Type 2 Diabetes Linked to Poor Cognitive Function in Middle Age

Findings from the Whitehall II study expand on previous research
that demonstrated poorer cognitive performance in older adults with type 2 diabetes.
Reviewed By Meena Kumari, PhD
Type 2 diabetes is associated with poor performance in some aspects of cognition in a middle-aged cohort from the UK’s Whitehall II study.

According to a study reported in Neurology, the association between diabetes and cognitive function extends to middle-aged adults. Study authors Meena Kumari, PhD, and Michael Marmot, FRCP, from the International Centre for Health and Society, London, said that the findings are important for two reasons. First, diabetes itself is associated with cognitive decline. Second, as the incidence of diabetes in younger age groups increases, there are implications for the management of diabetes in these groups, they said.


While the association between type 2 diabetes and poorer cognitive function was demonstrated in a number of studies among older participants, the association in younger cohorts is not well examined, the investigators wrote. “With the Whitehall II study we were able to expand on the research associating diabetes and impaired glucose tolerance [IGT] with cognitive performance, by examining this relation in a younger sample, a mostly middle-aged cohort of men and women.”

The Whitehall II study looked at cognition across various domains and assessed diabetes by oral glucose tolerance test (OGTT) on two separate occasions. Patients were recruited between 1985 and 1988 from 20 London-based civil service departments. Diabetes status was determined from OGTT performed in 1992 to 1993 and 1997 to 1999 (phases 3 and 5, respectively) and from self-reported diagnosis of diabetes in a baseline questionnaire in 1989 (phase 2), phase 3, 1995 (phase 4) and phase 5 of the study.

The researchers administered cognitive tests that were measured at phase 5 in 4,020 men and 1,627 women. These patients were free of stroke and had a mean age of 56 years. The cognitive tests involved five standard tasks, including a verbal memory test, the Alice Heim 4 inductive reasoning test, the Mill Hill verbal meaning test, and phonemic and semantic fluency tests (Table 1).


“There is a lack of standard criteria to judge poor performance in standard cognitive tests and assign clinical significance,” the investigators wrote. “We have adopted a previously used approach that identifies poor cognitive performance as that being in the worst sex-specific quintile.”

At phase 5, a total of 208 men (5%) and 101 women (6%) had diabetes and 405 men (10%) and 192 women (12%) had IGT. The patients with diabetes had an increased risk of poor performance on the Alice Heim 4 test compared with those without diabetes (men: OR 2.45; 95% CI, 1.77-3.38; women: OR, 1.83; 95% CI 1.09-3.08).

The researchers said these effects were independent of age, social position, vascular problems and health-related behaviors (Table 2). IGT was not related to any measure of cognition.

“Our observations suggest that effects on cognitive performance become apparent in as little as 2.5 to 5 years following diagnosis [of type 2 diabetes],” Drs. Kumari and Marmot wrote. “The timing of the diagnosis was particularly accurate in the study due to repeated administration of the OGTT.”

The investigators found that, although type 2 diabetes is associated with poorer cognition, there are no universal effects. Therefore no cross-sectional effects were apparent for memory, semantic or categorical fluency. However, the strongest effects were for inductive reasoning.


Comorbidities and health behaviors were associated with diabetes and poor cognition. While vascular problems, hypertension, lack of vigorous activity and no alcohol consumption were associated with poor cognitive performance, they did not explain the increased risk of poor cognitive performance associated with diabetes, the investigators said.

“Our findings suggest that lipids and other metabolic markers play a role in the association between diabetes and cognitive performance,” Drs. Kumari and Marmot wrote. “A number of mechanisms have been postulated to play a role in this relationship.” Follow-up of the Whitehall II cohort – when the metabolic syndrome variables will be reassessed – will allow the investigators to study the effects of chronic exposure to the metabolic syndrome, they added. 

Meena Kumari, PhD, is from the department of epidemiology and public health, at the International Centre for Health and Society, London, UK. She can be reached at M.Kumari@ucl.ac.uk.

Michael Marmot, FRCP is also from the International Centre for Health and Society.

Kumari M, Marmot M. Diabetes and cognitive function in a middle-aged cohort. Findings from the Whitehall II study. Neurology. 2005;65:1597-1603.
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