Understanding Memory: What is Amnesia? Links to Alzheimer's Disease

In simple terms, amnesia is the loss of memory. This includes memories such as facts, information and experiences. Although amnesia is a popular theme for movies and books, it is a very rare condition. And although having no sense of who you are is a common plot device in the media, real-life amnesia typically does not cause a loss of self-identity. What we call memory, the ability to recollect our life’s experiences, is a very complex process within the brain. Different areas of the brain are involved in memory depending on the type of memory.

The primary areas involved in memory formation include the prefrontal cortex, the hippocampus, the parahippocampal area, the amygdala and the cerebellum.[1]

The hippocampus is essential for memory, particularly the transfer from short- to long-term memory and control of spatial memory and behaviour.

The cerebral cortex, especially the pre-frontal cortex, is important in processing short-term memories and retaining long-term memories.

The amygdala plays a primary role in the processing and memory of emotional reactions and social and sexual behavior. The cerebellum processes “procedural” memory (explained below).[2]

How Are Memories Formed?

The model of memory which proposes that memory is actually a sequence of three stages rather than a unitary event is known as the Atkinson-Shiffrin model, first developed in 1968.[3]  According to this model, memory moves from sensory (very short-term) memory to short-term memory to long-term memory.[2]

Sensory memory

We take in enormous amounts of information through our senses but the vast majority of it cannot be processed due to the limitations of our memory. Sensory memory is an ultra-short-term memory and decays or degrades very quickly, typically in the region of 200 - 500 milliseconds (1/5 - 1/2 second) after the observation of an item, and certainly less than a second. Indeed, it lasts for such a short time that it is often considered part of the process of perception, but it nevertheless represents an essential step for storing information in short-term memory. Information is passed from the sensory memory into short-term memory (short-term memory) via the process of attention (the cognitive process of selectively concentrating on one aspect of the environment while ignoring other things), which effectively filters the stimuli to only those which are of interest at any given time.[3]

Short-term memory

This relates to memories of information which is retained by our senses long enough for it to be used. An example of this is a telephone number which needs to be remembered before being dialed. The Peterson and Peterson study of 19594 showed that short-term memory lasts for less than 30 seconds unless the information is attended to within that timeframe. It also intervenes during reading, to memorise the sentence you have just read, so that the next one makes sense.[3] The prefrontal cortex at the front of the brain appears to play a fundamental role in short-term memory.

The task of consolidating short-term memory into long-term memory is performed by the hippocampus, which is located in the brain's temporal lobe. short-term memory has a limited capacity. The often-cited experiments by George Miller in 1956 suggest that the number of objects an average human can hold in short-term memory is between 5 and 9.[5] The Atkinson-Shiffrin model proposes that short-term memory can be transferred to long-term memory if the information is processed and learned fast enough. This basically means we never lose the ability to store new information regardless of how long we live.[3]

Long-term memory

Despite our everyday occurrences of forgetting, it seems likely that long-term memory actually decays very little over time, and can store a seemingly unlimited amount of information almost indefinitely. Indeed, there is some debate as to whether we actually ever “forget” anything at all, or whether it just becomes increasingly difficult to access or retrieve certain items from memory. Short-term memory items become long-term memory through the process of "consolidation" which involves "rehearsal" (repetition) and meaningful association.[3] The process whereby the hippocampus and other medial temporal lobe structures contribute to long-term memory formation is still incompletely understood. Some researchers believe that the hippocampus acts as a temporary store for new information, which is then gradually transferred to permanent storage in the cortex. Other researchers believe that the hippocampus never actually stores information itself, but is needed by the cortex in the process of developing new memories. Another important structure is the amygdala, which lies near the hippocampus in the medial temporal lobes. The amygdala is critically involved in emotional memory.[7]

Explicit memory

Long-term memory is divided into two main types: explicit and implicit memory. An explicit memory is a memory that can be intentionally and consciously recalled. Information that you have to consciously work to remember is known as explicit memory, while information that you remember unconsciously and effortlessly is known as implicit memory.[3]

When we intentionally try to remember something (like a formula for a statistics class or the date and time of a doctor's appointment), this information is stored in explicit memory. 

