Chapter Notes: Organic Mental Disorders

Introduction

Organic mental disorders are caused by identifiable brain diseases, injuries, or damage that disrupt normal brain function. These disorders are characterized by a range of symptoms resulting from the impairment of cognitive abilities and consciousness.

1. Cognitive Impairment: Cognitive impairment refers to difficulties in mental processes essential for learning and understanding, including:

• Memory
• Language
• Orientation (awareness of time, place, and person)
• Judgment
• Praxis (performing actions)
• Problem-solving
• In organic mental disorders, one or more of these cognitive functions may be impaired, leading to symptoms such as:
  • Disorientation
  • Difficulty with attention and concentration
  • Memory disturbances, particularly recent memory, resulting in anterograde amnesia
• Due to these cognitive issues, organic mental disorders are often referred to as cognitive disorders.

2. Disturbances of Consciousness: Disturbances of consciousness can vary from full alertness to coma. Key levels of consciousness include:

• Alertness: Being aware of and able to respond to stimuli.
• Somnolence or lethargy: tendency to sleep when not stimulated.
• Obtundation: Difficulty waking up and confusion upon arousal.
• Stupor or semicoma: The patient is silent and immobile, with minimal response to stimuli.
• Coma: Total unresponsiveness with closed eyes.

Other terms describing disturbances of consciousness include confusional state, clouding of consciousness, and altered sensorium.

3. Hallucinations
Patients with organic mental disorders may experience various types of hallucinations, including:

• Visual hallucinations: Seeing things that are not present.
• Auditory hallucinations: Hearing sounds or voices that are not present.
• Olfactory hallucinations: Smelling odors that are not present.
• Gustatory hallucinations: Tasting substances that are not present.
• Tactile hallucinations: Feeling sensations on the skin that are not present.

4. Delusions: Delusions in organic mental disorders are typically temporary, and complex delusions are less common.

Types of Organic Mental Disorders:

• Delirium: sudden and severe confusion state, often with fluctuations in consciousness.
• Dementia: chronic and progressive decline in cognitive function, affecting memory, thinking, and social abilities.
• Amnestic disorders: Disorders primarily characterized by memory impairment, often related to specific events or information.

Delirium

Delirium is a common type of organic mental disorder that typically begins suddenly and is characterized by fluctuating symptoms. It is most often observed in older adults, particularly those who have undergone medical or surgical procedures in a hospital setting. Certain groups of patients are at a higher risk for developing delirium, including:

• Patients with hip fractures
• Individuals undergoing open heart surgery
• People with severe burns
• Patients with pneumonia
• Postoperative patients
• Critically ill patients

Delirium is marked by a sudden change in awareness, thinking, and psychiatric symptoms, including hallucinations and delusions. It can also be triggered by factors such as:

• Taking multiple medications, especially those with anticholinergic effects
• Withdrawal from substances like alcohol and sedatives

Additionally, older patients who wear eye patches after cataract surgery may experience a form of delirium known as black-patch delirium due to sensory deprivation.

Symptoms of Delirium

The clinical features of delirium are:

• Changes in consciousness, ranging from sleepiness to coma
• Difficulty paying attention
• Disorientation regarding time, place, and person
• Memory problems, particularly with recent and immediate recall
• Perceptual issues such as illusions and visual hallucinations, along with temporary delusions
• Fluctuations in activity levels, and symptoms of agitation
• Disturbances in the autonomic nervous system
• Disruptions in the sleep-wake cycle, including insomnia or reversed sleeping patterns
• Sundowning: Worsening of symptoms in the evening as daylight fades
• Floccillations: Aimless picking behaviors, such as fiddling with clothing or bed linens
• Occupational delirium: Behaving as though still at work, for example, a tailor requesting tools while in bed

The neurotransmitter associated with delirium is acetylcholine, and the brain area involved is the reticular formation, which plays a crucial role in maintaining awareness.

