Pauline Anderson

July 23, 2015

WASHINGTON, DC — Older patients with type 1 diabetes (T1D) have more than an 80% increased risk for dementia compared with those without diabetes, a new study suggests.

Previous research showed that older people with type 2 diabetes (T2D) have about a two-fold greater risk for dementia compared with people without diabetes, but the current study is the first to look at dementia risk in elderly adults with T1D.

"There has been a paucity of work in type 1 diabetes because only recently have they been living longer, and living long enough to be at risk for an age-related neurocognitive dysfunction," Rachel Whitmer, PhD, senior scientist, Division of Research, Kaiser Permanente, Oakland, California, told Medscape Medical News.

Dr Whitmer presented the results here at the Alzheimer's Association International Conference (AAIC) 2015.

Living Longer

The study included 490,344 persons aged 60 years and older who were members of Kaiser Permanente Northern California, none of whom had dementia. Of these, 334 had T1D.

Over a 12-year period, 16% of the patients with T1D were diagnosed with dementia compared with 12% of those without T1D.

Compared with participants without T1D, those with T1D were 83% more likely to get dementia (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.3 - 2.5) after adjustment for differences in age, sex, race, and vascular risk factors. After adjustments for stroke, peripheral artery disease, and hypertension, the HR was 1.61.

Another analysis excluded participants with T2D, which resulted in a somewhat larger dementia risk for those with T1D (HR, 1.93; 95% CI, 1.3 - 2.6). This fell to an HR of 1.73 (95% CI, 1.2 - 2.3) when fully adjusted.

Patients with T1D are now living longer, in large part because of changes in standard of care that were introduced in the 1990s. At that time, it became clear that tight glycemic control reduced complications of diabetes.

Older patients with T1D represent a unique population that has been little studied. "When these people reach old age or an age where they might be at risk of dementia, they have been living with this disease for an average of 40 years," said Dr Whitmer.

T1D is different from other types of the disease in that it's usually juvenile onset and requires insulin right away, so some participants in the study have been taking insulin for decades, according to Dr Whitmer. Patients with T1D tend to have more microvascular risk factors than those with T2D and have less adiposity, she said.

In contrast, patients with T2D are more likely to have macrovascular risk factors, such as end-stage renal disease or retinopathy, and a relatively high risk for stroke.

"Even though type 1 diabetes is a rare disease," said Dr Whitmer, studying both diseases will help to understand how and why they are associated with dementia.

Another factor separating diabetes types is that even if the patients generally have taken good care of themselves, those with T1D are three times more likely to have had had hypoglycemic episodes, said Dr Whitmer.

"Part of taking good care of yourself is that you walk this tightrope between trying not to be hyperglycemic and trying not to be hypoglycemic, and we know from work we have done in type 2 diabetes that hypoglycemia, in particular very severe episodes that land you in the hospital emergency room, are strongly associated with dementia."

Studying dementia risk in T1D may also shed new light on possible glycemic and vascular mechanisms for brain aging, she said.

Among the next steps for the researchers is to "figure out what is driving this," said Dr Whitmer. "Is it hypoglycemia; is it microvascular risk factors; is it depression?"

Future work, she said, will "try to tease apart" dementia risk factors as well as any protective factors. Another research direction might be to determine the neuropathology — whether it's Alzheimer's disease or other forms of dementia that is raised in patients with T1D.

This work is becoming increasingly relevant as the incidence of both T1D (as well as other autoimmune disorders) and T2D is also increasing. For T2D, it's likely driven by rising rates of obesity, but for T1D, it could be somehow related to lack of immune system stimulation.

According to anecdotal reports, the prevalence of a gene closely linked to T1D is the same in Finland and nearby Russia, but Finland has a much higher rate of T1D. The difference, said Dr Whitmer, could be that Russia has a higher infection rate and therefore the immune system of residents may be sufficiently stimulated.

Hypoglycemia the Culprit?

Asked to comment, Suzanne Craft, PhD, professor, Gerontology and Geriatric Medicine, Wake Forrest School of Medicine, Winston-Salem, North Carolina, and a member of the Alzheimer's Association Medical and Scientific Advisory Council, said the connection between T1D and dementia risk may lie in the fact that this population is more likely to have hypoglycemia.

"The area of brain that supports memory — the hippocampus — is very dependent on having a constant supply of glucose and if that supply goes too low, it can cause damage to the cells in the hippocampus," said Dr Craft. "I don't think that the danger of low blood sugar is emphasized quite as much as it should be by physicians."

It's possible that younger patients with T1D today will be better managed than the participants in the current study. In that case, they may have fewer hypoglycemic episodes and possibly a better dementia risk profile.

On the other hand, hyperglycemia can cause inflammation and oxidative stress, which also negatively affect the hippocampus through a different pathway, said Dr Craft.

She also noted that T2D is increasing among children — a "scary fact," she said — which raises the question about how this will affect their dementia risk in years to come.

Also contributing a comment was Maria Carrillo, PhD, chief science officer, Alzheimer's Association. The study results raise the question about whether more vigilance is needed surrounding cognition in people with T1D as they age, said Dr Carrillo.

"Perhaps we should be doing more to ensure that their cognition is protected as much as possible; should they be engaging in more enrichment activities; should we be keeping an eye on their cognition from an earlier time point; should they perhaps get cognitive testing earlier, starting in their 40s and 50s in their primary care physician's offices."

Dr Whitmer receives funding from the National Institute on Aging.

Alzheimer's Association International Conference (AAIC) 2015. Oral session 02-03-06. Presented July 20, 2015.


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