Study
shows omega-3 fatty acids prevent memory decline in alzheimer's
disease patients
More than 200 early-stage
Alzheimer’s patients included in placebo-controlled
study.
LYSAKER,
Norway (October, 09, 2006) --Results from a placebo-controlled
intervention study in patients with early stage Alzheimer’s
disease were presented by Yvonne Freund-Levi, MD, of the
Karolinska Hospital in Stockholm, Sweden at the 10th International
Conference on Alzheimer’s Disease and Related Disorders
(ICAD) in Madrid. Dr. Freund-Levi, a psychiatrist and geriatrician,
and colleagues were able to demonstrate that patients given
an omega-3 concentrate high in DHA (docosahexaenoic acid),
often known as the “brain-omega-3 fatty acid,”
halted further memory decline while patients on placebo
continued to deteriorate. The study was published in the
October 2006 issue of Archives of Neurology.
Two
hundred four (204) patients in an early stage of Alzheimer’s
diseases were included in the study and randomly given EPAX
1050 TG, a pharmaceutical grade omega-3 concentrate high
in DHA, or placebo. The memory capacity was measured with
the MMSE (Mini Mental State Examination). Normally these
patients will lose four points on the MMSE scale in one
year due to the progressive pattern of the diseases (Fig.
1).
Fig.
1 Natural history of memory decline in patients with early
stage of Alzheimer’s Dementia, MMSE scale.
The
intervention group was given four grams of the DHA concentrate
for 12 months. The placebo group was given corn oil for
six months and subsequently the DHA concentrate for the
next six months. All patients were treated with acetylcholine
esterase inhibitors, standard treatment for Alzheimer’s
today. One hundred seventy four (174) patients completed
the study. The patients on active treatment did not demonstrate
significant progression of memory decline while the placebo
group closely followed the natural history with a two-point
memory decline in six months. However, when switched to
active treatment, memory decline was arrested even in this
group (Fig. 2).
Fig. 2 Patients on active treatment halted memory decline
while the placebo group continued to deteriorate. When switched
to active treatment even this group halted further memory
decline.
“These
results are very positive and rather unsuspected,”
said Dr Freund-Levi. “Acetylcholine esterase inhibitors
are effective to some extent, but they do not inhibit memory
decline. The DHA concentrate seems to do just that.”
About
Alzheimer’s Disease
Alzheimer’s disease is caused by deposition of pathologic
proteins called amyloid on the surface and within brain
cells leading to cell death and shrinkage of the brain.
This amyloid-beta peptide is derived from a normal cell
membrane protein which is located in the frontal and temporal
brain, regions mainly engaged in intellectual functions.
Why this normal protein deteriorates forming amyloid having
toxic effects on brain cells has been a matter of scientific
interest for many years.
Amyloid
peptides are formed by cleavage of the normal protein chain
by specific enzymes, called secretases. Some of the secretases
produce nonamyloidogenic fragments while others generate
a variety of potentially amyloidogenic species. The reason
for this pathophysiologic reaction is not known but it is
probably related to genetic modifications suppressing the
normal and promoting formation of potentially harmful protein
secretases. Amyloid, as such, is nothing more than accumulation
of peptide chains, not in the normal configuration of spacious
chains, but solid packing of amyloid fibrils practically
resistant to degradation and removal. When accumulation
has started and a critical mass of amyloid has been deposed,
a point of no return seems to be reached with only little
effect of degradation mechanisms.
Alzheimer’s
Disease and DHA
Whether these mechanisms are normal events in the aging
process of the organism or a pathological feature induced
by some risk factors is a matter of discussion. DHA is concentrated
in brain cells and exerts actions related to normal cell
function such as propagation of electrical signals conducted
in the neurons. DHA is decreased in patients with Alzheimer’s
(1) but low serum content of DHA has even been correlated
with general memory decline in people not diagnosed with
Alzheimer’s disease (2).
Scientists
have wondered what the delicate function of DHA is in the
brain related to memory. Epidemiologic studies in healthy
people have clearly demonstrated a protective effect against
development of Alzheimer’s by eating fish. Cohort
studies from Holland (3), France (4), and the United States
(5) have unanimously demonstrated lower risk of developing
dementia in people with a regular intake of seafood compared
to non-fish eaters.
Recently
a neuroprotective effect of DHA has been demonstrated in
an animal model of brain damage (6). Other experiments with
so called transgenic mice developing neuron amyloid resembling
human amyloid deposition in brain cells leading to Alzheimer’s
disease have provided better understanding of the pathophysiology
of the diseases. These animals provide a tool for development
of new therapeutic regimes such as DHA. One study demonstrated
a protective effect of DHA on brain cell death (7). Another
study showed positive effects in the prevention of amyloid
formation in the mouse brain (8). Together these studies
confirm the protective and even preventive effect of DHA
or its metabolites in Alzheimer’s disease.
“We
are now starting to realize the importance of DHA in the
brain as being not only a structural component of brain
cells, but moreover, a natural compound guarding the aging
brain cells from degradation by neurotoxic mechanisms,”
said Dr. Freund-Levi. “In a clinical context this
would mean that DHA normally integrated in the nerve cell
wall has protective effects against brain cell death induced
by the pathologic formation of amyloid as well as a prophylactic
effect against the formation of amyloid itself. At this
stage we do not know whether formation of amyloid beta peptide
is a degenerative function of aging or induced by some other
pathological event in the brain. However, DHA and its metabolites
seem to exert a preventive effect against development of
brain cell death.”
REFERENCES:
1) Soderberg M, et al. Fatty acid composition of brain phospholipids
in aging and Alzheimer’s disease. LIPIDS 1991;26:421-425
2) Conquer JA, et al. Fatty acid analysis of blood plasma
of patients with Alzheimer’s disease, other types
of dementia, and cognitive impairment. Lipids 2000;35:1305-1312
3) Kalmijn S, et al. Dietary fat intake and the risk of
incident dementia in the Rotterdam Study. Ann Neurol 1997;42:776-82
4) Barberger-Gateau P, et al. Fish, meat, and risk of dementia:
cohort study. BMJ 2002;325:932-3.
5) Morris MC, et al. Consumption of fish and n-3 fatty acids
and risk of incident Alzheimer disease. Arch Neurol 2003;60:940-6.
6) Marceselli VL, et al. Novel docosanoids inhibit brain
ischaemia-reperfusion-mediated leukocyte infiltration and
pro-inflammatory gene expression. J Biol Chem 2003;278:43807-43817
7) Calon F, et al. Docosahexaenoic acid protects from dendritic
pathology in an Alzheimer’s disease mouse model. Neuron
2004;43:633-645
8) Lim GP, et al. A diet rich with the omega-3 fatty acid
docosahexaenoic acid reduces amyloid burden in an aged Alzheimer
mouse model. J Neurosci 2005;25:3032-3040
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