Type 2 Diabetes and association with neuropathological changes and domain specific cognitive decline

Type 2 Diabetes (T2DM) and Alzheimer's disease (AD) are common diseases in aging populations in the US. Multiple large epidemiological studies suggest that T2DM is strongly associated with cognitive impairment. However, the association between T2DM and AD is still controversial. The current study was conducted to investigate the association of diabetes history with neuropathological and cognitive features.Participant data were drawn from the National Alzheimer's Coordinating Center (NACC). Diabetes status was determined based on any reported diabetes diagnosis or diabetic treatment during annual assessments. Standardized z scores in memory, attention, language, and executive function were derived from neuropsychological test scores assessed at each annual visit. Multivariable linear mixed-effects models assessed associations between cognitive domain scores and diabetes and APOE ε4 interaction adjusting for sex, age at each visit, education, hypertension, time and center. In a subset of 5190, autopsied participants, logistic regression was used to examine the association of diabetes and specific neuropathology changes adjusting for sex, age at death, education, hypertension, years of follow-up and center.After excluding participants who reported any other type of diabetes, whose age at baseline were < 60 years, and who had missing APOE genotype data, diabetes was present in 4,899 participants (13.5%) with a mean age at last visit of 77.2 ±8.5 (Table 1). Participants with diabetes history had lower odds for AD neuropathology changes (ADNC), OR=0.77 (95% CI=0.63-0.94). Diabetes history was associated with increased odds of brain infarcts/lacunes (OR=1.47 and 95% CI=1.21-1.78) and moderate arteriosclerosis (OR=1.37 and 95%CI=1.05-1.79). Diabetes history plus APOE ε4 allele was associated with lower attention domain scores (Figure 1).Diabetes was positively associated with cerebrovascular pathology and negatively associated with ADNC. APOE ε4 genotype modified the association between diabetes and cognitive features.