Source: Abnormal Psychology, University of Florida
Tags: neurocognitive disorder, NCD, major NCD, mild NCD, dementia, Alzheimer's disease, vascular NCD, Parkinson's, Lewy body disease, Huntington's disease, delirium, aphasia, apraxia, agnosia, neurofibrillary tangles, beta-amyloid plaques, acetylcholine, APoE, sundowning, DSM-5
Difficulty: Intermediate to Advanced | Prerequisites: Chapter 10 overview of neurodevelopmental vs. neurocognitive disorders, basic neuroanatomy (hippocampus, cortex, frontal lobe), introductory genetics.
Big picture: Neurocognitive disorders represent the other end of the lifespan from neurodevelopmental disorders. Where ADHD and autism emerge in childhood, neurocognitive disorders typically appear in older age and involve decline from a previous level of functioning. The chapter distinguishes major NCD (severe impairment that interferes with independence) from mild NCD (modest decline without significant functional impairment), and covers the main types: Alzheimer's disease, vascular NCD, Parkinson's, Lewy body disease, Huntington's, and others. Delirium is covered separately as a temporary, reversible condition that must be distinguished from the progressive neurocognitive disorders.
Neurocognitive disorders involve cognitive decline from a previous level, ranging from mild (noticeable but independent) to major (interferes with daily life, formerly called dementia). Alzheimer's accounts for two-thirds of cases and involves neurofibrillary tangles and beta-amyloid plaques. Delirium is a separate, often reversible condition marked by sudden-onset confusion and attentional disturbance.
Major neurocognitive disorder (major NCD)
Significant cognitive decline from a previous level that interferes with independence in everyday activities. More commonly known as dementia when referring to older adults with degenerative conditions like Alzheimer's. Think of it as the point where cognitive loss prevents someone from managing their own daily life.
Mild neurocognitive disorder (mild NCD)
Modest cognitive decline from a previous level of performance without significant impairment in functioning. The person notices the decline, and testing confirms it, but they can still manage independently. Think of it as the warning stage before major NCD.
Aphasia
Deterioration of language ability, particularly difficulty producing names of objects. People may use vague words like "things" to hide their inability to retrieve concrete names (e.g. saying "thing for drinking" instead of "cup"). In simple terms, the words are lost.
Apraxia
Impairment of the ability to execute common motor actions (waving goodbye, putting on a shirt), not caused by motor or sensory problems. The person understands what to do but cannot carry it out.
Agnosia
Failure to recognise objects or people despite intact sensory function. The eyes work, but the brain cannot make sense of what they see.
Executive functions
Higher-order brain functions that allow a person to plan, initiate, monitor, and stop complex behaviours. In simple terms, these are the "management" functions of the brain. They are progressively lost in major NCD.
Neurofibrillary tangles
Twisted, tangled filaments inside nerve cells, made up of a protein called tau. They impede the movement of nutrients and essential supplies through cells, eventually killing the cells. A hallmark of Alzheimer's disease.
Beta-amyloid plaques
Deposits of a neurotoxic protein called beta-amyloid that accumulate between cells in the cerebral cortex, hippocampus, amygdala, and other brain structures critical to memory and cognition. The second hallmark of Alzheimer's.
Apolipoprotein E gene (APoE)
A gene on chromosome 19 that regulates a protein involved in cholesterol transport. It also binds beta-amyloid. The e4 allele is a risk factor: inheriting one copy increases Alzheimer's risk 2–4x; inheriting it from both parents increases risk 8–12x. Linked to reduced hippocampus and cortex volume.
Acetylcholine
A neurotransmitter critical to memory function. Levels are reduced in Alzheimer's disease. Cholinesterase inhibitors (drugs that prevent its breakdown) can slow cognitive decline.
Vascular neurocognitive disorder
NCD caused by cerebrovascular disease, where blood supply to brain areas is blocked, causing tissue damage. Associated with significant declines in processing speed, attention, and executive functions. Tissue damage is identified via MRI or PET scan.
Stroke
Sudden damage to an area of the brain due to blockage of blood flow or haemorrhaging. Approximately 25% of stroke patients develop a neurocognitive disorder.
Lewy body disease
The second most common type of NCD after Alzheimer's. Caused by abnormal round structures (Lewy bodies) that develop in the brain.
