Alzheimer's, Dementia & Mental Health
Memory Loss, Dementia Much More Likely for Seniors
with Abdominal Fat in Middle Age
There are several risk factors of dementia and
abnormal fat metabolism has been previously identified as a risk for
memory and learning
Oct. 9, 2013 - People with high amounts of
abdominal fat in their middle age are 3.6 times as likely to develop
memory loss and dementia later in their life. Results from this study
funded by the Alzheimer’s Association and the National Institutes of
Health are published in Cell Reports.
Neurological scientists at the Rush University
Medical Center in collaboration with the National Institutes of Health
have discovered that same protein that controls fat metabolism in the
liver resides in the memory center of the brain (hippocampus) and
controls memory and learning.
Although problems with memory become increasingly
common as people age, in some persons, memories last a long time, even a
life time. On the other hand, some people experience milder to
substantial memory problems even at an earlier age.
Although there are several risk factors of
dementia, abnormal fat metabolism has been previously identified as a
risk for memory and learning.
“We need to better understand how fat is connected
to memory and learning so that we can develop effective approach to
protect memory and learning,” said Kalipada Pahan, PhD, the Floyd A.
Davis professor of neurology at Rush University Medical Center.
The liver is the body’s major fat metabolizing
organ. Peroxisome proliferator-activated receptor alpha (PPARalpha) is
known to control fat metabolism in the liver. Accordingly, PPARalpha is
highly expressed in the liver.
“We are surprised to find high level of PPARalpha
in the hippocampus of animal models,” said Pahan.
“While PPARalpha deficient mice are poor in
learning and memory, injection of PPARα to the hippocampus of PPARalpha
deficient mice improves learning and memory," said Pahan.
Since PPARalpha directly controls fat metabolism,
people with abdominal fat levels have depleted PPARalpha in the liver
and abnormal lipid metabolism. At first, these individuals lose
PPARalpha from the liver and then eventually from the whole body
including the brain. Therefore, abdominal fat is an early indication of
some kind of dementia later in life, according to Pahan.
By bone marrow chimera technique, researchers were
able to create some mice having normal PPARalpha in the liver and
depleted PPARalpha in the brain. These mice were poor in memory and
learning. On the other hand, mice that have normal PPARalpha in the
brain and depleted PPARalpha in the liver showed normal memory.
“Our study indicates that people may suffer from
memory-related problems only when they lose PPARalpha in the
hippocampus”, said Pahan.
CREB (cyclic AMP response element-binding protein)
is called the master regulator of memory as it controls different
memory-related proteins. “Our study shows that PPARalpha directly
stimulates CREB and thereby increases memory-related proteins”, said
“Further research must be conducted to see how we
could potentially maintain normal PPARalpha in the brain in order to be
resistant to memory loss”, said Pahan.
Other Rush researchers involved in this study
include Avik Roy, PhD, research assistant professor; Malabendu Jana, PhD
assistant professor; Grant Corbett, neuroscience graduate student;
Shilpa Ramaswamy, instructor; and Jeffrey H. Kordower, PhD, the Jean
Schweppe Armour professor of neurological sciences.
Alzheimer’s disease is the most common human
disorder associated with memory loss. This disease slowly destroys
memory and thinking skills, and eventually even the ability to carry out
the simplest tasks. Nationwide, the total payments for services for
people with Alzheimer’s and other forms of dementia will total $203
billion in 2013. By 2050, the total costs are expected to increase 500
percent to a staggering $1.2 trillion.
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