Background and aims: Cognitive impairment in type 2 diabetes has a multi-factorial aetiology. In a previous study of 76-year old participants in the Fremantle Diabetes Study (FDS), cognitive impairment and dementia were independently predicted by peripheral vascular disease and by diabetes duration assessed an average 8 years previously. The aim of the present study was to conduct a similar study in FDS participants who underwent a comprehensive assessment of diabetes and related factors during middle age.
Methods: Survivors of the FDS, who were aged 57.4±9.0 years when first assessed, underwent cognitive assessment 14.6±1.1 years later when aged 72.0±9.0 years. Cognitive screening using the Mini-mental State Examination (MMSE) was followed by Clinical Dementia Rating (CDR) if MMSE score ≤26/30.
Results: Of 307 classifiable survivors, 26 (8.5%) had mild degree cognitive impairment (CDR=0.5) and 11 (3.6%) had dementia. Comparing those with normal cognition with any cognitive impairment, there were significant differences between the groups in prior educational status and baseline use of insulin. There were also statistical trends for retinopathy, microalbuminuria and fasting glucose but no difference in diabetes duration, HbA1c, cardiovascular risk-factors, macrovascular diseases or other microvascular complications. With logistic regression and including all plausible variables with P<0.2, independent baseline predictors of cognitive impairment were: education beyond primary school (odds ratio (95% CI): 0.30 (0.13-0.68), P=0.004), fasting glucose concentration (0.81, (0.70-0.95), P=0.007), insulin therapy (4.47 (1.54-12.92), P=0.006) and retinopathy (3.12 (1.14-8.57), P=0.027).
Conclusions: Different aetiological factors, including educational status, affect the risk of clinical cognitive impairment at different life stages in type 2 diabetes. A microvascular pathophysiology during middle age may be superseded by macrovascular disease later in life. Associations with insulin treatment and glycaemia have several possible explanations each with important clinical implications. Long-term observational studies are helpful in clarifying this complex disease pathway.