Neurocognitive Disorders (Dementia)

DSM-5 TR Criteria for Neurocognitive Disorders

• Cognitive impairment represents a gradual, continuing decline from a previous higher level of function.
• Identified through history (from the person or someone close to them) and objective cognitive assessment.
• Objective cognitive assessment: Neuropsychology is the gold standard.
• Cognitive or behavioral deficit must involve a minimum of two different cognitive domains:
  • Memory
  • Language
  • Executive functions: decision making, problem-solving, organizing time, initiating/stopping behaviors, flexibility of thinking, reasoning.
  • Visual-spatial abilities: seeing objects in space and recognizing them.
  • Changes in personality, behavior, or comportment.
• The deficits are not explained by another neurological or mental disorder, including delirium.

Mild vs. Major Neurocognitive Disorder

• Classification is related to function and independence in daily life.
• Mild Neurocognitive Disorder: Cognitive deficits do not interfere with independence in daily activities (shopping, finances, cooking, housekeeping, driving).
• Major Neurocognitive Disorder: Cognitive deficits interfere with independence in daily activities.
• Both require objective measurement of decline in at least two cognitive domains.

Specific Types of Neurocognitive Disorders

• Alzheimer's disease
• Frontotemporal lobar degeneration
• Lewy body disease
• Vascular disease
• Traumatic brain injury
• Substance/medication-induced
• HIV infection
• Prion disease
• Parkinson's disease
• Huntington's disease
• Due to another medical condition (e.g., infection)
• Unspecified or due to multiple etiologies

Prevalence of Dementia

• Prevalence is low in people aged 65-69 and increases with age.
• More common in females (possibly due to longer lifespans).
• Alzheimer's disease is the most common type, followed by vascular dementia and Lewy body disease.
• Frontotemporal dementia is the most common type in younger people.
• Huntington's disease is rare.

Alzheimer's Disease (AD)

• Alois Alzheimer described microscopic changes in the brain of a woman with memory problems.
• Gross Changes (Cortical Level):
  • Alterations in the frontal, parietal, temporal, and occipital cortices.
  • Widened sulci (space between gyri) and thinned gyri (less neurons). $(\text{gyri} = \text{thick bits})$ $(\text{sulci} = \text{in between gyri})$
• Specific Changes in the Hippocampus:
  • Shrinkage of the hippocampus (bilateral change in medial temporal lobes).
• Ventricular Changes:
  • Enlarged ventricles (more space where cerebrospinal fluid is) due to brain shrinkage.
• Microscopic Changes:
  • Amyloid Plaques: Buildup of beta-amyloid protein outside the neuron (extracellular).
  • Neurofibrillary Tangles: Tau protein loses capacity to bind to microtubules within neurons, causing tangles inside the neurons.

PET Imaging

• Alzheimer's disease and mild cognitive impairment (MCI) are associated with elevated amyloid burden, visible on PET imaging.
• A PET tracer (e.g., C. Pittsburgh Compound B or PIB) binds to amyloid in the brain.
• Healthy older adults have little or no amyloid accumulation.
• Mild cognitive impairment shows some amyloid accumulation.
• Alzheimer's disease shows a lot more red, indicating amyloid accumulation.
• PET imaging for tau is also emerging.

Alzheimer's Disease Progression

• Long disease course: 15-20 years from normal to abnormal.
• Stages:
  • Preclinical: Amyloid accumulation (evident on cerebrospinal fluid or PET imaging).
  • Synaptic Changes: Hypometabolism (reduced metabolism of sugar and oxygen in the brain).
  • Tau Injury: Tau accumulation.
  • Brain Structure: Atrophy (shrinkage) evident on MRI.
  • Cognition: Cognitive decline (mild cognitive impairment).
  • Function: Functional changes (difficulties with shopping, managing life).
• The PISA study is a longitudinal aging study measuring changes in cognition, imaging, blood, and lifestyle with detail in healthy. High risk for Alzheimer's disease.