Diagnosing Delirium

• Diagnosis of delirium is based on the presence of the symptoms described above, with key indicators being:
  • Sudden onset of symptoms
  • Fluctuating nature of symptoms over time
• Bedside assessments such as the Mini Mental Status Examination (MMSE) and Mental Status Examination (MSE) are useful in evaluating cognitive impairment.
• EEG findings in delirium typically show generalized slowing, though results can differ based on the underlying cause, such as alcohol or sedative withdrawal, which may present with low voltage fast activity.

To distinguish between delirium and dementia:

• Delirium is characterized by a sudden onset and fluctuating symptoms, while dementia progresses gradually with stable symptoms.
• Delirium involves disturbances of consciousness, a feature not present in dementia.
• Some patients with dementia may experience superimposed delirium, known as confused dementia.

To differentiate delirium from schizophrenia:

• Hallucinations and delusions in delirium are temporary and disorganized, whereas in schizophrenia, they are more constant and structured.
• Delirium is marked by attention deficits and disturbances in consciousness, which are not seen in schizophrenia.

Treatment of Delirium

• Treatment of delirium focuses on addressing the underlying cause of the condition.
• Antipsychotic medications may be used to manage symptoms such as delusions, hallucinations, and agitation.
• Benzodiazepines are preferred for treating insomnia and are the first-line treatment for alcohol withdrawal delirium, also known as delirium tremens.

Dementia

Dementia is a condition that becomes more common as people get older. It affects around 5% of individuals over 65 years old and 20-40% of those over 85 years old. The causes of dementia can be either permanent or reversible.

Symptoms 

The following are the symptoms of dementia:
1. Cognitive impairment characterized by the four A's: amnesia, aphasia, apraxia, and agnosia.

• Amnesia: Amnesia refers to memory loss, starting with recent memories, then immediate memories, and finally older memories.
  • Memory impairment can be categorized into:
    • Episodic memory (memory of events)
    • Semantic memory (memory of facts)
    • Visuospatial deficits (awareness of space)
  • Episodic memory loss follows a gradient, with recent events disappearing first.
  • Semantic memory typically remains intact in the early stages but deteriorates later.
  • Visuospatial issues can lead to disorientation in new places and getting lost in familiar surroundings.
• Aphasia: Aphasia refers to language difficulties, starting with problems in finding words and progressing to more severe language issues.
• Apraxia: Apraxia is the inability to perform learned actions, such as buttoning a shirt or combing hair.
• Agnosia: Agnosia is the inability to recognize sensory input, such as faces (prosopagnosia) or even one's own face (autoprosopagnosia).
  • Besides the four A's, difficulties with executive functioning (planning, organizing, sequencing, and abstract thinking) are also important.

2. Behavioral and psychological symptoms may include:

• Personality changes: Patients may become withdrawn or aggressive, particularly with frontal and temporal lobe involvement.
• Hallucinations and delusions: Common delusions include feelings of persecution or theft.
• Symptoms of depression, mania, and anxiety.
• Apathy, agitation, aggression, wandering, and disturbances in sleep patterns.
• Catastrophic reaction: Emotional outbursts due to awareness of cognitive deficits in stressful situations.

3. Focal neurological signs: Observed in vascular dementia, such as exaggerated reflexes and abnormal walking patterns.

Types

Dementia can be categorized into reversible and irreversible types. A thorough assessment is crucial because approximately 15% of cases are reversible. Reversible causes of dementia include:

• Neurosurgical conditions: Such as subdural hematoma, normal pressure hydrocephalus, brain tumors, and brain abscesses.
• Infectious causes: Including meningitis, encephalitis, neurosyphilis, and Lyme disease.
• Metabolic causes: Such as vitamin B12 or folate deficiency, thyroid disorders, and parathyroid disorders.
• Other causes: Including drugs, toxins, alcohol misuse, and autoimmune encephalitis.