Explicit memory is also called declarative memory, since it can be consciously recalled and the information can be explained or 'declared.'  Explicit or declarative memory is further divided into two categories:

• Episodic memory: recall of personal facts
• Semantic memory: recall of general facts

Episodic memory: Episodic memory refers to that portion of long-term memory that involves the recall of facts, events or episodes in one's personal life. The ability to remember where you had dinner last evening, who you were with, and the items you ordered are all features of an episodic memory. Other examples of episodic memory include remembering where you parked your car or the more remote memory of where you were when you heard about the September 11th attacks. As we age, these memories become more difficult to create and maintain. This means elderly people are less likely to form new episodic memories as they age but will likely keep the ones from their youth.[8]

Semantic memory: Semantic memory refers to that portion of long-term memory that processes ideas and concepts that are not drawn from personal experience but rather from the recall of general facts. Semantic memory includes things that are common knowledge such as the names of colors, the capitals of countries, the rules for playing football, and other basic facts acquired over a lifetime.[9]

Implicit memory

Implicit memory is sometimes referred to as unconscious memory or automatic memory. Implicit memory uses past experiences to remember things without thinking about them. The performance of implicit memory is enabled by previous experiences, no matter how long ago those experiences occurred.[10]

• Procedural memory: The largest subset of implicit memory, procedural memory, enables us to perform many everyday physical activities, such as walking and riding a bike, without having to give it thought. A large majority of implicit memories are procedural in nature. Procedural memory primarily involves learning new motor skills and depends on the cerebellum and basal ganglia.[10]
   
• Priming: Priming is another, smaller subset of implicit memory. It involves using pictures, words or other stimuli to help someone recognise another word or phrase in the future.  Examples include using green to remember grass and red to remember apple.[10]

Causes of Amnesia

Amnesia may result either from organic causes (damage to the brain through physical injury, neurological disease or the use of certain drugs) or from psychogenic causes (e.g. mental disorders, post-traumatic stress or psychological defense mechanisms).

Neurological amnesia

Amnesia caused by brain injury or damage is known as neurological amnesia. Possible causes of neurological amnesia include:[11]

• Head injuries - such as those that occur in car accidents and contact sports (hockey, football)
• Stroke
• Encephalitis (inflammation of the brain, most often due to infection)
• Lack of adequate oxygen supply to the brain from a heart attack, respiratory distress or carbon monoxide poisoning
• Long-term alcohol abuse leading to thiamin (vitamin B-1) deficiency (Wernicke-Korsakoff syndrome)
• Tumours in areas of the brain that control memory
• Degenerative brain diseases, such as Alzheimer's disease and other forms of dementia
• Certain seizure disorders
• Certain medications: zolpidem (Stilnox)
• ECT (electroconvulsive therapy) - also known as electroshock therapy. This is a well- established psychiatric treatment in which seizures are induced for therapeutic effect on anaesthetised patients. It is sometimes used for patients with major depression whose illness has not responded to other treatment. ECT is also sometimes used for treating schizophrenia, bipolar disorder and catatonia. (the memory loss is nearly always temporary).[12]

Psychogenic amnesia

Two types of amnesia are psychogenic in origin: dissociative amnesia and dissociative fugue.

Dissociative amnesia: Dissociative amnesia may occur when a person suffers a physically or emotionally overwhelming event or trauma. The memories of the traumatic event and the circumstances surrounding it are so upsetting that they are repressed. This is caused by an emotional shock, such as:

• Being the victim of a violent crime
• Sexual abuse
• Child abuse
• Being involved in combat (soldiers)
• Being involved in a natural disaster
• Being present during a terrorist act

The repression does not occur consciously, and it may be temporary (lasting anywhere from a few seconds to years) or it may be permanent. In this disorder, a person may lose personal memories and autobiographical information, but usually only briefly.[11]

Dissociative fugue: Dissociative fugue, formally fugue state or psychogenic fugue, is a rare psychiatric disorder characterised by reversible amnesia for personal identity, including the memories, personality, and other identifying characteristics of individuality. The state is usually short-lived (ranging from hours to days), but can last months or longer. Dissociative fugue usually involves unplanned travel or wandering, and is sometimes accompanied by the establishment of a new identity.[13]

Different Types of Amnesia

There are two main types of amnesia: anterograde and retrograde amnesia. Anterograde amnesia, the more common of the two, is associated with injury to the hippocampus. A person with anterograde amnesia cannot convert new information into long-term memory. In retrograde amnesia, a person’s past memories are lost.

Anterograde amnesia

Anterograde amnesia is a selective memory deficit, resulting from brain injury, in which the individual is severely impaired in learning new information. Memories for events that occurred before the injury may be spared, but events that occur after the injury are not remembered. In practice, this means that an individual with anterograde amnesia may have good memory for childhood and for the years before the injury, but may remember little or nothing after the injury. short-term memory is generally spared, which means that the individual may be able to carry on a conversation; but as soon as he is distracted, the memory of the conversation fades.[14] The hippocampus seems to act as a "gateway" through which new information must pass before being permanently stored in memory. It is responsible for encoding new memory. If it is damaged due to brain injury or illness, no new information can enter memory storage although older information which has already passed through the gateway may be safe.

