Psych - Dementia

Question 1

What is the most comprehensive test of cognitive function?

Answer 1

Addenbrooke’s Cognitive Examination

(ACE-iii or ACE-R for revised)

• Tests 5 basic executive functions
• Score out of 100
• < 82 = considered abnormal (NOT a diagnostic test)

Question 2

What 5 aspects of cognition does an ACE-iii examine?

Answer 2

1. Memory
2. Attention
3. Fluency
4. Visuospatial skills
5. Language

N.B. informally it also tests your higher executive function i.e. task planning / management - which requires the above basic executive functions.

Question 3

Name 2 short/simple cognitive assessments?

Answer 3

• MOCA (Montreal Cognitive Assessment)
  
  • Score out of 30
  • < 26 = suggests MCI (mild cognitive impairment)
  • < 17 = suggests dementia)
• MMSE (mini mental state examination) - less used due to copyright issues

Question 4

What assessment tool can be used to discriminate between dementias with impact on frontal executive function and Alzheimer’s dementia?

Answer 4

Frontal Assessment Battery (FAB)

• Can be used in mildly demented pts or better (MMSE > 24)
• Total score is out of 18 (higher score = better performance)

Question 5

Dementia syndromes can be divided into cortical and subcortical.

To what do these regions refer to?

How are cortical and subcortical dementia characterised?

Answer 5

Cortical = outer layer i.e. cerebral cortex

Subcortical = areas beneath cortex e.g. basal ganglia, limbic system (amygdala, hippocampus), diencephalon (thalamus, hypothalamus)

• Cortical dementia = early symptoms include higher function difficulty e.g. memory, language, dyspraxia (visuospatial), lack extra-pyramidal features
• Subcortical dementia = early symptoms don’t tend to involve higher function, but do include; behaviour, mood/affect, motor slowing, extra-pyramidal features

Question 6

Dementia syndromes can be divided into cortical and subcortical.

Give examples of each cortical and subcortical dementia.

Answer 6

Cortical:

• Alzheimer’s dementia
• Lewy-body dementia (memory before motor)
• Fronto-temporal dementia (Pick’s disease)

Subcortical:

• Vascular dementia
• Parkinson’s dementia (motor before memory)
• Wilson’s dementia
• Huntington’s
• HIV/AIDS dementia
• MND / MS dementia
• Alcohol related dementias

Question 7

Which parts of the brain does Alzheimer’s disease characteristically affect?

Answer 7

• Medial temporal lobe i.e. hippocampus - impacts episodic memory (anterograde amnesia)
• Lateral temporal lobe i.e. Wernicke’s area - can cause receptive dysphasia (difficulty understnading written or spoken language but have fluent speech without meaning i.e. word salad)
• Anterior + inferior temporal lobe - impacts semantic memory (general knowledge e.g. facts, ideas, concepts)

Question 8

What are the four most common types of dementia?

Answer 8

1. Alzheimer’s disease (2/3rds of dementia)
2. Vascular dementia
3. Lewy Body dementia (~15% of dementia)
4. Fronto temporal dementia

Question 9

What investigations are reccomended for someone with suspected dementia?

Answer 9

• Bloods:
  
  • Done to exclude reversible causes
  • FBC, U&E, LFTs, calcium, glucose, TFTs, vitamin B12 and folate levels
• MRI / CT:
  
  • Done to exclude reversible causes e.g. subdural haematoma, normal pressure hydrocephalus

Question 10

What are the recommended pharmacological management steps for Alzheimer’s disease?

Answer 10

1. One of the 3 acetylcholinesterase (AChE) inhibitors - mild-moderate AD
   
   • Donepezil
     
     • ​once daily, long-half life, start 5mg and ↑ to 10mg after 1 month
   • Galantamine​
     
     • Oral solution, tab and modified release cap
   • Rivastigmine (also a butyrylcholinesterase inhibitor)
     
     • short half life (1hr), BD, daily patch more common
2. Memantine (NMDA receptor antagonist) recommended:
   
   • Monotherapy in severe AD OR
   • Moderate AD + intolerant / contraindication to AChE inhibitors OR
   • In addition to AChE inhibtors for moderate-severe AD

Question 11

What are the recommended pharmacological management steps for NON- Alzheimer’s disease?

