Lecture 9.2: The Ageing Brain and Dementia Flashcards
What is Dementia?
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
What is Delerium?
An acutely disturbed state of mind characterised by restlessness, illusions and incoherence caused by an underlying condition or event in vulnerable people
Most common causes of Dementia (6)
- Alzheimer’s Disease
- Vascular Dementia
- Dementia with Lewy Bodies
- Frontotemporal Dementia
- Parkinson’s Disease
- Plus Mixed Dementia
Symptoms of Minor Problems with Cognition (5)
- 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
Why are MCIs clinically relevant?
An individual with MCI is more likely to develop dementia
Risk Factors for Dementia: Non-Modifiable (6)
- Age
- Mild Cognitive Impairment
- Learning Disability e.g Trisomy 21
- Gender M<F
- Genetics
- Ethnicity
Risk Factors for Dementia: Modifiable (9)
- High Alcohol Intake
- Cognitive Inactivity & Educational Attainment
- Depression
- Diabetes Mellitus
- Hyperlipidaemia
- Obesity
- Physical Inactivity
- Smoking
- Social Isolation
Progressive Stages of Dementia: Early Features
- Loss of memory for recent events
- Global disruption of personality
- Gradual development of abnormal behaviour
Progressive Stages of Dementia: Intermediate Features
- Loss of intellect
- Mood changes blunting of emotions
- Cognitive impairment with failure to learn
Progressive Stages of Dementia: Late Features
- Reduction in self-care
- Restless wandering
- Incontinence
What percentage of dementias are Alzheimers Disease?
50-60%
What type of dementia can present with young onset?
Frontotemporal Dementia (FTD)
What are some other causes of Dementia? (8)
- Huntingtons Disease
- Prion Diseases
- Chronic Inflammation
- Toxic Poisoning of the Brain
- Infection
- Malignancy
- Trauma
- Metabolic
What is Alzheimer’s Disease characterised by deterioration in? (3)
- Thinking
- Conceiving
- Reasoning
What are some Non-Cognitive Symptoms of Alzheimer’s Disease? (5)
- Agitation
- Behavioural
- Depression
- Delusions
- Hallucinations
What happens in Early Alzheimer’s Disease? (2)
- Memory disturbance
- Impairment of recent memory function and
attention
What happens in Middle Alzheimer’s Disease? (4)
- Global cognitive decline
- Failure of language
- Failure of visual-special orientation
- Failure of abstract thinking and judgement
What happens in Late Alzheimer’s Disease? (3)
- Sever global decline
- Failure of self care
- Incontinence and total dependence
Early Onset AD
- Strong genetic link – familial disease
- <10% of AD cases
- Autosomal dominant
- Genes on chromosomes 1, 14 & 21
Late onset AD
- Sporadic
- Genetic risk factors - complex
- Most common on chromosome 19: APOE
- Several alleles exist, most common ε2, ε3, ε4
ε2 allele in Late onset AD
Rare and maybe protective (later onset)
ε3 allele in Late onset AD
Common and disease neutral
ε4 allele in Late onset AD
- 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
Pathophysiology of AD (5)
- Cerebral atrophy starting in the temporal lobes
- Loss of synaptic connections
- Neurofibrillary tangles
- Senile plaques
- Inflammation
What are Neurofibrillary Tangles in AD?
Collections of intra-neuronal cytoskeletal filaments esp phosphorylated tau
What are Senile Plaques in AD?
Extracellular deposits of abnormal protein and consist of amyloid-β-protein
What is Inflammation in AD?
Abnormal proliferation of astrocytes and microglia
Aβ results from cleavage of …1… by 2 peptidases
…2… and …3…
1) APP
2) β-secretase
3) γ-secretase
What are the most common Aβ’s produced in ‘normal’ brain? (2)
- Aβ40 and Aβ42
- Aβ40 > Aβ42
Mutations in APP associated with early-onset Alzheimer’s increase…?
- The relative production of Aβ42
- Aβ42 is more fibrillogenic
- Soluble oligomers of Aβ are more toxic than plaques
- Particularly impair functionality of synapses
What are some issues with the amyloid hypothesis?
- 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
