M05.11.13 Neurocognitive disorders

Neurocognitive disorders encompass a range of conditions that result in impaired cognitive functioning. Understanding these disorders is crucial for medical students, as they involve complex interactions between physical, psychological, and social factors. Below is a detailed and organized overview of various neurocognitive disorders, their definitions, examples, treatments, and associated points to remember.

1. Delirium

Definition

Delirium is an acute onset of impaired cognitive functioning that is fluctuating, brief, and reversible.

Characteristics

• Acute onset
• Fluctuating course
• Lasts days to weeks
• Hallucinations common
• Disorientation

Points to Remember

• Often caused by underlying medical conditions.
• Requires immediate attention to the underlying cause.

2. Neurocognitive Disorder

Definition

Neurocognitive disorder (NCD) involves a loss of cognitive abilities, impairment of social functioning, memory loss, and/or personality changes that may be progressive or static. It is reversible only 15% of the time.

Types

• Mild Neurocognitive Disorder: Moderate cognitive decline with minimal interference in daily functioning.
• Major Neurocognitive Disorder: Significant cognitive decline that interferes with daily functioning and independence.

Points to Remember

• Evaluate for both reversible and irreversible causes.
• Consider the impact on daily living and social interactions.

3. Neurocognitive Disorder Due to Alzheimer Disease

Definition

A common form of NCD characterized by gradual cognitive decline.

Characteristics

• Seen in >50% of nursing home patients and 50–60% of those with NCD.
• Gradual deterioration with an average duration from onset to death of ~8 years.
• Rarely presents with focal neurologic symptoms.

Risk Factors

• Female
• Family history
• Head trauma
• Down syndrome

Neuroanatomic Findings

• Cortical atrophy
• Flattened sulci
• Enlarged ventricles

Histopathology

• Senile plaques (amyloid deposits)
• Neurofibrillary tangles
• Neuronal loss
• Synaptic loss
• Granulovacuolar degeneration of neurons

Treatment

• Long-acting cholinesterase inhibitors (e.g., donepezil, rivastigmine, galantamine)
• Memantine
• Antipsychotics for psychotic symptoms (with caution)

Points to Remember

• Associated with chromosome 21 (amyloid precursor protein gene).
• Decreased acetylcholine (ACh) and norepinephrine (NE).

4. Vascular Neurocognitive Disorder

Definition

NCD resulting from cerebrovascular disease, also known as multi-infarct NCD.

Characteristics

• Seen in 15–30% of NCD cases.
• Deterioration can be stepwise or gradual.

Risk Factors

• Male
• Advanced age
• Hypertension
• Cardiovascular disorders

Examination Findings

• Carotid bruits
• Fundoscopic abnormalities
• Enlarged cardiac chambers
• MRI: Hyperintensities, focal atrophy

Treatment

• Address underlying conditions (e.g., hypertension, diabetes).
• Control of risk factors (e.g., smoking, hyperlipidemia).

Points to Remember

• Focal neurologic symptoms (pseudobulbar palsy, dysarthria, dysphagia) are common.
• Abnormal reflexes and gait disturbances often present.

5. Frontotemporal Neurocognitive Disorder (Pick Disease)

Definition

A type of NCD characterized by atrophy in frontal and temporal lobes.

Characteristics

• Atrophy in frontal and temporal lobes
• Pick bodies (intraneuronal argentophilic inclusions)
• Pick cells (swollen neurons)

Risk Factors

• Most common in men with a family history of Pick disease.

Associated Features

• May include Klüver-Bucy syndrome (hypersexuality, hyperphagia, passivity).

Points to Remember

• Difficult to distinguish from Alzheimer disease.
• Etiology is unknown.

6. Neurocognitive Disorder Due to Prion Disease

Definition

A rare, rapidly progressive NCD caused by prions.