Dementia can also be classified based on the affected area of the brain:

• Cortical dementias: Involving early damage to the cortex, leading to symptoms like amnesia, apraxia, aphasia, agnosia, and acalculia. The most common type is Alzheimer's disease, followed by Creutzfeldt-Jakob disease and frontotemporal dementias.
• Subcortical dementia:
  •  These disorders are characterized by early involvement of subcortical structures like basal ganglia, brain stem nuclei and cerebellum. 
  •  These disorders are characterized by early presentation of motor symptoms (abnormal movements like tics, chorea, dysarthria, etc), significant disturbances of executive functioning and prominent behavioral and psychological symptoms like apathy, depression, bradyphrenia (slowness of thinking). 
  •  The examples include Parkinson's disease, Wilson's disease, Huntington's disease, multiple sclerosis, progressive supra nuclear palsy, normal pressure hydrocephalus. 
  •  Some dementias such as vascular dementia, dementia with Lewy body have mixed presentation. 

Alzheimer's Disease (Dementia of Alzheimer's Type)

• Alzheimer's disease is the most common cause of dementia.
•  The occurrence of Alzheimer's disease increases with age: 
  •  About 5% of people aged 65 and older have it. 
  •  For those over 85 years old, the rate rises to 20-30%. 
•  There are two types of Alzheimer's disease based on the age it starts: 
  • Early onset (presenile): Begins at age 65 or earlier. 
  • Late onset (senile): Begins after age 65. 
•  At all ages, women are affected more than men, with a ratio of 2 or 3:1, except in cases of early onset familial forms where the ratio is 1:1. 
•  The disease usually starts slowly and gets worse gradually. 
•  People often lose awareness of their illness early on. 
•  In the initial stages, symptoms may include: 
  • Memory problems
  • Gradually developing issues like apraxia (difficulty with movement), agnosia (inability to recognize objects), aphasia (difficulty with language), and acalculia (difficulty with numbers).
  • Loss of executive functions (ability to plan and organize).
•  In later stages, more severe neurological disabilities can appear, such as: 
  • Tremors
  • Rigidity
  • Spasticity
• Pathophysiology: The main neuroanatomical feature of Alzheimer's disease is widespread brain shrinkage with flattened grooves on the brain's surface and enlarged brain cavities.
  • The typical microscopic features include neuritic (senile) plaques and neurofibrillary tangles.
  • Senile plaques, also known as amyloid plaques, are made up of a specific protein called amyloid beta (Aβ).
  • This protein comes from a larger protein called amyloid precursor protein (APP) through the actions of enzymes called beta-secretase and gamma-secretase.
  • The Aβ protein clusters together to form fibrils. These senile plaques are deposits that occur outside of cells and can be found throughout the brain, including in the striatum and cerebellum.
  • The amyloid beta peptide can also build up in the walls of blood vessels, leading to a condition called cerebral amyloid angiopathy (CAA).
  • Senile plaques can appear in older adults who do not have Alzheimer's, and their numbers tend to increase with age. Thus, senile plaques are not exclusive to Alzheimer's disease.
  • The presence of amyloid plaques does not necessarily indicate how severe the dementia is.
  • Neurofibrillary tangles (NFTs) are clusters of a protein called tau inside neurons.
  • The tau protein found in these tangles is in a highly phosphorylated and dysfunctional state.
  • Normally, tau helps to stabilize microtubules, which are crucial for transporting materials within neurons. However, in Alzheimer's, this process is disrupted.
  • Neurofibrillary tangles are widely found in the brain's cortical areas and the hippocampus, but they do not appear in the cerebellum.
  • Numerous studies have shown that the amount and location of NFTs are linked to the duration and severity of dementia.
  • Both senile plaques and neurofibrillary tangles can be found in older adults without dementia.
  • However, in individuals with dementia, these features are extensive and widespread.
  • To diagnose Alzheimer's disease, there must be a significant presence of both senile plaques (which are extracellular) and neurofibrillary tangles (which are intracellular).
• Granulovacuolar degeneration (GVD) and Hirano bodies are types of abnormalities that can be found in the cytoplasm of neurons in the hippocampus.
  • These abnormalities are often observed in patients with Alzheimer's disease.
  • While GVD and Hirano bodies can also occur in older individuals who do not have dementia, their presence is much more pronounced in those with Alzheimer's.
  • In Alzheimer's disease, these abnormalities are not only more severe but also more widespread compared to those found in healthy elderly individuals.
• Amyloid Cascade Hypothesis:  According to this hypothesis, changes in the APP gene near the cleavage site increase the chance of being cut by β and γ secretase, leading to the production of amyloid beta (Aβ). 
  • The Aβ peptides combine to form oligomers that trigger the phosphorylation of tau, resulting in the formation of neurofibrillary tangles. 
  •  The tau protein, when highly phosphorylated, cannot stabilize microtubules, which leads to granulovascular degeneration of neurons, causing the loss of neurons and synapses. 
• Neurochemistry: Alzheimer's disease mainly affects cholinergic neurons, with consistent loss of these neurons in the nucleus basalis of Meynert. 
  • In addition to acetylcholine, norepinephrine and serotonin have also been linked to some cases of Alzheimer's. 
• Genetics: There is a connection between Alzheimer's disease and chromosomes 1, 14, and 21. 
  •  A few cases of Alzheimer's are early onset and familial, inherited in an autosomal dominant manner. 
  • Mutations in three genes have been found in most familial cases: 
    • Amyloid precursor protein (APP) on chromosome 21
    • Presenilin-1 on chromosome 14
    • Presenilin-2 on chromosome 1
  • Most cases of Alzheimer's are sporadic and occur later in life. The APO E4 gene is linked to a higher risk of developing Alzheimer's, but testing for it is not advised as it is not very accurate. 
  • Down's syndrome patients have a significantly higher risk of developing Alzheimer's disease. 
  •  The APP gene is located on chromosome 21. 
• Risk factors: The most significant risk factor is age. 
• Other risk factors include: 
  • Head injury
  • Hypertension
  • Insulin resistance
  • Depression
•  Some studies suggest that smoking may protect against Alzheimer's, but this has been challenged by other research. 
•  Higher education levels and staying physically and mentally active later in life can help protect against Alzheimer's disease. 