Changes in Alzheimer's Disease (AD)

• Mild Stages:
  • Increasing plaques and tangles.
  • Physically healthy but cognitively difficulties
  • Problems with instrumental activities of daily living (iADLs): shopping, laundry, preparing meals, housework, managing medication, transportation.
  • Subtle personality changes.
  • Unawareness or denial of cognitive decline.
• Moderate to Severe Stages:
  • Difficulties with basic activities of daily living (BADLs): bathing, dressing, eating, using the toilet, transferring from sit to stand, incontinence.
  • Motor or coordination difficulties, agitation, anger, psychosis.
  • Need for more intense supervision.
  • Carer affected. Described as 'a funeral that never ends' or the 'sandwich generation'.
• Severe End:
  • Complete loss of independence.
  • Inability to speak or move.
  • Seizures, coma, death (often from pneumonia or infection).

Diagnosis of Alzheimer's Disease

• Diagnosis is by exclusion of other medical conditions and from cognitive assessment.
• History from informant, medical assessment, and specialist referral.
• Neuropsychological assessment (full or screen).
• Memory clinics (standardized tests, bloods, MRI data).
• PET imaging is only available in research studies (not standard of care).
• Cognition is central to diagnosis.

Cognitive Symptoms

• Neuropsychological Assessment:
  • Estimate the level of optimal or pre-morbid function.
  • Measure different areas of cognition and compared to level of optimal function.
    • Intellectual functions (IQ measure)
    • Learning and memory, plus orientation
    • Language (comprehension and expression)
    • Visual and space perception
    • Processing speed
    • Attention and concentration
    • Executive functions
    • Social and emotional cognition (social functioning)

Memory and Learning in Alzheimer's Disease

• Memory loss is the diagnostic hallmark of Alzheimer's disease (amnestic type).
• Inability to learn new information and retain it over time.
• Antegrade episodic memory: Acquiring new verbal and visual information (word lists, stories, designs, faces, pictures of places).
• Encoding: Loss of ability means it's harder.
• Retrieval Active recall process or recognition memory (familiarity).
• Spatial and temporal component to episodic memory (specific to time and place). Episodic example = the lecture in the UQ centre April 2nd time.
• Semantic memory linked to language and comprehension general knowledge about world. Understanding of concepts not specific to time and place.

Language

• Impaired language is called aphasia.
• Expression of language (producing speech).
  • Naming test (showing a patient a banana image and asking what it is).
• Receptive/comprehension (matching the name to the picture).
• Movie: Still Alice

Visual and Space Perception

• Agnosia: Inability to know what it is.
• Visually, can you recognize an object (what it is)? Spatially, can you locate that in the environment, is where it is?
• Incomplete letters test: Assesses visual perceptual ability.

Speed and Attention

• Attention: Ability to focus concentration.
  • Digit span subtest (repeating a series of digits).
  • Working memory required to list the digits in reverse. Measured the auditory verbal working memory.
  • Normal digit capacity $(\approx 7 \pm 2)$
• Visual motor speed of processing.

Executive Functions

• Higher-order abilities involved in more complex thought.
• Enable goal-directed or adaptive behavior.
• Reasoning, judgment, problem-solving, initiating/inhibiting a response, being flexible.
• Disruptions lead to behavioral disorders (apathy or impulsivity).
• Examples:
  • STROOP test (naming the color of ink even though it's a different color than what you read).
  • Trail making test (connecting numbers and letters in sequence).

Social Cognition and Emotion

• Emotion recognition (Eckman faces).
• Theory of mind: Understanding the intention or belief of someone else (e.g., understanding sarcasm).
• Important for maintaining social relationships and empathy.

