Dementia and Huntington's

Question 1

Define Dementia.

Answer 1

Acquired, chronic, and progressive cognitive impairment, sufficient to impair ADLs.

Question 2

What are the generalised signs and symptoms of Dementia?

Answer 2

• 1st: Forgetfulness
• 2nd: Disorientation (time then place then person)
  
  • Wandering
  • Sleep-disturbance
  • Delusions
  • Hallucinations
  • Calling out
  • Inappropriate behaviour / aggression
• Behavioural and Psychological Symptoms
  
  • Mood changes
  • Abnormal behaviour
  • Hallucinations / delusions

Question 3

What are the appropriate investigations for suspected Dementia?

Answer 3

• Cognitive Assessment:
  
  • Screening - AMTS, GPCOG
    
    • AMTS (score <7 suggests cognitive impairment)
    • GPCOG (GP Assessment of Cognition)
  • Detailed - Addenbrooke’s, MMSE, MoCA
    
    • MMSE = 30 questions (18-23 is mild; <18 severe)
    • ACE-R = 100 questions
• Dementia/delirium screen:
  
  • TFTs
  • LFTs (Korsakoff’s)
  • U&Es and dipstick (infection, diabetes)
  • HbA1c
  • Vitamin B12 and folate

Question 4

What additional tests can be ran for suspected Alzheimer’s?

Answer 4

• FDG-PET
• CSF
• MRI
  
  • Grey matter atrophy
  • Wide ventricles & sulci
  • Temporal lobe atrophy

Question 5

What additional tests can be ran for suspected Vascular Dementia?

Answer 5

• ECG (AF with emboli)
• MRI/CT

Question 6

What additional tests can be ran for suspected Lewy Body?

Answer 6

• ¹²³I-FP-CIP SPECT (DaTScan; a tracer 123I-FP-CIP used in Single Photon Emission CT)
• I-MIBG

Question 7

What additional tests can be ran for suspected Frontotemporal?

Answer 7

• FDG-PET
• Perfusion SPECT
• MRI - frontal lobe shrinkage

Question 8

Define Alzheimer’s Disease.

Answer 8

Dementia with a steady progression

• Most common - 70%

Question 9

What are the 3 theories of Alzheimer’s pathophysiology?

Answer 9

• Amyloid
  
  1. APP cleaved by b-secretase
  2. sAPPb released and the C99 fragment remains
  3. C99 is digested by g-secretase releasing b-amyloid (Ab) protein
  4. Ab protein forms the toxic aggregates
• Tau
  
  1. Hyperphosphorylated tau is insoluble so self-aggregates
  2. The self-aggregates form neurofibrillary tangles (neurotoxic)
  3. The tangles result ultimately in microtubule instability and neurotoxic damage to neurones
• Inflammation
  
  1. Increased inflammatory mediators & cytotoxic proteins
  2. Increased phagocytosis
  3. Decreased levels of neuroprotective proteins

Question 10

What are the risk factors of Alzheimer’s Disease?

Answer 10

• Biological
  
  • Age – 1% at 60yo, risk doubles every 5 years
  • Sex – 2:1 Female to Male
  • Genetics (8% of risk, 92% sporadic – Presenilin 1 gene (Chr14), Presenilin 2 gene (Chr1), Beta-amyloid precursor protein (APP) gene (Chr21)
    
    • Co-existent Down’s syndrome increases risk
  • Head Injury
  • Vascular Risk Factors – HTN ect
• Psychological
  
  • Low IQ
  • Poor education level

Question 11

What are the signs and symptoms of Alzheimer’s Dementia?

Answer 11

• Presentation: “The Four A’s”
  
  • Amnesia - recent memories lost first; disorientation occurs early
  • Aphasia - Broca’s, speech muddled/disjointed
  • Agnosia - typically “visual” (i.e. prosopagnosia – recognising faces)
  • Apraxia - typically “dressing” (skilled tasks, despite normal motor functioning)
• BPSD = mood change, abnormal behaviour, hallucinations/delusions
  
  • Psychiatric presentations - delusions (15%), depression (20%), GAD
  • Behavioural disturbances - aggression, wandering, sexual disinhibition, explosive temper

Question 12

What are the good and bad prognostic factors for Alzheimer’s Dementia?

Answer 12

• Good prognostic indicator = female
• Bad prognostic indicators = male, depression, behavioural problems, severe focal cognitive deficit

Question 13

What is the management of Alzheimer’s Dementia?

Answer 13

• Biological
  
  • 1st line: Anticholinesterases
    
    • Donepezil
    • Galantamine
    • Rivastigmine
  • 2nd line: NMDA (Glutamate) partial receptor agonist
    
    • Memantine
• Psychological
  
  • Structural group cognitive stimulation sessions
  • Other: group reminiscence therapy, validation/reassure therapy, multisensory therapy (improve other senses)
• Social
  
  • Explain diagnosis
  • Optimise health in other areas (i.e. hearing aids, glasses)
  • Identify future wishes (i.e. advanced directives, lasting power of attorney)
• Follow-Up (every 6 months) - with yourself and a single named care manager

Question 14

What are the side effects of Anticholinesterases?

Answer 14

• GI - N&V, diarrhoea, anorexia
• Fatigue
• Dizziness
• Headache

Question 15

What are the absolute and relative contraindications of Anticholinesterases?

