Lecture 9.2: The Ageing Brain and Dementia Flashcards

1
Q

What is Dementia?

A

Dementia is an umbrella term for diseases that cause symptoms of progressive and largely irreversible clinical syndrome that is characterised by global deterioration in intellectual function, behaviour and personality in the presence of normal consciousness and perception

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2
Q

What is Delerium?

A

An acutely disturbed state of mind characterised by restlessness, illusions and incoherence caused by an underlying condition or event in vulnerable people

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3
Q

Most common causes of Dementia (6)

A
  • Alzheimer’s Disease
  • Vascular Dementia
  • Dementia with Lewy Bodies
  • Frontotemporal Dementia
  • Parkinson’s Disease
  • Plus Mixed Dementia
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4
Q

Symptoms of Minor Problems with Cognition (5)

A
  • Memory –forgetting recent events or repeating the
    same question
  • Reasoning, planning or problem-solving – struggling
    with thinking things through
  • Attention - being very easily distracted
  • Language - taking much longer than usual to find the
    right word for something
  • Visual depth perception - struggling to interpret an
    object in 3D, judge distances or navigate stairs
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5
Q

Why are MCIs clinically relevant?

A

An individual with MCI is more likely to develop dementia

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6
Q

Risk Factors for Dementia: Non-Modifiable (6)

A
  • Age
  • Mild Cognitive Impairment
  • Learning Disability e.g Trisomy 21
  • Gender M<F
  • Genetics
  • Ethnicity
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7
Q

Risk Factors for Dementia: Modifiable (9)

A
  • High Alcohol Intake
  • Cognitive Inactivity & Educational Attainment
  • Depression
  • Diabetes Mellitus
  • Hyperlipidaemia
  • Obesity
  • Physical Inactivity
  • Smoking
  • Social Isolation
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8
Q

Progressive Stages of Dementia: Early Features

A
  • Loss of memory for recent events
  • Global disruption of personality
  • Gradual development of abnormal behaviour
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9
Q

Progressive Stages of Dementia: Intermediate Features

A
  • Loss of intellect
  • Mood changes blunting of emotions
  • Cognitive impairment with failure to learn
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10
Q

Progressive Stages of Dementia: Late Features

A
  • Reduction in self-care
  • Restless wandering
  • Incontinence
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11
Q

What percentage of dementias are Alzheimers Disease?

A

50-60%

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12
Q

What type of dementia can present with young onset?

A

Frontotemporal Dementia (FTD)

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13
Q

What are some other causes of Dementia? (8)

A
  • Huntingtons Disease
  • Prion Diseases
  • Chronic Inflammation
  • Toxic Poisoning of the Brain
  • Infection
  • Malignancy
  • Trauma
  • Metabolic
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14
Q

What is Alzheimer’s Disease characterised by deterioration in? (3)

A
  • Thinking
  • Conceiving
  • Reasoning
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15
Q

What are some Non-Cognitive Symptoms of Alzheimer’s Disease? (5)

A
  • Agitation
  • Behavioural
  • Depression
  • Delusions
  • Hallucinations
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16
Q

What happens in Early Alzheimer’s Disease? (2)

A
  • Memory disturbance
  • Impairment of recent memory function and
    attention
17
Q

What happens in Middle Alzheimer’s Disease? (4)

A
  • Global cognitive decline
  • Failure of language
  • Failure of visual-special orientation
  • Failure of abstract thinking and judgement
18
Q

What happens in Late Alzheimer’s Disease? (3)

A
  • Sever global decline
  • Failure of self care
  • Incontinence and total dependence
19
Q

Early Onset AD

A
  • Strong genetic link – familial disease
  • <10% of AD cases
  • Autosomal dominant
  • Genes on chromosomes 1, 14 & 21
20
Q

Late onset AD

A
  • Sporadic
  • Genetic risk factors - complex
  • Most common on chromosome 19: APOE
  • Several alleles exist, most common ε2, ε3, ε4
21
Q

ε2 allele in Late onset AD

A

Rare and maybe protective (later onset)

22
Q

ε3 allele in Late onset AD

A

Common and disease neutral

23
Q

ε4 allele in Late onset AD

A
  • Increases risk of AD
  • But not everyone with Alzheimer disease have the
    APOE ε4 allele, and not all people who have this
    allele will develop the disease
24
Q

Pathophysiology of AD (5)

A
  • Cerebral atrophy starting in the temporal lobes
  • Loss of synaptic connections
  • Neurofibrillary tangles
  • Senile plaques
  • Inflammation
25
Q

What are Neurofibrillary Tangles in AD?

A

Collections of intra-neuronal cytoskeletal filaments esp phosphorylated tau

26
Q

What are Senile Plaques in AD?

A

Extracellular deposits of abnormal protein and consist of amyloid-β-protein

27
Q

What is Inflammation in AD?

A

Abnormal proliferation of astrocytes and microglia

28
Q

Aβ results from cleavage of …1… by 2 peptidases
…2… and …3…

A

1) APP
2) β-secretase
3) γ-secretase

29
Q

What are the most common Aβ’s produced in ‘normal’ brain? (2)

A
  • Aβ40 and Aβ42
  • Aβ40 > Aβ42
30
Q

Mutations in APP associated with early-onset Alzheimer’s increase…?

A
  • The relative production of Aβ42
  • Aβ42 is more fibrillogenic
  • Soluble oligomers of Aβ are more toxic than plaques
  • Particularly impair functionality of synapses
31
Q

What are some issues with the amyloid hypothesis?

A
  • Aged brains often contain amyloid plaques with no
    cognitive impairment
  • Amyloid plaque burden poorly correlates with
    severity
  • Neurofibrillary tangles NFTs of tau correlate with
    cognitive impairment more closely
  • NFTs can exist without amyloid plaques
  • Tau is required for AD in experimental cell models