Amnesia can be divided into two broad groups, retrograde amnesia and anterograde amnesia. Retrograde amnesia is the loss of memory prior to the onset of amnesia and anterograde amnesia is the inability to form new memory. Memory can also be divided into two groups depending on the duration, short-term memory and long-term memory. Other types of amnesia are Psychological including repressive amnesia and dissociative fugue, infantile amnesia, neurological amnesia (Alzheimer’s disease, Pick’s disease), post-traumatic Amnesia, drug-Induced Amnesia, transient global amnesia, amnesia due to nutritional deficiency (thiamine, vitamin B12). Richard Semon in 1904 described that experiences cause some changes in the neurons and these changes are referred to as engram and they form memory of the particular experience in those neurons. Reactivation of these neurons occur when patient tries to recall those memories. Amnesia results from damage to different memory centers in the brain, such as the medial temporal lobe and the hippocampus, which are involved in acquiring and restoring memory. Common causes of amnesia include medications, head trauma, depression and aging. Less common cause of amnesia are childhood sexual abuse, traumatic incident, hypoxia, psychological trauma, thiamine deficiency, alcohol abuse, Alzheimer’s disease, Pick’s disease, Parkinson’s disease, benzodiazepines, hypoglycemia, stroke, electroconvulsive therapy. The underlying etiology of memory loss must be differentiated on the basis of duration of memory loss, presence of anterograde amnesia or retrograde amnesia, associated features, and cognitive impairment. Memory impairment tends to increase with age. Forty percent of the population over age sixty have some degree of memory loss. Amnesia and mild cognitive impairment is more prevalent in middle-aged to older Non-Hispanic Black and older Latino as compared to non-Hispanic Whites. Aging, depression, chronic stress, head trauma, chronic sleep deprivation and medications are risk factors ​for amnesia. Amnesia may progress slowly or suddenly, and maybe transient or permanent. The natural history and prognosis depends upon the underlying etiology. Patients with memory loss could suffer from depression and grief long term. Quality of life and activities of daily living are difficult to maintain which causes decreased socialization and a decline in cognitive functions in the elderly.Amnesia is largely a clinical diagnosis, a detailed history of memory impairment and associated symptoms should be obtained. Focal examination including vital signs, altered mental status, mini mental status exam (MMSE), Glasgow Coma Scale, nystagmus, papilledema, gait, instruments of daily activities should be assessed. Head CT scan and MRI may be helpful in identifying structural and functional abnormalities including bleeding, stroke, tumor, atrophy or any changes suggestive of amnesia. Positron emission tomography PET may show hypometabolism in areas of brain associated with memory in patients with history of amnesia but with no visible structural or functional brain damage on CT scan or MRI. Other diagnostic studies helpful in the diagnosis of the cause amnesia are EEG for epilepsy, CSF fluid analysis for encephalitis.Treatment can be offered in cases of reversible conditions. If not, provision of supportive care can help to improve a patient’s condition. Etiology specific treatment plan should be followed to improve memory and delay progression. Surgical intervention is not recommended for the management of memory loss. Measures for the primary prevention of amnesia include preventing brain trauma, managing stress, avoid alcohol abuse, manage stroke risk factors, good sleep habits, social integration, optimum nutrition and exercise routine. Effective measures for the secondary prevention of memory loss include, sustainable daily routine, healthy eating habits, social integration, exercise routine, reduce and manage stress, adequate sleep, reading and playing strategic games like puzzles and word games.

Richard Semon in 1904 described that experiences cause some changes in the neurons and these changes are referred to as engram and they form memory of the particular experience in those neurons. Reactivation of these neurons occur when patient tries to recall those memories. Theodule-Armand Ribot, a French psychologist determined that memory loss affects recent memories first. Memories are lost in reverse order of their development.

Amnesia can be divided into two broad groups, retrograde amnesia and anterograde amnesia. Retrograde amnesia is the loss of memory prior to the onset of amnesia and anterograde amnesia is the inability to form new memory. Other types of amnesia are Psychological including repressive amnesia and dissociative fugue, infantile amnesia, neurological amnesia (Alzheimer’s disease, Pick’s disease), post-traumatic Amnesia, drug-Induced Amnesia, transient global amnesia. Memory can also be divided into two groups depending on the duration, short-term memory and long-term memory.