Answer 11

Lewy-Body:

1. Offer donepezil or rivastigmine
2. Consider galantamine (only if donepezil or rivastigmine not tolerated)
3. Consider memantine (if AChE inhibitors not tolerated/contraindicated)
4. Some parkinson’s medication (e.g. levodopa) can help with movement impairment

Vascular:

1. Only consider AChE inhibitors or memantine for vascular IF they have suspected comorbid AD, PD dementia or Lewy-body

Fronto-temporal dementia or MS cognitive impairment:

1. DO NOT offer AChE inhibitor OR memantine

Question 12

What investigations need to be done prior to starting a AChE inhibitor or NMDA receptor antagonist (memantine)?

Answer 12

• ECG - to assess HR, arrhythmias and QTc interval
  
  • AChE inhibitors are contraindicated for pts with; bradykinesia, Left Bundle Branch Block or a ↑ QTc interval
  • AChE inhibitors also contraindicated if Hx of; gastric ulcers or seizures
• U+Es:
  
  • Memantine can cause acute renal failure

Question 13

What are some common side effects of AChE inhibitors?

Answer 13

1. Nausea / vomiting
2. Diarrhoea
3. Urinary incontinence
4. Headache / dizziness
5. Insomnia
6. Muscle cramps
7. ↓ Appetite –> weight loss

Question 14

In addition to cognitive symptoms of dementia, what other categories of symptoms are there?

Answer 14

Non-cognitive i.e.

Behavioural and Psychological symptoms of dementia (BPSDs) e.g.

1. Hallucinations
2. Delusions
3. Anxiety
4. Behaviour: marked agitation, aggression, wandering, hoarding, sexual disinhibition, apathy and disruptive vocal activity such as shouting

Question 15

What psychological treatments are available for the management of cognitive + BPSDs in dementia?

Answer 15

1. Cognitive stimulation therapy (CST)
2. CBT
3. Reminiscence therapy
4. Aromatherapy
5. Sensory stimulation
6. Music therapy

Question 16

What pathological changes occur to a brain with Alzheimer’s?

Answer 16

Macroscopic:

1. Widespread cerebral cortical atrophy
2. Medial temporal lobe atrophy (particularly hippocampus)
3. Enlarged ventricles (due to cerebral atrophy)

Microscopic:

1. Beta-amyloid plaques (cortex)
2. Neurofibrillary tangles (intraneuronal aggregation of tau protein)

Biochemical:

1. Acetylcholine deficit (due to factors above) - loss of cholinergic neurons and ↓ ACh

Question 17

Describe dementia in layman’s terms.

Answer 17

A chronic, often progressive, mental disorder caused by brain disease or injury and marked by:

1) memory changes
2) personality changes
3) impaired reasoning / ↓ executive function
4) Impact on ADLs

Question 18

What are some risk factors for dementia?

Answer 18

• Age
• Gender:
  
  • Female (AD)
  • Male (VD and DLB)
• Ethnicity:
  
  • South asians and Afro-Caribbean (VD)
  • African (AD)
• Depression - if in mid-life or later life
• Head injuries (Parkinson’s dementia)
• Lifestyle factors: smoking, alcohol, exercise, education

Question 19

How does Alzheimer’s present clinically?

Answer 19

• Four A’s:
  
  • Amnesia (most common)
  • Aphasia (language impairment - production or comprehension of speech)
  • Agnosia (inability to process sensory info e.g. can’t recognise objects, sounds, smells, get lost etc.)
  • Apraxia (motor planning impairment due to brain damage)
• Others:
  
  • Apathy - ↓ motivation + anhedonia
  • Misplace / lose items (memory or visuospatial decline)
  • ↓ ADLs
  • Slow progressive
  • Late / early onset

Question 20

What pattern of inheritance does early onset Alzheimer’s follow?

What genes are involved?

Answer 20

Follows autosomal dominant pattern (50% chance inheritance)

Genes:

• Chromosome 14 PSEN-1 (presenilin 1) gene
  
  • 80% of familial AD
  • Symptoms as young as 30yrs
• Chromosome 1 PSEN-2 (presenilin 2) gene
  
  • Symptoms later than PSEN-1
• Chromosome 21 APP (amyloid precursor protein) gene

Question 21

What genetic disorder conveys a high risk of also developing Alzheimer’s?