Huntington's disease
A rare genetic disorder caused by a single dominant gene on chromosome 4. Causes progressive NCD and chorea (irregular jerks, grimaces, twitches). If one parent carries the gene, offspring have a 50% chance of inheriting it.
Delirium
A state of disorientation, recent memory loss, and clouding of attention. Develops suddenly (hours to days), fluctuates during the day, and often worsens at night (sundowning). Temporary and reversible if detected quickly. Distinguished from NCD by its sudden onset and fluctuating course.
Sundowning
The pattern in delirium where symptoms become worse at night. A quiet person may become suddenly loud and verbally abusive; agitation and confusion intensify after dark.
Cholinesterase inhibitors
Drugs (donepezil/Aricept, rivastigmine/Exelon, galantamine/Reminyl) that prevent the breakdown of acetylcholine, slowing cognitive decline in Alzheimer's. Side effects include nausea, diarrhoea, and anorexia.
Memantine (Namenda)
A drug that regulates the neurotransmitter glutamate (involved in learning and memory), used in the treatment of Alzheimer's.
Major NCD
Cannot remember fundamental facts of their lives, express themselves through language, or carry out basic everyday tasks.
More commonly called dementia in the context of older adults with degenerative disorders.
5–10% of people over 65 have Alzheimer's-type major NCD.
30% of people over 85 live with NCD.
Mild NCD
Modest cognitive decline from a previous level of performance.
No significant impairment in daily functioning.
The person (or an informant or clinician) notices the decline.
A: Evidence of significant cognitive decline from a previous level in 1+ cognitive domain (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition).
Supported by concern from the individual, an informant, or a clinician.
Documented by standardised neuropsychological testing or other quantified clinical assessment.
B: Cognitive deficits interfere with independence in everyday activities at minimum.
C: Deficits do not occur exclusively in the context of delirium.
D: Deficits are not better explained by another disorder.
Memory deficits
Early stages resemble ordinary forgetfulness, but the memory never returns spontaneously and cannot be retrieved with reminders or cues.
Misplacing items, repeating questions, forgetting to check calendars, making up answers to hide memory loss.
Eventually long-term memory is impaired: forgetting the order of major life events, and later being unable to recall them at all. May forget their own name.
Aphasia
Difficulty producing names of objects. Use vague words ("thing for drinking" instead of "cup").
Echolalia (repeating what they hear) and palilalia (repeating their own words) may develop.
Apraxia
Cannot execute common actions (waving, dressing) despite intact motor and sensory function.
Agnosia
Cannot recognise objects or people.
Executive function loss
Difficulty planning, initiating, monitoring, and stopping complex behaviours.
Difficulty with abstract thinking needed to evaluate new situations.
Emotional and personality changes
Depression, shoplifting, unrealistic or dangerous actions, paranoia, anger toward people perceived as restricting their freedom, belief that others are conspiring against them.
Alzheimer's Disease
Accounts for approximately two-thirds of all NCD cases.
Psychiatric symptoms: agitation, irritability, apathy, dysphoria. Hallucinations and delusions in later stages.
Usually begins around age 65. Early-onset type progresses more quickly; death within 8–10 years.
4.5 million people in the U.S., 18 million worldwide. Expected to increase by 300% by 2050.
Brain pathology (discovered by Alois Alzheimer):
Neurofibrillary tangles: twisted filaments of tau protein inside nerve cells, blocking nutrient transport, killing cells.
Beta-amyloid plaques: neurotoxic protein deposits between cells in the cortex, hippocampus, amygdala, and other memory/cognition structures.
Extensive cell death in the cortex, resulting in cortical shrinking.
Genetics:
24–49% of first-degree relatives are affected. Lifetime risk is 1.8–4x greater with a family history.
MZ twin concordance: 44% (men), 58% (women). DZ: 25% (men), 45% (women).
APoE gene (chromosome 19): the e4 allele increases risk 2–4x; homozygous e4 increases risk 8–12x. Linked to reduced hippocampus and cortex volume.
Chromosome 21 gene (near the APP gene, amyloid protein precursor): linked to less common forms of Alzheimer's (relevant to the Down syndrome connection).
All known genes together account for less than 50% of cases.
Neurotransmitters:
Acetylcholine, norepinephrine, serotonin, somatostatin, and peptide Y are all affected.
Acetylcholine is the most critical for memory. Drugs that protect acetylcholine levels can slow decline.
Vascular NCD
Caused by cerebrovascular disease (blocked blood supply causing tissue damage in the brain).
