Dementia and Diabetes - A Confusing Relationship

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The news often carries stories that link diabetes and Alzheimer's disease or dementia and make it sound as if a diabetes diagnosis may also doom you to developing these terrible, incurable, life-ruining conditions.

These media reports are often based on poor understanding of the studies they cite. Here are what several important studies have really found about this relationship.

Dementia Risk Rises with A1c--Not Diabetes Diagnosis

The most important point is this: it isn't "diabetes" that raises your risk of developing dementia, it is your average blood sugar. There is a close relationship between A1c and your likelihood of developing dementia.

One study that demonstrates this was published in this Diabetes Care in January of 2009. It looked at data from the notorious ACCORD study and concluded two things: "Higher A1C levels are associated with lower cognitive function in individuals with diabetes" and "FPG was not associated with [mental functioning] test performance."

Relationship Between Baseline Glycemic Control and Cognitive Function in Individuals With Type 2 Diabetes and Other Cardiovascular Risk Factors.(ACCORD-MIND) trial. Tali Cukierman-Yaffe et al.Diabetes Care 32:221-226, 2009

The study found that a 1% rise in A1c (i.e. from 6.0% to 7.0%) was associated with a significant decline in scores on three different tests of mental functioning.

Though this is depressing news if you have a high A1c, people with diabetes frequently lower their A1cs by huge amounts. For some examples (and these are just a very few examples drawn from public postings and emails I get) visit The 5% Club: They Normalized Their Blood Sugar and So Can You

Be very clear about this: The risk factor is not a Diabetes diagnosis. It is high blood sugars--the high blood sugars too many doctors consider "good control" for people with diabetes--blood sugars that result in A1cs near 7.0%. It is very likely that if you are diagnosed with diabetes at any age, but control your blood sugars to a normal level--A 5% A1c, for example--you can have the same health as anyone else would who had not gotten the diagnosis.

Note, that this finding may explain why a Swedish twin study found more than twice as much dementia in twins diagnosed in midlife with diabetes as in those without a diabetes diagnosis. The lack of concordance among twins suggests that the dementia is not due to the underlying genetics which we know produce diabetes, but to the effect of the damagingly high blood sugars that doctors consider "good control" in people diagnosed with diabetes.

Mid- and Late-Life Diabetes in Relation to the Risk of Dementia:A Population-Based Twin Study.Weili Xu et al, Diabetes 58:71-77, 2009

High Blood Sugar Correlates with Vascular Dementia, Not Alzheimer's

Despite the many news articles linking Alzheimer's to diabetes it turns out that a study that examine this issue in dept finds a much stronger association between diabetes and vascular dementia than between diabetes and Alzheimer's Disease, at least in people whose average age was the mid-80s.

Alzheimer's Disease is a form of progressive dementia that can only be diagnosed decisively on autopsy, at which time it is possible to see that the brain has been invaded by plaques and tangles of a substance called beta-amyloid. Vascular dementia is a different condition from Alzheimer's and has a different pattern of progressing. Vascular dementia is a condition characterized by the occurrence of mini-stokes in the brain, especially the subcortical "deep brain", which gradually destroy its ability to function.

This autopsy study examined brains of several hundred people with and without diabetes. The researchers had blood sugar test result data for both groups, which makes it even more informative.

Different Patterns of Cerebral Injury in Dementia With or Without Diabetes
Joshua A. Sonnennot et al. Arch Neurol.2009;66(3):315-322

This study quantified the heightened incidence of dementia in people with diabetes diagnoses. It found 26% of the 125 people whose brains were autopsied who died in their 80s without dementia had been diagnosed with diabetes while 36% of the 71 who were demented had been diagnosed with diabetes.

The researchers doing this study had access to the A1cs and fasting blood sugars of the group as a whole, as well as their medication history. Based on this they noted that the A1cs of those people with diabetes who had not developed dementia were lower than that of those who did--(7.4% compared to 7.8%). This confirms the finding of the study linking A1c to dementia above. though it is worth noting that 63% of those who developed dementia did not have diabetes.

