Week 4 Lecture 4a - Late Life Disorders (DN) Flashcards Preview

• Prevalence
  • Worldwide: 25 million (0.4% population)
  • Australia: 245,000 (quadruple by 2050)
  • Increases with age
• Prognosis
  • Highly individual

• Stage 1 (MILD)
  • Difficulty remembering things; forget simple things; forget words for items;
  • awareness of memory lapses;
  • mood swings
• Stage 2 (MODERATE)
  • More severe memory impairment; asking repetitive questions;
  • Difficulty in every day life; become messy; social withdrawal;
  • recite the past often;
  • personality changes;
  • inability to recognize familiar people;
  • socially withdrawn;
  • sleep disturbances;
  • loss of inhibition 
• Stage 3 (SEVERE)
  • Oblivious to surrounding environment;
  • Unable to care for self;
  • may lose ability to communicate;
  • Sleep often;
  • Often vulnerable to other illnesses.

20:00

• Alzheimers
• Frontotemporal
• Vascular

• Observed by Alzheimer in 1906
  • Brain tissue irreversibly dies
  • marked deterioration on memory & cognition

22:30

• Absentmindedness,
• irritability
• attention
• short-term/working memory

As progresses

• Language problems, word finding, disorientated
• socially withdrawn
• Depression
• changes in sleep & appetite
• not recognising others

Plaques & Tangles

• beta-amyloid accumulates
  • forming abnormal amyloid protein plaques
  • kills the cell (neuron)

25:00

• either too much is produced or
• not enough broken down

from protein Tau

• Healthy brain
  • produces beta-amyloid (normal cell function)
  • excess is then broken down 
• Alzheimer's brain
  • accumulation of beta-amyloid

• PET Scan
• Cerebrospins Fluid (CSF)

• Normally too late by this stage
  • by this stage the disease has normally progressed
• Need to locate early biomarkers

1. Accumulation of beta-amyloid plaques (start in PFC)
2. Tangles (start in Hippocampus)
   • from protein Tau which stabilises axon
   • axons strangle themselves & crumble
3. Synaptic deficits
4. Loss of Neurons
5. Cognitive decline

Physical Appearance of Brain

• Brain shrinkage
• Increased Ventrical Size

24:50

• Genetics
• Heritability estimates – 79%
  • meaning 79% variance in Alzheimer's is attributable to genetics
  • 21% to other factors (e.g., environmental)

Early-onset (risk sits on different gene to late-life onset)

• Single gene identified for early-onset Alzheimer’s – chromosome 21.
  • same as Down Syndrome (3rd pair) - more likely to develop early onset Alz
  • extra risk on that chromosome

Risk Factor in Later Life

• Chromosome 19 – APOE-4. (alipo protein gene)
  • APOE is polymorphic (APOE 2, 3) but the inc risk is on 4
  • Increased risk from one E 4 allele = ~30%
  • Increased risk from two E 4 allele = ~90%
  • ~50% of Alzheimer’s patients have one E 4 allele,
  • ~30% are APOE- 4 negative.
  • so clearly it is not causal, but contributory

28:25

• beta-amyloid

32:30

Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL)

Risk Factors

• Environment
  • smoking, being single, depression, low social support

Protective Factors

• Use it or lose it
• Cognitive enhancement
  • people engaged cognitively have fewer deposits of bet-amyloid plaques
• Nun study - kept diaries
  • coded diaries for linguistic ability
  • 90% of those with low linguistic ability - developed Alz
  • 10% of those with high linguistic ability - developed Alz
• Protection of Puzzles
• Mediterranan diet, exercise, education

• Progressive neurodegenerative disorder
  • loss of neurons in frontal and temporal regions
• Typical onset – mid-late 50s
  • Mean age 52.8y
  • M:F ratio – 14:3
• Prevalence
  • 4-20% of Dementia’s 
• Characteristics:
  • Executive Dysfunction
    • due to changes in PFC
  • Emotional regulation
    • massive personality & mood changes
    • difficult to care for a person with this
• Prognosis
  • Poor (death within 5yrs)
• Strong genetic component