Damage to the hippocampus (and medial temporal lobes) can occur with any of the following conditions:[14]

• Stroke
• Aneurysm
• Epilepsy
• Encephalitis
• Carbon monoxide poisoning
• Near-drowning
• Near-suffocation
• Alcohol-induced blackouts
• Benzodiazepines
• Other sedatives
• Traumatic brain injury

Alcohol-induced blackouts are a type of anterograde neurological amnesia. Drinking too much alcohol and becoming intoxicated blocks the neural pathways in the brain from forming new memories. People experiencing a blackout may talk and interact normally, but the next morning, all will be blank.[15]

Korsakoff’s syndrome. Anterograde amnesia can also sometimes occur with damage to the diencephalon (a set of structures deep in the brain including the medial thalamic nuclei) Korsakoff’s syndrome, caused by chronic alcoholism. Chronic alcohol abuse often leads to malnutrition and a thiamine (vitamin B1) deficiency. Thiamine deficiency is a condition which damages the diencephalon and causes anterograde amnesia. The memory impairment that is pathognomonic to Korsakoff’s syndrome predominantly affects declarative memory,[16] leaving non-declarative memory (which is mainly procedural) intact.[17]

Benzodiazepines. The short-term use of benzodiazepines adversely affects multiple areas of brain function, the most notable one being that it interferes with the formation and consolidation of memories of new material and may induce complete anterograde amnesia.[18] This has also been recorded in non-benzodiazapine sedatives which act on the same set of receptors, such as zolpidem and zopiclone.[19]

Traumatic brain injury. Globally, traumatic brain injury (TBI) is the leading cause of death and disability in children and adults and is involved in nearly half of all trauma deaths.[20] A subset of mild TBI is concussion, reflecting a complex pathophysiological process resulting from trauma to the brain. Common symptoms include headache, amnesia, confusion, blurred vision, dizziness, nausea, balance problems and fatigue. Loss of consciousness is reported in 10%–20% of cases. Most concussions resolve within a few days to weeks, but in some cases the symptoms can be prolonged.[21-23] Whether anterograde amnesia predicts more severe concussion or slower recovery remains unclear.

The American Academy of Pediatrics' 2010 clinical report on concussions.[24]  stated that, "along with loss of consciousness, anterograde amnesia may be an important indicator of more serious injury." A 2011 study[25] by researchers at the University of Pittsburgh, however, found  that neither anterograde nor retrograde amnesia were predictive of protracted recovery (21 days or more to return to play), which the authors said may be because they are part of the normal acute response to a concussion and resolve relatively quickly with little lasting effects. Their findings "should be interpreted cautiously", they said, "as previous research had supported retrograde amnesia and post-traumatic amnesia as predictors of poor concussion outcomes (although not protracted recovery times per se). Nevertheless, the consensus statement issued after the fourth quadrennial international conference on concussion in sport issued in March 2013,[26] continues to view amnesia as a "modifying" factor that may predict the potential for prolonged or persistent symptoms, although it noted that, "in some cases, the evidence for their efficacy is limited." Likewise, the American Academy of Neurology's evidence-based guidelines for the evaluation and management of concussion in sports issued in March 2013[27] includes "early amnesia" as among the "probable risk factors for persistent neurocognitive problems or prolonged return to play."

Most recently, however, a study issued in April 2013[28] found, after analysing data for numerous variables, including total score of concussed athletes on the  Post-Concussion Symptom Scale (PCSS) at initial visit, age, and amnesia symptoms, that only the total score on the PCSS was independently associated with symptoms lasting longer than 28 days; the higher the score, the greater chance of a prolonged recovery time. Researchers found that, contrary to earlier studies, neither age nor amnesia were risk factors for prolonged concussion recovery.

Retrograde amnesia

Retrograde amnesia usually follows damage to areas of the brain other than the hippocampus (the part of the brain involved in encoding new memories) because already existing long-term memories are stored in various different brain regions.  Although there have been reported cases where an individual sustains pure retrograde amnesia as the result of physical brain injury, retrograde amnesia is usually accompanied by some degree of anterograde amnesia.[30]

Retrograde amnesia can result from physical brain injury or illness or from psychiatric disorders. The most common causes of retrograde amnesia include:

• Traumatic brain injury
• Psychogenic amnesia (dissociative amnesia and fugue)
• Dementia
• Korsakoff syndrome
• Electroconvulsive therapy (commonly known as shock therapy)

Diseases such as dementia cause gradual retrograde amnesia. The best known and most common type of dementia is Alzheimer’s disease, which accounts for 50-75% of all dementias. Dementia is characterised by progressive memory loss combined with other cognitive dysfunction such as aphasia (loss of ability to produce or understand language), apraxia (the inability to make certain movements), agnosia (difficulty remembering familiar persons or objects), and executive function (inability to plan, organise, or reason).

