Overview of Amnesia and Amnestic Disorders

Memory Disorders

This lecture integrates previous knowledge to discuss memory disorders, focusing on what happens when brain regions and neurobiological processes related to memory break down.

Amnesia

Amnesia is a broad term describing impairment in episodic memory, specifically the memory for events and experiences. There are various types of amnesia resulting from different brain diseases and implicated brain regions. The lecture focuses on the distinction between anterograde and retrograde amnesia.

Anterograde Amnesia

Anterograde amnesia is the inability to form new memories after a brain injury. Using a timeline analogy, if a brain injury occurs at a certain point, anterograde amnesia impairs episodic memory for everything that happens after that point. Pure anterograde amnesia involves the inability to form new memories, while memories from before the injury remain intact.

Retrograde Amnesia

Retrograde amnesia is the opposite of anterograde amnesia; it involves the inability to recall past memories while still being able to form new ones. It's more than just normal forgetfulness; it's a significant difficulty or impossibility in recalling past memories. "Retro" means "in the past," so retrograde amnesia involves the loss of memories from the past.

Amnesia vs. Forgetfulness

Amnesia is distinct from normal forgetfulness. The following scenario is given as an example of normal forgetfulness, not amnesia:

"I was at work last Wednesday, sitting at my desk in the middle of an important conversation. I was looking at my boss, and I just couldn't think of her name. I remember feeling really embarrassed. I didn't know what to say. When she walked away, her name suddenly came to me, but I'm really worried about it. I just could not remember her name."

This is NOT amnesia because the person stored and recalled a lot of episodic detail (being there, the context, when it was, who it was, what it was). Amnesia involves a complete loss of information, not a transient loss of access.

Amnesia is a foundational aspect of cognition and a significant part of who we are and how we interact with the world. People with amnesia can present as "blank." They may retain semantic knowledge but lack episodic memories. When asked about past events, they might confabulate, which involves filling in the gaps with vague or inaccurate information unintentionally.

Henry Molaison (H.M.)

Henry Molaison, previously known as H.M., suffered from severe epilepsy. To treat it, he underwent a medial temporal lobectomy, which involved removing parts of his medial temporal lobes, including the hippocampus.

After the surgery, Molaison experienced:

• Retrograde amnesia for the three years prior to the surgery.

• Inability to form new long-term declarative or explicit memories (anterograde amnesia).

However, he had preserved implicit memory. For example, he could improve on the mirror-drawing task (drawing something while looking at your hand in a mirror) over time, demonstrating motor learning. Yet, each time he performed the task, he believed it was entirely new. He also had intact short-term memory; he could hold a conversation or remember a word list temporarily.

Amnestic Disorders

Amnesia can be caused by various factors:

• Brain infection

• Stroke (blood clot or bleed in the brain)

• Traumatic brain injury

• Surgical resection (e.g., for tumors)

• Epilepsy (either during a seizure or due to hippocampal damage)

• Dissociative disorders or trauma responses

• Alzheimer's disease

• Korsakoff's syndrome

The lecture focuses on Alzheimer's disease and Korsakoff's syndrome.

Alzheimer's Disease (AD)

Alzheimer's disease is a progressive neurodegenerative disease characterized by:

• Accumulation of amyloid plaques (proteins) outside of cells.

• Neurofibrillary tangles (tau protein) inside of cells.

These accumulations lead to atrophy and death of brain tissue. Alzheimer's is the most common cause of dementia, where dementia is the clinical phenotype (symptoms), and Alzheimer's disease is the pathology (disease entity). It is more common in older age (onset over 65), but early-onset forms exist with genetic links. Current theory suggests it's not inevitable with age but a disease that affects some more than others.

The progression of AD over time:

1. Early Stages: Predominant involvement of medial temporal structures, including the hippocampus (memory difficulties).

2. Progression: Involvement of lateral temporal lobes (language impairment).

3. Later Stages: Severe damage to medial temporal structures, affecting most of the brain (visual difficulties, executive dysfunction).

Imaging and autopsy show atrophy in the Alzheimer's brain (more empty space on MRI, thinner structures at autopsy).

The clinical difficulties map onto the disease progression:

• Early hippocampal involvement: memory impairment.

• Broadening to temporal lobes: language impairment.

• More severe stages involving the cortex: visual difficulties, executive dysfunction.

Memory impairment specifics:

• Prominent anterograde amnesia.

• Rapid forgetting: Information decays quickly once stored.

• Later in the disease: retrograde amnesia (older memories are better preserved).

• Intact implicit memory (early stages).

• Intact semantic memory (early stages).

Korsakoff's Syndrome

To explain Korsakoff's, Wernicke's encephalopathy needs to be explained first.

Wernicke's encephalopathy results from alcohol abuse/misuse, which leads to malnutrition and thiamine deficiency. It's characterized by:

• Delirium (temporary disturbance of mental state).

• Ataxia (loss of full control of bodily movements).

• Eye movement disorders.

It is treatable and can resolve with treatment. However, without treatment, it can progress to Korsakoff's syndrome, a severe and progressive disorder causing irreversible brain damage.

Korsakoff's syndrome involves preferential involvement of the medial thalamus and its connections to the hippocampus and cerebellum. CT scans show bright sections in the medial temporal lobes and medial structures and wider ventricles (indicating brain tissue atrophy).

In Korsakoff's syndrome:

• Early stages: anterograde amnesia (trouble learning new information).

• Short-term memory is intact, but transferring information to long-term memory is difficult.

• No rapid forgetting (unlike Alzheimer's).

• Untreated: retrograde amnesia progresses over time.

• Trouble with source monitoring (difficulty identifying the source of information).