not well studied. Objective: To investigate effects of comorbid DM on cognition in PD independent from PD-specific primary neurodegenerations. Methods: Cross-sectional study. Patients with PD (n=148); age 65.6±7.4 years, Hoehn and Yahr stage 2.4±0.6, with (n=15) and without (n=133) comorbid type II DM, underwent [¹¹C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) PET imaging to assess cortical cholinergic denervation, [¹¹C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation, and neuropsychological assessments. A global cognitive Z-score was calculated based on normative data. Analysis of covariance was performed to determine cognitive differences between subjects with and without DM while controlling for nigrostriatal denervation, cortical cholinergic denervation, levodopa equivalent dose and education covariates. Results: There were no significant differences in age, gender, Hoehn and Yahr stage or duration of disease between diabetic and non-diabetic PD subjects. There was a non-significant trend toward lower years of education in the diabetic PD subjects compared with non-diabetic PD subjects. PD diabetics had significantly lower mean (±SD) global cognitive Z-scores (-0.98±1.01) compared to the non-diabetics (-0.36±0.91; F=7.78, P=0.006) when controlling for covariate effects of education, striatal dopaminergic denervation, and cortical cholinergic denervation (total model F=8.39, P<0.0001). Conclusion: Diabetes mellitus is independently associated with more severe cognitive impairment in PD likely through mechanisms other than disease-specific neurodegenerations.