Severity of Diabetes Complications Linked to Dementia

Veronica Hackethal, MD

July 15, 2015

The risk of developing dementia correlates with the severity of diabetes complications such as neuropathy, according to a 12-year Taiwanese study.

The research represents the first nationwide effort to look at the progression and severity of diabetes and risk for dementia and was published online July 9 in the Journal of Clinical Endocrinology & Metabolism.

"[In our study], the risk of dementia was increased from diabetes onset and was associated with diabetic complication severity and progression," commented first author Wei-Che Chiu, MD, PhD, of the department of psychiatry, Cathay General Hospital and the School of Medicine, Fu Jen Catholic University, in Taipei, Taiwan.

"Progression of diabetic severity in the early years of [type 2] diabetes could predict the risk of dementia," he added.

Past studies have shown a consistent link between diabetes and an increased risk for dementia, with some suggesting that diabetes increases the risk for dementia up to threefold, according to background information in the article.

Moreover, diabetic complications and poor glucose control have been linked to mild cognitive impairment, which can be an indicator of early dementia. The nature of the association between diabetes severity and dementia, though, has remained unclear — making it challenging to predict the risk of dementia in diabetes.

Asked to comment, Robert Lash, MD, professor of medicine at the University of Michigan and a spokesperson for the Endocrine Society, said that despite these new findings, it's too soon to add dementia to the list of diabetes complications, because the relationship between the two diseases is "complicated."

Early Change in Diabetes Severity Index Could Predict Dementia

The population-based cohort study used data from the Taiwan National Health Insurance Research Database spanning January 1999 to December 2010. Researchers included patients aged 50 years and over who had newly diagnosed type 2 diabetes.

They evaluated diabetic progression and severity using the adapted Diabetes Complications Severity Index (aDCSI). The aDCSI covers seven diabetes complications — cardiovascular disease, nephropathy, retinopathy, peripheral vascular disease, stroke, neuropathy, and metabolic abnormalities — and can be used to predict mortality, hospitalizations, and severity of these complications.

Dementia was defined using the International Classification of Diseases, ninth revision codes (ICD9), excluding vascular dementia. The analysis included 431,178 patients, out of whom 6.2% (n = 26,856) developed dementia within 12 years.

Diabetic severity and progression were associated with increased risk for dementia, and this remained significant even after adjustment for gender, comorbidity, diabetes medications, and drug adherence. However the researchers lacked information about potential confounders like smoking, alcohol use, body mass index, and education level.

Increasing aDCSI scores of 1, 2, 3, and greater than 3 were associated with a 4%, 40%, 54%, and 70% increased risk of dementia, respectively (P < .001 for trend).

And compared with patients with mildly progressive diabetes, patients with more rapidly progressing diabetes had greater risk of dementia.

The adjusted hazard ratios for dementia increased as the aDCSI increased.

Hazard Ratios (HR) for Dementia per Change in aDCSI Score/Year vs <0.50

Change in aDCSI score/y 2-y HR Final HR
0.51–1.00 1.30 2.38
1.01–2.00 1.53 6.95
>2.00 1.97 24.0
P < .001 for trend

Thus, an early change in the aDCSI score "could predict the risk of dementia in new-onset diabetic patients," Dr Chiu and colleagues observe.

Watch Out for Hypoglycemia…

Hypoglycemia was also associated with a 30% increased risk of dementia. Insulin therapy lasting over 180 days, though, did not seem to increase this risk and may have exerted a protective effect on rapidly progressive patients, compared with mildly progressive patients.

"The prevention of diabetic progression is an important factor in reducing the risk of dementia. From our research, diabetic complications should be monitored closely and comprehensively," Dr Chiu emphasized. "Tighter glycemic control is important to prevent diabetic progression."

But this is a balancing act, he stressed — tight control needs to be executed carefully because "hypoglycemic episodes were higher in the [very drug-adherent] patients in our study."

Dr Lash said that because this study did not specifically look at glycemic control but instead looked at the diabetic complication severity index, it is not possible to say whether improving glucose control would decrease the risk of dementia.

However, "what this study shows is that the more severe your diabetes is in terms of complications, the bigger the risk of progressing to dementia, which is another good reason to have good glucose control," he told Medscape Medical News.

Dementia Cannot Be Added to List of Diabetic Complications

But Dr Lash emphasized that "this study doesn't add dementia to the list of diabetic complications. Diabetes does increase your risk of dementia. We know that already, but it's a complicated story. There's a lot of ways that diabetic complications contribute to the development of dementia."

For example, diabetes increases the risk for atherosclerotic disease, which in turn increases the risk for vascular dementia. Diabetes also increases the risk for coronary artery disease, which can cause atrial fibrillation and ministrokes that increase the risk of dementia.

And as shown by Dr Chiu and colleagues, even frequent hypoglycemia can increase the risk for dementia, explained Dr Lash.

"Dementia scares people. It's hard to put it in a 'yes' or 'no' bucket," he emphasized.

"You can't guarantee that someone's not going to get cardiovascular disease if they have good glucose control and you can't guarantee that they're not going to have dementia if they have good glucose control. All you can do is lower that risk and improve their chances [with tighter glucose control]."

The authors report they have no relevant financial relationships, as does Dr Lash.

J Clin Endocrinol Metab. Published online July 9, 2015. Abstract


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