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June 24, 2010 — Middle-aged patients with type 2 diabetes have roughly a 3 times greater decline in certain cognitive functions during a 5-year period than people without diabetes, a new study suggests.
"Cognitive decline should be assessed and monitored in middle-aged people with type 2 diabetes," write Astrid C.J. Nooyens, PhD, and colleagues, of the Centre for Prevention and Health Services Research, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
The study was published online June 2 in Diabetes Care.
Doetinchem Cohort Study
The current analysis was part of the Doetinchem Cohort Study, an ongoing prospective study that aims to study the impact of lifestyle changes and biological risk factors on various aspects of health. It included 2613 people (1288 men and 1325 women) aged 43 to 70 years who participated in 2 cognitive measurements carried out from 1995 to 2002 and 2000 to 2007.
The cognitive testing involved 4 tests: the 15 Word Verbal Learning Test, the Stroop Color-Word Test, a Fluency Test, and the Letter Digit Substitution Test. The battery of tests measures global cognitive function and specific cognitive domains of memory, speed of cognitive processes, and cognitive flexibility.
The researchers determined diabetes status on the basis of self-report confirmed by a general practitioner, self-report without general practitioner confirmation if none was available, or a random plasma glucose level of 11.1 mmol/L or more.
After adjustment for age, sex, and educational level, patients with diabetes at baseline (prevalent diabetes) had statistically significantly greater declines in memory function, cognitive flexibility, and global cognitive function than people without diabetes. Participants in whom diabetes developed (incident diabetes) showed approximately twice the decline than people without diabetes, but this was only significant for memory, speed, and flexibility in people 60 years and older.
In a model that adjusted for additional factors (high-density lipoprotein cholesterol levels, systolic blood pressure, use of blood pressure–lowering medications, history of myocardial infarction, depression, physical activity, alcohol consumption, smoking, waist circumference, and baseline cognitive score), cognitive declines in memory (–2.5), flexibility (–3.6 in those > age 60 years and –3.4 in those ≤ age 60 years), and global cognitive function (–2.6) were greater in patients with prevalent diabetes vs people without diabetes (–1.0 for all cognitive function scores). However, this was statistically significant only for flexibility in those 60 years and older and for global cognitive function. The differences in cognitive decline in memory and speed between patients with incident diabetes and patients without diabetes were no longer statistically significant in the fully adjusted model.
"The magnitude of decline in cognitive function in persons who developed diabetes during follow-up was in between that of persons without diabetes and those who had diabetes at baseline, but was not statistically significantly different from either group after adjustment for other cardiovascular risk factors," the study authors write.
The study results suggest that hyperglycemia affects various cognitive functions at different stages of the disease process. They write, "For instance, memory seems to be affected continuously (lower score at baseline and a [borderline significantly] greater decline during follow up for diabetes patients), while speed of cognitive processes seems to be affected during the first years of hyperglycaemia only (worse score at baseline, but no greater decline over follow up for diabetes patients than person without diabetes, while incident diabetes patients show a greater decline in speed of cognitive processes)."
These results, they added, "suggest that early treatment of hyperglycaemia could prevent some of the decline in speed of cognitive processes, but probably less so in the case of memory."
The overall conclusion, the authors state, "is that diabetes is associated with greater cognitive decline in middle aged persons, but that it remains uncertain which cognitive domain is affected most."
Because adjusting for cardiovascular risk factors that may accompany diabetes and influence cognitive function (eg, hypertension) did not substantially alter the findings, comorbidities of diabetes might only partly explain the association between diabetes and cognitive decline.
Study Strengths and Limitations
Strengths of the study are its prospective design, the inclusion of a relatively young population, and its long follow-up period with repeated assessment of cognitive function. One of the study's limitations is the dropout rate of 20%, although the study authors believe the effects of this are "only marginal." Some cases of diabetes may have been missed, as glucose levels were measured randomly (ie, no fasting levels were checked), and possible misclassifications in diabetes groups may have led to underestimation of the observed differences. As well, the study could not relate longer-term glucose levels to cognitive changes, as no data on hemoglobin A1c levels were available.
Possible Pathways Involved in Disease Process
The study authors described possible pathways leading from diabetes to cognitive decline. For example, hyperglycemia causing oxidative stress can have a detrimental effect on brain cells, and higher fasting plasma glucose levels may cause functional changes in regional cerebral perfusion. Cognitive dysfunction in diabetes may result from an interaction between metabolic abnormalities such as hyperglycemia; diabetes complications such as retinopathy and neuropathy; and other diabetes-related disorders such as ischemic heart disease, cerebrovascular disease, hypertension, central obesity, and depression.
The study authors have disclosed no relevant financial relationships.
Diabetes Care. Published online June 2, 2010. Abstract
More on the interrelationship between Type 2 diabetes and cognitive decline can be found on the Cochrane Collaboration
Type 2 diabetes mellitus is considered to be a risk factor for cognitive impairment, vascular dementia, and Alzheimer's disease.
Although the underlying mechanisms are unclear, these may involve metabolic abnormalities associated with diabetes and/or
other diabetes-related disorders, such as ischemic heart disease.
Most previous studies of the association between cognitive functioning and diabetes were cross-sectional or were limited to
elderly subjects. Longitudinal studies are needed to clarify how cognitive function declines with time in relationship to
the onset and duration of diabetes.