On close examination of these people's brains the researchers found:
Most interestingly, "Individuals without DM but with dementia (DM-/dementia+) had a greater amyloid-beta peptide load and increased levels of F2-isoprostanes in the cerebral cortex, while DM+/dementia+ patients had more microvascular infarcts and an increased cortical IL-6 (interleukin 6) concentration. The number of microvascular infarcts was greater in deep cerebral structures in patients with dementia whose diabetes was treated, whereas amyloid plaque load tended to be greater for untreated diabetic patients with dementia.
This means found fewer Alzheimer-like plaques and tangles among the people with diabetes than among people without, and also more IL-6 in the cortex. IL-6 is a marker for inflammation. They also found more sub-cortical lesions in people with diabetes--strokes deep in the brain which may have to do with the nature of the blood supply to those regions.

But what is really interesting is that the people "with diabetes" in this group, who were not "treated" i.e. medicated, had brains more like those of people without diabetes in terms of the amount of beta-amyloid plaques and tangles. The researchers comment that the drop in beta amyloid tangles is,
a result consistent with a recent report from a large autopsy series that showed that decreased senile plaque burden was associated with insulin therapy.
But the researchers also note that they found more evidence of deep brain strokes in the treated group which they note had much higher A1cs than the nonmedicated diabetics. (6.3% unmedicated, 8.6% medicated.)

Unfortunately, the researchers also explain, "A weakness of our study was the limited numbers of DM+/dementia+ cases available for analysis of treatment effects, which made it impossible to analyze specific diabetes treatments."Another weakness not cited by the researchers but revealed in the data is that the group who were not demented had a slightly lower average age. Since the people (including diabetics) with vascular dementia were two years older on average than those without, and since vascular dementia can arise and kill very quickly, the increased incidence of vascular dementia in this group may be partially explained by greater age.

Still, this study suggests that there is a slightly higher likelihood of developing dementia among people with diabetes, especially among those with Average A1cs of 8.6% and that this appears to be due to their propensity for having tiny deep brain strokes and brain inflammation.

At the same time--what the news reports ignore is that this study, like most, shows that the overwhelming majority of people who develop dementia do not have diabetes.

Other Stronger Predictors of Dementia Not Pointing to Blood Sugar

High Blood Pressure and High Triglycerides

Before you get too worried about any study linking diabetes to dementia, consider the findings of another study:

The Metabolic Syndrome and Development of Cognitive Impairment Among Older Women Kristine Yaffe, et al.Arch Neurol. 2009;66(3):324-328.

This study It found a much stronger link than the one shown in the study we just discussed between vascular dementia and the presence of so-called "metabolic syndrome" in people 92% of whom did not have elevated blood sugars.

In that study, which examined "4895 older women (mean age, 66.2 years)
A total of 497 women (10.2%) had the metabolic syndrome and, of these, 36 (7.2%) developed cognitive impairment compared with 181 (of 4398 or 4.1%) without the syndrome (age-adjusted odds ratio, 1.66; 95% confidence interval, 1.14-2.41).
The incidence of dementia was almost twice as high in the group with metabolic syndrome, though it was low overall, probably because this group was younger than the group studied above.

But given that less than 8% of this group had elevated blood sugars, one wonders about the extent to which the microvascular damage in either study was due to blood sugar rather than high blood pressure and high triglycerides which were strongly predictive factors in this second study, independent of blood sugar.

The ambiguity of the connection between blood sugar and dementia s gets more confusing, because of the results of another study:

Midlife and Late-Life Obesity and the Risk of Dementia Annette L. Fitzpatrick, Arch Neurol. 2009;66(3):336-342

This is a cohort study of a large number of 2798 people followed from 1992-1999 which came up with this odd result:
In evaluations of midlife obesity, an increased risk of dementia was found for obese (BMI >30) vs normal-weight (BMI 20-25) persons, adjusted for demographics (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.03-1.87) and for cardiovascular risk factors (1.36; 0.94-1.95). The risk estimates were reversed in assessments of late-life BMI. Underweight persons (BMI <20) had an increased risk of dementia (1.62; 1.02-2.64), whereas being overweight (BMI >25-30) was not associated (0.92; 0.72-1.18) and being obese reduced the risk of dementia (0.63; 0.44-0.91) compared with those with normal BMI.
In short, as you get older the fatter you are, the less likely you are to develop dementia, though if you are middle aged being overweight is more highly associated with dementia.