Amnesia results from damage to different memory centers in the brain, such as the medial temporal lobe and the hippocampus, which are involved in acquiring and restoring memory.

Common causes of amnesia include medications, head trauma, depression and aging. Less common cause of amnesia are childhood sexual abuse, traumatic incident, hypoxia, psychological trauma, thiamine deficiency, alcohol abuse, Alzheimer’s disease, Pick’s disease, Parkinson’s disease, benzodiazepines, hypoglycemia, stroke, electroconvulsive therapy.

The underlying etiology of memory loss must be differentiated on the basis of duration of memory loss, presence of anterograde amnesia or retrograde amnesia, associated features, and cognitive impairment.

Memory impairment tends to increase with age. Forty percent of the population over age sixty have some degree of memory loss. Amnesia and mild cognitive impairment is more prevalent in middle-aged to older Non-Hispanic Black and older Latino as compared to non-Hispanic Whites.

Aging, depression, chronic stress, head trauma, chronic sleep deprivation and medications are risk factors ​for amnesia.

Amnesia may progress slowly or suddenly, and maybe transient or permanent. The natural history and prognosis depends upon the underlying etiology. Patients with memory loss could suffer from depression and grief long term. Quality of life and activities of daily living are difficult to maintain which causes decreased socialization and a decline in cognitive functions in the elderly.

There is no diagnostic study of choice to diagnose amnesia. The best approach is to obtain a detailed history followed by a focused physical examination.

It is critical to perform a formal and exhaustive assessment of the patient to look for any indications of memory disorders and to hear any subjective complaints. With this information, preventative measures and care can be specifically addressed to the patient’s needs. A detailed history of memory loss and associated symptoms is crucial for understanding the etiology of amnesia.

Patients with amnesia may have variable general appearance depending on the underlying cause of memory loss. Amnesia is largely a clinical diagnosis. Focal examination including vital signs, altered mental status, mini mental status exam (MMSE), Glasgow Coma Scale, nystagmus, papilledema, gait, instruments of daily activities should be assessed.

There is no laboratory test to diagnose memory loss. however, it is important to obtain toxicology screening, alcohol, glucose, electrolytes level.

There are no ECG findings associated with amnesia.

There are no x-ray findings associated with amnesia.

There are no echocardiography/ultrasound findings associated with amnesia. Although a case of transient global amnesia has been reported in a patient undergoing a transesophageal echocardiogram (TEE).

Head CT scan may be helpful in the diagnosis of the cause of amnesia. Structural and functional abnormalities are identified to detect any bleeding, stroke, tumor, atrophy or any changes suggestive of amnesia.

Head MRI may be helpful in the diagnosis of the cause of amnesia in some cases including, Alzheimer’s disease, or brain trauma. In majority of the cases of amnesia the brain appears normal on MRI.

Positron emission tomography PET may show hypometabolism in areas of brain associated with memory in patients with history of amnesia but with no visible structural or functional brain damage on CT scan or MRI.

Other diagnostic studies helpful in the diagnosis of the cause amnesia are EEG for epilepsy, CSF fluid analysis for encephalitis.

Treatment can be offered in cases of reversible conditions. If not, provision of supportive care can help to improve a patient’s condition. Etiology specific treatment plan should be followed to improve memory and delay progression. When memory loss is a symptom of a more severe disease, it may be reversed as soon as the underlying condition is identified and cured. Memory loss due to aging cannot be cured, but the symptoms may be improved by preventative measures.

Surgical intervention is not recommended for the management of memory loss.

Measures for the primary prevention of amnesia include preventing brain trauma, managing stress, avoid alcohol abuse, manage stroke risk factors, good sleep habits, social integration, optimum nutrition and exercise routine.

Effective measures for the secondary prevention of memory loss include, sustainable daily routine, healthy eating habits, social integration, exercise routine, reduce and manage stress, adequate sleep, reading and playing strategic games like puzzles and word games.

Richard Semon in 1904 described that experiences cause some changes in the neurons and these changes are referred to as engram and they form memory of the particular experience in those neurons. Reactivation of these neurons occur when patient tries to recall those memories. Theodule-Armand Ribot, a French psychologist determined that memory loss affects recent memories first. Memories are lost in reverse order of their development.