Answer 21

Down Syndrome (Trisomy 21)

• 3 copies of APP (amyloid precursor protein)
• 50% of Down’s syndrome people who live to 60 get AD

Question 22

What are the features of dementia with Lewy-bodies?

Answer 22

1. Progressive cognitive impairment:
   
   • Visuo-spatial decline, language, dyspraxia
2. Parkinsonism triad:
   
   • Bradykinesia, rigidity, tremor
3. Visual hallucinations e.g. children/little people or animals
4. Autonomic dysregulation: urinary incontinence, constipation
5. Sleep disturbances: nightmares, aggressive movements, disturbed sleep
6. Antipsychotic sensitivity - can develop irreversible parkinsonism

Question 23

Which of the following are mandatory parts of a standard dementia screening of an individual with memory loss which are essential for dementia diagnosis? (Select TWO)

• Neuropsychological assessment
• Cognitive testing
• History-taking
• SPECT scan
• Brain imaging - MRI/CT

Answer 23

Although all 5 are useful - these 2 are REQUIRED for dementia diagnosis:

1. History taking (most important)
2. Cognitive testing

• SPECT scan - type of functional neuroimaging that can help to differentiate between Alzheimer’s and Frontotemporal dementia
• MRI/CT - never diagnostic but could help to settle the diagnosis and show cerebrovascular issues

Question 24

How would you summarise the treatment available for Alzheimer’s?

(think conservative and pharmacological/medical)

Answer 24

Conservative:

• CBT, Cognitive stimulation therapy
• Aromatherapy, music therapy, reminiscence therapy

Medical:

• AChE Inhibitors (Donepezil, Galantamine, Rivastigmine)
• NDMA receptor antagonist (Memantine)

Question 25

**Vascular Dementia:** 1. What are the risk factors? 2. What is the pathophysiology? 3. How would you summarise the treatment?

Answer 25

**Risk Factors:** * AF, HTN, hyperlipidemia, smoking, diabetes (all risk factors for stroke/TIA) **Pathophysiology**: * Microvascular disease (e.g. atherosclerosis) --\> thrombi / emboli --\> infarcts --\> neuronal death * **STEP-WISE decline** **Treatment:** * Stop smoking * Manage the same as stroke/TIA: * Acute: aspirin (2 weeks) * Prevention: Statin, anticoagulation, antihypertensives

Question 26

What investigations would you do as part of a confusion screen? (think: bedise, bloods, imaging)

Answer 26

**Beside**: * Clinical history (**+ collateral**) * Observations - can identify sepsis * Physical examination e.g. abdo (suprapubic tenderness - UTI?), head trauma, alcohol withdrawel (tremor, fever, sweating) * MSE * Cognitive assessment Bloods: * FBC - ↑ WCC (infection) * CRP - ↑ in context of infection * U+Es - uraemia, hyponatraemia, hyper/hypocalcemia * B12 & Folate - deficiency can cause confusion * TFTs - confusion mor eommon in hypothyroidism * Glucose - hypoglycaemia * LFTs - liver failure (hepatic encephalopathy) * Coagulation / INR - important in context of cranial bleed **Imaging**: * CT head --\> MRI head

Question 27

Anticholinergic drugs DECREASE the effect of AChE inhibitors. Name some anti-cholingeric drugs.

Answer 27

Image shows **anticholinergic burden table** - mild, moderate, severe impact on ACh levels and thus their impact on ↓ AChE inhibitor efficacy. * **All antipsychotics** have anticholinergic properties * Beta-blockers + AChE-Is --\> ↑ each others effects --\> worsening bradycardia + syncope * Memantine + glutamate-R antagonists (e.g. ketamine, amantadine) --\> ↑ each others effects --\> pharmacotoxic psychosis

Question 28

Seperate the following statements by whether they are true of Alzheimers or DLB. * More common in men * Gradual decline in cognitive impairment * Fluctuating cognitive impairment * More common in women * Physical deterioration usually at a late stage * Decrease in facial expression develops later in disease * Visual hallucinations occur early * Hallucinations may occur, but in late stages * Early problems with balance * Face shows very little emotion from early in the disease

