Diabetes, Memory and
Dementia
Badly controlled diabetes are known to affect the brain
causing memory and learning problems and even increased incidence of dementia,
although how this occurs is not clear.
Elderly people with pre-diabetes and type 2 diabetes suffer
from an accelerated decline in brain size and mental capacity in as little as
two years according to new research presented at the joint International
Congress of Endocrinology/European Congress of Endocrinology in Florence,
Italy.
Now a study in mice with type 2 diabetes has discovered how
diabetes affects a brain area called hippocampus causing memory loss, and also
how caffeine can prevent this.
Diabetes, Alzheimer’s
and Parkinson’s
Curiously, the neurodegeneration that Rodrigo Cunha from the Centre for Neuroscience and Cell
Biology of the University of Coimbra in Portugal see caused by diabetes is the
same that occurs at the first stages of several neurodegenerative diseases,
including Alzheimer’s and Parkinson’s, suggesting that caffeine (or drugs with
similar mechanism) could help them too.
João Duarte, Rodrigo Cunha and colleagues take advantage of
a new mouse model of diabetes type 2, which, like humans, develops the disease
in adults as result of a high-fat diet, to look at one of the least understood
complications of diabetes – the disease effect on the brain, more specifically,
on memory. They also investigate a possible protective effect by caffeine as
this psychostimulant has been suggested to prevent memory loss in a series of
neurodegenerative diseases, maybe even in diabetes, although how this happens
is not known.
And when we consider that coffee is the world leading
beverage right after water, with about 500 billion cups consumed annually,
this, if true, needs to be better understood.
Caffeine and Neurodegeneration
With that aim the Portuguese researchers compared four
groups of mice - diabetic or normal animals without or with caffeine
(equivalent to 8 cups of coffee a day) in their water – to find that long-term
consumption of caffeine not only diminished the weight gain and the high levels
of blood sugar typical of diabetes, but also prevented the mice's memory loss
(diabetic animals had significantly poorer memory than normal ones). This
confirmed that caffeine could, in fact, protect against diabetes as well as
prevent memory impairment, probably by interfering with the neurodegeneration
caused by toxic sugar levels.
To investigate this, next, the researchers looked at a brain
region linked to memory and learning, which is often atrophied in diabetics,
called hippocampus. And in fact, diabetic mice had abnormalities in this area
showing synaptic degeneration (synapses are the structures at the end of each
neuron used to communicate between neurons) and astrogliosis (an abnormal
increase of the cells that surround neurons normally as result of the deathof
nearby neurons). Both phenomena are known to affect memory and caffeine
consumption prevented the abnormalities.
Caffeine and A2AR Inhibition
But to be able to develop drugs based on caffeine’s
protective effect, it was necessary to understand its molecular mechanisms. So
next the researchers looked at the only brain molecules known to respond to
caffeine – the adenosine receptors A1R and A2AR - in the hippocampus. And here,
A2AR seemed to be the key for caffeine’s memory rescue since its density -
which increases with noxious insults - was high in diabetic animals but normal
in those treated with caffeine. This agrees with the previous studies that
showed that A2AR inhibition protected against synaptic degeneration and memory
dysfunction.
Chronic Consumption
of Caffeine, Neurodegeneration and Memory Impairment
In conclusion, Duarte and Cunha’s work – using an animal
model of diabetes type 2 that closely mimics the human form of the disease –
suggests that diabetes affects memory by causing synaptic degeneration,
astrogliosis and increased levels of A2AR. The study indicates as well that
chronic consumption of caffeine can prevent the neurodegeneration and the
memory impairment. And this not only in diabetes, since synaptic degeneration
and astrogliosis are both part of a cascade of events common to several
neurodegenerative diseases, suggesting that caffeine (or similar drugs) could
help them too through the same mechanisms.
So does this means that we should drink eight cups of coffee
a day to prevent memory loss in old age or diabetes?
Not really as Rodrigo Cunha, the team leader explains:
“Indeed, the dose of caffeine shown to be effective is just too excessive. All
we can take from here is that a moderate consumption of caffeine should afford
a moderate benefit, but still a benefit. Such experimental design is common in
pre-clinical studies: in order to highlight a clear benefit, one dramatises the
tested doses. But it's an important first step. Our ultimate goal is the design
of a drug more potent and selective (i.e. with less potential side effects)
than caffeine itself; animal studies enable us to pinpoint the likely target of
caffeine with protective benefits in type 2 diabetes. So now we will be testing
chemical derivates of caffeine, which act as selective adenosine A2A receptor
antagonists,to try to prevent diabetic encephalopathy. It might turn out to be
a therapeutic breakthrough for this devastating disease”.
And a breakthrough in a disease that is already affecting
6.4% of the population and growing can never come too soon.
Type 2 diabetes (which
accounts for about 90% of all diabetic cases) is a full blown public health
disaster – 285 million people affected worldwide (6.4% of the world population)
with numbers expected to almost double by 2030. And this without counting
pre-diabetic individuals. The problem is that the disease is triggered by
obesity, sedentary lifestyle and bad eating habits (although there is also a
genetic predisposition), all of which are increasingly widespread.
Diabetes is caused by
high levels of sugar in the blood, and in type 2 this occurs because the body
becomes increasingly resistant to insulin –the hormone that allows the cells to
take the sugar from the blood to use it as “fuel” – resulting in toxic high
levels of sugar in the blood that damage
nerves and blood vessels and, with time, cause severe complications
###
The above report is based on the May 6, 2012 news release by
the European Society of Endocrinology and on the May 7, 2012 news release by
Ciência Viva - Agência Nacional para a Cultura Científica e Tecnológica, via
AlphaGalileo.
The research by João Duarte, Rodrigo Cunha and colleagues is
published in PLos ONE: João M. N. Duarte, Paula M. Agostinho, Rui A. Carvalho,
Rodrigo A. Cunha. Caffeine Consumption
Prevents Diabetes-Induced Memory Impairment and Synaptotoxicity in the
Hippocampus of NONcZNO10/LTJ Mice. PLoS
ONE, 2012; 7 (4): e21899 DOI: 10.1371/journal.pone.0021899. Click HERE to
read the full text.
For illustrative purpose only. Talk to our pharmacists. |
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