• Richard Semon in 1904 described that experiences cause some changes in the neurons and these changes are referred to as engram and they form memory of the particular experience in those neurons. Reactivation of these neurons occur when patient tries to recall those memories.^[1]
• Theodule-Armand Ribot, a French psychologist determined that memory loss affects recent memories first. Memories are lost in reverse order of their development.^[2]
• In 1763, Sauvages recognized amnesia as a medical disorder.^[3]
• In early 19th century clinical description of amnesia was identified.^[3]
• Caroline Miles and Henri & Henri first described infantile amnesia in 1893 and 1895,respectively. It was further explained by Sigmund Freud in 1953.^[4]
• Alzheimer’s disease was first described in 1906 by Alois Alzheimer, a psychiatrist and a pathologist of German origin.^[5]
• Korsakoff syndrome was discovered in late 19th century by a neuropsychiatrist of russian origin named, Sergei Korsakoff.^[6]

Amnesia can be divided into two broad groups, retrograde amnesia and anterograde amnesia. Retrograde amnesia is the loss of memory prior to the onset of amnesia and anterograde amnesia is the inability to form new memory. Other types of amnesia are Psychological including repressive amnesia and dissociative fugue, infantile amnesia, neurological amnesia (Alzheimer’s disease, Pick’s disease), post-traumatic Amnesia, drug-Induced Amnesia, transient global amnesia.Memory can also be divided into two groups depending on the duration, short-term memory and long-term memory.

• Amnesia can be divided into two broad groups:
  • Anterograde amnesia: The inability to form new memory. Past memory is intact.
  • Retrograde amnesia: The loss of memory prior to the onset of amnesia. Patient can form new memories.
• Memory can also be divided into groups depending on the duration:
  • Short-term memory are for short period of time and use existing neuronal network.
  • Long-term memory are long lasting and are formed by structural/functional changes in neuronal network.^[1]

Types of Amnesia	Main Features
Dissociative Amnesia	Temporary, episodic retrograde memory loss without structural brain damage. Cause is psychological in origin. Dissociative Amnesia is also referred to as psychological amnesia. It has variable presentation: Repressed amnesia is seen in patients where they are unable to recall a stressful or traumatic incident from the past due to psychological defense mechanism. Dissociative fugue has been observed in these patients where the identity and memory is lost. It is reversible and has variable time duration.[2][3]
Transient global amnesia	Sudden episodic loss of anterograde and partial retrograde memory. Usually last less than twenty four hours.[4]
Post-traumatic Amnesia	Amnesia that follows head trauma could be temporary or permanent. The span of memory loss is uncertain it could present with retrograde, anterograde or combined. Extent of injury and duration of loss of consciousness are important prognostic factors in determining the severity of amnesia. [5]
Infantile Amnesia	Also known as childhood amnesia. Early childhood memory is lost, usually up to the age of fours year. Influenced by cultural norms and sexual repression.[6]
Drug-Induced Amnesia	Benzodiazepine are the most common group of drugs that can cause drug-induced amnesia, especially if used with alcohol. Memory loss could be long term or short term.[7] Amnesia is anterograde from the time the drug was introduced and patient has impairment in forming new memories. It is reversible upon discontinuation of the drug.
Neurological Amnesia	Alzheimer’s Disease, Pick’s Disease, Parkinson’s Disease
Amnesia in Korsakoff’s Syndrome	Caused by thiamine deficiency due to prolonged alcohol use or severe malnutrition. Anterograde amnesia, retrograde amnesia, and confabulation.[8]
Selective Amnesia	Certain memory is lost. Patient may forget about certain relationships, talents, events, or traumatic incidents.
Epileptic Amnesia	Observed in patients with temporal lobe epilepsy.[9] Anterograde amnesia with short-term memory loss.
Lacunar amnesia	Memory of a particular event is lost. Lacuna mean ‘a gap’, which refers to leaving ‘a gap’ in memory.[10]

Memory is the stored information in the hippocampal region of the brain. depending on the duration, memory is divided into short term and long term.