This is not a freak result, as NHANES data has long supported the finding that after age 70, any weight loss correlated with a higher likelihood of death and that people in the overweight category seem to do better, long term as they age than people of so-called normal weight. You'll find links to the data supporting this conclusion here:

Diabetes Update: Overweight Is The Healthiest Weight

Prescription Drugs that Cause Dementia

Research outside of the diabetes community comes up with important information linking the use of common prescription drugs with an enhanced likelihood of developing dementia.

Cumulative Anticholinergic Exposure Is Associated with Poor Memory and Executive Function in Older Men. Journal of the American Geriatrics Society, Han et al. 2008; 56 (12): 2203

You can read a detailed summary of this password protected study in Science Daily:

Science Daily: Common Medication Associated with Cognitive Decline in the Elderly.

This study linked anticolinergic medications to a significant loss of memory and found, in the words of Science Daily,
The degree of memory difficulty and impairment in daily living tasks also increased proportionally to the total amount of drug exposure, based on a rating scale the authors developed to assess anticholinergicity of the drugs.
Anticholinergic drugs are used for many conditions. The drugs used to treat overactive bladders are strong anticholinergics. So are some drugs used to treat cold symptoms, breathing difficulties, digestive difficulties and a host of other symptoms.

Here is a list of anticholinergic agents: Anticholinergic Agents

Because these drugs block a class of chemicals that naturally decline as we age, and which are associated with memory function, you might want to review the medications you are taking to make sure you aren't taking one of them.

There is also some evidence that statin drugs contribute to memory problems in older people. Cholesterol is a vital component of the brain and lowering it inappropriately may harm the aging brain. Research backing this finding is documented here:

Other Dangerous Drugs for People with Diabetes

One last pharmaceutical cause of dementia may be drugs used for chemotherapy, which may be required to save your life but leave you with what is often called "chemo brain." The older you are the more likely chemotherapy is to cause this condition. Discuss this issue with your oncologist if you must have chemo to see if there are options that might be safer and preserve your mental acuity.

American Cancer Society: Chemo Brain

What You Can Do to Minimize Dementia Risk

So what should we conclude from all this? Are the headlines unnecessarily alarmist? I'd say, yes. In fact there is no connection here between classic Alzheimer's disease and diabetes. In fact, the opposite seems to be true. People using insulin appear to have less Alzheimer's.

That said, uncontrolled high blood sugars do seem to increase your chance of developing vascular dementia, but not any more than does being overweight in middle age and having high blood pressure and high triglyceride levels.

Looking at the broader picture, none of these factors make that much of a difference in your risk of developing dementia once you are past middle age--the time when most people develop dementia, because the overwhelming number of older people who develop dementia do not have diabetes and more importantly, as people get older, the overweight that is so demonized by doctors appears to protect people from developing dementia rather than promoting it.


ACE Inhibitors or ARBs may help


Bottom line: There is much you cannot control when it comes to developing dementia, but to make a slight improvement in your chances do the following:
  • Keep your blood sugars under control
  • Keep your blood pressure normal
  • Keep your triglycerides down.
You lower your triglycerides by keeping your carbohydrate intake low because triglycerides are produced when you eat more dietary dietary glucose than your body can burn right away.

If you have diabetes, you can normalize your risk of dementia by keeping your A1c in the normal range. Your risk for dementia will go way up if you maintain an A1c in the 8% range.

A Last Bit of Good News

The first study cited above gave us some numbers for the blood sugar of "normal" people whose risk for dementia was lower than those with diabetes.

Their average A1c was 5.9% and their average fasting glucose was 105 mg/dl (5.8 mmol/L).

These are VERY attainable numbers for all people with diabetes so if the association of "diabetes" with dementia worries you, shoot for those numbers.

 

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