38:25

Fronto-temporal Dementia

• earlier onset mid-late 50's
• more male

Alzheimers 

• later onset
• more female

• Pharmacological
  • TREAT: Drugs that increase levels of acetycholine (Alzheimers)
    • as Alzheimer's destoys cells in cholinergic system
  • PREVENT: Production of an antibody which binds to APP – prevents beta amyloid. 
  • Antipsychotics/Antidepressants/Benzodiazepines/Sedatives 
• Psychological
  • Psychotherapy (especially for family members)
  • Exercise
  • Behavioural intervention to reduce agitation & anxiety
  • Cognitive enhancement

40:30

• Clare referred us to text
• said if its in the text, yes its examinable
• didn't spend any time on this in lecture

• an antibody which binds to the amyloid precursor protein
  • which is the precursor to beta-amyloid
• if can stop that process, may be able to stop the disorder

41:25

• Changes in sleep due to natural ageing

Prevalence

• 25% of mild-moderate AD and
• 50% moderate-severe = sleep disturbance

What problems do they experience?

• Sundowning - wander around, almost like a delirium

Does this provide insight into cognitive functioning?

• sleep impacts cognitive function of healthy adults
• sleep takes a hit in normal ageing
• AD sufferers are ageing & have already got cognitive dysfunction
• add poor sleep to the mix!!!

Sundowning

Sleep disturbance

Dont know which causes which, but we do know the co-occur

45:30

• 59% MCI patients have poor sleep
  • consistent across reporting types
• poor sleep in MCI associated with poorer outcomes on
  • nonverbal learning
  • attention
  • executive function 
• Circadian timing advanced (go to bed earlier & wake earlier)
• Biological (internal) timing  
  • i.e., Melatonin expression shifts forward (associated
  • greater the shift forward, the greater the level of cognitive impairment

45:30

• how does delaying biological timing systems
• preimposed timing systems
• does this give improved sleep, cognitive outcomes

• bright light and melatonin intervention in institutionalised patients with dementia
• randomised control
• long term, double-blind, placebo-controlled, 2 x 2
  • Whole day bright light (1000 lux) vs. dim light (300lux)
  • Evening melatonin vs. placebo
• Assessed at baseline, 6 weeks
• and every 6mths for 3.5 years

48:10

Light

• Reduction of cognitive deficits by 5%
  • No deceleration of decline
• Reduced depressive symptomology by 19%
• Attenuated gradual increase in functional limitations by 53%

Melatonin

• Reduced mood (ameliorated by the light)
• Attenuated agitation when combined with light by 9%
• Reduced sleep onset by 19%
• Increased total sleep duration by 6%
• Increased duration of uninterrupted sleep by 25%

50:00

comparable to the cholinergic medication currently prescribed to patients with dementia

cost effective, easy to employ, very few side effects with similar outcomes to pharmacological approach

50:20

aided sleep

• A clouded state of consciousness
• Lack of concentration and attention
• Disturbances in the sleep/wake cycle
• Perceptual disturbances are frequent
• Delusions relatively common (~25%)
• Mood Swings

• Drug/Medication Complications
• Metabolic/Nutritional Imbalances
• Infections/Fevers
• Neurological Disorders
• Extreme Stress

53:00

• Depression in late life
  • can be a myth
  • linked to changing time of life, losses
• Treatment of Depression in late life
  • Medication versus behavioural intervention
  • 60% successful

56:50

• similar to younger adults
• behavioural & pharmacological
• Implications for medication
  • anxiolitics - short term solution but
  • linked to cognitive decline, morbidity, can be addictive
  • elderly often awake thru night for toilet - drowsy, fall risk

• Older adults are less likely to have a mental health issue - 10-20% prevalence
  • is this a cohort effect (i.e., stigma - not reporting it having grown up in a different era)
• If they do have a mental disorder
  • is it a new disorder? - unlikely
  • 97% had experienced GAD & 94% depression before 65yrs old
• Early mortality for Anxiety & Depressives - so this also impacts elderly population