Memory is the stored information in the hippocampal region of the brain. According to Richard Semon (1904), experiences cause some structural and functional changes in the neurons and these changes are referred to as engram and they form memory of that experience. Reactivation of these neurons occur when patient tries to recall those memories.^[1] Memory is divided into groups depending on the duration:

• Sensory memory: Information from around us is stored as sensory memory.^[2]
• Short-term memory are for short period of time and use existing neuronal network.
• Long-term memory are long lasting and are formed by structural/functional changes in neuronal network.^[3]

Types of Amnesia	Pathogenesis
Dissociative Amnesia	Psychological origin.
Transient global amnesia	Precipitated by brain ischemia, migraine, epileptic seizure, venous congestion, psychological trauma.[4]
Post-traumatic Amnesia	Amnesia that follows head trauma could be temporary or permanent.[5]
Infantile Amnesia	Influenced by cultural norms and sexual repression.[6]
Drug-Induced Amnesia	Benzodiazepine are the most common group of drugs that can cause drug-induced amnesia, especially if used with alcohol.[7]
Neurologically Derived Amnesia	Brain regions involved are the hippocampus and the medial temporal lobes.[8]
Amnesia in Korsakoff’s Syndrome	Caused by thiamine deficiency due to prolonged alcohol use or severe malnutrition. Deficiency of thiamine damages medial thalamus, mammillary bodies and causes cerebral atrophy due to lack of pyruvate decarboxylation.[9]
Epileptic Amnesia	Rare, episodic amnesia seen in patients with temporal lobe epilepsy.[10]
Lacunar amnesia	Occurs due to brain damage. These patients have a gap in memory.[11]

• Alzheimer’s disease:^[12]
  • Late-onset: Apolipoprotein E (APOE) gene on chromosome 19. This gene has variable risk of developing Alzheimer’s disease depending on the allele. APOE ε4 increases the risk, APOE ε3 neither increases nor decreases and APOE ε2 allele provides some protection against the disease.
  • Early-onset: Amyloid precursor protein (APP) on chromosome 21, presenilin 1 (PSEN1) on chromosome 14 and presenilin 2 (PSEN2) on chromosome 1 are associated with early-onset Alzheimer’s disease.
• Deficiency of RbAp48 protein encoded by RBBP4 gene have been co-related to memory loss.^[13]

On gross pathology, generalized cortical atrophy, more pronounced in hippocampus and medial temporal lobe is seen in patients with Alzheimer’s disease.^[14]

• Korsakoff’s syndrome:^[15]
  • Gliosis and microhemorrhages found in periaqueductal and paraventricular region.,
  • Mamillary bodies atrophy and
  • Atrophy seen in thalamus
• Microscopic features seen in Alzheimer’s disease are, amyloid plaques, intracellular neurofibrillary tangles, tau-positive neuropil threads, dystrophic neurites, activated microglia, reactive astrocytes, eosinophilic Hirano bodies, granulovacuolar degeneration and cerebral amyloid angiopathy.^[14]

Common causes of amnesia include medications, head trauma, depression and aging. Less common cause of amnesia are childhood sexual abuse, traumatic incident, psychological trauma, hypoxia, thiamine deficiency, alcohol abuse, Alzheimer’s disease, Pick’s disease, Parkinson’s disease, benzodiazepines, hypoglycemia, stroke, electroconvulsive therapy.

• Common causes of amnesia include medications, head trauma, depression and aging.^[1]

Amnesia

Neurological

Trauma

Psychological

Drug Induced

Nutrition deficiency

•Alzheimer’s Disease •Parkinson’s Disease •Dementia with Lewy bodies •Frontotemporal lobar degeneration •Stroke

•Vascular dementia •Radiation[2]

•Depression[1] •Anxiety •Childhood sexual abuse

•Marijuana abuse •Benzodiazepine[3] •Chemotherapy[2] •Electroconvulsive therapy[4]

•Thiamine deficiency •Vitamin B12 deficiency •Hypoxia[1] •Hypoglycemia[1]

The underlying etiology of memory loss must be differentiated on the basis of duration of memory loss, presence of anterograde amnesia or retrograde amnesia, associated features, and cognitive impairment.

