Biology 202
2002 Third Paper
On Serendip

"I lost my keys again," my mother exclaimed at dinner a few nights ago, "I really am getting old." This use of old age as a justification for memory deficits is extremely common. Many people relate old age with loss of memory and other neurobiological functions. Why is it that aging seems to go hand in hand with losing and forgetting things? Is there a neurobiological explanation for this phenomenon?

It is clear to neurobiologists that aging results in a decrease in brain size as well as a decrease in the efficiency of brain functions. It has been a widely held belief that aging causes neurons to die and for the overall number of neurons to decrease as one reaches old age. Studies conducted by Dr. David Merrill refute this idea, sighting a lack of neuronal loss in the entohinal cortex after running an MRI on a healthy subject. Instead, Merill indicates that loss of neurons may occur in degenerative disorders, such as Alzheimers, but not in healthy brains. However, it remains true that some aspects of cognition do decline as age increases, such as short term and long term memory. Since these effects are not caused by a decrease in the number of neurons present, there must be another neurobiological explanation.

In order to understand memory loss it is necessary to understand how memory works in a normal brain without any cognitive deficits. Memory can be separated into three distinct parts: working memory, declarative memory, and procedural memory (1). Working memory is the most short term, and it involves repeating something that someone has just said in conversation or remembering something you had just seen briefly. This part of memory does not ever become fully stored in the brain, does not become permanent memory, and can be erased once something new is put into the same part of the brain. (1). Therefore, once one sees something else or takes part in a new conversation is it difficult to remember all of the details from the one before. Declarative memory includes remembering facts one has used effort to learn in the past, and things one has tried to remember. The last part of memory, procedural memory, consists of everything one has learned by repetition, such as playing an instrument or sport, driving a car, or walking.

The brain is dividing into several sections, including the cerebellum, the frontal lobe, and the temporal lobe, among others. The temporal lobe exists in two parts, one on each side of the brain close to the ears. It is largely responsible for the memory system (2). On the medial surface of the temporal lobe there are three important structure that are essential for human functioning. These structures are named, in order from rostral to caudal, the olfactory cortex, the amygdala, and the hippocampus. Together these three structures are referred to as the "limbic system" (1). Their functions became understood after studying how the brain functions upon loss of each structure. For example, in 1953, a patient suffering from epilepsy underwent surgery which removed most of his medial temporal lobe (1). After the surgery, the patient was able to remember who he was and was able to carry out coherent, intelligent conversations. However, if the person with whom he was talking left the room, he would have no recollection of the conversation when it was over. This led scientists to believe that declarative memory is recorded in the mendial temporal lobe. Without this lobe, the patient could not remember any facts.

The mechanism of recording memories in the hippocampus is not yet fully understood. However, there are speculations on how the hippocampus functions in order for the brain to remember facts and figures. Information is initially stored in the neocortex, then travels to the hippocampal trace (3). The hippocampus allows for a one-way flow of information (1), in which synapses move through the gap between two areas of the hippocampus (called the subiculum to the dentate gyrus). After the information jumps between the gap, it continues in a loop formation and ends up in the subiculum again. Here in the subiculum it is involved in a short term memory consolidation, referred to as cohesion, followed by long term consolidation (3). Once the information has been fully consoliated and is ready to be stored in long term memory it is either sent to the hypothalamus or mammillary bodies, or to the entohinal cortex to be relayed back to the sensory cortex (1). The flow of information through this complicated hippocampal network is speculated to provide for memory storage.

Patients who suffer from degenerative Alzheimer's disease have a particularly difficulty with memory. In early stages of Alzheimer's disease, patients are unable to remember things on a short term basis. As the disease progresses, patients become fully dependent on others and can be unable to walk, move, or involve themselves in other basic activities (4). Since Alzheimer's disease is best known for degeneration of memory, the study of the disease is extremely helpful in understanding how memory collapses, and how memory changes as a function of age.

