Alzheimer’s Disease

Epidemiology

  • Common cause of dementia (50-70% of cases).  Risk increases with age.  Females=males.

Aetiology

  • Autosomal dominant in 5-10% of cases (early, pre-senile onset).
  • Down’s syndrome patients are particularly at risk of early onset type (30-40 years old).
  • Amyloid Precursor Protein gene mutations may play a role, as may presenilin 1 & 2, gamma secretase genes and Apolipoprotein E (ApoE- 3 alleles associated with dementia: e4 most causative; e2 preventative; e3 normal).
  • Smoking, HRT and NSAIDs may be protective.

Pathophysiology

  • Loss of cortical neurons with the presence of:
    • Intracellular neurofibrilliary tangles (NFTs)- phosphorylated Tau proteins
    • Extracellular senile plaques containing amyloid β protein
      • A fragment of the product of the amyloid precursor protein (APP) gene on Ch 21.
  • Multiple neurotransmitter abnormalities with profound cholinergic loss.

Diagnosis

  • Progressive deterioration in memory (usually early)
    • Insidious development over >10 years with prominent impairment of episodic memory
    • Disturbance of recent memory function before and more affected than distant memory (Ribot’s law)
  • Deficits in 2 or more areas of cognition
    • Loss of ability to carry out daily tasks
    • Change in language (lexical ataxia)
    • Impairment of insight, judgement or planning
    • Orientation problems
    • Neuropsychiatric problems e.g. hallucination, delusion, mood change
  • Behaviour and Psychological Symptoms of Dementia (BPSD)
    • Prominent throughout AD and include depression; delusions; hallucinations; aggression; apathy; agitation etc.  Can lead to carer stress and institutionalisation.
  • Most often >65
  • Absence of systemic disorders that could account for sx
  • No disturbance of consciousness
  • Full Cognitive testing (e.g. Addenbrookes) should be performed

End-stage symptoms

  • Incontinence, motor disturbance, extra-pyramidal signs, stereotypic behaviour and primitive reflexes.

Staging

  • Very mild (Mild cognitive impairment- MCI)
    • MMSE 27-30
    • Isolated deficits in memory but functions well
    • Around 15% will develop AD proper
  • Mild AD
    • MMSE 20-26
    • Memory impairment is the most prominent deficit
    • Language well preserved other than isolated word-fingding problems
    • Deficits in reasoning and visuospatial processing
  • Moderate AD
    • MMSE 10-19
    • Dependent on others for higher level daily activities- requiring prompts and reminders
    • Failure of recognition
    • Prominent disturbance of language
    • Neuropsychiatric symptoms
  • Severe AD
    • MMSE <10
    • 24 hour care required
    • Motor apraxia also common
    • Seizures possible
    • Speech impoverished
    • Fragmentory cognition
    • Neuropsychiatric sx

Management

  • Cognitive Enhancers (Acetylcholinesterase inhibitors)
    • Donepezil (aricept- OD- reversible competitive inhibitor)
    • Rivastigmine (Exelon- BD/patch- reversible competitive inhibitor/nicotinic receptor agonist)- also of interest for dementia in PD
    • Galantamine (Reminyl- OD- reversible non-competitive inhibitor)
  • for “symptomatic treatment” of mild-moderate AD (also used in Lewy Body dementia sensitive to neuroleptic medication).  Should be used with caution, particularly in those with:
    • bradycardia/conductivity defects/sick sinus syndrome
    • GI ulcers
    • Epilepsy/ Parkinson’s disease
    • Severe COPD or any asthma
    • Urinary outflow obstruction
  • due to their cholinergic side-effects (although these are usually mild and transient).
  • Other side effects include
    • N&V&D
    • Headache, dizziness
    • Fatigue
    • Muscle cramps
    • Sweating
    • Bradycardia
    • Weight loss
    • Disturbed sleep
  • Memantine
    • Non-competitive NMDA receptor antagonist- may protect neurons from glutamate excitotoxicity.  Only for moderate-severe AD.
    • Side effects include vertigo, excitation/agitation and insomnia
  • For Behavioural and Psychological symptoms of dementia (BPSDs)
    • Use any psychotropic medications with great caution- avoid if possible.  Start low/slow.  Avoid particularly the typical antipsychotics- use newer atypicals.  Use short acting BZDs if required, but non-pharmacological therapies should be tried first where possible.
    • Search for a physical/organic cause in the first instance (i.e. most commonly delirium)
Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s