Factors such as blood pressure, blood glucose levels, and cholesterol levels could predict the onset of dementia in individuals with type 2 diabetes up to 20 years beforehand, say UK researchers who hope the findings could help prevent or delay the condition.
"While this study cannot confirm causal associations," said lead researcher Dr Eszter Vamos, Imperial College London, in a news release, "These results show that blood pressure and other cardiometabolic factors could be contributing to dementia development up to two decades before diagnosis."
She added that the findings "emphasise the importance of carefully managing cardiometabolic factors such as blood pressure, cholesterol, and glucose levels early for people with type 2 diabetes".
The research was presented at the Diabetes UK Professional Conference 2021 on April 27.
Elizabeth Robertson, PhD, director of research at Diabetes UK, which funded the study, underlined that this is the "first time researchers have uncovered a pattern of changes in people with type 2 diabetes that are associated with dementia".
"Knowing which factors contribute to the development of dementia, and when they have the biggest impact, is vital in giving people with type 2 diabetes the best possible care to prevent or delay dementia onset," she said.
Extreme Caution
However, a leading expert told Medscape News UK that "one has to be extremely cautious in the interpretation of retrospective data", as the "research questions examined were thought up much later" and "the assessment of dementia was not standardised over time".
Professor Katherine Samaras, leader of the Healthy Ageing Research Theme at the Garvan Institute and an endocrinologist at St Vincent's Hospital, Sydney, Australia, added that the associations identified in the study are "small".
This may suggest the impact of diabetes on future dementia risk, however, is so great that it "overwhelms the association of traditional risk factors such as lipids, blood pressure etc".
Diabetes and Dementia Coexist
Dr Vamos began her presentation by noting that 7.2% of the population in England have progressive cognitive decline, which translates to 748,000 people aged over 65 years and a current cost of £29.5 billion per annum.
Diabetes and dementia commonly coexist in elderly individuals, and previous research has indicated that diabetes is associated with a 1.5–2.5-fold increased risk of dementia.
However, there is "no evidence" that the link is causal, and metabolic and vascular factors such as mid-life hypertension, weight measures and dyslipidaemia have been proposed as contributors.
Linked Data
To examine long-term changes in modifiable cardiometabolic risk factors before dementia onset, the team collated data from the Clinical Practice Research Datalink for the period January 1999 to December 2018.
They extracted patients aged ≥42 years in 1999 who had type 2 diabetes but were free of dementia at study entry. The patients’ records were then linked to the Hospital Episode Statistics database and the Office for National Statistics mortality records.
This yielded 227,580 type 2 diabetes patients, who were followed up until dementia diagnosis, death, transfer out of the database or the end of the study.
A dementia diagnosis was given on the basis of having a clinical diagnosis of dementia, the prescription of drugs indicating Alzheimer’s disease or a screening test indicating dementia. In addition, probable dementia cases were identified via, for example, referral to a memory clinic.
Baseline Differences
Of the patients with type 2 diabetes included in the study, 10.2% went on to develop dementia.
At baseline, those with dementia were older, at an average age of 82.3 years versus 72.4% for those without, and were less likely to be male, at 43.0% versus 53.7%.
Those with dementia were more likely to be White (91.8% versus 84.7%) and were less likely to be smokers, at 22.7% versus 31.7% for those who did not develop dementia.
Long-term Changes
Examining eight cardiometabolic risk factors and looking back from either the date of dementia diagnosis or the last follow-up in those without the condition, the team found they could identify differences between the groups stretching back up to two decades.
For example, while systolic blood pressure levels were lower in the dementia group at the time of diagnosis, they were higher than those in control patients 11 years beforehand, at a fixed effects coefficient of 0.45.
Similarly, low density lipoprotein cholesterol levels were lower at the time of diagnosis among dementia patients but were higher than those seen in controls 19 years before the diagnosis.
Blood Glucose Differences
HbA1c levels were also higher in patients with dementia from 19–17 years before diagnosis, at a coefficient of -1.98. The difference contracted but remained present over the intervening years.
Fasting plasma glucose levels were almost identical between dementia and non-dementia cases approximately 17 years before diagnosis but separated over time, with levels higher in patients with the condition.
A notable difference in body mass index was identified between dementia and non-dementia patients 11 years before diagnosis, with cases having a lower weight that not only was maintained but also widened as time went on.
Next, the researchers will examine whether diabetes-related complications such as eye and kidney problems are associated with dementia risk.
A Useful Dataset
Professor Samaras explained that the retrospective design of the investigation "is one of weakest forms of study methodology". She underlined that the database "did not set out to examine dementia", and did not appear to take into account stroke, which is known to affect future dementia risk.
Nevertheless, it "might be a useful dataset to ask clinically important questions" and "may yield findings that could be considered as a starting point for asking more questions using more robust methodology".
Another limiting factor is the "lack of an important control group": people without diabetes. This, Professor Samaras said, would be the "ideal denominator for the cohort".
She continued that the differences in traditional cardiometabolic risk factors between people with and without dementia were "surprising", especially given previous prospective datasets "demonstrating detrimental associations between elevated blood pressure, hyperlipidaemia and specific apolipoprotein E genotypes with future risk of dementia".
Professor Samaras said: "One interpretation that could be considered...is that the impact of diabetes overwhelms traditional cardiovascular risk factors; hence the apparently small associations seen even when examining relationships that might go back 20 years."
The research was funded by Diabetes UK.
Dr Vamos receives funding from Diabetes UK.
Diabetes UK Professional Conference 2021: Abstract A38. Presented 27 April.
