Cognitive impairment develops with Pre-diabetes, but

Dementia is a complication of diabetes

Why is working memory such a big deal? Working memory is the system that is responsible for the temporary holding and processing of new and recently stored information. Without efficient functioning, there is a major disruption of reasoning, comprehension, learning, and memory updating. The big deal comes in when you consider that many common disorders across the human lifespan features impaired working memory.

How does working memory operate? Its subsystems store and manipulate visual images or verbal information representing the possible moves, and awareness of the flow of information into and out of memory, all stored for a limited amount of time.

The subsystems are dedicated to the retention of visual and verbal patterns and their serial order by storage in longer-term memory. In addition, working memory tasks require monitoring as part of completing goal-directed actions in the setting of interfering processes and distractions.

The cognitive processes needed to achieve this include the executive and attention control of short-term memory, which permit interim integration, processing, disposal, and retrieval of information. These processes are sensitive to age: working memory is associated with cognitive development. In fact, research shows that its capacity tends to decline with old age. Working memory is a theoretical concept central both to cognitive psychology and neuroscience. Neurological studies demonstrate a link between working memory and learning and attention.

The big deal comes in when you 
consider that many common 
disorders across the human lifespan 
features impaired working memory.

The Pathogenesis of Working Memory Decline

A recent metabolic study conducted in Taiwan to determine whether the natural products turmeric and cinnamon might enhance the underlying biological mechanisms (pathogenesis) of working memory (WM) decline.1 The subjects of the study (≥ 60 years; n=48) had newly recognized pre-diabetes, which had not yet been treated. Because of the increased risk of cognitive impairment and dementia in diabetes, it is important to identify the phenomenon as early as possible and reverse or slow it down. Diabetes and dementia may serve as a risk factor for the other thus initiating a vicious cycle. This makes early detection and intervention imperative.

The Rational Behind Turmeric

The evidence to date is not clear that current pharmacotherapy alters the risk of dementia in diabetes, with the possible exception of metformin. Vitamin B12supplementation along with metformin may help sustain metformin’s potential value thus denying the exception. Also on the supplement stage, there are indications epidemiologically and experimentally that turmeric may reduce the risk of dementia and that its aromatic turmerone content may induce neural stem cell proliferation.2,3  For consideration in the metabolic study, blood concentrations of the curcuminoid metabolites from turmeric are measurable within a short time of ingestion, so that their presence in a meal might be metabolically and cognitively beneficial.4 Of interest, the taste and smell of cinnamon are mainly due to cinnamaldehyde, which is converted to sodium benzoate by the lesser cinnamon components cinnamic acid and cinnamyl alcohol. Benzoate itself has neuroprotective properties.5

The principal question raised in the thinking that preceded the metabolic study1 was whether it might be possible to reduce the risk of cognitive impairment seen in association with hyperglycemia in diabetes or pre-diabetes. Cinnamon was considered because of its anti-hyperglycaemic properties, and because it might reduce the risk of neurodegeneration through inhibition of neurofibrillary tangle formation and the promotion of their disassembly.6

Why Cinnamon Is in the Study

Cinnamon might even be adjunctive to the role that turmeric might have in reducing the detriments of hyperglycemic states. Supporting this, a clinical trial in Thailand has shown that turmeric’s curcumin compound reduced the risk of type 2 diabetes in those with pre-diabetes while improving beta-cell function.7

Previous studies have indicated that pre-diabetes is associated with cognitive impairment. However, because cognitive impairment is comparable if not greater prevalence than diabetes, it is important to arrest both the trajectories towards diabetes and dementia.

Remember that WM is a simple yet effective measure and predictor of cognitive processes that involve central executive roles and attention. The researchers therefore hypothesized that, in pre-diabetes, a refined carbohydrate meal might compromise cognitive function as reflected in WM. If correct, it would be possible to improve WM after a meal with turmeric or cinnamon. Measuring biomarkers that reflect neurodegeneration could show this, those that respond in concert with WM. These biomarkers would explain in part the natural product effects on WM.

To investigate these ends, the researchers studied apparently healthy and independent community-based people aged 60 years or over with newly recognized pre-diabetes and before the implementation of any management plan. The subjects (n=48; evenly divided between men and women) were also required to have a body mass index within 18.5 – 30 kg/m2, and a fasting glucose between 100 – 125 mg/dL, but have no history of medication usage for diabetes, no severe chronic disease and no recent acute illness or hospitalization in the preceding two months. They were randomized to a double-blind protocol comparing the effects of placebo (n=12), or 1 g turmeric (n=12), or 2 g cinnamon (n=12), or both 1 g turmeric and 2 g cinnamon (n=12), ingested at a white bread (119 g) breakfast.