Marked by significant declines in processing speed, attention, and executive functions.
Requires evidence of a recent vascular event or cerebrovascular disease, confirmed by MRI or PET scan.
Stroke (sudden brain damage from blood flow blockage or haemorrhage) is a common cause. About 25% of stroke patients develop NCD.
Parkinson's Disease
75% of people with Parkinson's develop NCD.
Characterised by tremors, muscle rigidity, and inability to initiate movement.
Symptoms result from death of brain cells.
Lewy Body Disease
Second most common NCD type after Alzheimer's.
Caused by abnormal round structures (Lewy bodies) in the brain.
Huntington's Disease
Rare genetic disorder, single dominant gene on chromosome 4.
50% inheritance risk if one parent carries the gene.
Causes progressive major NCD and chorea (involuntary jerks, grimaces, twitches).
Other causes
HIV (antiretroviral therapies have reduced onset and severity).
Prion disease (rare), brain tumours, endocrine conditions, infections, multiple sclerosis, TBI.
10% of chronic alcohol abusers may develop NCD (slow, insidious onset).
Protective and risk factors
Lower education levels are associated with higher NCD diagnosis rates (less education correlates with more brain deterioration).
The Nun Study found that nuns who entered old age with greater intellectual strengths were less likely to develop severe NCD, even when their brains showed tangles and plaques. The level of linguistic skill in journal writing from their twenties predicted outcomes decades later.
Pharmacological
Cholinesterase inhibitors (donepezil/Aricept, rivastigmine/Exelon, galantamine/Reminyl): prevent acetylcholine breakdown. Side effects: nausea, diarrhoea, anorexia.
Memantine (Namenda): regulates glutamate (learning and memory neurotransmitter).
Antidepressants and antianxiety drugs for secondary symptoms; antipsychotics also used.
Behavioural therapies
Control angry outbursts and emotional instability.
Reduce stress and emotional distress in family members/carers.
Clinical presentation
Disorientation, recent memory loss, and clouding of attention.
Difficulty focusing, sustaining, or shifting attention.
Affects 15–20% of older people; the most common psychiatric syndrome in general hospitals.
High mortality rate: 15–40% die within a month (2x normal).
Signs arise suddenly (hours to days), fluctuate during the day, and often worsen at night (sundowning).
A quiet person may become suddenly loud or verbally abusive.
Often accompanied by agitation, fear, disrupted sleep-wake cycles, incoherent speech, delusions, and hallucinations. Sometimes presents as simple confusion.
Memory affected in order: immediate memory first, then intermediate (past 10 minutes), then distant memory.
Temporary and reversible if detected quickly.
Males and African Americans at greater risk (the latter partly due to late diagnosis from lack of insurance).
DSM-5 Criteria (pg. 308)
A: Disturbance in attention and orientation to the environment and awareness.
B: Develops over a short period, represents a change from baseline, and fluctuates in severity during the day.
C: An additional disturbance in cognition.
D: Not explained by another disorder and does not occur in the context of severely reduced arousal (e.g. coma).
E: Evidence that the disturbance is a direct physiological consequence of a medical condition, toxin exposure, or multiple causes.
Causes
NCD, stroke, congestive heart failure, infectious diseases, high fever, HIV.
Intoxication with illicit drugs and withdrawal.
Electrolyte imbalances, medication side effects, toxic substances.
Neurotransmitters involved: acetylcholine, GABA, dopamine, serotonin.
Treatments
First priority: treat the underlying medical condition.
Antipsychotics used to manage confusion.
Physical restraints sometimes necessary to prevent harm.
A reassuring atmosphere helps reduce agitation.
Alzheimer's disease is one of the most significant public health challenges globally, with costs projected to be enormous as populations age. The Nun Study is a landmark piece of research suggesting that lifelong intellectual engagement may provide a degree of protection against NCD, even when the brain's physical pathology is present. This has practical implications for public health messaging around cognitive engagement in ageing populations.
Students often equate all cognitive decline in older adults with Alzheimer's. Alzheimer's accounts for about two-thirds of NCD cases; vascular NCD, Lewy body disease, Parkinson's-related NCD, and Huntington's are distinct conditions with different mechanisms.
Students sometimes confuse delirium with major NCD. Delirium is sudden-onset, fluctuating, and typically reversible. Major NCD is gradual, progressive, and irreversible.
