Ever heard of type III diabetes?
Tens of thousands of Canadians could be suffering from
it, according to a new study. They just know it by a
different name: Alzheimer's disease.
Levels of insulin and of its receptors
diminish significantly in the brain in early Alzheimer's,
and continue to fall as the disease progresses, according
to research published in the November issue of the Journal
of Alzheimer's Disease. "Insulin disappears early
and dramatically in Alzheimer's disease," senior author
Dr Suzanne M de la Monte, a neuropathologist and professor
of pathology at Brown Medical School, said in a press
release. "And many of the unexplained features of Alzheimer's,
such as cell death and tangles in the brain, appear
to be linked to abnormalities in insulin signalling.
This demonstrates that the disease is most likely a
neuroendocrine disorder, or another type of diabetes."
THE
NEW DIABETES
Dr de la Monte analyzed insulin and insulin receptor
function in 45 postmortem brains from either normal
elderly patients or Alzheimer's patients at various
stages of disease. They found that insulin expression
declined in step with Braak stages, the standard system
of neurodegeneration classification. "In the most advanced
stage of Alzheimer's, insulin receptors were nearly
80% lower than in a normal brain," Dr de la Monte said.
What's more, the ability of insulin and its related
growth factor IGF-I to bind to corresponding receptors
also diminished, creating a cellular resistance to these
proteins that ultimately led to cell death.
One task of insulin in the brain
is to stimulate the expression of choline acetyltransferase
(ChAT), the enzyme responsible for making acetylcholine,
the researchers discovered. This provides them with
a causal link between their own findings and acetylcholine
deficiency, a known marker of Alzheimer's disease.
Whether this brings us any closer
to a treatment is another question. It's hardly reassuring
to know that the incurable disease Alzheimer's has now
been linked to the incurable disease diabetes. Dr de
la Monte is optimistic but cautious: "If you could target
the disease early, you could prevent the further loss
of neurons. But you would have to target not just the
loss of insulin but the resistance of its receptors
in the brain."
THE
CHOLESTEROL CONNECTION
While this research offers a mechanism but offers no
immediate treatment, a paper published in the Journal
of Neurology, Neurosurgery and Psychiatry reports
on a treatment with no obvious mechanism. French researchers
investigating the relationship between cholesterol and
cognitive decline found that Alzheimer's patients who
took lipid-lowering drugs saw slower disease progression
than those who didn't.
The study followed 342 Alzheimer's
patients at a memory clinic over three years. Roughly
one-third had dyslipidemia, or high cholesterol, and
were taking lipid-lowering agents, another third had
untreated dyslipidemia, and the remaining had normal
cholesterol levels. Those taking lipid-lowering agents,
either statins or fibrates, showed significantly slower
declines on a mini-mental state examination, losing
an average of 1.5 points a year off their score compared
to 2.5 in the other groups.
What's most striking about these
findings is that the drugs' effect on Alzheimer's progression
appeared to be independent of cholesterol levels. Patients
with high cholesterol who took lipid-lowering agents
declined slower than healthy ones who weren't on the
meds. And patients with normal lipid levels fared no
better in terms of cognition than dyslipidemic patients
who didn't take anything. In other words, it appeared
that some other quality in the drugs, independent of
their cholesterol-busting properties, was giving a protective
effect.
Regrettably, the study was too
small to allow statistically meaningful comparison between
the fibrate-taking patients and those prescribed statins.
Both drug types have anti-inflammatory and antioxidant
qualities that could be behind the cognitive effects.
The best way to tease out the truth, said the authors,
is to design studies that test the impact of lipid-lowering
agents in Alzheimer's patients who don't have high cholesterol.
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