Vascular Dementia or Multi-infarct Dementia
Vascular dementia is the second most common type of dementia. It results from multiple cerebral infarctions caused by the blockage of cerebral vessels due to arteriosclerotic plaques or thromboemboli. This blockage leads to a gradual decline in brain functions, ultimately resulting in dementia. Symptoms can worsen suddenly in response to new infarcts, leading to a stepwise deterioration of symptoms.

• Symptoms:
  • General symptoms of dementia are usually present.
  • Patients may exhibit focal neurological deficits related to the site of infarction.
  • There is often a history of previous strokes or transient ischemic attacks.
  • Patients typically present with hypertension and other cardiovascular risk factors.
• Treatment: 
  • Treatment for vascular dementia involves managing risk factors and using cholinesterase inhibitors.

Binswanger's Disease: Binswanger's disease, also known as subcortical arteriosclerotic encephalopathy, is characterized by multiple small white matter infarctions. These infarctions can lead to symptoms of subcortical dementia.

Lewy Body Disease (Dementia with Lewy Body)

• The clinical signs and symptoms are similar to Alzheimer ' s disease.
• Patients experience fluctuating levels of attention and alertness.
• They may have recurrent visual hallucinations.
• Common features include tremors, rigidity, and bradykinesia (slow movement).
• Antipsychotic medications should be avoided as these patients are very sensitive to them.
• Certain antipsychotics may lead to drug-induced parkinsonism.

