T2D effect on dementia varies by subtype

Type 2 diabetes (T2D) may be associated with an elevated risk of dementia, but the effect varies according to dementia subtype, according to a study presented at EASD 2020.

“Individuals with T2D have a higher risk of all-cause dementia. However, the risk was higher for vascular dementia compared to other forms of dementia, such as Alzheimer’s disease (AD) and non-vascular dementia,” presented study author Dr Carlos Celis-Morales from the Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

A total of 378,299 adults with T2D (mean age 64.13 years, 54.7 percent male) listed in the Swedish National Diabetes Register in 1998–2013 were age- and sex-matched with 1,886,022 controls from the general population (mean age 64.07 years, 54.8 percent male). They were followed up for a median 6.7 years, during which time, 10,143 patients with T2D and 46,479 controls developed dementia.

Initial analysis suggested the association between T2D and dementia was highest for vascular dementia (hazard ratio [HR], 1.35) compared with the control group, with a less evident association between T2D and non-vascular dementia (HR, 1.08). Conversely, the risk of AD appeared lower in the T2D vs control group (HR, 0.92). [EASD 2020, oral abstract 6]

The effect of T2D on the various dementia subtypes appeared to be influenced by glycaemic control (ie, HbA_1c levels). Individuals with T2D with poor glycaemic control (HbA_1c ≥87 mmol/mol) had an almost twofold risk of vascular dementia (HR, 1.93, 95 percent confidence interval [CI], 1.53–2.42) compared with those with better glycaemic control (HbA_1c <52 mmol/mol).

The risks of non-vascular dementia (HR, 1.67, 95 percent CI, 1.45–1.91) and AD (HR, 1.34, 95 percent CI, 1.03–1.75) were also increased among patients with HbA_1c ≥87 vs <52 mmol/mol.

In a landmark analysis at 3 years, the risks remained elevated for vascular and non-vascular dementia, but not AD.

The results also showed that modifiable and non-modifiable risk factors had different impacts on the various dementia subtypes.

For instance, cardiovascular disease (CVD)-related factors explained up to 40 percent of the relative influence of T2D on vascular dementia, and only 10 and 20 percent of the relative influence of T2D on AD and non-vascular dementia, respectively, said Celis-Morales.

BMI and blood pressure, which were among the key modifiable risk factors explaining the T2D–dementia risk, have significant “public health relevance”, he continued. “[I]dentification of high-risk individuals and tailored interventions of treatment could attenuate the dementia risk attributable to T2D,” he said.

“[O]ur findings underscore the importance of good blood sugar control,” he continued. “[However, they] by no means suggest that most who have diabetes will go on to develop vascular dementia in later life. But with the number of people with T2D doubling over the past 30 years, the importance of a healthy lifestyle is clearer than ever,” he said.

Echoing this was study co-author Professor Naveed Sattar, also from the University of Glasgow. “A 36 percent higher risk is in itself an argument for preventive measures such as healthier lifestyle.”

“Diabetes and dementia share certain risk factors that might contribute to these associations including obesity, smoking, and lack of physical activity. The importance of prevention is underscored by the fact that, for the majority of dementia diseases, there is no good treatment,” he pointed out.

The authors acknowledged the potential for residual confounding and that the observational study design precluded conclusions on cause and effect. Studies with longer follow-up may help establish the findings, considering that dementia onset often occurs several years prior to diagnosis, they said.