Alzheimer's disease is a degenerative brain disease that results in cognitive and behavioral impairment. It accounts for around 70% of dementia cases. The hallmarks of the disease are amyloid plaques and neurofibrillary tangles in the brain. Symptoms include memory loss, confusion, changes in personality and behavior, and problems with language and visual-spatial skills. Treatment focuses on acetylcholinesterase inhibitors and memantine to manage symptoms, as well as non-pharmacological approaches to improve quality of life. The disease is progressive and currently has no cure.
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