1. Alzheimer’s Disease
Alzheimer’s is a degenerative disease of the brain, resulting in:
cognitive and behavioural impairment, it interferes significantly with
social and occupational functioning.
It is often Medically referred to as DAT:
‘Dementia of Alzheimer’s Type’
Epidemiology:
 The MOST COMMON cause of Dementia – accounts for ~70% of cases
 Prevalence = 500, 000 (UK) and 30 million (Worldwide)
 Risk increases with age:
o 1% at 60 years
o 40% at 85 years
 Men and women are at equal risk, however women have a longer life span – therefore
there is a higher prevalence of women with Alzheimer’s than men
 Burden is likely to increase with more of the population reaching old age (>65 years)
Risk Factors:
Protective Factors:
Pathophysiology:
o Up to 50% of Neurons and Synapses in the Cortex and Hippocampus are lost
o There are TWO universal hallmarks of Alzheimer’s – as identified by Alois Alzheimer in his
original description of the disorder:
1. Amyloid Plaques
 Insoluble B-amyloid peptide deposits as Senile Plaques
 Present in: Hippocampus / Amygdala / Cerebral Cortex
 ↑Density = Advanced disease
2. Neurofibrillary Tangles (NFT’s)
 Phosphorylated Tau Protein
 Present in: Hippocampus / Substantia Nigra / Cerebral
Cortex
 DDx: Down’s Syndrome; Dementia Pugilistica;
Progressive Supranuclear Palsy

2. Genetics:
Chromosome 21 Gene codes  Amyloid Precursor Protein (APP) - also implicated in Down’s
Chromosome 19 Gene codes  Apolipoprotein E4 – alleles of which increase risk of DAT
Chromosome 14 Gene codes  Presenilin 1 – Implicated in B-amyloid peptide
Chromosome 1 Gene codes  Presenilin 11 – Implicated in B-amyloid peptide
Cholinergic Hypothesis:
o The Pathological changes above  degeneration of cholinergic nuclei in the Forebrain
o This results in reduced Cortical Acetylcholine
Clinically
Early symptoms: ↑ Forgetfulness; deteriorating self-care; Wandering and Irritability
THREE Main groups of symptoms:
1. Confusion:
 Amnesia: Universal, mainly for recent events
 Disorientation: Common – Person / Place / Time (Time especially)
 Declining Executive Function
2. Changes in:
 Personality: Often an exaggeration of its pre-morbid form with coarsening of affect and
increasing egocentricity
 Behaviour: Aggression, wandering, explosive temper, sexual disinhibition, incontinence,
excessive eating and searching behaviour
3. Development of:
 Psychiatric symptoms:
o Depression is common
o Delusions (15% - Usually paranoid)
o Auditory and/or Visual Hallucinations (10%)
 Focal Cognitive Defects:
o Aphasia: Receptive and Expressive
o Agnosia = Inability to recognise parts of the body
o Apraxia = Awkwardness of sequence of dressing
o Visual Spatial Impairment
 Spastic Paraparesis: Can occur but is an unusual and late
feature
Investigations:
 Mental State Examination (MSE): Assess Cognitive functioning
 Screening: Depression and Psychosis
 Physical Examination: Focal signs, reflexes, plantar responses, gait and signs of Parkinson’s
Disease
 Bloods: FBC, U&E’s, LFTs, TFT, Glucose, B12/Folate, MCV and Toxicology
 EEG: If you need to exclude Delirium or vCJD
 Brain Imaging:
o CT: Cortical atrophy (>Parietal and Temporal
Lobes) + Ventricular Enlargement
o MRI: Atrophy of Grey Matter (Hippocampus,
Amygdala, Medial Temporal lobe)
o SPECT: ↓ Regional Cerebral Blood flow
(Temporal, Parietal and later Frontal lobes)
o PET: 20-30% ↓Oxygen and Glucose
metabolism (Temporal and Parietal lobes)
o MRS (Magnetic Resonance Spectroscopy) =
↓N-Acetylaspartate

3. Prognosis:
 Natural History = Gradual and progressive decline, without
distinguishing features
 Risk factors for a poor prognosis:
o Males / Young Onset (<65years) /Parietal Lobe Damage /
Prominent behaviour problems / Focal deficits e.g. Apraxia /
Depression / Absence of misidentification syndrome – oddly.
Management
 Non-Pharmacological:
o Nursing Care – this can be in the community or in a residential home
o Timelines – reminding patients of significant events in their lives
o Timetables – reminding patients of day to day activities
o Activities to improve QOL e.g. Outings / Music or Animal Therapy (!)
 Pharmacological:
o Acetylcholinesterase Inhibitors
 1st
line in Mild to Moderate Alzheimer’s (MSE >12):
 Diagnosis: In a specialist clinic, according to standard diagnostic criteri
 Initiated by: Old age Psychiatrists / Neruologists / Care of the Elderly
Physicians, only.
 Review: 2-4months after reaching maintenance dose
 Follow up: 6 monthly, stop if having no benefit / MSE drops to <12
 Act by enhancing Acetylcholine at Cholinergic synapses in the CNS
 In this way, they may slow progression of the disease – reducing time spent in full
nursing care. They have beneficial effects on:
 Cognitive; Functional and Behavioural symptoms
 1st
Generation:
 Tacrine QDS – less used as can cause Hepatoxicity
 2nd
Generation:
 Donepezil Contraindicated in Asthma, OD
 Rivastigmine BD Not Contraindicated in Asthma or COPD
 Galantamine BD
o NMDA Receptor Antagonist
 Blocks the excessive levels of Glutamate that may lead to neuronal dysfunction
 Memantine – used in moderate to severe Alzheimer’s disease
 RCT’s show that memantine has a positive effects on: Cognition, Mood,
Behaviour and Functioning. However there is no evidence that is slows down
neurodegenration in Alzheimer’s
o Others “in the pipeline”
 Anti-oxidants e.g. Vitamin E and Selegiline
 Anti-inflammatories e.g. NSAIDs
 Amyloid Beta peptide Vaccination
 Cholesterol lowering drugs e.g. Statins
 Red wine (!)
Key Points:
 Alzheimer’s disease is the most common form of Dementia
 Pathophysiology: Amyloid Plaques and Neurofibrillary Tangles
 CT scan = Cortical Atrophy + Widening of Ventricles
 Acetylcholinesterase Inhibitors (MSE >12) = Donepezil, Rivastigmine and Galantamine
References:
1. Semple, D. Oxford Handbook of Psychiatry: 2nd
Edition. Oxford University Press; 2009
2. Bourke, Castle and Cameron. Crash Course Psychiatry. 3rd
Edition. Mosby Elsevier; 2008