The Reason for the Use of White Bread

White bread was used because cognitive function is lowered by a high-glycemic index (GI) following a meal comprised of it.8 A low-GI diet is preferable in the prevention of the risk of cognitive decline as a result of less efficient glucose regulation. Because white bread has an immediate effect on glycemia, it compared unfavorable with a slow-release white bread (containing guar gum) with regard to raising WM and selective attention in another study.9

After an over-night fast from 10 pm the night before, a questionnaire was administered in the morning along with a mini-mental state examination (MMSE) — a standard test for dementia. Also WM was recorded and anthro­pometric measurements (weight, height and abdominal circumferences) and blood pressure were taken prior to breakfast. BMI (Body Mass Index in (kg)/height (m2)) was calculated.

Then, after a finger prick glucose and venipuncture, each participant ate a standard breakfast together with one of the treatments in capsule form (placebo or natural products) at 0800 h. There were 4 sampling time points: baseline, 2, 4 and 6 hours. At 2-hourly intervals, the researchers monitored the blood glucose by finger prick and obtaining venous blood. WM was repeated at 6 hours In the study, observations were made over 6 hours for pre- and post-WM, glycemic and insulin responses and biomarkers of Alzheimer-s disease (AD) at 0, 2, 4 and 6 hours.

The most significant finding of the 
study is that post-prandial (after 
eating) WM was increased 
over 6 hours in older people with 
pre-diabetes by a modest addition of 
1 g of turmeric.

Differences between natural product users and non-users were determined by Wilcoxon pre-tests and post-tests for WM. Interaction between turmeric and cinnamon was tested by 2-way analysis of variance test — a statistical test that can be used in cases where there are more than two groups. Another test, multivariable linear regression took account of BMI, glycaemia, insulin and AD biomarkers in the WM responses to turmeric and cinnamon.

What Role Diet May Have Played

Figure 1. Working memory responses to turmeric, over the 6 hours of observation by comparison with the non-users.
Men and women were studied in equal numbers with the median ages were 71 – 75 years; and the educational level comparable between the groups. The background diet was of Chinese cultural orientation, generally rice and noodle-based with regular consumption of green leafy vegetables, root vegetables, mushrooms, tofu of various kinds, pork, chicken, occasional beef, fish and crustaceans more than once a week, seasonal fruits and assorted small side dishes of condiments like chilli, garlic and soy sauce.

Exercise and Alcohol

Participants exercised an average of about 4 times per week. There were few smokers (<15%), but more than a third drank alcohol sometimes or regularly. More than half were known to be hypertensive. The mean BMI was 25 kg/m2 and not different between the groups. As the entry requirement, all had impaired fasting glycaemia with an average of 117 mg/100 mL.

Measure of Dementia

Hyperlipidemia had been recognized in more than 20% of participants. The mean MMSE on the day of study was between 26.7 and 28.2 (maximum 30), depending on group, but not significantly different between groups. The mean pre-test WM was 2.50 – 2.61 (out of 3) by group, but also not significantly different between groups.

No interaction between turmeric and cinnamon was detected. However, WM improved in the turmeric users over the 6 hours of observation by comparison with the non-users (see Fig.1), increasing from 2.6 to 2.9 out of 3.0 with turmeric, but was unchanged with cinnamon. WM improvement was inversely associated with insulin resistance, but not with AD biomarkers.

There were significant negative correlations between the insulin responses (AUC, area under the curve) and the change in WM, which also applied to the AUC for the insulin: glucose ratio although not for the AUC for glucose. The AD biomarker AUCs were significantly inter-correlated, but these were not correlated with WM.

Most Important Findings

The most significant finding of the study is that post-prandial (after eating) WM was increased over 6 hours in older people with pre-diabetes by a modest addition of 1 g of turmeric added to a rather nutritionally-bland breakfast of white bread.

Taking turmeric supplements constitutes an easy way to improve cognition during the course of daily life, at least for those whose WM is less than perfect, or for those who see the benefit of more efficient levels of memory. The trajectories of mild cognitive impairment are known and could be of negative consequence in the absence of regular turmeric consumption. Thus the findings of the study may be relevant in the longer term, in diabetes, in those vulnerable to diabetes, and in others with cognitive impairment.


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