Characteristics

• Spongiform encephalopathy
• Rapid progression from mild symptoms to severe NCD and death
• EEG abnormalities: sharp, triphasic, synchronous discharges

Symptoms

• Visual and gait disturbances
• Choreoathetosis
• Myoclonus

Points to Remember

• Other prions (e.g., Kuru) can also cause NCD.
• Personality changes and malaise precede severe symptoms.

7. Neurocognitive Disorder Due to Huntington Disease

Definition

A rare, progressive neurodegenerative disease with NCD and motor symptoms.

Characteristics

• Loss of GABAergic neurons in the basal ganglia
• Clinical onset around age 40
• Commonly involves suicidal behavior

Genetics

• Autosomal dominant gene on chromosome 4

Neuroanatomic Findings

• Atrophy of the caudate nucleus
• Ventricular enlargement

Points to Remember

• Involves choreoathetosis, psychosis, and cognitive decline.

8. Neurocognitive Disorder Due to Parkinson Disease

Definition

A common, progressive neurodegenerative disease with NCD and motor symptoms.

Characteristics

• Onset between ages 50–65
• Motor symptoms: resting tremor, rigidity, bradykinesia, gait disturbances
• NCD occurs in 40% of cases

Pathogenesis

• Loss of dopaminergic neurons in the substantia nigra

Treatment

• Dopamine precursors (e.g., levodopa, carbidopa)
• Dopamine agonists (e.g., bromocriptine)
• Anticholinergics (e.g., benztropine, trihexyphenidyl)
• Amantadine
• Selegiline

Points to Remember

• Environmental toxins, infections, and genetics may contribute.
• Antiparkinsonian medications can cause cognitive and personality changes.

9. Neurocognitive Disorder with Lewy Bodies

Characteristics

• Hallucinations
• Parkinsonian features
• Fluctuating cognition
• REM sleep behavior disorder

Treatment

• Antipsychotics may worsen behavior.

Points to Remember

• Extrapyramidal signs are common.
• Fluctuating cognition is a key feature.

10. Neurocognitive Disorder Due to HIV Infection

Characteristics

• HIV progressively destroys brain parenchyma.
• Clinically apparent in at least 30% of AIDS patients.

Symptoms

• Personality changes
• Diffuse and multifocal brain destruction
• Motor findings: gait disturbance, hypertonia, hyperreflexia, pathologic reflexes, oculomotor deficits
• Mood disturbances: apathy, emotional lability, behavioral disinhibition

Points to Remember

• Delirium is often present.
• Early intervention can slow progression.

11. Wilson Disease

Characteristics

• Ceruloplasmin deficiency
• Hepatolenticular degeneration
• Kayser-Fleischer rings in the eye
• Asterixis

12. Normal Pressure Hydrocephalus

Characteristics

• Enlarged ventricles
• Normal pressure
• Symptoms: NCD, urinary incontinence, gait apraxia

Treatment

• Shunt placement

Points to Remember

• Early diagnosis and treatment can improve symptoms.

13. Pseudodementia

Characteristics

• Seen in elderly patients with depressive disorders
• Symptoms resemble NCD

Treatment

• Antidepressants

Points to Remember

• Symptoms improve with treatment.
• Onset of symptoms can usually be dated.

14. Comparative Tables

Table 1: Alzheimer Disease vs. Vascular Disorder

Table 2: Delirium vs. Neurocognitive Disorder

15. Bibliography

1. American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.).
2. Sadock, B. J., Sadock, V. A., & Ruiz, P. (2014). Kaplan & Sadock’s Comprehensive Textbook of Psychiatry (10th ed.). Wolters Kluwer Health.
3. Laumann, E. O., Paik, A., & Rosen, R. C. (1999). Sexual Dysfunction in the United States: Prevalence and Predictors. JAMA.
4. Masters, W. H., & Johnson, V. E. (1966). Human Sexual Response. Little, Brown.
5. National Institute on Aging. (2020). Alzheimer’s Disease Fact Sheet. Retrieved from https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-fact-sheet