Types of Dementia

• Alzheimer's Disease:
  • Amnestic Presentation: Episodic memory impairment.
  • Non-Amnestic Presentations:
    • Language presentation (word-finding deficits).
    • Visuospatial presentation (deficit in object, face, or space recognition). Also called Posterior Cortical Atrophy.
    • Executive dysfunction presentation (deficits in executive areas, apathy, disinhibition)
• Posterior Cortical Atrophy / PCA:
  • Marked visual-spatial impairment that's progressive.
  • From patient scans: Atrophy is the parietal occipital area.
  • Symptoms include visual spatial impairment (hallucinations), visual agnosia, simultagnosia (inability to see multiple things), topographical disorientation (getting lost in familiar places).
  • Good verbal memory and comprehension.
• Frontotemporal Dementia (FTD):
  • Described by Arnold Pick.
  • Progressive loss of speech and decline.
  • Shrunken, atrophied brain in specific areas of frontal and temporal lobes.
    • Includes language forms, i.e. semantic (understanding of object is lost.) & progressive non fluent which affects facial expression.
    • Behavioural form. Knows what it is to be used.
  • Behavioral Variant: Disorder of personality, behavior, social conduct. Early disinhibition, apathy, loss of empathy, perseveration, stereotyped behaviors, dietary changes, but memory, vision, and language may be relatively intact.
  • Non-Fluent Progressive Aphasia: Disorder of speech production. Effortful speech, distortion of sounds, naming errors, poor grammar, comprehension.
  • Semantic Dementia: Deficit of semantic representations. Loss of meaning and understanding of concepts; comprehension disorder.
• Motor Neuron Disease:
  • Up to 50% of patients have cognitive impairment.
  • 15% fulfill criteria for frontotemporal dementia.
  • Genetic overlap (TDP-43 protein, C9ORF72 gene).
• Parkinsonian Disorders (Parkinson's disease, corticobasal syndrome, progressive supranuclear palsy):
  • Executive dysfunction and language impairments.
  • Differential diagnosis is tricky but important for finding drug therapies.

Protection, Treatment, and Management (Dementia)

• Education and occupation: Cognitive reserve from intellectual challenges. Bilingualism is also protective.
• Accurate diagnosis is paramount in management. Manage memory with behaviour is different to language disorders.
• Distinction between delirium and dementia. Delirium can be treated, but dementia is much harder.
• Return to optimal or premorbid level of function is unlikely.
• Rehabilitation to enhance or maintain function and maximize quality of life.
• Future planning for management when one doesn't have capacity for consent to treatments/ decisions.
• Early decision-making for people moving house should learn a new location.
• Medications: Acetylcholine blockers. Donepezil/Aricept improves the effects with minimal impact.
• New drugs target amyloid or tau but are dangerous and don't change the endpoint of cognition. There were concerns around safety and efficacy. They have huge risk along with costs and don't affect cognition.
• Accurate diagnosis and management are paramount for appropriate dementia management.
• Environmental and behavioral management.
• Patients with dementia experience fewer emotional problems and are less agitated if they follow a structured and predictable daily schedule.
• Help to remain active and interested in their everyday events.
• Adjust directions to their level of function.
• Removing distractive from the environment.
• Don't forget the caregivers.
• Loneliness and sadness of the person who's living with the person who's declining.
• Caring with tangible stressors: Tangible stresses can be irritating asked the same over and over. Massive adaptation for the carer as well.
• Guilt, frustration, depression, grief and loss.

Delirium

• Rule out delirium when looking at a diagnosis of dementia.
• Delirium in criteria is a disturbances in attention and awareness.
• The disturbance develops over a short period of time. Represents a change in baseline attention and awareness, where severity fluctuates.
• Cognition may be disturbed, may be disorientated.
• A & C are not better explained by neurocognitive disorder and do not occur in the context of severed reduce level of arousal.
• Evidence show the disturbance are due to medical reason substance intoxication or direct medication.
• Frequency is common with elderly, frequent on hospital wards.
• Causes a confusional state and disturbance in awareness. It's a reduced stability to maintain to shift a shift of attention.
• Onset is rapid and symptom are worse at night. Sleep may be disturbed with regular sleep and make cycle.
• Perceptual disturbances are common, e.g. hallucinations.
• Result from medical reason while dementia is the lost a neurons. Need to reviewed with a number of medications. Also require a environmental cues and education.

Delirium vs. Dementia

Causes of Delirium

• Drugs: Antidepressants, antipsychotics, benzodiazepines, drugs for heart conditions, painkillers, stimulants (caffeine).
• Medical conditions: Infection (urinary tract infection).

*Treatment depends on the underlying cause.+

Programs

• Amazing art program running running the Queensland Art Gallery for early dementia plus carer/family members!
• Dementia friendly choirs give support network and new learning curve!