Diseases	Differentiating Features
	Duration of Amnesia	Associated Features	Cognitive Impairment
Post-traumatic amnesia[1]	Varies	Head Trauma	Variable, depends on the extent of brain injury[2]
Dissociative Amnesia[3][4]	Variable. Could last minutes, hours, or rarely even months or years	Usually follows an incident that caused a lot of stress and trauma	No cognitive impairment
Transient global amnesia[5]	Less than 24hrs	Brain ischemia, migraine, seizure, venous congestion, psychological trauma.	No cognitive impairment
Drug-Induced Amnesia[6]	Once drug is stopped, memory gradually regained	Benzodiazepines	No cognitive impairment
Neurological Amnesia	Does not resolve, patient experiences progressive memory loss.	Alzheimer’s disease, Pick’s disease, Parkinson’s disease	Progressive cognitive impairment
Transient epileptic amnesia[7]	Episodic transient amnesia	History of temporal lobe epilepsy	No cognitive impairment
Age-Related Amnesia[8]	Slow and progressive memory loss	Diagnosis of exclusion	No cognitive impairment

Memory impairment tends to increase with age. Forty percent of the population over age sixty have some degree of memory loss. Amnesia and mild cognitive impairment is more prevalent in middle-aged to older Non-Hispanic Black and older Latino as compared to non-Hispanic Whites.

• The prevalence of dissociative amnesia is 1,000 to 2,600 per 100,000 (1.0% to 2.6%) of the overall population.^[1]
• Prevalence of Alzheimer’s disease is 20% over the age of 85.^[2]
• The prevalence of dissociative fugue is approximately 0.2%. This might be underestimated as dissociative fugue is under diagnosed.^[3]
• Worldwide prevalence of Korsakoff Syndrome is 0-2% and 1-2% in the United States. Prevalence is higher in elderly living by themselves, psychiatric inpatients and the homeless.^[4]

• Worldwide, the incidence of transient global amnesia is approximately 2.9– 10 per 100,000 cases per year. ^[5]
• Incidence of dissociative disorder is higher in substance abuse cases.^[6]

• Higher prevalence of Alzheimer’s disease is seen in women than men.^[7]
• Males are more affected by Korsakoff Syndrome than females.

• Memory loss and mild cognitive impairment is more prevalent in middle-aged to older Non-Hispanic Black and older Latino as compared to non-Hispanic Whites.^[8]

• Memory impairment tends to increase with age. Forty percent of the population over age sixty have some degree of memory loss.^[9]

Aging, depression, chronic stress, head trauma, chronic sleep deprivation and medications are risk factors for amnesia.

• A psychologically traumatic incident in the past can increase chances of developing dissociative amnesia (psychogenic amnesia).^[1]
• Head trauma increases the risk of post traumatic amnesia.^[2]
• Sexual repression in childhood and cultural norms can cause infantile/childhood amnesia in adults.^[3]
• Prolonged trauma and childhood sexual abuse can increase risk of dissociative fugue.
• Sleep deprivation^[4]
• Head trauma, depression, hypertension, Down syndrome and family history can increase the risk of developing Alzheimer’s disease.^[5]
• Risk factors for Korsakoff Syndrome include prolonged alcohol use, chemotherapy, dialysis, extreme dieting, severe malnutrition, genetic factors.^[6]
• Chronic stress^[7]
• Decreased socialization^[8]

Amnesia may progress slowly or suddenly, and maybe transient or permanent. The natural history and prognosis depends upon the underlying etiology. Patients with memory loss could suffer from depression and grief long term. Quality of life and activities of daily living are difficult to maintain which causes decreased socialization and a decline in cognitive functions in the elderly.

• Amnesia may progress slowly or suddenly, and maybe transient or permanent. The natural history and prognosis depends upon the underlying cause.
• Without treatment Korsakoff’s syndrome can cause mental disability with permanent memory loss, apathy, confabulation.^[1]

• Patients with memory loss could suffer from depression and grief long term.^[2]
• Quality of life and activities of daily living are difficult to maintain which causes decreased socialization and a decline in cognitive functions in the elderly.^[3]
• Repeated episodes of transient global amnesia can result in long lasting loss of memory.^[4]

• In patients with post traumatic amnesia, the extent of injury and duration of loss of consciousness are important prognostic factors in determining the severity of amnesia. ^[5]
• Dissociative fugue could last from days to months and once recovery occurs it is rapid and complete. Some refractory cases have been observed but usually it is just one episode.^[2]
• If Korsakoff’s syndrome is detected early and treatment optimally it can be reversed to some extent and can prevent further brain and nerve damage.^[1]