Students may think aphasia means inability to understand language. Aphasia in NCD primarily involves difficulty producing words and names, not necessarily comprehension loss (though that can come later).
Students occasionally believe cholinesterase inhibitors cure Alzheimer's. They slow the rate of decline but do not halt or reverse it.
⚠️ Be able to distinguish major NCD from mild NCD and both from delirium (onset, course, reversibility).
⚠️ Know the two hallmark brain pathologies of Alzheimer's: neurofibrillary tangles (tau protein) and beta-amyloid plaques.
⚠️ The APoE gene and the e4 allele are frequently tested: one copy = 2–4x risk, two copies = 8–12x risk.
⚠️ Understand the role of acetylcholine in Alzheimer's and how cholinesterase inhibitors work.
⚠️ Know the key features of delirium: sudden onset, fluctuating course, sundowning, and reversibility.
⚠️ Be able to name the main types of NCD (Alzheimer's, vascular, Parkinson's, Lewy body, Huntington's) and distinguish them.
⚠️ The Nun Study is a commonly tested example: intellectual engagement as a protective factor.
True or false: Delirium develops gradually over months. (False, it arises suddenly, within hours or days.)
Fill in the blank: Neurofibrillary tangles are made up of a protein called ________. (Tau.)
True or false: Alzheimer's disease accounts for approximately one-third of all NCD cases. (False, approximately two-thirds.)
Fill in the blank: The pattern of delirium symptoms worsening at night is called ________. (Sundowning.)
True or false: Huntington's disease is caused by a recessive gene. (False, it is caused by a single dominant gene on chromosome 4.)
Q: What are the key differences between delirium and major neurocognitive disorder?
A: Delirium has a sudden onset (hours to days), fluctuates in severity during the day, and is typically temporary and reversible if the underlying cause is treated. Major NCD has a gradual onset, follows a progressive course, and is irreversible.
Q: Describe the two hallmark brain pathologies of Alzheimer's disease.
A: Neurofibrillary tangles are twisted filaments of tau protein inside nerve cells that block nutrient transport and kill cells. Beta-amyloid plaques are neurotoxic protein deposits that accumulate between cells in the cortex, hippocampus, amygdala, and other structures critical to memory and cognition.
Q: How does the APoE gene relate to Alzheimer's risk?
A: The APoE gene on chromosome 19 regulates a protein involved in cholesterol transport that also binds beta-amyloid. The e4 allele is a risk factor: one copy increases risk 2–4x, and inheriting e4 from both parents increases risk 8–12x. It is linked to reduced hippocampus and cortex volume.
Q: What was the key finding of the Nun Study?
A: Nuns who entered old age with greater intellectual strengths were less likely to develop severe NCD, even when their brains showed significant neurofibrillary tangles and plaques. The level of linguistic skill in journal writing from their twenties predicted later outcomes, suggesting that lifelong intellectual engagement provides some protection.
Q: Name three types of neurocognitive disorder other than Alzheimer's and state one distinguishing feature of each.
A: Vascular NCD (caused by cerebrovascular disease/stroke, with significant declines in processing speed and executive functions); Parkinson's-related NCD (associated with tremors, muscle rigidity, and inability to initiate movement; 75% of Parkinson's patients develop NCD); Huntington's disease (rare, caused by a single dominant gene on chromosome 4, involves chorea and progressive NCD).
Alzheimer's connects to Down syndrome (chromosome 21 link, near-universal Alzheimer's development after age 40 in Down syndrome). The neurotransmitter discussion (acetylcholine, dopamine, serotonin) ties into pharmacology across the course. Delirium relates to substance use disorders (intoxication and withdrawal as causes) and medical psychology. Huntington's disease illustrates autosomal dominant inheritance, linking to the genetics discussions in earlier chapters. The Nun Study connects to broader research on cognitive reserve and the protective effects of education.
Neurocognitive disorder, NCD, major NCD, mild NCD, dementia, Alzheimer's disease, vascular neurocognitive disorder, cerebrovascular disease, stroke, Parkinson's disease, Lewy body disease, Huntington's disease, chorea, delirium, sundowning, aphasia, apraxia, agnosia, executive functions, neurofibrillary tangles, tau protein, beta-amyloid plaques, APoE, apolipoprotein E, e4 allele, acetylcholine, cholinesterase inhibitors, donepezil, Aricept, memantine, Namenda, Nun Study, cognitive reserve, prion disease, HIV-related NCD, palilalia, echolalia