Huntington ' s Disease, Parkinson ' s Disease, Wilson ' s Disease and Multiple Sclerosis

• These are primarily motor diseases linked to the development of dementia.
• The type of dementia observed is subcortical.
• This type is marked by more motor abnormalities and less focus on amnesia, apraxia, aphasia, and agnosia.

HIV-Associated Neurocognitive Disorder

• The diagnosis of HIV-associated neurocognitive disorder (HAND) involves several criteria:
• There must be laboratory evidence indicating systemic HIV infection.
• The individual should exhibit cognitive deficits.
• There should be the presence of motor abnormalities.
• Additionally, there may be changes in personality, which can include:
• Apathy (lack of interest or motivation)
• Emotional lability (rapid and extreme mood changes)
• Disinhibition (reduced impulse control)

Head Trauma Related Dementia

• Dementia can be a consequence of head trauma.
• Dementia pugilistica, commonly referred to as punch drunk syndrome, is a condition that can develop in boxers due to repeated head injuries.

Frontotemporal Dementia (FTD)

• Frontotemporal dementias encompass a group of disorders with similar symptoms, but they can stem from different underlying causes.
• One specific type of FTD is Pick's disease, which is characterized by the presence of Pick's bodies in the brain.
• These dementias generally onset at an earlier age, typically between 45 to 65 years. Common features include:
• Behavioral changes
• Alterations in personality
• Notably, memory function is usually intact in the early stages.
• There are three recognized forms of FTD, each distinguished by its clinical presentation:
• Frontal variant FTD:
  • This variant primarily impacts the function of the frontal lobe, leading to symptoms such as:
  • Stereotyped behaviours (repetitive actions)
  • Disinhibition (difficulty controlling impulses)
  • Apathy (lack of interest or motivation)
• Semantic dementia:
  • This type of dementia is associated with the loss of functions in the temporal lobe, and individuals may present with:
  • Complaints of forgetting words or having difficulty finding the right words.
• Progressive nonfluent aphasia: 
  • ​It presents with speech dysfluency and word finding difficulties.

Pseudodementia: In elderly individuals, depression can mimic the symptoms of dementia, a condition known as pseudodementia. When a patient is depressed, they may score low on the Mini-Mental State Examination (MMSE) because they lack the motivation to respond to the questions. Therefore, a low MMSE score should be interpreted cautiously if depression is suspected.

Management of Dementia

•  The assessment of cognitive functions is often carried out using the Mini-Mental Status Examination (MMSE). 
•  A score of less than 24 out of a possible 30 may suggest the presence of dementia. 
•  According to the cholinergic hypothesis, cholinesterase inhibitors are commonly prescribed to help with cognitive issues in Alzheimer's disease. 
•  Some examples of these medications include donepezil, rivastigmine, galantamine, and tacrine. 
•  Additionally, memantine, which is an NMDA receptor antagonist, has been approved for treatment as well. 
•  For addressing the behavioral and psychological symptoms associated with dementia, various symptomatic treatments may be utilized. 
•  These treatments can include antidepressants, antipsychotics, and benzodiazepines. 

Amnestic Disorders

Amnestic disorders encompass a range of conditions that significantly impact memory, making it crucial to comprehend them for effective treatment. 
Amnestic syndrome is characterized by:

• The inability to form new memories (anterograde amnesia)
• The inability to recall information that was previously known (retrograde amnesia)

Generally, short-term and recent memories are compromised, while older and immediate memories tend to remain intact. 
The primary causes of amnestic disorders include:

• Thiamine deficiency (as seen in Korsakoff syndrome)
• Hypoglycemia
• Primary brain conditions, such as:
  • Head trauma
  • Seizures
  • Cerebral tumors
  • Cerebrovascular disease
  • Hypoxia
  • Electroconvulsive therapy
  • Multiple sclerosis
• Substance-related disorders, including those related to alcohol and benzodiazepines, which can also contribute to amnestic disorders.