Researchers made two important observations in studying a brain with Alzheimer's and comparing it to a normal brain: the brain with Alzheimer's was smaller, and contained traces of a plaque build-up (5). The shrinkage of the brain seemed to be due to neuronal loss in the entohinal cortex, which is a section of the brain that controlled memory storage. The plaque build-up was found to be amyloid proteins which cannot be broken down in the brain due to the indigestible quality of their fibers (6). As the plaque grows, the sections of the brain it surround is pushed tightly compressed, limiting neural function. The amyloid plaque builds up in the gray matter of the brain, littering the space between synapses and making brain functions highly inefficient.

The cause of amyloid plaque build-up is still uncertain, but it is speculated that it is linked to an amino acid glycoprotein called Apolipoprotein E (5). This protein is synthesized mainly in the liver but is also found in small amounts in the central nervous system. It can be inherited in three different forms, as an E2, E3 or E4 allele. However, the E4 allele is the only one that seems to have an effect on amyloid plaque build-up. Scientists believe that Apolopoprotein E in the E4 form promotes the synthesis of amyloid plaque, therefore heightening the risk for Alzheimer's disease in any individual possessing this gene (7).

While memory loss in a hallmark trait of Alzheimer's disease, it also occurs in normal aging processes. Studies have shown that in normal aging, subjects have small amounts of difficulty processing and retrieving new information, specifically on recalling words and concentrating under divided attention (8). In Alzheimer's disease, subjects have greater difficulty learning new tasks and moving new information into long-term memory (8).

One study suggested that stress too could be a factor in memory loss in elderly individuals. Individuals with high levels of cortisol, a hormone associated with stress, had increased difficulty with memory (9). The same observation was true in individuals with Alzheimer's disease. In order to understand these findings, magnetic resonance imaging (MRI) tests were done on individuals with high cortisol levels as well as normal to low cortisol levels. The results were compared, and it was found that those with high cortisol levels had significantly smaller hippocampus sections in their brains (9). These findings show that high stress levels have an effect on hippocampus shrinkage and also promote memory loss. Therefore, hippocampus shrinkage is most likely a factor in memory loss for both normal aging subjects as well as for patients with Alzheimer's disease.

Other studies have also shown the importance of the hippocampas in memory. According to Dr. Stephen Salloway, in normal aging the structure of the hippocampus varies (10). As individuals grow older, the hippocampus still functions but its formation changes slightly, making it difficult for individuals to use their declarative memory as they used to. In addition, amnesia has been found to be the effect of hippocampus degradation or disruption. In certain cases of amnesia in which spatial memory and autobiographical memory is effected, MRIs have been done that demonstrate damage in the hippocampus.

In conclusion, age does indeed have a profound effect on brain function. A study conducted at the Univeristy of Kuopio in which a random sample of eldery individuals were tested for neuropsychological processes showed that the eldery had difficulty not only in memory tests, but also in tests of functions associated with the frontal lobe of the brain (11). Memory, along with executive functions of the frontal lobe, involve the hippocampus and other parts of the medial temporal lobe. This indicates that this part of the brain is responsible for certain aspects of memory, and a loss of memory most likely is the result of either degradation of this sector of the brain or disruption of its network. These disruptions may be caused by accidents, pharmacology (alcohol intakes or other drugs), or genetic disorders such as Alzheimer's disease or Schizophrenia. While there are no known way to prevent Alzheimer's disease from effecting the brain there are, however, ways to slow normal aging in the brain and to put off losing brain function and memory. These include keeping alcohol intake to a minimum, exercising the memory by using sharpening skills and memory games, and consciously trying hard to remember important details.

References

References
1)Washington University.

2)Albert, Marilyn S.: Harvard Hahoney Neuroscience Institute Letter, "On the Brain," Vol. 2..

3)Nadel and Moscovitch. "Memory Consolidation, Retrograde Amnesia and the Hippocampal Complex..

3)Nadel and Moscovitch. "Memory Consolidation, Retrograde Amnesia and the Hippocampal Complex..

4) The Symptoms of Alzheimer's. .

5) Greenwood. .

6) Alzheimer's Secondary Victims. .

7)Alipoprotein E. .

8) Determining the Cause of Memory Loss in the Elderly .

9)Stress tied to Memory Loss .

10)11) University of Kuopio, Series Reports, Department of Neurology .


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