Dementia

Notes

Overview

Dementia is a disorder that is characterized by impairment of cognition, typically involving memory and at least one other cognitive deficit, such as aphasia, apraxia, agnosia, or disturbance in executive functioning. These must represent a decline from previous level of function and be severe enough to interfere with daily function and independence. Decrease in intellectual function without an effect on the level of consciousness.

Definition

Dementia: Cognitive impairment typically caused by anatomic changes in the brain, has slower onset, and is generally irreversible. Dementia mainly affects memory.
Delirium: Cognitive impairment typically caused by acute illness or drug toxicity (sometimes life threatening) and is often reversible. Delirium mainly affects attention.
Agnosia: Failure to recognize or identify objects despite intact sensory function.
Aphasia: Language impairment.
Apraxia: Impaired ability to carry out motor activities despite intact motor function.
Executive Functioning: Planning, organizing, sequencing, abstracting.

Risk Factors

Cardiometabolic factors

Atherosclerosis
Diabetes mellitus
Hypertension
Hypercholestrolaemia
Smoking
Metabolic syndrome
Obesity and BMI
Vascular disease
Atrial fibrillation

Other weaker factors

Head trauma
Alcohol
Chronic kidney disease
Homocysteine
Dietary fat
Oestrogens
Hearing loss
Gait impairment
Vitamin D deficiency
Inflammatory markers
Medical illness
Obstructive sleep apnoea
Toxin exposure
Medications
Depression

Signs and Symptoms

Clinical Presentation

A reasonably healthy elderly person who is experiencing an insidious onset of problems with memory and organizational ability, which worsened markedly over the past few months.

Memory deficits
Apraxia
Aphasia
Agnosia
Loss of abstract thought
Behavioural/personality changes
Impaired judgement
Loss of complex motor skills

Clinical Examination

Signs of stroke?
Signs of the reversible causes of dementia?

Aetiology

Reversible Causes of Dementia

Hypothyroidism

Depression

Vitamin B12 deficiency

Normal pressure hydrocephalus

Neurosyphilis

Chronic Alcohol use

Opiates

Differential Diagnosis

Differential Diagnosis (4D’s of cognitive decline)

Depression
Delirium
Decline (normal age related)
Dementia

the reversible causes of dementia such as hypothyroidism, chronic alcohol use and vitamin B12 deficiency.

Both depression and dementia are relatively common and often coexist. Over 20% of people with an early degenerative dementia may be depressed or apathetic. This sometimes reflects a depressive reaction to the onset of dementia.

Definition

Dementia: Cognitive impairment typically caused by anatomic changes in the brain, has slower onset, and is generally irreversible. Dementia mainly affects memory.
Delirium: Cognitive impairment typically caused by acute illness or drug toxicity (sometimes life threatening) and is often reversible. Delirium mainly affects attention.

Difference between Dementia and Delirium
	Dementia	Delirium
Onset	Sub-acute	Acute
Conscious level	Normal	Fluctuates
Hallucinations	Late event	Common
Agitation/agression	Uncommon until late	Common
Thought form	Poverty of thought late	Flight of ideas
Memory	Slow decline	Poor

Investigations

Cases of reversible dementia are uncommon, but their identification is important. Effective treatment may reverse the impairment and prevent its progression.

Assessment of Cognition

Mini Mental State Examination
Abbreviated Mental Test Score
General Practitioner Assessment of Cognition
Montreal Cognitive Assessment
Addenbrook’s Cognitive Examination

Bloods

FBC – ↑MCV suggests alcoholism, or low B12 or folate
ESR – Malignancy
EUC, LFT – renal/hepatic failure, alcoholism
BSL
Thyroid Function test – hypothyroidism?
VitB₁₂
ANA (antinuclear antibodies)
STD screen (syphilis, HIV)

Other

CXR – Sarcoidosis
CT/MRI Brain – exclude treatable structural lesions (hydrocephalus, subdural haematoma)
EEG – Creutzfeldt-Jakob disease
CSF analysis – suspected infection, neurological diseases
Urine bedside tests
MCS
Lumbar puncture – if CNS infection is suspected
Electroencephalogram – if seizure activity is suspected

Indications for Neuroimaging

Early onset (<65 years old)

Sudden onset or brisk decline

Focal CNS signs or symptoms

High risk of structural pathology (e.g., infarct, subdural hematoma, normal-pressure hydrocephalus, or tumor)

Diagnosis

DSM-V Criteria of Dementia

Significant cognitive impairment in at least one of the following cognitive decline:

Learning and memory
Language
Executive function
Complex attention
Perceptual-motor function
Social cognition

With the following:

Acquired and a significant decline from previous level of functioning.
Deficits interfere with independence in ADLs.
Disturbances aren’t occurring exclusively during course of delirium
Disturbances aren’t accounted for by another mental disorder

Aetiology

AETIOLOGY
Irreversible Causes	Reversible Causes
Alzheimer’s disease	Hypothyroidism
Lewy body dementia	Depression
Huntington’s disease	Vitamin B12 deficiency
Pick’s disease	Normal pressure hydrocephalus
Cerebral infarct	Neurosyphilis
Creutzfeldt-Jakob disease	Chronic Alcohol use
Chronic substance abuse	Opiates

