Armando Hasudungan
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Dementia

Overview

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.

Categories

Major dementia syndromes

  • Alzheimer’s Disease (50-70%) – 15% are familiar in origin including early-onset dementia
  • Vascular Disease (10-20%) – Accumulation of small (lacunar) or large infarctions
  • Lewy-Body Dementia (10%) – Clinically characterised by dementia and signs of Parkinson’s disease. Often inherited – mutations in alpha-synuclein and beta-synuclein
  • Frontaltemporal Lobe Dementia
Remember It is important to diagnose the type of dementia as treatment differs
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

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

  1. Early-onset disease with autosomal dominant inheritance
  2. 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
Side note 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

Remember 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.
Side note 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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