Dementia and Huntington's Flashcards
Define Dementia.
Acquired, chronic, and progressive cognitive impairment, sufficient to impair ADLs.
What are the generalised signs and symptoms of Dementia?
- 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
What are the appropriate investigations for suspected Dementia?
-
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
- Screening - AMTS, GPCOG
- Dementia/delirium screen:
- TFTs
- LFTs (Korsakoff’s)
- U&Es and dipstick (infection, diabetes)
- HbA1c
- Vitamin B12 and folate
What additional tests can be ran for suspected Alzheimer’s?
- FDG-PET
- CSF
- MRI
- Grey matter atrophy
- Wide ventricles & sulci
- Temporal lobe atrophy
What additional tests can be ran for suspected Vascular Dementia?
- ECG (AF with emboli)
- MRI/CT
What additional tests can be ran for suspected Lewy Body?
- 123I-FP-CIP SPECT (DaTScan; a tracer 123I-FP-CIP used in Single Photon Emission CT)
- I-MIBG
What additional tests can be ran for suspected Frontotemporal?
- FDG-PET
- Perfusion SPECT
- MRI - frontal lobe shrinkage
Define Alzheimer’s Disease.
Dementia with a steady progression
- Most common - 70%
What are the 3 theories of Alzheimer’s pathophysiology?
- Amyloid
- APP cleaved by b-secretase
- sAPPb released and the C99 fragment remains
- C99 is digested by g-secretase releasing b-amyloid (Ab) protein
- Ab protein forms the toxic aggregates
- Tau
- Hyperphosphorylated tau is insoluble so self-aggregates
- The self-aggregates form neurofibrillary tangles (neurotoxic)
- The tangles result ultimately in microtubule instability and neurotoxic damage to neurones
- Inflammation
- Increased inflammatory mediators & cytotoxic proteins
- Increased phagocytosis
- Decreased levels of neuroprotective proteins
What are the risk factors of Alzheimer’s Disease?
- 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
What are the signs and symptoms of Alzheimer’s Dementia?
- 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
What are the good and bad prognostic factors for Alzheimer’s Dementia?
- Good prognostic indicator = female
- Bad prognostic indicators = male, depression, behavioural problems, severe focal cognitive deficit
What is the management of Alzheimer’s Dementia?
- Biological
- 1st line: Anticholinesterases
- Donepezil
- Galantamine
- Rivastigmine
- 2nd line: NMDA (Glutamate) partial receptor agonist
- Memantine
- 1st line: Anticholinesterases
- 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
What are the side effects of Anticholinesterases?
- GI - N&V, diarrhoea, anorexia
- Fatigue
- Dizziness
- Headache
What are the absolute and relative contraindications of Anticholinesterases?
- Absolute contraindications
- Anticholinergics (block ACh from binding)
- Beta-blockers
- NSAIDs
- Muscle relaxants
- Relative contraindications
- Asthma
- COPD
- GI disease
- Bradycardia
- Sick sinus syndrome
- AV block
Define Vascular Dementia.
Infarcts caused by thromboemboli or narrowing of arteries due to HTN leading to step-wise deterioration in cognitive function
What are the risk factors for Vascular Dementia?
- Age
- Male
- Obesity
- Lack of exercise
- Smoking
- AF
- DM
- HTN
- CVA history - stroke, TIA
What are the signs and symptoms of Vascular Dementia?
- 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
What is the management of Vascular Dementia?
- 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
Define Dementia with Lewy Bodies.
Dementia with the presence of Lewy Bodies - a-synuclein with ubiquitin
What is the distribution of Lewy Bodies in DLB and Parkinson’s?
- DLB - LB are found in the brainstem, cingulate gyrus and neocortex
- Parkinson’s - LB are found in the brainstem
What are the signs and symptoms of Dementia with Lewy Bodies?
- ≥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
What is the management of Dementia with Lewy Bodies?
- 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
Define Frontotemporal Dementia.
Atrophy of fronto-temporal regions
What are the signs and symptoms of Frontotemporal Dementia?
- 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
What is the management of Frontotemporal Dementia?
- 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
What is the prognosis of Frontotemporal Dementia?
- Death in 5-10 years
What is Huntington’s Disease?
Autosomal dominant trinucleotide expansion disorder resulting in abnormal Huntington protein and the triad of movement, cognitive and psychiatric disease
What is the typical age of onset of Huntington’s Disease?
- Onset 30-50yo
- Onset and severity may be younger and greater in successive generations
- A feature of all trinucleotide expansion disorders
- Onset and severity may be younger and greater in successive generations
Name 2 trinucleotide expansion disorders.
Huntington’s
Fragile X syndrome
What are the signs and symptoms of Huntington’s Disease?
- 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
What investigations should you do for suspected Huntington’s?
- Genetic analysis (HTT gene)