Retrograde amnesia targets the most recent memories first. The more severe the case, the farther back in time the memory loss extends. This pattern of destroying newer memories before older ones is called “Ribot's law.” It happens because the neural pathways of newer memories are not as strong as older ones that have been strengthened by years of retrieval.[15] Typically, episodic memory is more severely affected than semantic memory, so that the patient may remember words and general knowledge (such as who their country’s leader is, how everyday objects work, colours, etc) but not specific events in their lives. Procedural memories (memory of skills, habits and how to perform everyday functions) are typically not affected at all.[3]

Transient global amnesia

Transient global amnesia is a form of memory loss that appears suddenly and causes confusion, disorientation, and forgetfulness for 30 minutes to 24 hours. The patient with transient global amnesia has severe anterograde amnesia. The loss of past memories is milder.[31] During a typical attack the patient has sudden onset of severe memory impairment for events of the present and the recent past coupled with ongoing anterograde amnesia which lasts for at least several hours and resolves gradually. Although alarming to patients and their families, this amnesia is nearly always benign, rarely recurs and almost never evolves into a complete stroke. Many mechanisms have been proposed, but no single cause can explain fully all the features of transient global amnesia. These include migraine variant, temporal lobe seizure and transient ischemic attack (‘mini-stroke’). If a patient is young or has repeated attacks, then the possibility of seizure or even migraine is higher.[31]

Treating Amnesia 

There is no specific treatment for amnesia, but techniques for enhancing memory and psychological support can help people with amnesia and their families cope. Since the bulk of amnesia cases involve anterograde amnesia, treatment focuses on ways to retain new information and build habits through your implicit memory.

Anterograde amnesia

Approaches used to treat those who suffer from anterograde amnesia often use interventions which focus on compensatory techniques. such as, beepers, written notes, diaries or through intensive training programs involving the active participation of the individual concerned, along with their supporting network of family and friends.

The use of compensatory strategies for memory disorders has been shown to be effective in individuals with minor traumatic brain injuries.[32] Compensatory techniques may include the use of computers, beepers, written notes, diaries or through intensive training programs involving the patient and his or her circle of friends and family. By integrating memory tools into everyday life, amnesia patients can recall memories as often as possible to try to strengthen them. Amnesiacs manage to remember to use these memory tools by creating habits, or implicit memories, so they instinctively know to check their calendar in the morning for appointments, for instance. Pocket calendars or PDAs (personal digital assistants) can be helpful to persons with anterograde amnesia. A typical PDA is a handheld device that can function as a cellular phone, fax sender, Web browser, and personal organiser. Access to personal and general data from such an easily portable device can increase the patient's sense of independence and lighten the burden on caretakers. In addition, establishing patterns of living are integral for amnesia patients to get on with daily life.[15]

It is now becoming apparent that while anterograde amnesia devastates memory for facts or events, it may spare memory for skills or habits. Thus, an individual with anterograde amnesia can be taught a new skill, such as how to play a game or how to write backwards. The next day, the amnesic individual will claim to have no memory of the prior session, but when asked to try executing the skill, can often perform quite well indicating that some memories have been formed. It is an important area of current research to document exactly which kinds of memory can be formed in amnesia, and how this may be used to help rehabilitate amnesic individuals.[14]

Retrograde amnesia

Treatment of retrograde amnesia should be directed at its cause. While there is no actual cure for retrograde amnesia, “jogging” the victim’s memory by exposing them to familiar objects, photographs, smells, and sound (music) from their past will often speed the rate of recall. Family support is crucial in helping a patient with amnesia get better.

Korsakoff’s syndrome. Patients with amnesia caused by alcoholism (Korsakoff's syndrome) require vitamin B1 supplements to help stop brain deterioration.

Dissociative amnesia

Patients with dissociative amnesia benefit from psychotherapy by working through the traumatic event. Although somewhat controversial, given the fact that many recovered memories of childhood sexual abuse have proven to be false, hypnosis may also be used to help patients recall lost memories of past events.[33] Hypnosis, as well as other meditative techniques, can help to relax the patient thereby relieving stress and making memories more accessible. A similar result may be achieved through interviewing under sedation, possibly using cues to guide the patient.[33]

Dementia

Patients with Alzheimer’s disease or other dementia benefit from certain medications as well as from behavioural interventions.

Medications: Medications for Alzheimer’s disease are prescribed to improve memory, attention, reason, language and the ability to perform simple tasks. They include cholinesterase inhibitors such as donepezil (Aricept), rivastigmine (Exelon), and galantamine. Memantine is reserved for the treatment of moderate to severe Alzheimer’s disease.[34]

Behavioural interventions. Behavioural strategies in patients intended to simplify and stabilise their environment include creating predictable routines, avoiding sensory overload, and labeling items in the environment. Reality orientation has also been shown to improve cognition when accompanied by medication. It is an approach where the environment, including dates, locations, and current surroundings, is frequently pointed out and woven into the conversations with the person who has dementia.[35]

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