Pathophysiology

The pathophysiology section will focus on the most common irreversible causes of dementia:

Alzheimer’s Disease (50-70%)
Vascular Disease (10-20%)
Lewy-Body Dementia (10%)
Frontaltemporal Lobe Dementia

Alzheimer’s Disease (50-70%) 15% are familial with two main groups

Early-onset disease with autosomal dominant inheritance
Later-onset (inheritance polygenic)

Pathogenesis

Cortical atrophy
Senile plaques and neurofibrillary tangles
Accumulation of beta amyloid precursor proteins → progressive neurological damage

Vascular Dementia (10-20%) Accumulation of small (lacunar) or large infarctions

Pathogenesis

Focal or diffuse infarcts or haemorrhage
Small vessel disease; white matter ischaemia

One way of differentiating between Alzheimer’s disease and vascular dementia is with a trial of cholinesterase inhibitors which is effective in Alzheimer’s but much weaker in vascular.

Lewy-Body Dementia (10%) Clinically characterised by dementia and signs of Parkinson’s disease. Often inherited – mutations in alpha-synuclein and beta-synuclein

Pathogenesis

Accumulation or protein aggregates in neurons
Lewy bodies in cerebral cortex – cytoplasmic inclusion bodies composed of ubiquitin and alpha-synuclein

Frontaltemporal Lobe Dementia (Pick’s Disease)

Pathogenesis

Atrophy of frontal/temporal lobes
Agyrophilic cytoplasmic inclusion bodies of tau

Management

Involve the patient in her own therapy.

Non-Pharmacological Management

Education for families and carers
Encourage patients to maintain social, physical and recreational activities
Brain stimulation and engagement therapy

Pharmacological Management

Treatment of Dementia

Cholinesterase inhibitors – for Alzheimer’s disease only
- Loss of cholinergic neurones = ↓ acetylcholine levels
- Cholinesterase inhibitors act to prolong effects of acetylcholine
Antiglutaminergic treatment
- NMDA antagonist = ↓ glutamate-induced neuronal degradation

Pharmacology

Cholinesterase Inhibitors or ChEIs (donepezil, rivastigmine and galantamine) work by inhibiting cholinesterase, an enzyme responsible for the break down of acetylcholine. ChEIs result in ↑acetylcholine molecules that are available to interact with the postsynaptic acetylcholine receptors, which results in an increase in central nervous system acetylcholine activity. ChEIs offer symptomatic benefit through stabilization of cognition (NOT A CURE). The underlying disease continues to progress at the same rate. Side effects: nausea, vomiting, diarrhea, anorexia, weight loss, dizziness, bradycardia, myalgias, and insomnia.

In Alzheimer disease, atrophy of the nuclei in the cells in key areas of the brain, such as the basal forebrain, leads to a demonstrable decrease in cholinergic function.

Treatment of behavioural and psychological symptoms

Antidepressant with minimal anticholinergic side effects

Treatment of Agitation

Antipsychotic medications (Caution with Lewy body dementia as it worsens Parkinsonism)
Benzodiazepines
Mood stabilisers – Sodium valproate

Pharmacology

The GABA-A receptor is a ligand-gated chloride-selective ion channel. The GABA molecule is inhibitory in nature and thus reduces the excitability of neurons. GABA produces a calming effect on the brain. Benzodiazepines also known as Benzo’s, are GABA-A agonists. They work by binding to GABA-A receptors in the brain increasing the affinity of GABA and its receptor (benzodiazepines potentiate GABAergic neurotransmission). Side effects: drowsiness, lethargy, and fatigue. At higher dosages, impaired motor coordination, dizziness, vertigo, slurred speech, blurry vision, mood swings, and euphoria can occur, as well as hostile or erratic behavior in some instances. Tolerance, dependence, and withdrawal are adverse effects associated with long-term use.

Complications and Prognosis

Complications many with continuing management and abuse. This also encompasses problems towards the careers.

Driving problems
Falls risk
Wandering
Aggression – by a patient toward caregivers or family is usually verbal, but sometimes physical or sexual. It may lead to caregivers to refuse to work with a patient.
Elder abuse may be difficult to identify, as the patient may not complain (due to fear or cognitive problems).
Neglect of self-care is often with poor insight.
Fire risk
Financial abuse
Medication administration

References

Australian Doctor, How to treat, Dementia, A/Prof S. Mcfarlane and Prof D. O’Connor, 2010 http://www.australiandoctor.com.au/cmspages/getfile.aspx?guid=afc00636-61e7-4a49-9e13-9bf87db4efbd
BestPractice
Colledge, N. R., Walker, B. R., Ralston, S., & Davidson, S., Sir. (2010). Davidson’s principles and practice of medicine(21st ed.). New York;Edinburgh;: Churchill Livingstone/Elsevier.
Dementia, eTG, Published July 2013. Amended October 2015. © Therapeutic Guidelines Ltd (eTG March 2016 edition)
Oxford Handbook of Geriatric Medicine
NPS, Treating the symptoms of Dementia, Assoc Profressor Michael Woddward http://www.nps.org.au/publications/health-professional/prescribing-practice-review/2008/nps-prescribing-practice-review-43
Murtagh, J. (2011). John murtagh’s general practice (5th ed.). North Ryde, N.S.W: McGraw-Hill.
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