Answer 15

• Absolute contraindications
  
  • Anticholinergics (block ACh from binding)
  • Beta-blockers
  • NSAIDs
  • Muscle relaxants
• Relative contraindications
  
  • Asthma
  • COPD
  • GI disease
  • Bradycardia
  • Sick sinus syndrome
  • AV block

Question 16

Define Vascular Dementia.

Answer 16

Infarcts caused by thromboemboli or narrowing of arteries due to HTN leading to step-wise deterioration in cognitive function

Question 17

What are the risk factors for Vascular Dementia?

Answer 17

• Age
• Male
• Obesity
• Lack of exercise
• Smoking
• AF
• DM
• HTN
• CVA history - stroke, TIA

Question 18

What are the signs and symptoms of Vascular Dementia?

Answer 18

• Sudden onset (may follow CVA) with stepwise deterioration
  
  • 1st: emotional and minor personality changes (labile emotion)
  • 2nd: cognitive deficit
• Focal neurological signs (S/S reflect site of infarct) –
• Co-morbid depression
• Relatively preserved personality

Question 19

What is the management of Vascular Dementia?

Answer 19

• Biological:
  
  • Daily Aspirin (if indicated due to CVA/AF risk)
  • Reduce risk factors (exercise, less alcohol, treat HTN, stop smoking, treat AF, control DM)
• Psychological
  
  • Structural group cognitive stimulation sessions
  • Other: group reminiscence therapy, validation/reassure therapy, multisensory therapy (improve other senses)
• Social
  
  • Explain diagnosis
  • Optimise health in other areas (i.e. hearing aids, glasses)
  • Identify future wishes (i.e. advanced directives, lasting power of attorney)
• Follow-Up (every 6 months) - with yourself and a single named care manager

Question 20

Define Dementia with Lewy Bodies.

Answer 20

Dementia with the presence of Lewy Bodies - a-synuclein with ubiquitin

Question 21

What is the distribution of Lewy Bodies in DLB and Parkinson’s?

Answer 21

• DLB - LB are found in the brainstem, cingulate gyrus and neocortex
• Parkinson’s - LB are found in the brainstem

Question 22

What are the signs and symptoms of Dementia with Lewy Bodies?

Answer 22

• ≥2 of 3 – general gradual decline:
  
  • Fluctuating confusion with marked variations in alertness levels - may resemble delirium
  • Vivid visual hallucinations (Lilliputian hallucinations) – animals or humans
  • Parkinsonism - shuffling gait, bradykinesia, rigidity, amimia
  • Frequent falls
  • Co-morbid depression

Question 23

What is the management of Dementia with Lewy Bodies?

Answer 23

• Biological:
  
  • 1st line: Acetylcholinesterase inhibitors - Donepezil or Rivastigmine
  • Do not offer antipsychotics (increased risk of cerebrovascular disease)
• Psychological
  
  • Structural group cognitive stimulation sessions
  • Other: group reminiscence therapy, validation/reassure therapy, multisensory therapy (improve other senses)
• Social
  
  • Explain diagnosis
  • Optimise health in other areas (i.e. hearing aids, glasses)
  • Identify future wishes (i.e. advanced directives, lasting power of attorney)
• Follow-Up (every 6 months) - with yourself and a single named care manager

Question 24

Define Frontotemporal Dementia.

Answer 24

Atrophy of fronto-temporal regions

Question 25

What are the signs and symptoms of Frontotemporal Dementia?

Answer 25

* Frontotemporal dementia - *frontal lobe syndrome (disinhibition, social/personality changes)* * Semantic dementia - *progressive loss of understanding of verbal and visual meaning* * Progressive non-fluent aphasia - *1st: naming difficulties; 2nd: mutism* * Memory tends to be affected much later

Question 26

What is the management of Frontotemporal Dementia?

Answer 26

* Biological: * **Antidepressants** (treat frontal lobe syndrome) * Psychological * **Structural group cognitive stimulation sessions** * Other: group reminiscence therapy, validation/reassure therapy, multisensory therapy (improve other senses) * Social * Explain diagnosis * Optimise health in other areas (i.e. hearing aids, glasses) * Identify future wishes (i.e. advanced directives, lasting power of attorney) * Follow-Up (every 6 months) - with yourself and a single named care manager

Question 27

What is the prognosis of Frontotemporal Dementia?

Answer 27

* Death in 5-10 years

Question 28

What is Huntington's Disease?

Answer 28

Autosomal dominant trinucleotide expansion disorder resulting in abnormal Huntington protein and the triad of movement, cognitive and psychiatric disease

Question 29

What is the typical age of onset of Huntington's Disease?

Answer 29

* Onset 30-50yo * Onset and severity may be younger and greater in successive generations * A feature of all trinucleotide expansion disorders

Question 30

Name 2 trinucleotide expansion disorders.

Answer 30

Huntington's Fragile X syndrome

Question 31

What are the signs and symptoms of Huntington's Disease?

Answer 31

* Movement – *chorea, speech/swallowing, stumbling/clumsiness* * Cognitive – *organising tasks, flexibility, impulse control, learning new information, difficulty concentrating* * Psychiatric – *depression, irritability/mood swings, suicide in 9% of cases, personality change* * Lack of insight

Question 32

What investigations should you do for suspected Huntington's?

Answer 32

* Genetic analysis (HTT gene)