Answer 28

**Alzheimers**: 1. More common in **women** 2. **Gradual** decline in cognitive impairment 3. **Hallucinations** may occur, but in **late stages** 4. Physical deterioration usually at a late stage 5. Decrease in facial expression develops later in disease **DLB**: 1. More common in **men** 2. **Fluctuating** cognitive impairment 3. Visual **hallucinations** occur **early** 4. Early problems with balance 5. Face shows very little emotion from early in the disease

Question 29

What do the BMJ list as **core clinical features** of dementia with **Lewy-bodies**? (supportative clinical features or biomarkers are less important but can add to picture)

Answer 29

**Core clinical features**: (first 3 often occur early) 1. **Fluctuating cognition** + pronounced variability in attention/ alertness 2. **Visual hallucinations** (typically well formed and detailed) 3. **REM sleep behaviour disorder** (RBD - acting out dreams) 4. 1 or more **parkinsonism** features: bradykinesia, rest tremor, rigidity For PROBABLE DLB diagnosis, 2 or more core clinical features are needed or 1 + indicative biomarkers (see BMJ criteria - don't need to know) Supportive clinical features: 1. Severe sensitivity to antipsychotics 2. Autonomic dysfunction: constipation, orthostatic hypotension, urinary incontinence) 3. Postural instability (poor balance) 4. Repeated falls 5. Delusions 6. Depression

Question 30

What is the pathology underpinning DLB?

Answer 30

**alpha-synuclein deposits** within neurons in brain location of lewy-bodies influences symptom profile

Question 31

What medication can be given to manage REM sleep behaviour disorder (RBD - can be a feature of dementia with lewy-bodies)?

Answer 31

**Clonazepam** Benzodiazepine tranquilizer - enhances activity of GABA by binding to benzodiazepine receptor on GABA_A

Question 32

In patients with DLB and who have psychotic symptoms which are making the patient challenging (e.g. shouting, hitting etc) - if you choose to give an anti-psychotic, what are the best choices?

Answer 32

Pts with DLB or Parkinson's dementia are at risk of antipsychotic sensitivity!! 1. **Quetiapine** (low dose) 2. **Clozapine** (involves a lot of monitoring - thus quetiapine is preferred)

Question 33

How can you differentiate between DLB and Parkinson's disease with dementia?

Answer 33

**DLB**: * Dementia starts **BEFORE** and **WITHIN 1 YEAR** of the onset of PD symptoms **Parkinson's** **dementia**: * Dementia starts **\> 1 YEAR** after onset of PD symptoms Lewy Body Disease: * If time frame of dementia / PD symptoms is unknown then the name Lewy-Body disease might be used

Question 34

What are common features of Fronto-temporal dementia also called Pick's disease?

Answer 34

1. **Insidious** onset **\< 65** yrs 2. Relatively **preserved memory** + **visuospatial** 3. **Language issues**: * non-fluent aphasia - slow, hesitant speech, grammer errors, can't understand complex scentences * semantic dementia - anomia, describe items, can't recognise familiar people 4. **Personality changes**: * loss of sympathy / empathy * change in eating habits (e.g. crave sweet or fatty food, no table manners, don't stop eating / drinking) 5. **Social / behaviour problems**: * socially disinhibited + impulsive * apathy * repetitive, compulsive ritualised behaviours (hoarding, repeating phrases/gestures)

Question 35

What are the features (symptoms and radiological) of normal pressure hydrocephalus?

Answer 35

**Symptoms**: 1. **Fluctuating dementia** and bradyphrenia (slowness of thought) 2. **Urinary incontinence** 3. **Gait** **abnormality** (often similar to Parkinson's disease i.e. shuffling) **Radiological**: 1. Ventriculomegaly - widening of temporal horns of lateral ventricles, enlarged 4th ventricle 2. Callosal angle \< 90 degrees (angle between superior parts of lateral ventricles) 3. Absence of substantial sulcal atrophy 4. Tight high convexity - CSF spaces over convexity (superior brain) are narrowed